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Lammi C, Ottaviano E, Fiore G, Bollati C, d'Adduzio L, Fanzaga M, Ceccarani C, Vizzuso S, Zuccotti G, Borghi E, Verduci E. Effect of docosahexaenoic acid as an anti-inflammatory for Caco-2 cells and modulating agent for gut microbiota in children with obesity (the DAMOCLE study). J Endocrinol Invest 2025; 48:465-481. [PMID: 39186221 PMCID: PMC11785711 DOI: 10.1007/s40618-024-02444-w] [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: 02/28/2024] [Accepted: 08/12/2024] [Indexed: 08/27/2024]
Abstract
PURPOSE Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid. We investigated the dual health ability of DHA to modulate gut microbiota in children with obesity and to exert anti-inflammatory activity on human intestinal Caco-2 cells. METHODS In a pilot study involving 18 obese children (8-14 years), participants received a daily DHA supplement (500 mg/day) and dietary intervention from baseline (T0) to 4 months (T1), followed by dietary intervention alone from 4 months (T1) to 8 months (T2). Fecal samples, anthropometry, biochemicals and dietary assessment were collected at each timepoint. At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (H2O2) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively. RESULTS Ten children were included in final analysis. No major changes were observed for anthropometric and biochemical parameters, and participants showed a low dietary compliance at T1 and T2. DHA supplementation restored the Firmicutes/Bacteroidetes ratio that was conserved also after the DHA discontinuation at T2. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In Caco-2 cells, DHA decreased H2O2-induced reactive oxygen species (ROS) and nitric oxide (NO) production via iNOS pathway modulation. Additionally, DHA modulated proinflammatory (IL-1β, IL-6, IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokine production in LPS-stimulated Caco-2 cells. CONCLUSION An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. The ability to modulate gut microbiota, matches also with an anti-inflammatory effect of DHA on Caco-2 cells.
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Affiliation(s)
- C Lammi
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - E Ottaviano
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
| | - G Fiore
- Department of Health Sciences, University of Milan, 20142, Milan, Italy.
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy.
| | - C Bollati
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - L d'Adduzio
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - M Fanzaga
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - C Ceccarani
- Institute for Biomedical Technologies, CNR, Segrate, Italy
| | - S Vizzuso
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy
| | - G Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, 20157, Milan, Italy
| | - E Borghi
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
| | - E Verduci
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
- Metabolic Diseases Unit, Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, 20157, Milan, Italy
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Al-Daghri NM, Yakout SM, Hussain SD, Alnaami AM, Veronese N, Barbagallo M, Sabico S. Hypomagnesemia in adults with type 2 diabetes mellitus in Riyadh, Saudi Arabia: A cross-sectional study. Medicine (Baltimore) 2025; 104:e41253. [PMID: 39833091 PMCID: PMC11749644 DOI: 10.1097/md.0000000000041253] [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: 08/28/2024] [Accepted: 12/19/2024] [Indexed: 01/22/2025] Open
Abstract
This study investigates the prevalence of hypomagnesemia in adults with type 2 diabetes mellitus (T2DM) in Riyadh, Saudi Arabia, and examines its association with various metabolic parameters. Conducted as a cross-sectional study at King Saud University, Riyadh, it included 294 Saudi adults aged 25 to 65 years, comprising 119 T2DM patients, 80 prediabetics, and 95 nondiabetic controls. Participants underwent physical examinations, and fasting blood samples were analyzed for glucose, glycated hemoglobin (HbA1c), lipid profile, and serum magnesium levels. Statistical analysis revealed that lower magnesium levels were significantly more prevalent in T2DM patients (1.65 ± 4.9 mg/L) compared to prediabetes (2.48 ± 5.2 mg/L) and controls (2.9 ± 5.4 mg/L; P < .001). T2DM patients with magnesium deficiency exhibited higher levels of fasting glucose (11.2 ± 3.9 mmol/L), HbA1c (8.6 ± 2.1 mmol/L), and triglycerides (2.1 ± 0.9 mmol/L), along with increased insulin resistance (Homeostatic Model Assessment of Insulin Resistance = 6.6) and decreased insulin sensitivity (Quantitative Insulin Sensitivity Check Index = 0.29). Magnesium levels correlated negatively with glucose (R = -0.58) and HbA1c (R = -0.61). The area under the curve for serum magnesium in predicting HbA1c > 5.7 was 0.88, and for HbA1c ≥ 6.5, it was 0.91, indicating high diagnostic accuracy. These findings suggest that magnesium deficiency significantly impacts the metabolic profile of T2DM patients in Riyadh. Therefore, routine monitoring of magnesium levels is crucial in diabetes management, and further research is needed to explore the benefits of magnesium supplementation in T2DM care.
