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Kullmann S, Wagner L, Hauffe R, Kühnel A, Sandforth L, Veit R, Dannecker C, Machann J, Fritsche A, Stefan N, Preissl H, Kroemer NB, Heni M, Kleinridders A, Birkenfeld AL. A short-term, high-caloric diet has prolonged effects on brain insulin action in men. Nat Metab 2025; 7:469-477. [PMID: 39984682 PMCID: PMC11946887 DOI: 10.1038/s42255-025-01226-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 01/30/2025] [Indexed: 02/23/2025]
Abstract
Brain insulin responsiveness is linked to long-term weight gain and unhealthy body fat distribution. Here we show that short-term overeating with calorie-rich sweet and fatty foods triggers liver fat accumulation and disrupted brain insulin action that outlasted the time-frame of its consumption in healthy weight men. Hence, brain response to insulin can adapt to short-term changes in diet before weight gain and may facilitate the development of obesity and associated diseases.
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Affiliation(s)
- Stephanie Kullmann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
- German Center for Diabetes Research (DZD), Neuherberg, Germany.
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Lore Wagner
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Robert Hauffe
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Science, Department of Molecular and Experimental Nutritional Medicine, University of Potsdam, Nuthetal, Germany
- German Institute of Human Nutrition, Junior Research Group Central Regulation of Metabolism, Nuthetal, Germany
| | - Anne Kühnel
- Section of Medical Psychology, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Bonn, Bonn, Germany
| | - Leontine Sandforth
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Ralf Veit
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Corinna Dannecker
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Section on Experimental Radiology, Department of Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Nobert Stefan
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Hubert Preissl
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Nils B Kroemer
- Section of Medical Psychology, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Bonn, Bonn, Germany
- Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health (TüCMH), University of Tübingen, Tübingen, Germany
| | - Martin Heni
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University of Ulm, Ulm, Germany
| | - André Kleinridders
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Science, Department of Molecular and Experimental Nutritional Medicine, University of Potsdam, Nuthetal, Germany
- German Institute of Human Nutrition, Junior Research Group Central Regulation of Metabolism, Nuthetal, Germany
| | - Andreas L Birkenfeld
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
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Pletsch-Borba L, Wernicke C, Machann J, Meyer NM, Huong Nguyen T, Pohrt A, Hornemann S, Gerbracht C, Pfeiffer AF, Spranger J, Mai K. Increase in PUFA and protein, and decrease in carbohydrate intake improves liver fat in 12 months and the role of weight loss as a mediator: A randomized controlled trial. Clin Nutr 2024; 43:361-369. [PMID: 39577067 DOI: 10.1016/j.clnu.2024.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 11/04/2024] [Accepted: 11/07/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND & AIMS Recently, a beneficial effect of high intake of unsaturated fatty acids (UFA) and protein on intrahepatic lipids (IHL) was demonstrated over 12 months within a randomized controlled trial (the NutriAct trial). We now aimed to explore the specific macronutrient components driving this IHL improvement within this trial in middle-aged and elderly subjects (50-80 y) at risk for age-related diseases. METHODS The NutriAct trial (n = 502) analyzed the effect of a high-protein and high-UFA diet on age related diseases including fatty liver disease. Individuals who completed 3-day food records with available IHL data both at baseline and at month 12 were included in this analysis. The impact of each macronutrient (E%) on IHL (measured by magnetic resonance spectroscopy) was analyzed by linear regression analyses and mediation analysis. Adherence in the intervention group was defined as intake at month 12 of ≥1 g protein/kg bodyweight or ≥25%E UFA intake; in the control group it was defined as intake of ≥15%E protein or ≥17%E UFA. RESULTS 248 participants were included in the analyses (34 % male, median age 66 y). Although BMI changed similarly in both groups within 12 months (mean change -0.41 kg/m2 in the control and -0.70 kg/m2 in the intervention group, p within groups <0.001, p between groups = 0.09), IHL improved more strongly in the compliant intervention participants than in compliant controls (estimate of relative change 0.21 % (95 % CI 0.01, 0.40), p = 0.03). Participants with stronger increase in protein and PUFA intake and a greater decrease in carbohydrate intake showed a stronger improvement in IHL (estimate for linear relative change -0.04 % (95%CI -0.06, -0.02), estimate 4th quartile vs. 1st quartile -0.40 % (95%CI -0.65, -0.16), and 0.32 % (95%CI 0.05, 0.59), respectively). These associations were partially mediated by BMI changes. Increase in PUFA intake was also directly associated with IHL improvement independently of BMI changes (estimate for linear relative change -0.03 % (95%CI -0.05, -0.01)). CONCLUSIONS Beneficial effects of increased protein and decreased carbohydrate intake on IHL are mediated by BMI changes in middle-aged and elderly subjects. The effect of high PUFA intake on IHL improvement was partly independent of weight loss. These results give insight into the understanding of a macronutrient specific effect on IHL changes in a long-term dietary intervention. CLINICAL TRIAL REGISTRATION The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.
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Affiliation(s)
- Laura Pletsch-Borba
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, Berlin, Germany
| | - Charlotte Wernicke
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Germany
| | - Nina Mt Meyer
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Thu Huong Nguyen
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Anne Pohrt
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Germany
| | - Silke Hornemann
- Human Study Center, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117, Berlin, Germany
| | - Christiana Gerbracht
- Human Study Center, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Andreas Fh Pfeiffer
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Human Study Center, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117, Berlin, Germany
| | - Joachim Spranger
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany; Max Rubner Center for Cardiovascular Metabolic Renal Research, 10115, Berlin, Germany
| | - Knut Mai
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117, Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany; Max Rubner Center for Cardiovascular Metabolic Renal Research, 10115, Berlin, Germany.
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Schuppelius B, Schüler R, Pivovarova-Ramich O, Hornemann S, Busjahn A, Machann J, Kruse M, Park SQ, Kabisch S, Csanalosi M, Ost AC, Pfeiffer AFH. Alterations in Glucagon Levels and the Glucagon-to-Insulin Ratio in Response to High Dietary Fat or Protein Intake in Healthy Lean Adult Twins: A Post Hoc Analysis. Nutrients 2024; 16:3905. [PMID: 39599691 PMCID: PMC11597242 DOI: 10.3390/nu16223905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 11/11/2024] [Accepted: 11/13/2024] [Indexed: 11/29/2024] Open
Abstract
Background/Objectives: Emerging data support evidence of the essential role of glucagon for lipid metabolism. However, data on the role of dietary fat intake for glucagon secretion is limited. This analysis investigated whether altering nutritional fat intake affects glucagon levels in healthy subjects. Methods: A total of 92 twins (age: 31 ± 14 years, BMI: 23 ± 3 kg/m2) consumed two 6-week diets: first a low-fat, high-carbohydrate diet (LFD) followed by an isocaloric high-fat, low-carbohydrate diet (HFD). In total, 24 twins (age: 39 ± 15 years, BMI: 24 ± 2 kg/m2) continued with a high-protein diet (HPD). Clinical investigations were performed after 6 weeks of the LFD, after 1 and 6 weeks of the HFD and after 6 weeks of the HPD. Results: The LFD caused a significant decrease in fasting glucagon (-27%, p < 0.001) compared to baseline. After 6 weeks of the HFD, glucagon increased (117%, p < 0.001 vs. LFD), while free fatty acids decreased. Six weeks of the HPD further increased glucagon levels (72%, p = 0.502 vs. HFD), although fasting amino acid levels remained constant. Fasting insulin and HOMA-IR moderately increased after one week of the HFD, while six weeks of the HPD significantly decreased both. The fasting glucagon-to-insulin ratio decreased during the LFD (p < 0.001) but increased after the HFD (p < 0.001) and even further increased after the HPD (p = 0.018). Liver fat, triglycerides and blood glucose did not increase during the HFD. The heritability of glucagon levels was 45% with the LFD. Conclusions: An HFD increases glucagon levels and the glucagon-to-insulin ratio under isocaloric conditions compared to an LFD in healthy lean subjects. This rise in glucagon may represent a metabolic response to prevent hepatic steatosis, as glucagon increases have been previously shown to induce hepatic fat oxidation.
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Affiliation(s)
- Bettina Schuppelius
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Rita Schüler
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
| | - Olga Pivovarova-Ramich
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
- Department of Molecular Metabolism and Precision Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany
| | - Silke Hornemann
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
| | - Andreas Busjahn
- HealthTwiSt GmbH, Robert-Rössle-Strasse 10, 13125 Berlin, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich, Otfried-Müller-Str. 10, 72076 Tübingen, Germany
- Section of Experimental Radiology, Department of Diagnostic and Interventional Radiology, University of Tübingen, Geissweg 3, 72076 Tübingen, Germany
| | - Michael Kruse
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
| | - Soyoung Q. Park
- German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany
- Department of Decision Neuroscience and Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
- Neuroscience Research Center, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Stefan Kabisch
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany
| | - Marta Csanalosi
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Anne-Cathrin Ost
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
| | - Andreas F. H. Pfeiffer
- Department of Endocrinology and Metabolism, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 München-Neuherberg, Germany
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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 328] [Impact Index Per Article: 328.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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Meyer NMT, Kabisch S, Dambeck U, Honsek C, Kemper M, Gerbracht C, Arafat AM, Birkenfeld AL, Schwarz PEH, Machann J, Osterhoff MA, Weickert MO, Pfeiffer AFH. IGF-1 and IGFBP-1 as Possible Predictors of Response to Lifestyle Intervention-Results from Randomized Controlled Trials. Int J Mol Sci 2024; 25:6400. [PMID: 38928106 PMCID: PMC11203659 DOI: 10.3390/ijms25126400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 06/04/2024] [Accepted: 06/07/2024] [Indexed: 06/28/2024] Open
Abstract
Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions.
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Affiliation(s)
- Nina M. T. Meyer
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; (N.M.T.M.)
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Stefan Kabisch
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; (N.M.T.M.)
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Ulrike Dambeck
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Caroline Honsek
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Margrit Kemper
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Christiana Gerbracht
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Ayman M. Arafat
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; (N.M.T.M.)
| | - Andreas L. Birkenfeld
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany
- Department of Internal Medicine IV—Endocrinology, Diabetology, and Nephrology, University Hospital Tübingen, 72076 Tübingen, Germany
- Department of Diabetes, School of Life Course Science and Medicine, King’s College London, London WC2R 2LS, UK
| | - Peter E. H. Schwarz
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Department for Prevention and Care of Diabetes, Clinic of Medicine III, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- Paul Langerhans Institute Dresden, Helmholtz Center Munich, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany
- Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Martin A. Osterhoff
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
| | - Martin O. Weickert
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- The ARDEN NET Centre, ENETS CoE, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Centre of Applied Biological & Exercise Sciences (ABES), Faculty of Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
- Translational & Experimental Medicine, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Andreas F. H. Pfeiffer
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; (N.M.T.M.)
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
- Department of Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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7
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Reshef N, Gophna U, Reshef L, Konikoff F, Gabay G, Zornitzki T, Knobler H, Maor Y. Prebiotic Treatment in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)-A Randomized Pilot Trial. Nutrients 2024; 16:1571. [PMID: 38892505 PMCID: PMC11174003 DOI: 10.3390/nu16111571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 05/10/2024] [Accepted: 05/17/2024] [Indexed: 06/21/2024] Open
Abstract
Several studies show that gut microbiotas in patients with nonalcoholic fatty liver disease (NAFLD) differ from those in a healthy population, suggesting that this alteration plays a role in NAFLD pathogenesis. We investigated whether prebiotic administration affects liver fat content and/or liver-related and metabolic parameters. Patients with NAFLD and metabolic syndrome (age: 50 ± 11; 79% men) were randomized to receive either 16 g/day of prebiotic (ITFs-inulin-type fructans) (n = 8) or placebo (maltodextrin) (n = 11) for 12 weeks. Patients were instructed to maintain a stable weight throughout the study. Liver fat content (measured by H1MRS), fecal microbiota, and metabolic, inflammatory, and liver parameters were determined before and after intervention. Fecal samples from patients who received the prebiotic had an increased content of Bifidobacterium (p = 0.025), which was not observed with the placebo. However, the baseline and end-of-study liver fat contents did not change significantly in the prebiotic and placebo groups, neither did the liver function tests' metabolic and inflammatory mediators, including fibroblast growth factor-19 and lipopolysaccharide-binding protein. Body weight remained stable in both groups. These findings suggest that prebiotic treatment without weight reduction is insufficient to improve NAFLD.