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Affiliation(s)
- Nasser M. Al-Daghri
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Sobhy M. Yakout
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Syed Danish Hussain
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Abdullah M. Alnaami
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Nicola Veronese
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Mario Barbagallo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Shaun Sabico
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Raju S, Sierra P, Tejwani V, Staggers KA, McCormack M, Villareal DT, Rosas IO, Hanania NA, Wu TD. Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study. Diabetes Care 2025; 48:143-148. [PMID: 39571139 DOI: 10.2337/dc24-1754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/28/2024] [Indexed: 12/22/2024]
Abstract
OBJECTIVE Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04-1.70), ILAs (OR 1.35; 95% CI 1.05-1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.
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Affiliation(s)
- Sarath Raju
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD
| | - Paula Sierra
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Vickram Tejwani
- Department of Pulmonary Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH
- Department of Systems Biology and Genome Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Kristen A Staggers
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX
| | - Meredith McCormack
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD
| | - Dennis T Villareal
- Section of Endocrine, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX
- Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX
| | - Ivan O Rosas
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Nicola A Hanania
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
| | - Tianshi David Wu
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX
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Moshkovits Y, Goldman A, Chetrit A, Moshkovitz Shrem H, Dankner R. A comparison between lipid-based vs. glycemic-based insulin sensitivity indices for the association with abnormal ECG findings and 20-year mortality among older adults. Cardiovasc Diabetol 2024; 23:438. [PMID: 39696234 PMCID: PMC11656852 DOI: 10.1186/s12933-024-02533-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND A direct comparison between glycemic-based and lipid-based insulin sensitivity indices (ISIs) for ECG findings and all-cause and cardiovascular mortality is lacking. METHODS 963 community-dwelling older adults, examined as part of the third phase of the Glucose intolerance, Obesity, and Hypertension study between 1999 and 2008, were followed until December 2016 and December 2019 for cardiovascular and all-cause mortality, respectively. Eleven different ISIs were calculated and evaluated against ECG findings, all-cause, and cardiovascular mortality with multivariable regression models. The area under the receiver operating curve (AUC) and net reclassification improvement (NRI) analysis were implemented to compare ISIs performance. RESULTS Mean age was 72.3 ± 7 years and 471 (49%) were females. Ischemic ECG changes were observed in 107 (11.2%) individuals. Upper quartile (Q4) of triglyceride-glucose waist-to-height ratio (TyG-WTHR) was associated with 220% greater odds for ischemic changes on ECG compared with lower quartiles (Q1-3) (95%CI:1.3-3.7, p = 0.004), an association that was not observed with other ISIs. During a median follow-up of 13 [IQR-8] and 11 [IQR-6] years for all-cause and CV mortality, respectively, 466 (48.4%) participants died, of them, 179 (38.4%) were attributed to cardiovascular causes. TyG-WTHR was the only ISI that was associated with both all-cause (HR = 1.3, 95%CI:1.0-1.6, p = 0.04) and cardiovascular (HR = 1.7, 95%CI:1.2-2.4, p = 0.004) mortality. Lipid based and glycemic ISIs showed similar predicative ability with slightly better predictive performance for TyG-WTHR for all-cause mortality (AUC = 0.46, 95%CI:0.4-0.5, p = 0.02). The NRI analysis revealed better reclassification ability for triglyceride-high-density-lipoprotein ratio (95%CI: 0.02-0.27, p = 0.03) and TyG-WTHR (95%CI: 0.0004-0.01, p = 0.03) for all-cause mortality while TyG-WTHR-based model correctly reclassified 19% of participants (95%CI: 0.02-0.36, p = 0.03) for cardiovascular mortality compared with model unadjusted for any ISIs and correctly reclassified 3% (95%CI:0.003-0.05, p = 0.02) compared with QUICKI based-model for all-cause mortality. CONCLUSIONS TyG-WTHR was the only ISI associated with ischemic changes on ECG and all-cause and cardiovascular mortality and significantly improved the predictive performance for all-cause cardiovascular mortality. While most glycemic-based and lipid-based ISIs showed similar predictive ability, TyG-WTHR stands as the preferred ISI and should be considered for screening at-risk individuals for cardiovascular morbidity and mortality.