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Affiliation(s)
- Naama Reshef
- Institute of Diabetes and Metabolism-Kaplan Medical Center, Rehovot 7661041, Israel; (T.Z.); (H.K.)
- School of Nutritional Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University, Jerusalem 9112102, Israel
| | - Uri Gophna
- Shmunis School of Biomedicine and Cancer Research, Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 6423906, Israel; (U.G.); (L.R.)
| | - Leah Reshef
- Shmunis School of Biomedicine and Cancer Research, Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 6423906, Israel; (U.G.); (L.R.)
| | - Fred Konikoff
- Institute of Gastroenterology and Hepatology-Meir Medical Center, Kefar Sava 4428164, Israel; (F.K.)
- Faculty of Medicine, Tel-Aviv University, Tel Aviv 6423906, Israel
| | - Gila Gabay
- Institute of Gastroenterology and Hepatology-Meir Medical Center, Kefar Sava 4428164, Israel; (F.K.)
| | - Taiba Zornitzki
- Institute of Diabetes and Metabolism-Kaplan Medical Center, Rehovot 7661041, Israel; (T.Z.); (H.K.)
- Hadassah School of Medicine, The Hebrew University, Jerusalem 9112102, Israel;
| | - Hilla Knobler
- Institute of Diabetes and Metabolism-Kaplan Medical Center, Rehovot 7661041, Israel; (T.Z.); (H.K.)
- Hadassah School of Medicine, The Hebrew University, Jerusalem 9112102, Israel;
| | - Yaakov Maor
- Hadassah School of Medicine, The Hebrew University, Jerusalem 9112102, Israel;
- Institute of Gastroenterology and Hepatology-Kaplan Medical Center, Rehovot 7661043, Israel
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8
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Poxleitner M, Hoffmann SHL, Berezhnoy G, Ionescu TM, Gonzalez-Menendez I, Maier FC, Seyfried D, Ehrlichmann W, Quintanilla-Martinez L, Schmid AM, Reischl G, Trautwein C, Maurer A, Pichler BJ, Herfert K, Beziere N. Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis. J Neuroinflammation 2024; 21:129. [PMID: 38745337 PMCID: PMC11092112 DOI: 10.1186/s12974-024-03080-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 03/29/2024] [Indexed: 05/16/2024] Open
Abstract
Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer's disease. [18F]FDG, [18F]FTHA, and [18F]GE-180 were used for in vivo PET imaging in wild-type and APPPS1 mice. Ex vivo flow cytometry and histology in brains complemented the in vivo findings. 1H- magnetic resonance spectroscopy in the liver, plasma metabolomics and flow cytometry of the white adipose tissue were used to confirm metaflammatory condition in the periphery. We found disrupted glucose and fatty acid metabolism after Western diet consumption, with only small regional changes in glial-dependent neuroinflammation in the brains of APPPS1 mice. Further ex vivo investigations revealed cytotoxic T cell involvement in the brains of Western diet-fed mice and a disrupted plasma metabolome. 1H-magentic resonance spectroscopy and immunological results revealed diet-dependent inflammatory-like misbalance in livers and fatty tissue. Our multimodal imaging study highlights the role of the brain-liver-fat axis and the adaptive immune system in the disruption of brain homeostasis in amyloid models of Alzheimer's disease.
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Affiliation(s)
- Marilena Poxleitner
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Sabrina H L Hoffmann
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Georgy Berezhnoy
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Tudor M Ionescu
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Irene Gonzalez-Menendez
- Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Florian C Maier
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Dominik Seyfried
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Walter Ehrlichmann
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Leticia Quintanilla-Martinez
- Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Andreas M Schmid
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Gerald Reischl
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Christoph Trautwein
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Andreas Maurer
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Bernd J Pichler
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany
- Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", Eberhard Karls University, Tübingen, Germany
| | - Kristina Herfert
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
| | - Nicolas Beziere
- Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Tübingen, Germany.
- Cluster of Excellence CMFI (EXC 2124) "Controlling Microbes to Fight Infections", Eberhard Karls University, Tübingen, Germany.
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9
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Haueise T, Schick F, Stefan N, Machann J. Comparison of the accuracy of commercial two-point and multi-echo Dixon MRI for quantification of fat in liver, paravertebral muscles, and vertebral bone marrow. Eur J Radiol 2024; 172:111359. [PMID: 38325186 DOI: 10.1016/j.ejrad.2024.111359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 02/03/2024] [Indexed: 02/09/2024]
Abstract
PURPOSE Excess fat accumulation contributes significantly to metabolic dysfunction and diseases. This study aims to systematically compare the accuracy of commercially available Dixon techniques for quantification of fat fraction in liver, skeletal musculature, and vertebral bone marrow (BM) of healthy individuals, investigating biases and sex-specific influences. METHOD 100 healthy White individuals (50 women) underwent abdominal MRI using two-point and multi-echo Dixon sequences. Fat fraction (FF), proton density fat fraction (PDFF) and T2* values were calculated for liver, paravertebral muscles (PVM) and vertebral BM (Th8-L5). Agreement and systematic deviations were assessed using linear correlation and Bland-Altman plots. RESULTS High correlations between FF and PDFF were observed in liver (r = 0.98 for women; r = 0.96 for men), PVM (r = 0.92 for women; r = 0.93 for men) and BM (r = 0.97 for women; r = 0.95 for men). Relative deviations between FF and PDFF in liver (18.92 % for women; 13.32 % for men) and PVM (1.96 % for women; 11.62 % for men) were not significant. Relative deviations in BM were significant (38.13 % for women; 27.62 % for men). Bias correction using linear models reduced discrepancies. T2* times were significantly shorter in BM (8.72 ms for women; 7.26 ms for men) compared to PVM (13.45 ms for women; 13.62 ms for men) and liver (29.47 ms for women; 26.35 ms for men). CONCLUSION While no significant differences were observed for liver and PVM, systematic errors in BM FF estimation using two-point Dixon imaging were observed. These discrepancies - mainly resulting from organ-specific T2* times - have to be considered when applying two-point Dixon approaches for assessment of fat content. As suitable correction tools, linear models could provide added value in large-scale epidemiological cohort studies. Sex-specific differences in T2* should be considered.
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Affiliation(s)
- Tobias Haueise
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Fritz Schick
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Norbert Stefan
- German Center for Diabetes Research (DZD), Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany; Department of Diabetology, Endocrinology and Nephrology, University Hospital Tübingen, Tübingen, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany.
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10
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Sandforth A, von Schwartzenberg RJ, Arreola EV, Hanson RL, Sancar G, Katzenstein S, Lange K, Preißl H, Dreher SI, Weigert C, Wagner R, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Katsouli N, Ntziachristos V, Dannecker C, Fritsche L, Perakakis N, Heni M, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Stumvoll M, Schwarz PEH, Hauner H, Lechner A, Seissler J, Yurchenko I, Icks A, Solimena M, Häring HU, Szendroedi J, Schürmann A, de Angelis MH, Blüher M, Roden M, Bornstein SR, Stefan N, Fritsche A, Birkenfeld AL. Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS). Lancet Diabetes Endocrinol 2023; 11:798-810. [PMID: 37769677 DOI: 10.1016/s2213-8587(23)00235-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 08/02/2023] [Accepted: 08/04/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Remission of type 2 diabetes can occur as a result of weight loss and is characterised by liver fat and pancreas fat reduction and recovered insulin secretion. In this analysis, we aimed to investigate the mechanisms of weight loss- induced remission in people with prediabetes. METHODS In this prespecified post-hoc analysis, weight loss-induced resolution of prediabetes in the randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS) was assessed, and the results were validated against participants from the Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 31, 2016, participants were recruited from eight clinical study centres (including seven university hospitals) in Germany and randomly assigned to receive either a control intervention, a standard lifestyle intervention (ie, DPP-based intervention), or an intensified lifestyle intervention for 12 months. For DPP, participants were recruited from 23 clinical study centres in the USA between July 31, 1996, and May 18, 1999, and randomly assigned to receive either a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their bodyweight were included in this analysis. Responders were defined as people who returned to normal fasting plasma glucose (FPG; <5·6 mmol/L), normal glucose tolerance (<7·8 mmol/L), and HbA1c less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or control intervention. Non-responders were defined as people who had FPG, 2 h glucose, or HbA1c more than these thresholds. The main outcomes for this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed models. FINDINGS Of 1160 participants recruited to PLIS, 298 (25·7%) had weight loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants were responders and 170 (57%) were non-responders. Responders were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; p<0·0001). The DPP validation cohort included 683 participants who lost at least 5% of their bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were non-responders. In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32·4 kg/m2 [SD 5·6] to mean at 12 months 29·0 kg/m2 [4·9] vs non-responders 32·1 kg/m2 [5·9] to 29·2 kg/m2 [5·4]; p=0·86). However, whole-body insulin sensitivity increased more in responders than in non-responders (mean at baseline 291 mL/[min × m2], SD 60 to mean at 12 months 378 mL/[min × m2], 56 vs 278 mL/[min × m2], 62, to 323 mL/[min × m2], 66; p<0·0001), whereas insulin secretion did not differ within groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163·7 pmol/mmol [60·6] vs non-responders 158·0 pmol/mmol [55·6] to 154·1 pmol/mmol [56·2]; p=0·46). IHL decreased in both groups, without a difference between groups (responders mean at baseline 10·1% [SD 8·7] to mean at 12 months 3·5% [3·9] vs non-responders 10·3% [8·1] to 4·2% [4·2]; p=0·34); however, VAT decreased more in responders than in non-responders (mean at baseline 6·2 L [SD 2·9] to mean at 12 months 4·1 L [2·3] vs 5·7 L [2·3] to 4·5 L [2·2]; p=0·0003). Responders had a 73% lower risk of developing type 2 diabetes than non-responders in the 2 years after the intervention ended. INTERPRETATION By contrast to remission of type 2 diabetes, resolution of prediabetes was characterised by an improvement in insulin sensitivity and reduced VAT. Because return to normal glucose regulation (NGR) prevents development of type 2 diabetes, we propose the concept of remission of prediabetes in analogy to type 2 diabetes. We suggest that remission of prediabetes should be the primary therapeutic aim in individuals with prediabetes. FUNDING German Federal Ministry for Education and Research via the German Center for Diabetes Research; the Ministry of Science, Research and the Arts Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes to Fight Infections; and the German Research Foundation.