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Affiliation(s)
- Yonatan Moshkovits
- Department of Internal Medicine F, Sheba Medical Center, Ramat-Gan, Israel
- School of Medicine, Faculty of Medicine, Tel-Aviv University, Tel‑Aviv, Israel
- Sheba Research Authority, Sheba Medical Center, Ramat-Gan, Israel
| | - Adam Goldman
- Department of Internal Medicine F, Sheba Medical Center, Ramat-Gan, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Health Sciences and Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Angela Chetrit
- Public Health Research Center, the Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, 52621, Ramat Gan, Israel
| | | | - Rachel Dankner
- Department of Epidemiology and Preventive Medicine, School of Public Health, Faculty of Health Sciences and Medicine, Tel Aviv University, Tel Aviv, Israel.
- Public Health Research Center, the Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, 52621, Ramat Gan, Israel.
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Tiwari V, Kamboj A, Sheoran B, Chaudhary E, Yadav M, Kumari A, Krishania M, Ali U, Tiwari A, Garg M, Bhatnagar A. Anthocyanin-rich black wheat as a functional food for managing type 2 diabetes mellitus: a study on high fat diet-streptozotocin-induced diabetic rats. Food Funct 2024. [PMID: 39688703 DOI: 10.1039/d4fo05065g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is associated with insulin resistance, hyperglycemia, and hyperlipidemia. Anthocyanins, which are natural antioxidants, have been reported to manage T2DM-related complications. However, the potential of anthocyanin-rich black wheat as a functional food for managing diabetes remains unexplored. Aim: This study aimed to investigate the effects of anthocyanin-rich black wheat on glucose metabolism, insulin sensitivity, lipid profile, oxidative stress, inflammation, and organ protection in high fat diet-streptozotocin (HFD-STZ) induced T2DM rats. Methods: T2DM was induced in rats using HFD-STZ. The rats were fed with either white wheat or anthocyanin-rich black wheat chapatti. Glucose metabolism, insulin sensitivity, lipid profile, antioxidant enzymes, inflammatory markers, and glucose transporters were assessed. Histopathological analysis of the liver, kidneys, and spleen was performed. Results: Compared to white wheat chapatti, black wheat chapatti exhibited higher α-amylase and α-glucosidase inhibitory activities. Black wheat chapatti consumption significantly reduced blood glucose and HbA1c levels, and improved insulin sensitivity, oral glucose tolerance, and insulin tolerance. Antioxidant enzyme (superoxide dismutase and catalase) activities were enhanced. Atherogenic dyslipidemia was attenuated, with improved high-density lipoprotein cholesterol levels. Inflammatory markers (TNF-α, IL-1β, leptin, resistin and cortisol) were reduced, while adiponectin (Acrp-30) levels increased. Black wheat chapatti activated adiponectin-AMPK and PI3K-AKT pathways, upregulating glucose transporters (GLUT-2 and GLUT-4). Histopathology revealed protective effects on the liver, kidneys, and spleen. Conclusions: Anthocyanin-rich black wheat chapatti ameliorates insulin resistance and associated complications in HFD-STZ-induced T2DM rats. It modulates key signaling pathways and glucose transporters, demonstrating its potential as a functional food for managing T2DM and its complications.