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Affiliation(s)
- Arvid Sandforth
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Reiner Jumpertz von Schwartzenberg
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Cluster of Excellence Controlling Microbes to Fight Infections, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Elsa Vazquez Arreola
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Robert L Hanson
- Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA
| | - Gencer Sancar
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Sarah Katzenstein
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Karl Lange
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Hubert Preißl
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Simon I Dreher
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Cora Weigert
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Kostantinos Kantartzis
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Jürgen Machann
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Radiology, Section on Experimental Radiology, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Fritz Schick
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Radiology, Section on Experimental Radiology, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Andreas Peter
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Nikoletta Katsouli
- Central Institute for Translational Cancer Research, Technical University of Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany
| | - Vasilis Ntziachristos
- Central Institute for Translational Cancer Research, Technical University of Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany
| | - Corinna Dannecker
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Louise Fritsche
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Nikolaos Perakakis
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany
| | - Martin Heni
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Peter Paul Nawroth
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Stefan Kopf
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Andreas F H Pfeiffer
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Stefan Kabisch
- German Center for Diabetes Research, Neuherberg, Germany; German Institute of Human Nutrition Potsdam-Rehbrücke, Brandenburg, Germany
| | - Michael Stumvoll
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Peter E H Schwarz
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany
| | - Hans Hauner
- German Center for Diabetes Research, Neuherberg, Germany; Institute of Nutritional Medicine, Technical University of Munich, Munich, Germany
| | - Andreas Lechner
- German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany
| | - Jochen Seissler
- German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany
| | - Iryna Yurchenko
- German Center for Diabetes Research, Neuherberg, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Andrea Icks
- German Center for Diabetes Research, Neuherberg, Germany; Institute for Health Services Research and Health Economics, Centre for Health and Society, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michele Solimena
- German Center for Diabetes Research, Neuherberg, Germany; Paul-Langerhans-Institut Dresden, Helmholtz Center Munich, University Clinic Carl Gustav Carus, Dresden, Germany
| | - Hans-Ulrich Häring
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Julia Szendroedi
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Annette Schürmann
- German Center for Diabetes Research, Neuherberg, Germany; German Institute of Human Nutrition Potsdam-Rehbrücke, Brandenburg, Germany
| | - Martin Hrabé de Angelis
- German Center for Diabetes Research, Neuherberg, Germany; School of Medicine and School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany; Institute of Experimental Genetics, Helmholtz Center Munich, Munich, Germany
| | - Matthias Blüher
- German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Michael Roden
- German Center for Diabetes Research, Neuherberg, Germany; Department of Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Medical Faculty and University Hospital, Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Stefan R Bornstein
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine III, Technical University Dresden, Dresden, Germany; Department of Diabetes, Life Sciences and Medicine, Cardiovascular Medicine and Sciences, Kings College London, London, UK
| | - Norbert Stefan
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research, Neuherberg, Germany; Department of Internal Medicine IV, Division of Diabetology, Endocrinology and Nephrology, Eberhard-Karls University of Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls University of Tübingen, Tübingen, Germany; Department of Diabetes, Life Sciences and Medicine, Cardiovascular Medicine and Sciences, Kings College London, London, UK.
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Wernicke C, Pohrt A, Pletsch-Borba L, Apostolopoulou K, Hornemann S, Meyer N, Machann J, Gerbracht C, Tacke F, Pfeiffer AF, Spranger J, Mai K. Effect of unsaturated fat and protein intake on liver fat in people at risk of unhealthy aging: 1-year results of a randomized controlled trial. Am J Clin Nutr 2023; 117:785-793. [PMID: 36804020 DOI: 10.1016/j.ajcnut.2023.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 01/08/2023] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Short-term trials indicate improvement of intrahepatic lipids (IHLs) and metabolism by dietary protein or unsaturated fatty acids (UFAs) beyond weight loss. OBJECTIVES We aimed to assess the effect of a dietary intervention high in protein and UFAs on IHLs and metabolic outcome after 12 mo, as long-term effects of such a combined intervention are unknown. METHODS Within a 36-mo randomized controlled trial, eligible subjects (aged 50 to 80 y, ≥1 risk factor for unhealthy aging) were randomly assigned to either intervention group (IG) with high intake of mono-/poly-UFAs [15-20 percent of total energy (%E)/10%-15%E, respectively], plant protein (15%-25%E), and fiber (≥30 g/d), or control group [CG, usual care, dietary recommendations of the German Nutrition Society (fat 30%E/carbohydrates 55%E/protein 15%E)]. Stratification criteria were sex, known cardiovascular disease, heart failure, arterial hypertension, type 2 diabetes, and cognitive or physical impairment. Nutritional counseling and supplementation of foods mirroring the intended dietary pattern were performed in the IG. Diet-induced effects on IHLs, analyzed by magnetic resonance spectroscopy, as well as on lipid and glucose metabolism were predefined secondary endpoints. RESULTS IHL content was analyzed in 346 subjects without significant alcohol consumption at baseline and in 258 subjects after 12 mo. Adjusted for weight loss, sex, and age, we observed a comparable decline of IHLs in IG and CG (-33.3%; 95% CI: -49.3, -12.3%; n = 128 compared with -21.8%; 95% CI: -39.7, 1.5%; n = 130; P = 0.179), an effect that became significant by comparing adherent IG subjects to adherent CG subjects (-42.1%; 95% CI: -58.1, -20.1%; n = 88 compared with -22.2%; 95% CI: -40.7, 2.0%; n = 121; P = 0.013). Compared with the CG, decline of LDL cholesterol (LDL-C) and total cholesterol (TC) was stronger in the IG (for LDL-C P = 0.019, for TC P = 0.010). Both groups decreased in triglycerides and insulin resistance (P for difference between groups P = 0.799 and P = 0.124, respectively). CONCLUSIONS Diets enriched with protein and UFAs have beneficial long-term effects on liver fat and lipid metabolism in adherent older subjects. This study was registered at the German Clinical Trials Register, https://www.drks.de/drks_web/setLocale_EN.do, DRKS00010049. Am J Clin Nutr 20XX;xx:xx-xx.
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Affiliation(s)
- Charlotte Wernicke
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Anne Pohrt
- Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Germany
| | - Laura Pletsch-Borba
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Konstantina Apostolopoulou
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Silke Hornemann
- NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, München-Neuherberg, Germany
| | - Nina Meyer
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany
| | - Jürgen Machann
- German Center for Diabetes Research, München-Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Germany
| | - Christiana Gerbracht
- NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Hepatology and Gastroenterology, 10117 Berlin, Germany
| | - Andreas Fh Pfeiffer
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, München-Neuherberg, Germany
| | - Joachim Spranger
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
| | - Knut Mai
- Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany
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12
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Predicting Factors for Metabolic Non-Response to a Complex Lifestyle Intervention-A Replication Analysis to a Randomized-Controlled Trial. Nutrients 2022; 14:nu14224721. [PMID: 36432409 PMCID: PMC9699496 DOI: 10.3390/nu14224721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/17/2022] [Accepted: 11/07/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND T2DM heterogeneity affects responsiveness to lifestyle treatment. Beta-cell failure and nonalcoholic fatty liver disease (NAFLD) independently predict T2DM, but NAFLD inconsistently predicts metabolic response to lifestyle intervention. AIM We attempt to replicate a prediction model deducted from the Tübinger Lifestyle Intervention Program by assessing similar metabolic factors to predict conversion to normal glucose regulation (NGR) in a comparable lifestyle intervention trial. METHODS In the Optimal Fiber Trial (OptiFiT), 131 Caucasian participants with prediabetes completed a one-year lifestyle intervention program and received a fiber or placebo supplement. We compared baseline parameters for responders and non-responders, assessed correlations of major metabolic changes and conducted a logistic regression analysis for predictors of remission to NGR. RESULTS NGR was achieved by 33 participants, respectively. At baseline, for the placebo group only, 1 h and 2 h glucose levels, glucose AUC and Cederholm index predicted conversion to NGR. HOMA-beta, HOMA-IR or liver fat indices did not differ between responders and non-responders of the placebo or the fiber group. Changes in waist circumference or fatty liver index correlated with changes in glycemia and insulin resistance, but not with changes in insulin secretion. Insulin-resistant NAFLD did not predict non-response. Differences in compliance did not explain the results. CONCLUSIONS Higher post-challenge glucose levels strongly predicted the metabolic non-response to complex lifestyle intervention in our cohort. Depending on the specific intervention and the investigated cohort, fasting glucose levels and insulin sensitivity might contribute to the risk pattern. Beta-cell function did not improve in accordance with other metabolic improvements, qualifying as a potential risk factor for non-response. We could not replicate previous data suggesting that an insulin-resistant fatty liver is a specific risk factor for treatment failure. Replication studies are required.
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13
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Meyer NMT, Kabisch S, Dambeck U, Honsek C, Kemper M, Gerbracht C, Arafat AM, Birkenfeld AL, Schwarz PEH, Machann J, Osterhoff MA, Weickert MO, Pfeiffer AFH. Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients. Eur J Endocrinol 2022; 187:555-565. [PMID: 36005859 DOI: 10.1530/eje-22-0034] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 08/25/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVES Some individuals develop type 2 diabetes mellitus (T2DM) despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that insulin growth factor 1 (IGF1) and its binding proteins 1 and 2 predict the onset of T2DM in prediabetes patients and determine the capacity for metabolic regeneration. DESIGN We measured fasting serum IGF1, insulin growth factor-binding protein 1 (IGFBP1) and IGFBP2 in three randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up. METHODS Within a sample of 414 high-risk prediabetes patients (58% women; 28-80 years), we analyzed fasting serum concentrations of IGF1, IGFBP1 and IGFBP2 in relation to diabetes incidence and metabolic parameters over 2 years. Three hundred and forty-five subjects finished the first year of intervention. RESULTS The interventions significantly improved body weight (BMI: -3.24%, P < 0.001), liver fat (-36.8%, P < 0.001), insulin sensitivity (IS) (homeostatic model assessment-insulin resistance: -6.3%, P < 0.001) and insulin secretion (disposition index: +35%, P < 0.001) in the cohort. Fourteen percent developed T2DM within 2 years. Mean IGFBP1 levels at baseline were lower in prediabetes compared to a healthy population. Also, prediabetes patients with obesity and nonalcoholic fatty liver disease had lower IGFBP1. Those with impaired glucose tolerance had higher IGFBP1 compared to those with only impaired fasting glucose. Baseline IGF1 was lower (122.5 vs 146.6 µg/L) and IGFBP1 was higher (3.32 vs 2.09 µg/L) in subjects who developed T2DM (n = 57), resulting in a significant prediction of diabetes incidence (hazard ratio (HR) IGF1: 0.991 µg/L, P = 0.003; HR IGFBP1: 1.061 µg/L, P = 0.002). This translates into a 20% and 9% difference in T2DM incidence for IGF1 and IGFBP1, respectively. Despite reduced weight, visceral fat and hepatic fat in response to 1 year of lifestyle intervention, those who developed T2DM had not improved insulin sensitivity, glucose tolerance or IGFBP1. CONCLUSIONS Lower IGF1 and higher IGFBP1 in prediabetes predicted the incidence of T2DM, indicating an impairment of beta-cell function, which explains the unresponsiveness to lifestyle intervention.
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Affiliation(s)
- Nina M T Meyer
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Stefan Kabisch
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Ulrike Dambeck
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Caroline Honsek
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Margrit Kemper
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Christiana Gerbracht
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Ayman M Arafat
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhard Karls University of Tübingen, Tübingen, Germany
- Department of Internal Medicine IV - Endocrinology, Diabetology, and Nephrology, University Hospital Tübingen, Tübingen, Germany
- Department of Diabetes, School of Life Course Science and Medicine, King's College London, London, UK
| | - Peter E H Schwarz
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Departments for Prevention and Care of Diabetes and Medicine III, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the Eberhard Karls University of Tübingen, Tübingen, Germany
- Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Martin A Osterhoff
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Martin O Weickert
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, The ARDEN NET Centre, ENETS CoE, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Centre of Applied Biological & Exercise Sciences (ABES), Faculty of Health & Life Sciences, Coventry University, Coventry, UK
- Translational & Experimental Medicine, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK
| | - Andreas F H Pfeiffer
- Department of Endocrinology and Metabolism (Diabetes and Nutritional Medicine), Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Research Group Clinical Nutrition/DZD, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
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14
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Guo H, Tikhomirov AB, Mitchell A, Alwayn IPJ, Zeng H, Hewitt KC. Real-time assessment of liver fat content using a filter-based Raman system operating under ambient light through lock-in amplification. BIOMEDICAL OPTICS EXPRESS 2022; 13:5231-5245. [PMID: 36425639 PMCID: PMC9664892 DOI: 10.1364/boe.467849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/23/2022] [Accepted: 08/26/2022] [Indexed: 06/16/2023]
Abstract
During liver procurement, surgeons mostly rely on their subjective visual inspection of the liver to assess the degree of fatty infiltration, for which misclassification is common. We developed a Raman system, which consists of a 1064 nm laser, a handheld probe, optical filters, photodiodes, and a lock-in amplifier for real-time assessment of liver fat contents. The system performs consistently in normal and strong ambient light, and the excitation incident light penetrates at least 1 mm into duck fat phantoms and duck liver samples. The signal intensity is linearly correlated with MRI-calibrated fat contents of the phantoms and the liver samples.