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Affiliation(s)
- Vandita Tiwari
- Department of Biochemistry, Panjab University, Chandigarh, India
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
| | - Akhil Kamboj
- Department of Biochemistry, Panjab University, Chandigarh, India
| | - Bhawna Sheoran
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
- Regional Centre for Biotechnology, Faridabad, Haryana (NCR), Delhi, India
| | - Era Chaudhary
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
- Regional Centre for Biotechnology, Faridabad, Haryana (NCR), Delhi, India
| | - Mona Yadav
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
- Regional Centre for Biotechnology, Faridabad, Haryana (NCR), Delhi, India
| | - Anita Kumari
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
| | - Meena Krishania
- Center of Innovative and Applied Bioprocessing, Mohali, Punjab, India
| | - Usman Ali
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
| | - Apoorv Tiwari
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
| | - Monika Garg
- National Agri-Food Biotechnology Institute (NABI), Mohali, Punjab, India.
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Herascu A, Avram VF, Gaita L, Alexandra S, Reurean-Pintilei DV, Timar B. Interventions Targeting Insulin Resistance in Patients with Type 1 Diabetes: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2067. [PMID: 39768947 PMCID: PMC11678706 DOI: 10.3390/medicina60122067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025]
Abstract
Background and Objectives: Insulin resistance (IR) is the most important factor involved in the pathogenesis of type 2 diabetes but may also develop in type 1 diabetes (T1DM). Developing IR in patients with T1DM may generate a burden in achieving glycemic targets and may deteriorate the overall prognosis. This review aims to describe the pathogenesis of IR in T1DM, summarize the common associations of IR with other conditions in patients with T1DM, describe the consequences of developing IR in these patients, and present the interventions that target IR in people with T1DM. Results: The occurrence of IR in T1DM is multifactorial; however, it is frequently linked to overweight or obesity and sedentary lifestyle. Besides impairments in glycemic control and increased insulin requirements, the presence of IR is associated with an increased cardiovascular risk in patients with T1DM. Considering that patients with T1DM are insulin-treated, IR may be evaluated only using surrogate biomarkers, the most frequently used being the estimated glucose disposal rate. The most important interventions that are shown to be feasible in improving insulin sensitivity in patients with T1DM are lifestyle optimizations, including nutrition therapy or physical activity and pharmacotherapy with metformin, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinediones. Conclusions: Targeting the improvement of IR in patients with T1DM is a key element in achieving optimal glycemic control, as well as improving the overall patient's prognosis besides glycemic control.
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Affiliation(s)
- Andreea Herascu
- Doctoral School of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (L.G.); (S.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Vlad-Florian Avram
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (L.G.); (S.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Laura Gaita
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (L.G.); (S.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Sima Alexandra
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (L.G.); (S.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Delia-Viola Reurean-Pintilei
- Department of Medical-Surgical and Complementary Sciences, Faculty of Medicine and Biological Sciences, “Stefan cel Mare” University, 720229 Suceava, Romania;
- Department of Diabetes, Nutrition and Metabolic Diseases, Consultmed Medical Centre, 700544 Iasi, Romania
| | - Bogdan Timar
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (L.G.); (S.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
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Alagiakrishnan K, Halverson T. Role of Peripheral and Central Insulin Resistance in Neuropsychiatric Disorders. J Clin Med 2024; 13:6607. [PMID: 39518747 PMCID: PMC11547162 DOI: 10.3390/jcm13216607] [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: 10/07/2024] [Revised: 10/27/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
Insulin acts on different organs, including the brain, which helps it regulate energy metabolism. Insulin signaling plays an important role in the function of different cell types. In this review, we have summarized the key roles of insulin and insulin receptors in healthy brains and in different brain disorders. Insulin signaling, as well as insulin resistance (IR), is a major contributor in the regulation of mood, behavior, and cognition. Recent evidence showed that both peripheral and central insulin resistance play a role in the pathophysiology, clinical presentation, and management of neuropsychiatric disorders like Cognitive Impairment/Dementia, Depression, and Schizophrenia. Many human studies point out Insulin Resistance/Metabolic Syndrome can increase the risk of dementia especially Alzheimer's dementia (AD). IR has been shown to play a role in AD development but also in its progression. This review article discusses the pathophysiological pathways and mechanisms of insulin resistance in major neuropsychiatric disorders. The extent of insulin resistance can be quantified using IR biomarkers like insulin levels, HOMA-IR index, and Triglyceride glucose-body mass index (TyG-BMI) levels. IR has been shown to precede neurodegeneration. Human trials showed current treatment with certain antidiabetic drugs, as well as life style management, like weight loss and exercise for IR, have shown promise in the management of cognitive/neuropsychiatric disorders. This may pave the pathway to the development of new therapeutic approaches to these challenging disorders of dementia and psychiatric diseases. Recent clinical trials are showing some encouraging evidence for these pharmacological and nonpharmacological approaches for IR in psychiatric and cognitive disorders, even though more research is needed to apply this evidence into clinical practice. Early identification and management of IR may help as a strategy to potentially alter neuropsychiatric disorders onset as well as its progression.