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Affiliation(s)
- Hao Guo
- Department of Physics and Atmospheric Science, Dalhousie University, 6310 Coburg Road, Halifax, NS B3H 4R2, Canada
- Department of Medical Physics, Nova Scotia Health Authority, 5820 University Avenue Halifax, NS B3H 1V7, Canada
| | - Alexey B. Tikhomirov
- Department of Physics and Atmospheric Science, Dalhousie University, 6310 Coburg Road, Halifax, NS B3H 4R2, Canada
| | - Alexandria Mitchell
- Department of Physics and Atmospheric Science, Dalhousie University, 6310 Coburg Road, Halifax, NS B3H 4R2, Canada
- Department of Medical Physics, Nova Scotia Health Authority, 5820 University Avenue Halifax, NS B3H 1V7, Canada
| | - Ian Patrick Joseph Alwayn
- Department of Surgery, Leiden University Medical Center (LUMC) Transplant Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - Haishan Zeng
- Imaging Unit, Integrative Oncology Department, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada
| | - Kevin C. Hewitt
- Department of Physics and Atmospheric Science, Dalhousie University, 6310 Coburg Road, Halifax, NS B3H 4R2, Canada
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15
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Li YW, Jiao Y, Chen N, Gao Q, Chen YK, Zhang YF, Wen QP, Zhang ZM. How to select the quantitative magnetic resonance technique for subjects with fatty liver: A systematic review. World J Clin Cases 2022; 10:8906-8921. [PMID: 36157636 PMCID: PMC9477046 DOI: 10.12998/wjcc.v10.i25.8906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 05/25/2022] [Accepted: 07/22/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging. AIM To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver. METHODS We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https:// www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review. RESULTS Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed. CONCLUSION The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.
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Affiliation(s)
- You-Wei Li
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yang Jiao
- Department of Rehabilitation Psychology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Na Chen
- Department of Otorhinolaryngology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yu-Kun Chen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Yuan-Fang Zhang
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Qi-Ping Wen
- Department of Radiology, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
| | - Zong-Ming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing 100073, China
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16
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Fritsche A, Wagner R, Heni M, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Dannecker C, Fritsche L, Valenta V, Schick R, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Dambeck U, Stumvoll M, Blüher M, Birkenfeld AL, Schwarz P, Hauner H, Clavel J, Seißler J, Lechner A, Müssig K, Weber K, Laxy M, Bornstein S, Schürmann A, Roden M, de Angelis MH, Stefan N, Häring HU. Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS). Diabetes 2021; 70:2785-2795. [PMID: 34531293 DOI: 10.2337/db21-0526] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 09/08/2021] [Indexed: 11/13/2022]
Abstract
Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years' follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was -0.29 mmol/L [95% CI -0.54; -0.04], P = 0.025. Liver fat (-1.34 percentage points [95% CI -2.17; -0.50], P = 0.002) and cardiovascular risk (-1.82 percentage points [95% CI -3.13; -0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype-based LI may be beneficial for the prevention of diabetes.
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Affiliation(s)
- Andreas Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Martin Heni
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Kostantinos Kantartzis
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Section on Experimental Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany
| | - Fritz Schick
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Section on Experimental Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Andreas Peter
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Corinna Dannecker
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Louise Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Vera Valenta
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Renate Schick
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Peter Paul Nawroth
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
- Institute for Diabetes and Cancer, IDC Helmholtz Center, Munich, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Neuherberg, Germany
| | - Stefan Kopf
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Andreas F H Pfeiffer
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Stefan Kabisch
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Ulrike Dambeck
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Michael Stumvoll
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Matthias Blüher
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Medicine, Endocrinology and Nephrology, Universität Leipzig, Leipzig, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Peter Schwarz
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Hans Hauner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Julia Clavel
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany
| | - Jochen Seißler
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Diabetes Research Group, Medical Department 4, Ludwig-Maximilians University Munich, Munich, Germany
| | - Andreas Lechner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Diabetes Research Group, Medical Department 4, Ludwig-Maximilians University Munich, Munich, Germany
| | - Karsten Müssig
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Katharina Weber
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Laxy
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Health Economics and Health Care Management, Neuherberg, Germany
| | - Stefan Bornstein
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany
| | - Annette Schürmann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Martin Hrabe de Angelis
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Experimental Genetics, IEG Helmholtz Center Munich, Neuherberg, Germany
- Chair of Experimental Genetics, School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
| | - Norbert Stefan
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Diabetology, Endocrinology and Nephrology, Department of Internal Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
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17
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Liao R, Zhang D, Li X, Ma J, Yu J, Yang C, Xiong H, Zhou B, Huang X, Tang Z. A Preliminary Study on the Diagnostic Efficacy of Proton Magnetic Resonance Spectroscopy at 3.0T in Rabbit With VX2 Liver Tumor. Technol Cancer Res Treat 2021; 20:15330338211036852. [PMID: 34372732 PMCID: PMC8361547 DOI: 10.1177/15330338211036852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background: To investigate the diagnostic efficacy of choline (Cho) value of magnetic resonance spectroscopy (MRS) in rabbit with VX2 liver tumor via comparative and quantitative analysis with the choline compounds concentration measured by enzyme linked immunosorbent assay (ELISA). Methods: MRS was performed on normal liver and VX2 tumor. The Cho value of VX2 tumor was compared with that of normal liver. Tissues were harvested for ELISA to detect the concentrations of acetylcholine (ACh), glycophorophosphygholine (GPC) and phosphochorine (PC). The diagnostic performance of Cho value and concentrations of choline compounds were assessed by receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were discussed by the maximum Youden’s index. Results: The concentration of ACh was obviously higher than that of GPC and PC both in VX2 tumor and normal liver (P < 0.01). Furthermore, the concentration differences among ACh, GPC and PG were the third power of 10. Both the ACh concentration and Cho value of MRS in VX2 tumor were significantly higher than those in normal liver (P < 0.01). The AUC of ACh in VX2 tumor was 0.883, when the cutoff value was 7259000, the sensitivity and specificity of the diagnosis of liver cancer were 94.4% and 77.8%, respectively. The AUC of Cho in VX2 tumor was 0.807, when the cutoff value was 28.35, the sensitivity and specificity of the diagnosis of liver cancer were 83.3% and 77.8%, respectively. Conclusion: The change of Cho value in MRS between liver cancer and normal liver was consistent with the changes of concentrations of choline compounds measured by ELISA, especially the change of ACh concentration. The diagnostic efficiency of Cho value and that of choline compounds concentration in liver cancer were extremely similar, with the AUC more than 0.8. We conclude that MRS may be applied as an important, non-invasive biomarker for the diagnosis of liver cancer.
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Affiliation(s)
- Ruikun Liao
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Dan Zhang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Xiaojiao Li
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Jiang Ma
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Jiayi Yu
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Chao Yang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Hua Xiong
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Bi Zhou
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Xianlong Huang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
| | - Zhuoyue Tang
- Department of Radiology, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China.,Molecular and Functional Imaging Laboratory, Chongqing General Hospital, 74519University of Chinese Academy of Sciences, Chongqing, China
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18
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Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets. Sci Rep 2021; 11:8843. [PMID: 33893355 PMCID: PMC8065150 DOI: 10.1038/s41598-021-87360-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 02/03/2021] [Indexed: 11/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731–0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required. Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.
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19
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Kruse M, Kemper M, Gancheva S, Osterhoff M, Dannenberger D, Markgraf D, Machann J, Hierholzer J, Roden M, Pfeiffer AFH. Dietary Rapeseed Oil Supplementation Reduces Hepatic Steatosis in Obese Men-A Randomized Controlled Trial. Mol Nutr Food Res 2020; 64:e2000419. [PMID: 32920973 DOI: 10.1002/mnfr.202000419] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 08/13/2020] [Indexed: 01/01/2023]
Abstract
SCOPE Effective treatment for obesity associated non-alcoholic fatty liver disease (NAFLD) is limited. Dietary supplementation of n-3 polyunsaturated fatty acids, specifically alpha linolenic acid (ALA), can resolve intrahepatic lipid content (IHL). This study investigates the effect of daily supplementation of either refined rapeseed (RA), containing high amounts of ALA, or refined olive (OL) oil on IHL and glucose metabolism in NAFLD patients. METHODS AND RESULTS 27 obese men consumed an isocaloric diet including either 50 g of RA or OL daily for 8 weeks. Hepatic proton magnetic resonance spectroscopy, hyperinsulinemic-euglycemic clamp studies and blood tests are performed before and at the end of the study. At 8 weeks a significant reduction in IHL is observed for RA (13.1 ± 1.6 before versus 11.1 ± 1.6% after intervention) versus OL (13.3 ± 2.5 before versus 15.7 ± 2.7% after intervention). For RA, a 21% reduction (P < 0.02) in serum free fatty acids (FFA) and a 1.68-fold increase (P = 0.03) of serum interleukin-6 (IL-6) is observed after 8 weeks. CONCLUSION RA has a beneficial effect on hepatic lipid metabolism as shown by reduced IHL and serum FFA. RA induced IL-6 production seems to be liver protective confirming previous results.
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Affiliation(s)
- Michael Kruse
- German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Clinical Nutrition, 14558, Nuthetal, Germany.,Charité University Medicine Berlin, Department of Endocrinology, 10117, Berlin, Germany
| | - Margrit Kemper
- German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Clinical Nutrition, 14558, Nuthetal, Germany.,Charité University Medicine Berlin, Department of Endocrinology, 10117, Berlin, Germany.,German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany
| | - Sofiya Gancheva
- German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, 40225, Düsseldorf, Germany.,Institute for Clinical Diabetology, German Diabetes Center Düsseldorf, Leibniz Center for Diabetes Research at Heinrich-Heine University, 40225, Düsseldorf, Germany
| | - Martin Osterhoff
- German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Clinical Nutrition, 14558, Nuthetal, Germany.,Charité University Medicine Berlin, Department of Endocrinology, 10117, Berlin, Germany
| | - Dirk Dannenberger
- Leibniz Institute for Farm Animal Biology, Institute of Muscle Biology and Growth, 18196, Dummerstorf, Germany
| | - Daniel Markgraf
- German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany.,Institute for Clinical Diabetology, German Diabetes Center Düsseldorf, Leibniz Center for Diabetes Research at Heinrich-Heine University, 40225, Düsseldorf, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany.,Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076, Tübingen, Germany.,Section of Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, 72076, Tübingen, Germany
| | - Johannes Hierholzer
- Department of Diagnostic and Interventional Radiology, Ernst von Bergmann Hospital, 14467, Potsdam, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, 40225, Düsseldorf, Germany.,Institute for Clinical Diabetology, German Diabetes Center Düsseldorf, Leibniz Center for Diabetes Research at Heinrich-Heine University, 40225, Düsseldorf, Germany
| | - Andreas F H Pfeiffer
- German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Clinical Nutrition, 14558, Nuthetal, Germany.,Charité University Medicine Berlin, Department of Endocrinology, 10117, Berlin, Germany.,German Center for Diabetes Research (DZD), München, 85764, Neuherberg, Germany
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20
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Wernicke C, Apostolopoulou K, Hornemann S, Efthymiou A, Machann J, Schmidt S, Primessnig U, Bergmann MM, Grune T, Gerbracht C, Herber K, Pohrt A, Pfeiffer AF, Spranger J, Mai K. Long-term effects of a food pattern on cardiovascular risk factors and age-related changes of muscular and cognitive function. Medicine (Baltimore) 2020; 99:e22381. [PMID: 32991458 PMCID: PMC7523819 DOI: 10.1097/md.0000000000022381] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION The mean age of the German population increased over the last years, which resulted in a higher prevalence of cardiovascular diseases, type 2 diabetes, cognitive impairment, sarcopenia and bone fractures. Current evidence indicates a preservation of human wellbeing in the elderly by a healthy diet, although the recommended macronutrient composition and quality remains unclear and needs further long-term investigation. In this context we investigate the effect of a specific dietary pattern on age-related disorders in a randomized controlled multi-center trial (RCT). METHODS We assess the effect of a specific dietary pattern (NutriAct) with a high proportion of unsaturated fat, plant proteins and fibres (fat 35%-40% of total energy (%E) of which 15%E-20%E monounsaturated fatty acids (MUFA) and 10%E-15%E polyunsaturated fatty acids (PUFA), 15%E-25%E proteins, ≥30 g fibres per day and 35%E-45%E carbohydrates) on age-related impairment of health within a 36-months RCT conducted in the region of Berlin and Potsdam. 502 eligible men (n = 183) and women (n = 319), aged 50 to 80 years, with an increased risk to develop age-related diseases were randomly assigned to either an intervention group focusing on NutriAct dietary pattern or a control group focusing on usual care and dietary recommendations in accordance to the German Nutrition Society (DGE). In the intervention group, 21 nutrition counsellings as well as supplementation of rapeseed oil, oil cake and specific designed foods are used to achieve the intended NutriAct dietary pattern.The primary outcome is a composite endpoint of age-related disorders, including cardiovascular morbidity, decline of cognitive function as well as clinical features of sarcopenia. Secondary outcomes include diet-induced effects on quality of life, depression, frailty, cardiovascular function, bone density, fat distribution pattern, glucose, lipid and energy metabolism, as well as the identification of biomarkers linked with age-related disorders. DISCUSSION The findings of this trial will provide clinically relevant information regarding dietary effects on age-related impairment of health and will contribute to the definition of the optimal macronutrient composition in the context of healthy aging in the German population.
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Affiliation(s)
- Charlotte Wernicke
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
| | - Konstantina Apostolopoulou
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
| | - Silke Hornemann
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal
- German Center for Diabetes Research, München-Neuherberg
| | - Andriana Efthymiou
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen
- German Center for Diabetes Research, München-Neuherberg
- Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen
| | - Sein Schmidt
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin
| | - Uwe Primessnig
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin
- Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
| | - Manuela M. Bergmann
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal
| | - Tilman Grune
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal
| | - Christiana Gerbracht
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal
| | - Katharina Herber
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
| | - Anne Pohrt
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany
| | - Andreas F.H. Pfeiffer
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal
- German Center for Diabetes Research, München-Neuherberg
| | - Joachim Spranger
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin
| | - Knut Mai
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin
- NutriAct-Competence Cluster Nutrition Research, Berlin-Potsdam
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin
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21
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Scorletti E, Afolabi PR, Miles EA, Smith DE, Almehmadi A, Alshathry A, Childs CE, Fabbro SD, Beavis J, Moyses HE, Clough GF, Sethi JK, Patel J, Wright M, Breen DJ, Peebles C, Darekar A, Aspinall R, Fowell AJ, Dowman JK, Nobili V, Targher G, Delzenne NM, Bindels LB, Calder PC, Byrne CD. Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2020; 158:1597-1610.e7. [PMID: 31987796 PMCID: PMC7613160 DOI: 10.1053/j.gastro.2020.01.031] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 12/05/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (β = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).
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Affiliation(s)
- Eleonora Scorletti
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom; Department of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.
| | - Paul R. Afolabi
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK,National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
| | - Elizabeth A. Miles
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Debbie E. Smith
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK,National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
| | - Amal Almehmadi
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Albandri Alshathry
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Caroline E. Childs
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Stefania Del Fabbro
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Josh Beavis
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Helen E. Moyses
- National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
| | - Geraldine F. Clough
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Jaswinder K. Sethi
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK,Institute for Life Sciences, University of Southampton, Southampton, UK
| | - Janisha Patel
- Hepatology, Department of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Mark Wright
- Hepatology, Department of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - David J. Breen
- Department of Radiology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Charles Peebles
- Department of Radiology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Angela Darekar
- Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Richard Aspinall
- Department of Hepatology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
| | - Andrew J. Fowell
- Department of Hepatology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
| | - Joanna K. Dowman
- Department of Hepatology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
| | - Valerio Nobili
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy,Department of Pediatric, University "La Sapienza", Rome, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Nathalie M. Delzenne
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Laure B. Bindels
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Philip C. Calder
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK,National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK,Institute for Life Sciences, University of Southampton, Southampton, UK
| | - Christopher D. Byrne
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK,National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
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22
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Kahl S, Gancheva S, Straßburger K, Herder C, Machann J, Katsuyama H, Kabisch S, Henkel E, Kopf S, Lagerpusch M, Kantartzis K, Kupriyanova Y, Markgraf D, van Gemert T, Knebel B, Wolkersdorfer MF, Kuss O, Hwang JH, Bornstein SR, Kasperk C, Stefan N, Pfeiffer A, Birkenfeld AL, Roden M. Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. Diabetes Care 2020; 43:298-305. [PMID: 31540903 DOI: 10.2337/dc19-0641] [Citation(s) in RCA: 218] [Impact Index Per Article: 43.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 08/21/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute change of -1.8% (95% CI -3.4, -0.2; P = 0.02) and relative change in LFC of -22% (-36, -7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
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Affiliation(s)
- Sabine Kahl
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Sofiya Gancheva
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Klaus Straßburger
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Jürgen Machann
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Hisayuki Katsuyama
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Stefan Kabisch
- German Center for Diabetes Research, München-Neuherberg, Germany.,Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Elena Henkel
- Clinical Study Center of Metabolic Vascular Medicine, GWT-TUD GmbH, Dresden, Germany
| | - Stefan Kopf
- German Center for Diabetes Research, München-Neuherberg, Germany.,Department of Internal Medicine 1 and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Merit Lagerpusch
- German Center for Diabetes Research, München-Neuherberg, Germany.,Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Konstantinos Kantartzis
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Yuliya Kupriyanova
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Daniel Markgraf
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Theresa van Gemert
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
| | - Birgit Knebel
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany
| | | | - Oliver Kuss
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany
| | - Jong-Hee Hwang
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.,German Center for Diabetes Research, München-Neuherberg, Germany
| | - Stefan R Bornstein
- Paul Langerhans Institute Dresden, Helmholtz Center Munich at University Hospital MKIII, and Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Christian Kasperk
- German Center for Diabetes Research, München-Neuherberg, Germany.,Department of Internal Medicine 1 and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany
| | - Norbert Stefan
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Andreas Pfeiffer
- German Center for Diabetes Research, München-Neuherberg, Germany.,Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.,Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
| | - Andreas L Birkenfeld
- German Center for Diabetes Research, München-Neuherberg, Germany.,Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany .,German Center for Diabetes Research, München-Neuherberg, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
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Comment on: Validation of biochemical scores for liver steatosis before and 1 year after sleeve gastrectomy. Surg Obes Relat Dis 2019; 15:1453-1454. [PMID: 31405814 DOI: 10.1016/j.soard.2019.06.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 06/29/2019] [Indexed: 11/21/2022]
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Validation of biochemical scores for liver steatosis before and 1 year after sleeve gastrectomy. Surg Obes Relat Dis 2019; 15:1447-1453. [PMID: 31204247 DOI: 10.1016/j.soard.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/02/2019] [Accepted: 05/02/2019] [Indexed: 01/13/2023]
Abstract
BACKGROUND Bariatric surgery is a potential treatment for liver steatosis in morbidly obese patients, showing an improvement in approximately 90% of cases of fatty liver after surgery. Liver biopsy is the gold standard method to monitor liver steatosis. Imaging tests, such as magnetic resonance (MR) spectroscopy, have shown a good accuracy in the diagnosis of liver steatosis. Several biochemical markers have been proposed as diagnostic alternatives to evaluate fatty liver. OBJECTIVES The aim of this study was to analyze the potential of different biochemical markers for evaluating liver steatosis in morbidly obese patients before and after undergoing sleeve gastrectomy. SETTING Garcilaso Clinic, Madrid, Spain. METHODS A prospective observational study of patients undergoing sleeve gastrectomy was performed. Diverse biochemical markers were assessed and correlated with MR spectroscopy as the diagnostic method for liver steatosis. RESULTS One hundred consecutive patients were included. Twelve months after surgery, mean body mass index was 28.3 ± 3.7 kg/m2 and mean excess weight loss 82.5% ± 17.8%. Preoperatively, 67% of the patients had liver steatosis and 12 months after surgery the steatosis rate was reduced to 23%, as measured by MR spectroscopy. A significant direct correlation could only be observed between the percentage of lipid content, determined by MR spectroscopy and the liver fat score, at baseline and in the preoperative score. A cut-off point for liver fat score to determine the presence of liver steatosis was established at 1.22, for baseline and postoperative determinations. CONCLUSION The liver fat score is the most accurate biochemical score to correlate with the percentage of lipid content of the liver, determined by MR spectroscopy.
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25
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van de Weijer T, Schrauwen-Hinderling VB. Application of Magnetic Resonance Spectroscopy in metabolic research. Biochim Biophys Acta Mol Basis Dis 2019; 1865:741-748. [DOI: 10.1016/j.bbadis.2018.09.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Revised: 09/08/2018] [Accepted: 09/10/2018] [Indexed: 02/08/2023]
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26
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Kempe-Teufel D, Machicao F, Machann J, Böhm A, Schick F, Fritsche A, Stefan N, Hrabě de Angelis M, Häring HU, Staiger H. A Polygenic Risk Score of Lipolysis-Increasing Alleles Determines Visceral Fat Mass and Proinsulin Conversion. J Clin Endocrinol Metab 2019; 104:1090-1098. [PMID: 30649496 DOI: 10.1210/jc.2018-02042] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 01/07/2019] [Indexed: 01/12/2023]
Abstract
CONTEXT Primary dysregulation of adipose tissue lipolysis caused by genetic variation and independent of insulin resistance could explain unhealthy body fat distribution and its metabolic consequences. OBJECTIVE To analyze common single nucleotide polymorphisms (SNPs) in 48 lipolysis-, but not insulin-signaling-related genes, to form polygenic risk scores of lipolysis-associated SNPs, and to investigate their effects on body fat distribution, glycemia, insulin sensitivity, insulin secretion, and proinsulin conversion. STUDY DESIGN, PARTICIPANTS, AND METHODS SNP array, anthropometric, and metabolic data were available from up to 2789 participants without diabetes of the Tübingen Family study of type 2 diabetes characterized by oral glucose tolerance tests. In a subgroup (n = 942), magnetic resonance measurements of body fat stores were available. RESULTS We identified insulin-sensitivity-independent nominal associations (P < 0.05) of SNPs in 10 genes with plasma free fatty acids (FFAs), in 7 genes with plasma glycerol and in 6 genes with both, plasma FFAs and glycerol. A score formed of the latter SNPs (in ADCY4, CIDEA, GNAS, PDE8B, PRKAA1, PRKAG2) was associated with plasma FFA and glycerol measurements (1.4*10-9 ≤ P ≤ 1.2*10-5), visceral adipose tissue mass (P = 0.0326), and proinsulin conversion (P ≤ 0.0272). The more lipolysis-increasing alleles a subject had, the lower was the visceral fat mass and the lower the proinsulin conversion. CONCLUSIONS We found evidence for a genetic basis of adipose tissue lipolysis resulting from common SNPs in CIDEA, AMP-activated protein kinase subunits, and cAMP signaling components. A genetic score of lipolysis-increasing alleles determined lower visceral fat mass and lower proinsulin conversion.
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Affiliation(s)
- Daniela Kempe-Teufel
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
| | - Fausto Machicao
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany
| | - Jürgen Machann
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Anja Böhm
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
| | - Fritz Schick
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
| | - Norbert Stefan
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
| | - Martin Hrabě de Angelis
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Experimental Genetics, Helmholtz Center Munich, Neuherberg, Germany
- Chair of Experimental Genetics, Technical University Munich, Neuherberg, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
| | - Harald Staiger
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany
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Choline Supplementation in Cystic Fibrosis-The Metabolic and Clinical Impact. Nutrients 2019; 11:nu11030656. [PMID: 30889905 PMCID: PMC6471815 DOI: 10.3390/nu11030656] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 03/08/2019] [Accepted: 03/12/2019] [Indexed: 12/16/2022] Open
Abstract
Background: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. Methods: 10 adult male CF patients were recruited (11/2014–1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84–91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D9]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. Results: Supplementation increased plasma choline from 4.8 (4.1–6.2) µmol/L to 10.5 (8.5–15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D9-labeled PC was decreased (12.2 [10.5–18.3] µmol/L vs. 17.7 [15.5–22.4] µmol/L, p < 0.01), indicating D9-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9–74.8)% to 78.3 (60.1–83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37–8.82)% to 0.84 (0.56–1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. Conclusions: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.