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Affiliation(s)
| | - Tyler Halverson
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada;
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Evia-Viscarra ML, Jacobo-Tovar E, Meneses-Rojas LF, Guardado-Mendoza R. Oral glucose tolerance test curve shape in Mexican children and adolescents with and without obesity. J Pediatr Endocrinol Metab 2024; 37:850-858. [PMID: 39382514 DOI: 10.1515/jpem-2024-0250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/16/2024] [Indexed: 10/10/2024]
Abstract
OBJECTIVES Mexican children with obesity are at a higher risk of developing type 2 diabetes mellitus (T2DM). The aim of the study was to compare oral glucose tolerance test (OGTT) characteristics: time of peak glucose, glucose level ≥155 mg/dL at 1 h, presence of metabolic syndrome (MetS), sensitivity, secretion, and oral disposition index (oDI) in children with and without obesity, according to oral glucose tolerance curve shape: monophasic or biphasic. METHODS Cross-sectional study including 143 children. Groups were divided into (a) obese: biphasic (B-Ob) (n=55) and monophasic (M-Ob) (n=50), (b) without obesity: biphasic (B-NonOb) (n=20) and monophasic (M-NonOb) (n=18). RESULTS Late glucose peak was more frequent in the M-Ob group (p<0.001). Glucose levels ≥155 mg/dL and MetS were more frequent in the M-Ob group but did not show significance. The groups with obesity (biphasic and monophasic) had higher indices of insulin resistance and insulin secretion compared to the nonobese groups (biphasic and monophasic) (p<0.001). AUC glucose was higher in the M-Ob group (p<0.05), and AUC insulin was higher in the M-NonOb group. oDI (Matsuda) was significantly lower in the M-Ob group compared to the other groups (p<0.001), and oDI-HOMA IR was higher in M-NonOb group (p=0.03). CONCLUSIONS All OGTT parameters could help to identify Mexican children at increased risk of developing T2DM, not only fasting plasma glucose and 2 h glucose. M-Ob in non-T2DM Mexican children reflects an early defect in glucose metabolism. Higher level of IR indexes in M-NonOb vs. B-NonOb could indicate an increased risk for T2DM of genetic origin.