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Willmann C, Heni M, Linder K, Wagner R, Stefan N, Machann J, Schulze MB, Joost HG, Häring HU, Fritsche A. Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content: a randomized and controlled dietary intervention study. Am J Clin Nutr 2019; 109:288-296. [PMID: 30721948 DOI: 10.1093/ajcn/nqy307] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 10/06/2018] [Indexed: 12/23/2022] Open
Abstract
Background Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The "control" group (N = 40) only had this requirement. The "no red meat" group (N = 48) in addition aimed to avoid the intake of red meat, and the "fiber" group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results Participants in all groups lost weight (mean 3.3 ± 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r2 = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839.
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Affiliation(s)
- Caroline Willmann
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Martin Heni
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany
| | - Katarzyna Linder
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
| | - Robert Wagner
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany
| | - Norbert Stefan
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany.,Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Matthias B Schulze
- German Centre for Diabetes Research, München-Neuherberg, Germany.,German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany.,University of Potsdam, Institute of Nutritional Sciences, Nuthetal, Germany
| | - Hans-Georg Joost
- German Centre for Diabetes Research, München-Neuherberg, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany
| | - Andreas Fritsche
- Department of Internal Medicine IV, University Hospital of Tübingen, Tübingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.,German Centre for Diabetes Research, München-Neuherberg, Germany
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The rs1805193, rs5361, and rs5355 single nucleotide polymorphisms in the E-selectin gene (SEL-E) are associated with subclinical atherosclerosis: The Genetics of Atherosclerotic Disease (GEA) Mexican study. Immunobiology 2019; 224:10-14. [DOI: 10.1016/j.imbio.2018.11.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 11/07/2018] [Accepted: 11/08/2018] [Indexed: 01/08/2023]
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30
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Linder N, Rakete T, Stange R, Solty K, Kahn T, Busse H. In-vitro
validation of MR-based fat quantification at 1.5 T. Biomed Phys Eng Express 2018. [DOI: 10.1088/2057-1976/aae646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Buckley AJ, Thomas EL, Lessan N, Trovato FM, Trovato GM, Taylor-Robinson SD. Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints. Diabetes Res Clin Pract 2018; 144:144-152. [PMID: 30170074 DOI: 10.1016/j.diabres.2018.08.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/08/2018] [Accepted: 08/14/2018] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.
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Affiliation(s)
- Adam J Buckley
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - E Louise Thomas
- University of Westminster, Department of Life Sciences, London, United Kingdom.
| | - Nader Lessan
- Imperial College London, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine London, United Kingdom; Imperial College London Diabetes Centre, Research Department, Abu Dhabi, United Arab Emirates.
| | - Francesca M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Guglielmo M Trovato
- University of Catania, Department of Clinical and Experimental Medicine, Catania, Italy
| | - Simon D Taylor-Robinson
- Imperial College London, Division of Integrative Systems Medicine and Digestive Health, Department of Surgery and Cancer, London, United Kingdom.
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Sakai NS, Taylor SA, Chouhan MD. Obesity, metabolic disease and the pancreas-Quantitative imaging of pancreatic fat. Br J Radiol 2018; 91:20180267. [PMID: 29869917 DOI: 10.1259/bjr.20180267] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The association between pancreatic fat, obesity and metabolic disease is well-documented, and although a potentially exciting target for novel therapies, remains poorly understood. Non-invasive quantitative imaging-derived biomarkers can provide insights into pathophysiology and potentially provide robust trial endpoints for development of new treatments. In this review, we provide an overview of the pathophysiology of non-alcoholic fatty pancreas disease and associations with metabolic factors, obesity and diabetes. We then explore approaches to pancreatic fat quantification using ultrasound, CT and MRI, reviewing the strengths, limitations and current published evidence in the assessment of pancreatic fat. Finally, we explore the broader challenges of pancreatic fat quantification as we move toward translating these methods into the clinical setting.
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Affiliation(s)
- Naomi S Sakai
- 1 UCL Centre for Medical Imaging, Division of Medicine, University College London , London , UK
| | - Stuart A Taylor
- 1 UCL Centre for Medical Imaging, Division of Medicine, University College London , London , UK
| | - Manil D Chouhan
- 1 UCL Centre for Medical Imaging, Division of Medicine, University College London , London , UK
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Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease. Contemp Clin Trials 2018; 71:113-123. [PMID: 29787859 DOI: 10.1016/j.cct.2018.05.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/21/2018] [Accepted: 05/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. DESIGN In a randomised double-blind placebo-controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. METHODS Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640.
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Puri BK, Egan M, Wallis F, Jakeman P. Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds. World J Psychiatry 2018; 8:20-26. [PMID: 29568728 PMCID: PMC5862651 DOI: 10.5498/wjp.v8.i1.20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Revised: 12/17/2017] [Accepted: 01/07/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho).
METHODS Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability.
RESULTS The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test.
CONCLUSION It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.
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Affiliation(s)
- Basant K Puri
- Department of Medicine, Hammersmith Hospital, Imperial College London, London W12 0HS, United Kingdom
| | - Mary Egan
- Department of Radiology, University Hospital Limerick, Limerick V94 YVH0, Ireland
| | - Fintan Wallis
- Department of Radiology, University Hospital Limerick, Limerick V94 YVH0, Ireland
| | - Philip Jakeman
- Centre for Interventions in Infection, Inflammation and Immunity, University of Limerick, Limerick V94 PX58, Ireland
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Scorletti E, Byrne CD. Omega-3 fatty acids and non-alcoholic fatty liver disease: Evidence of efficacy and mechanism of action. Mol Aspects Med 2018; 64:135-146. [PMID: 29544992 DOI: 10.1016/j.mam.2018.03.001] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 03/07/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism. Since the pathogenesis of non alcoholic fatty liver disease (NAFLD) begins with the accumulation of liver lipid and progresses with inflammation and then several years later with development of fibrosis; it has been thought in patients with NAFLD omega-3 fatty acid treatment would be beneficial in treating liver lipid and possibly also in ameliorating inflammation. Meta-analyses (of predominantly dietary studies and small trials) have tended to support the assertion that omega-3 fatty acids are beneficial in decreasing liver lipid, but recent randomised controlled trials have produced conflicting data. These trials have suggested that omega-3 fatty acid might be beneficial in decreasing liver triglyceride (docosahexanoic acid also possibly being more effective than eicosapentanoic acid) but not in decreasing other features of steatohepatitis (or liver fibrosis). The purpose of this review is to discuss recent evidence regarding biological mechanisms by which long chain omega-3 fatty acids might act to ameliorate liver disease in NAFLD; to consider the recent evidence from randomised trials in both adults and children with NAFLD; and finally to discuss key 'known unknowns' that need to be considered, before planning future studies that are focussed on testing the effects of omega-3 fatty acid treatment in patients with NAFLD.
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Affiliation(s)
- Eleonora Scorletti
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research, Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
| | - Christopher D Byrne
- Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research, Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Lin H, Fu C, Kannengiesser S, Cheng S, Shen J, Dong H, Yan F. Quantitative analysis of hepatic iron in patients suspected of coexisting iron overload and steatosis using multi-echo single-voxel magnetic resonance spectroscopy: Comparison with fat-saturated multi-echo gradient echo sequence. J Magn Reson Imaging 2018. [PMID: 29513377 DOI: 10.1002/jmri.25967] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The coexistence of hepatic iron and fat is common in patients with hyperferritinemia, which plays an interactive and aggressive role in the progression of diseases (fibrosis, cirrhosis, and hepatocellular carcinomas). PURPOSE To evaluate a modified high-speed T2 -corrected multi-echo, single voxel spectroscopy sequence (HISTOV) for liver iron concentration (LIC) quantification in patients with hyperferritinemia, with simultaneous fat fraction (FF) estimation. STUDY TYPE Retrospective cohort study. POPULATION Thirty-eight patients with hyperferritinemia were enrolled. FIELD STRENGTH/SEQUENCE HISTOV, a fat-saturated multi-echo gradient echo (GRE) sequence, and a spin echo sequence (FerriScan) were performed at 1.5T. ASSESSMENT R2 of the water signal and FF were calculated with HISTOV, and R2* values were derived from the GRE sequence, with R2 and LIC from FerriScan serving as the references. STATISTICAL TESTS Linear regression, correlation analyses, receiver operating characteristic analyses, and Bland-Altman analyses were conducted. RESULTS Abnormal hepatic iron load was detected in 32/38 patients, of whom 10/32 had coexisting steatosis. Strong correlation was found between R2* and FerriScan-LIC (R2 = 0.861), and between HISTOV-R2_ water and FerriScan-R2 (R2 = 0.889). Furthermore, HISTOV-R2_ water was not correlated with HISTOV-FF. The area under the curve (AUC) for HISTOV-R2_ water was 0.974, 0.971, and 1, corresponding to clinical FerriScan-LIC thresholds of 1.8, 3.2, and 7.0 mg/g dw, respectively. No significant difference in the AUC was found between HISTOV-R2_ water and R2* at any of the LIC thresholds, with P-values of 0.42, 0.37, and 1, respectively. HISTOV-LIC showed excellent agreement with FerriScan-LIC, with a mean bias of 0.00 ± 1.18 mg/g dw, whereas the mean bias between GRE-LIC and FerriScan-LIC was 0.53 ± 1.49 mg/g dw. DATA CONCLUSION HISTOV is useful for the quantification and grading of liver iron overload in patients with hyperferritinemia, particularly in cases with coexisting steatosis. HISTOV-LIC showed no systematic bias compared with FerriScan-LIC, making it a promising alternative for iron quantification. LEVEL OF EVIDENCE 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.
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Affiliation(s)
- Huimin Lin
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Caixia Fu
- Application Development, Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China
| | | | - Shu Cheng
- Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Shen
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haipeng Dong
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Kabisch S, Bäther S, Dambeck U, Kemper M, Gerbracht C, Honsek C, Sachno A, Pfeiffer AFH. Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet. Nutrients 2018; 10:nu10020157. [PMID: 29385034 PMCID: PMC5852733 DOI: 10.3390/nu10020157] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 01/15/2018] [Accepted: 01/25/2018] [Indexed: 12/19/2022] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. Aim: We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Methods: Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Results: Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775–0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and changes of measures of obesity, ΔTG, and ΔALT (all low-fat, only) and between ΔIHL and ΔGGT (low-carb, only). With exception for a stronger decrease of triglycerides (TG) levels in the low-carb diet, there is no statistically significant difference in the effect of the diets on anthropometric or serum-based score parameters. Conclusion: While liver fat indices have proved useful in the early detection of NAFLD and may serve as a cost-saving substitute for expensive MR measurements in the cross-sectional evaluation of liver status, their capability to represent interventional changes of liver fat content appears to be diet-specific and lacks accuracy. Liver fat reduction by low-fat diets can be monitored with moderate precision, while low-carb diets require different measuring techniques to demonstrate the same dietary effect.
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Affiliation(s)
- Stefan Kabisch
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
| | - Sabrina Bäther
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
- Department of Geriatrics, Campus Virchow, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
| | - Ulrike Dambeck
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
- Department of Geriatrics, Campus Virchow, Charité University Medicine, Augustenburger Platz 1, 13353 Berlin, Germany.
| | - Margrit Kemper
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
| | - Christiana Gerbracht
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
| | - Caroline Honsek
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
| | - Anna Sachno
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
| | - Andreas F H Pfeiffer
- Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung e.V.), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
- Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203 Berlin, Germany.
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Alsina ME, Ruiz-Tovar J, Bernabeu A. Evolution of Liver Steatosis Quantified by MR Imaging and MR Spectroscopy, in Morbidly Obese Patients Undergoing Sleeve Gastrectomy: Short-Term Outcomes. Obes Surg 2018; 27:1724-1728. [PMID: 27885531 DOI: 10.1007/s11695-016-2473-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Currently, the standard procedure used to evaluate hepatic steatosis is the liver biopsy. This is an invasive practice that presents inherent risks. Increasing evidence suggests that magnetic resonance imaging (MRI) and MR spectroscopy (MRS) may represent an accurate method to determine the hepatic lipid content. The aim of this study was to evaluate the effect of sleeve gastrectomy on liver steatosis, quantified by MRI and MRS. PATIENTS AND METHODS A prospective observational study of patients undergoing laparoscopic sleeve gastrectomy was performed. All patients underwent a MRI and a MRS study 2 weeks before the intervention and 6 months after the surgery. Anthropometric, biochemical, and radiological parameters were analyzed. RESULTS Twenty-three patients were included, 21 females and 2 males, with a mean age of 47.6 ± 10.6 years and mean pre-op BMI 47.6 ± 6.7 Kg/m2. Six months after surgery, mean BMI was 32.2 ± 5.1 Kg/m2, with a mean excess weight loss of 68.2 ± 18.6%. Mean preoperative hepatic volume was 1999.9 ± 436.2 ml and 6 months after surgery it decreased to 1568 ± 170.3 ml (p = 0.005). Mean preoperative percentage of lipid content was 14.2 ± 15.4% and 6 months after surgery, it decreased to 4.3 ± 3.2% (p = 0.007). A significant reduction of steatosis grade was observed, with disappearance of preoperative steatosis in 54.9% of the patients. CONCLUSION Six months after sleeve gastrectomy, a significant reduction of liver steatosis is observed, as demonstrated by reduction in the percentage of intrahepatocitary lipids and liver volume, determined by MRS and MRI. These imaging techniques can be considered as noninvasive, accurate methods for monitoring liver steatosis in morbidly obese patients undergoing bariatric surgery.
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Affiliation(s)
| | - Jaime Ruiz-Tovar
- Department of Surgery, Bariatric Surgery Unit, University Hospital Rey Juan Carlos, Gladiolo s/n, 28933, Madrid, Spain.
| | - Angela Bernabeu
- Magnetic Resonance Department, Inscanner SL, Alicante, Spain
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Effect of aerobic exercise and diet on liver fat in pre-diabetic patients with non-alcoholic-fatty-liver-disease: A randomized controlled trial. Sci Rep 2017; 7:15952. [PMID: 29162875 PMCID: PMC5698376 DOI: 10.1038/s41598-017-16159-x] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 11/08/2017] [Indexed: 12/25/2022] Open
Abstract
The study aimed to assess whether aerobic exercise (AEx) training and a fibre-enriched diet can reduce hepatic fat content (HFC) and increase glycaemic control in pre-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Six-hundred-and-three patients from seven clinics in Yangpu district, Shanghai, China were recruited. Of them 115 individuals aged 50–65-year fulfilled the inclusion criteria (NAFLD with impaired fasting glucose or impaired glucose tolerance) and were randomly assigned into exercise (AEx n = 29), diet (Diet n = 28), exercise plus diet (AED n = 29), or no-intervention (NI n = 29) groups. Progressive supervised AEx training (60–75% VO2max intensity) was given 2-3 times/week in 30–60 min/sessions, and the diet intervention was provided as lunch with 38% carbohydrate and diet fibre of 12 g/day for 8.6-month. HFC was assessed by 1H MRS. We found that HFC was significantly reduced in the AEx (−24.4%), diet (−23.2%), and AED (−47.9%) groups by contrast to the 20.9% increase in the NI group (p = 0.001 for all) after intervention. However, only AED group significantly decreased HbA1c (−4.4%, p = 0.01) compared with the NI group (−0.6%). Aerobic exercise training combined with fibre-enriched diet can reduce HFC more effectively than either exercise or increased fibre-intake alone in pre-diabetic patients with NAFLD.
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Taibbi A, Picone D, Midiri M, La Grutta L, Bartolotta TV. Diffuse Liver Diseases: Role of imaging. Semin Ultrasound CT MR 2017; 39:193-205. [PMID: 29571555 DOI: 10.1053/j.sult.2017.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nowadays, the most common imaging techniques allow to study focal liver lesions with high diagnostic accuracy but a relatively recent emerging field of interest is represented by diffuse liver disease. They include a variegated series of storage and metabolic pathologies (ie, iron overload disorders and steatosis) requiring a precise diagnosis not always possible at imaging due to the overlapping of findings at conventional ultrasound, CT, or MR studies. In recent years, several imaging tecniques and specific softwares have been developed, especially for ultrasound and MR imaging, in order to identify different parameters useful in the noninvasive recognition and follow-up of these diffuse processes involving the liver. The aim of this article is to describe the most common and useful imaging findings of the most common and uncommon diffuse liver diseases illustrating the newest imaging technologies and developments at our disposal with corresponding advantages, limitations, and pitfalls.
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Affiliation(s)
- Adele Taibbi
- Department of Radiology, University Hospital, Palermo, Italy.
| | - Dario Picone
- Department of Radiology, University Hospital, Palermo, Italy
| | - Massimo Midiri
- Department of Radiology, University Hospital, Palermo, Italy
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Shi H, Wang Q, Yang L, Xie S, Zhu H. IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet. FEBS Open Bio 2017; 7:1379-1391. [PMID: 28904866 PMCID: PMC5586352 DOI: 10.1002/2211-5463.12272] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 07/12/2017] [Accepted: 07/19/2017] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2′,3′,5′‐tri‐acetyl‐N6‐(3‐hydroxylaniline) adenosine (IMM‐H007) can eliminate hepatic steatosis in hamsters fed a high‐fat diet (HFD), as a model of NAFLD. Compared with HFD‐only controls, IMM‐H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1H‐MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM‐H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM‐H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo, IMM‐H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM‐H007 resolves hepatic steatosis in HFD‐fed hamsters by the regulation of lipid metabolism. Thus, IMM‐H007 has therapeutic potential for NAFLD.
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Affiliation(s)
- Huijie Shi
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China.,Department of Pharmacology Shenzhen People's Hospital Second Clinical College Jinan University Shenzhen China
| | - Qingchun Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
| | - Liu Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
| | - Shouxia Xie
- Department of Pharmacology Shenzhen People's Hospital Second Clinical College Jinan University Shenzhen China
| | - Haibo Zhu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
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Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, Machann J, Petzke KJ, Hierholzer J, Lichtinghagen R, Herder C, Carstensen-Kirberg M, Roden M, Rudovich N, Klaus S, Thomann R, Schneeweiss R, Rohn S, Pfeiffer AFH. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Gastroenterology 2017; 152:571-585.e8. [PMID: 27765690 DOI: 10.1053/j.gastro.2016.10.007] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 09/02/2016] [Accepted: 10/09/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insulin resistance. We investigated the effects of diets high in animal protein (AP) vs plant protein (PP), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue. METHODS We performed a prospective study of individuals with type 2 diabetes and NAFLD at a tertiary medical center in Germany from June 2013 through March 2015. We analyzed data from 37 subjects placed on a diet high in AP (rich in meat and dairy foods; n = 18) or PP (mainly legume protein; n = 19) without calorie restriction for 6 weeks. The diets were isocaloric with the same macronutrient composition (30% protein, 40% carbohydrates, and 30% fat). Participants were examined at the start of the study and after the 6-week diet period for body mass index, body composition, hip circumference, resting energy expenditure, and respiratory quotient. Body fat and intrahepatic fat were detected by magnetic resonance imaging and spectroscopy, respectively. Levels of glucose, insulin, liver enzymes, and inflammation markers, as well as individual free fatty acids and free amino acids, were measured in collected blood samples. Hyperinsulinemic euglycemic clamps were performed to determine whole-body insulin sensitivity. Subcutaneous adipose tissue samples were collected and analyzed for gene expression patterns and phosphorylation of signaling proteins. RESULTS Postprandial levels of BCAAs and methionine were significantly higher in subjects on the AP vs the PP diet. The AP and PP diets each reduced liver fat by 36%-48% within 6 weeks (for AP diet P = .0002; for PP diet P = .001). These reductions were unrelated to change in body weight, but correlated with down-regulation of lipolysis and lipogenic indices. Serum level of FGF21 decreased by 50% in each group (for AP diet P < .0002; for PP diet P < .0002); decrease in FGF21 correlated with loss of hepatic fat. In gene expression analyses of adipose tissue, expression of the FGF21 receptor cofactor β-klotho was associated with reduced expression of genes encoding lipolytic and lipogenic proteins. In patients on each diet, levels of hepatic enzymes and markers of inflammation decreased, insulin sensitivity increased, and serum level of keratin 18 decreased. CONCLUSIONS In a prospective study of patients with type 2 diabetes, we found diets high in protein (either animal or plant) significantly reduced liver fat independently of body weight, and reduced markers of insulin resistance and hepatic necroinflammation. The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue. Negative effects of BCAA or methionine were not detectable. FGF21 level appears to be a marker of metabolic improvement. ClinicalTrials.gov ID NCT02402985.
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Affiliation(s)
- Mariya Markova
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany.
| | - Olga Pivovarova
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany; Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
| | - Silke Hornemann
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany
| | - Stephanie Sucher
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany
| | - Turid Frahnow
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany
| | - Katrin Wegner
- Institute of Food Chemistry, Hamburg School of Food Science, University of Hamburg, Hamburg, Germany
| | - Jürgen Machann
- German Center for Diabetes Research, Germany; Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany
| | | | - Johannes Hierholzer
- Department of Diagnostic and Interventional Radiology, Ernst von Bergmann Hospital, Potsdam, Germany
| | - Ralf Lichtinghagen
- Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | - Christian Herder
- German Center for Diabetes Research, Germany; Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
| | - Maren Carstensen-Kirberg
- German Center for Diabetes Research, Germany; Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research, Germany; Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Natalia Rudovich
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany; Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
| | - Susanne Klaus
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Ralph Thomann
- Institut für Getreideverarbeitung GmbH, Nuthetal, Germany
| | | | - Sascha Rohn
- Institute of Food Chemistry, Hamburg School of Food Science, University of Hamburg, Hamburg, Germany; Institute for Food and Environmental Research, Nuthetal, Germany
| | - Andreas F H Pfeiffer
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, Germany; Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
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Lăpădat AM, Jianu IR, Ungureanu BS, Florescu LM, Gheonea DI, Sovaila S, Gheonea IA. Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods. J Med Life 2017. [DOI: 10.25122/jml-2017-0019] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application.Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed.
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Idilman IS, Ozdeniz I, Karcaaltincaba M. Hepatic Steatosis: Etiology, Patterns, and Quantification. Semin Ultrasound CT MR 2016; 37:501-510. [DOI: 10.1053/j.sult.2016.08.003] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Di Martino M, Pacifico L, Bezzi M, Di Miscio R, Sacconi B, Chiesa C, Catalano C. Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents. World J Gastroenterol 2016; 22:8812-8819. [PMID: 27818597 PMCID: PMC5075556 DOI: 10.3748/wjg.v22.i39.8812] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 06/30/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a threshold value for liver fat content between healthy children and those with non-alcoholic fatty liver disease (NAFLD) by using magnetic resonance imaging (MRI), with liver biopsy serving as a reference standard.
METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel point-resolved ¹H MR-Spectroscopy (¹H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cut-off value. Lin coefficient test was used to evaluate the correlation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables.
RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF.
CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children.
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Rastogi R, Gupta S, Garg B, Vohra S, Wadhawan M, Rastogi H. Comparative accuracy of CT, dual-echo MRI and MR spectroscopy for preoperative liver fat quantification in living related liver donors. Indian J Radiol Imaging 2016; 26:5-14. [PMID: 27081218 PMCID: PMC4813074 DOI: 10.4103/0971-3026.178281] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background: It is of significant importance to assess the extent of hepatic steatosis in living donor liver transplant (LDLT) surgery to ensure optimum graft regeneration as well as donor safety. Aim: To establish the accuracy of non-invasive imaging methods including computed tomography (CT), dual-echo in- and opposed-phase magnetic resonance imaging (MRI), and MR spectroscopy (MRS) for quantification of liver fat content (FC) in prospective LDLT donors with histopathology as reference standard. Settings and Design: This retrospective study was conducted at our institution on LDLT donors being assessed for biliary and vascular anatomy depiction by Magnetic Resonance Cholangiopancreatography (MRCP) and CT scan, respectively, between July 2013 and October 2014. Materials and Methods: Liver FC was measured in 73 donors by dual-echoT1 MRI and MRS. Of these, CT liver attenuation index (LAI) values were available in 62 patients. Statistical Analysis: CT and MRI FC were correlated with histopathological reference standard using Spearman correlation coefficient. Sensitivity, specificity, positive predictive value, negative predicative value, and positive and negative likelihood ratios with 95% confidence intervals were obtained. Results: CT LAI, dual-echo MRI, and MRS correlated well with the histopathology results (r = 0.713, 0.871, and 0.882, respectively). An accuracy of 95% and 96% was obtained for dual-echo MRI and MRS in FC estimation with their sensitivity being 97% and 94%, respectively. False-positive rate, positive predictive value (PPV), and negative predicative value (NPV) were 0.08, 0.92, and 0.97, respectively, for dual-echo MRI and 0.03, 0.97, and 0.95, respectively, for MRS. CT LAI method of fat estimation has a sensitivity, specificity, PPV, and NPV of 73%, 77.7%, 70.4%, and 80%, respectively. Conclusion: Dual-echo MRI, MRS, and CT LAI are accurate measures to quantify the degree of hepatic steatosis in LDLT donors, thus reducing the need for invasive liver biopsy and its associated complications. Dual-echo MRI and MRS results correlate better with histological results in the study, as compared to CT LAI method for fat quantification.
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Affiliation(s)
- Ruchi Rastogi
- Department of Radiology, Indraprastha Apollo Hospital, Delhi, India
| | - Subhash Gupta
- Department of Surgery, Indraprastha Apollo Hospital, Delhi, India
| | - Bhavya Garg
- Department of Radiology, Indraprastha Apollo Hospital, Delhi, India
| | - Sandeep Vohra
- Department of Radiology, Indraprastha Apollo Hospital, Delhi, India
| | - Manav Wadhawan
- Department of Gastroenerology, Indraprastha Apollo Hospital, Delhi, India
| | - Harsh Rastogi
- Department of Radiology, Indraprastha Apollo Hospital, Delhi, India
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Choline Supplementation With a Structured Lipid in Children With Cystic Fibrosis: A Randomized Placebo-Controlled Trial. J Pediatr Gastroenterol Nutr 2016; 62:618-26. [PMID: 26465792 PMCID: PMC4805439 DOI: 10.1097/mpg.0000000000001004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Choline depletion is seen in cystic fibrosis (CF) and pancreatic insufficiency in spite of enzyme treatment and may result in liver, fatty acid, and muscle abnormalities. This study evaluated the efficacy and safety of an easily absorbed choline-rich structured lipid (LYM-X-SORB™ [LXS]) to improve choline status. METHODS Children with CF and pancreatic insufficiency were randomized to LXS or placebo in a 12-month double blind trial. Dietary choline intake, plasma cholines, plasma and fecal phospholipids, coefficient of fat absorption, pulmonary function, growth status, body composition, and safety measures were assessed. Magnetic resonance spectroscopy for calf muscle choline and liver fat were assessed in a subgroup and compared with a healthy comparison group matched for age, sex, and body size. RESULTS A total of 110 subjects were enrolled (age 10.4 ± 3.0 years). Baseline dietary choline, 88% recommended, increased 3-fold in the LXS group. Plasma choline, betaine, and dimethylglycine increased in the LXS but not placebo (P = 0.007). Plasma lysophosphatidylcholine and phosphatidylcholine increased, and fecal phosphatidylcholine/phosphatidylethanolamine ratio decreased (P ≤ 0.05) in LXS only, accompanied by a 6% coefficient of fat absorption increase (P = 0.001). Children with CF had higher liver fat than healthy children and depleted calf muscle choline at baseline. Muscle choline concentration increased in LXS and was associated with improvement in plasma choline status. No relevant changes in safety measures were evident. CONCLUSIONS LXS had improved choline intake, plasma choline status, and muscle choline stores compared with placebo group. The choline-rich supplement was safe, accepted by participants, and improved choline status in children with CF.
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Machicao F, Peter A, Machann J, Königsrainer I, Böhm A, Lutz SZ, Heni M, Fritsche A, Schick F, Königsrainer A, Stefan N, Häring HU, Staiger H. Glucose-Raising Polymorphisms in the Human Clock Gene Cryptochrome 2 (CRY2) Affect Hepatic Lipid Content. PLoS One 2016; 11:e0145563. [PMID: 26726810 PMCID: PMC4699770 DOI: 10.1371/journal.pone.0145563] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 12/04/2015] [Indexed: 01/22/2023] Open
Abstract
Circadian rhythms govern vital functions. Their disruption provokes metabolic imbalance favouring obesity and type-2 diabetes. The aim of the study was to assess the role of clock genes in human prediabetes. To this end, genotype-phenotype associations of 121 common single nucleotide polymorphisms (SNPs) tagging ARNTL, ARNTL2, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIMELESS were assessed in a study population of 1,715 non-diabetic individuals metabolically phenotyped by 5-point oral glucose tolerance tests. In subgroups, hyperinsulinaemic-euglycaemic clamps, intravenous glucose tolerance tests, and magnetic resonance imaging/spectroscopy were performed. None of the tested SNPs was associated with body fat content, insulin sensitivity, or insulin secretion. Four CRY2 SNPs were associated with fasting glycaemia, as reported earlier. Importantly, carriers of these SNPs’ minor alleles revealed elevated fasting glycaemia and, concomitantly, reduced liver fat content. In human liver tissue samples, CRY2 mRNA expression was directly associated with hepatic triglyceride content. Our data may point to CRY2 as a novel switch in hepatic fuel metabolism promoting triglyceride storage and, concomitantly, limiting glucose production. The anti-steatotic effects of the glucose-raising CRY2 alleles may explain why these alleles do not increase type-2 diabetes risk.
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Affiliation(s)
- Fausto Machicao
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Andreas Peter
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Ingmar Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Anja Böhm
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Stefan Zoltan Lutz
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Martin Heni
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Department of Internal Medicine, Division of Nutritional and Preventive Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Fritz Schick
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Norbert Stefan
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Harald Staiger
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- * E-mail:
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Kächele M, Hennige AM, Machann J, Hieronimus A, Lamprinou A, Machicao F, Schick F, Fritsche A, Stefan N, Nürnberg B, Häring HU, Staiger H. Variation in the Phosphoinositide 3-Kinase Gamma Gene Affects Plasma HDL-Cholesterol without Modification of Metabolic or Inflammatory Markers. PLoS One 2015; 10:e0144494. [PMID: 26658747 PMCID: PMC4675530 DOI: 10.1371/journal.pone.0144494] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 11/19/2015] [Indexed: 01/22/2023] Open
Abstract
Objective Phosphoinositide 3-kinase γ (PI3Kγ) is a G-protein-coupled receptor-activated lipid kinase mainly expressed in leukocytes and cells of the cardiovascular system. PI3Kγ plays an important signaling role in inflammatory processes. Since subclinical inflammation is a hallmark of atherosclerosis, obesity-related insulin resistance, and pancreatic β-cell failure, we asked whether common genetic variation in the PI3Kγ gene (PIK3CG) contributes to body fat content/distribution, serum adipokine/cytokine concentrations, alterations in plasma lipid profiles, insulin sensitivity, insulin release, and glucose homeostasis. Study Design Using a tagging single nucleotide polymorphism (SNP) approach, we analyzed genotype-phenotype associations in 2,068 German subjects genotyped for 10 PIK3CG SNPs and characterized by oral glucose tolerance tests. In subgroups, data from hyperinsulinaemic-euglycaemic clamps, magnetic resonance spectroscopy of the liver, whole-body magnetic resonance imaging, and intravenous glucose tolerance tests were available, and peripheral blood mononuclear cells (PBMCs) were used for gene expression analysis. Results After appropriate adjustment, none of the PIK3CG tagging SNPs was significantly associated with body fat content/distribution, adipokine/cytokine concentrations, insulin sensitivity, insulin secretion, or blood glucose concentrations (p>0.0127, all; Bonferroni-corrected α-level: 0.0051). However, six non-linked SNPs displayed at least nominal associations with plasma HDL-cholesterol concentrations, two of them (rs4288294 and rs116697954) reaching the level of study-wide significance (p = 0.0003 and p = 0.0004, respectively). More precisely, rs4288294 and rs116697954 influenced HDL2-, but not HDL3-, cholesterol. With respect to the SNPs’ in vivo functionality, rs4288294 was significantly associated with PIK3CG mRNA expression in PBMCs. Conclusions We could demonstrate that common genetic variation in the PIK3CG locus, possibly via altered PIK3CG gene expression, determines plasma HDL-cholesterol concentrations. Since HDL2-, but not HDL3-, cholesterol is influenced by PIK3CG variants, PI3Kγ may play a role in HDL clearance rather than in HDL biogenesis. Even though the molecular pathways connecting PI3Kγ and HDL metabolism remain to be further elucidated, this finding could add a novel aspect to the pathophysiological role of PI3Kγ in atherogenesis.
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Affiliation(s)
- Martin Kächele
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
| | - Anita M. Hennige
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Anja Hieronimus
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Apostolia Lamprinou
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Fausto Machicao
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Fritz Schick
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
- Department of Diagnostic and Interventional Radiology, Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Nutritional and Preventive Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Norbert Stefan
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Bernd Nürnberg
- Department of Experimental and Clinical Pharmacology and Toxicology, Division of Pharmacology and Experimental Therapy, University Hospital Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Harald Staiger
- Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany
- German Centre for Diabetes Research (DZD), Tübingen, Germany
- * E-mail:
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Ulbrich EJ, Fischer MA, Manoliu A, Marcon M, Luechinger R, Nanz D, Reiner CS. Age- and Gender Dependent Liver Fat Content in a Healthy Normal BMI Population as Quantified by Fat-Water Separating DIXON MR Imaging. PLoS One 2015; 10:e0141691. [PMID: 26554709 PMCID: PMC4640707 DOI: 10.1371/journal.pone.0141691] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 10/09/2015] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES To establish age- and sex-dependent values of magnetic resonance (MR) liver fat-signal fraction (FSF) in healthy volunteers with normal body-mass index (BMI). METHODS 2-point mDIXON sequences (repetition time/echo time, 4.2msec/1.2msec, 3.1msec) at 3.0 Tesla MR were acquired in 80 healthy volunteers with normal BMI (18.2 to 25.7 kg/m2) between 20 and 62 years (10 men/10 women per decade). FSF was measured in 5 liver segments (segment II, III, VI, VII, VIII) based on mean signal intensities in regions of interest placed on mDIXON-based water and fat images. Multivariate general linear models were used to test for significant differences between BMI-corrected FSF among age subgroups. Pearson and Spearman correlations between FSF and several body measures were calculated. RESULTS Mean FSF (%) ± standard deviations significantly differed between women (3.91 ± 1.10) and men (4.69 ± 1.38) and varied with age for women/men (p-value: 0.002/0.027): 3.05 ± 0.49/3.74 ± 0.60 (age group 20-29), 3.75 ± 0.66/4.99 ± 1.30 (30-39), 4.76 ± 1.16/5.25 ± 1.97 (40-49) and 4.09 ± 1.26/4.79 ± 0.93 (50-62). FSF differences among age subgroups were significant for women only (p = 0.003). CONCLUSIONS MR-based liver fat content is higher in men and peaks in the fifth decade for both genders.
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Affiliation(s)
- Erika J. Ulbrich
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Michael A. Fischer
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Andrei Manoliu
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Magda Marcon
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Roger Luechinger
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland
| | - Daniel Nanz
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
| | - Caecilia S. Reiner
- Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
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