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Affiliation(s)
- María Lola Evia-Viscarra
- Department of Pediatric Endocrinology, Servicios de Salud del Instituto Mexicano del Seguro Social para el Bienestar (IMSS-BIENESTAR), Hospital Regional de Alta Especialidad del Bajío, León, México
| | - Emmanuel Jacobo-Tovar
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, México
| | - Luis Fernando Meneses-Rojas
- Department of Gastroenterology, Hospital General de Zona 21, Instituto Mexicano del Seguro Social, León, México
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Schrank Y, Fontes R, Perozo AFDF, Araújo PB, Pinheiro MFMC, Gomes DMV, Vieira LMF. Proposal for fasting insulin and HOMA-IR reference intervals based on an extensive Brazilian laboratory database. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2024; 68:e230483. [PMID: 39529982 PMCID: PMC11554367 DOI: 10.20945/2359-4292-2023-0483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 05/28/2024] [Indexed: 11/16/2024]
Abstract
Objective Fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers. This study aimed to determine the RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro and, secondarily, to verify potential RI differences between sexes. Subjects and methods Serum insulin levels of 146,497 individuals (ages 20-60 years) who underwent blood sampling in the state of Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was measured using the electrochemiluminescence immunoassay method. After applying exclusion criteria, 21,684 individuals (18,576 [86%] women) were included. The RIs were estimated using a computational mining approach that integrates a selection of R packages. Results The 95% RIs in women and men and in the overall population were, respectively, 2.54-13.30 μU/mL (15.3-80.12 pmol/L), 2.43-11.89 μU/mL (14.6-71.7 pmol/L), and 2.52-13.14 μU/mL (15.2-79.2 pmol/L) for fasting insulin levels and 0.39-2.86, 0.38-2.81, and 0.39-2.86 for HOMA-IR values. Despite significant differences in insulin levels and HOMA-IR index between men and women, the use of sex-specific RIs was not justified. Conclusion The RIs of fasting insulin levels and HOMA-IR values found in the overall population can be applied to both sexes. Thus, for our population, we suggest the RIs of 2.52-13.14 μU/mL (15.1-78.8 pmol/L) for fasting insulin and 0.39-2.86 for the HOMA-IR index.
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Affiliation(s)
- Yolanda Schrank
- Diagnósticos da América S.A.São PauloSPBrasilDiagnósticos da América S.A. (DASA), São Paulo, SP, Brasil
- Hospital Federal de BonsucessoRio de JaneiroRJBrasilHospital Federal de Bonsucesso, Rio de Janeiro RJ, Brasil
| | - Rosita Fontes
- Diagnósticos da América S.A.São PauloSPBrasilDiagnósticos da América S.A. (DASA), São Paulo, SP, Brasil
- Instituto Estadual de Diabetes e Endocrinologia Luiz CapriglioneRio de JaneiroRJBrasilInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, RJ, Brasil
| | | | - Paula Bruna Araújo
- Rio de JaneiroRJBrasilIndependent Researcher, Rio de Janeiro, RJ, Brasil
| | - Maria Fernanda Miguens Castelar Pinheiro
- Diagnósticos da América S.A.São PauloSPBrasilDiagnósticos da América S.A. (DASA), São Paulo, SP, Brasil
- Instituto Estadual de Diabetes e Endocrinologia Luiz CapriglioneRio de JaneiroRJBrasilInstituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE), Rio de Janeiro, RJ, Brasil
| | | | - Luisane Maria Falci Vieira
- Diagnósticos da América S.A.São PauloSPBrasilDiagnósticos da América S.A. (DASA), São Paulo, SP, Brasil
- International Federation of Clinical Chemistry and Laboratory Medicine Task Force Global Reference Intervals DatabaseMilanoItalyInternational Federation of Clinical Chemistry and Laboratory Medicine Task Force Global Reference Intervals Database, Milano, Italy
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10
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Kosmas CE, Sourlas A, Oikonomakis K, Zoumi EA, Papadimitriou A, Kostara CE. Biomarkers of insulin sensitivity/resistance. J Int Med Res 2024; 52:03000605241285550. [PMCID: PMC11475114 DOI: 10.1177/03000605241285550] [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: 05/21/2024] [Accepted: 09/02/2024] [Indexed: 01/03/2025] Open
Abstract
In recent years, remarkable advancements in elucidating the intricate molecular underpinnings of type 2 diabetes mellitus (T2D) have been achieved. Insulin resistance (IR) has been unequivocally acknowledged as the driving pathogenetic mechanism of T2D, preceding disease onset by several years. Nonetheless, diagnostic tools for ascertaining IR are lacking in current clinical practice, representing a critical unmet need; use of the hyperinsulinemic-euglycemic glucose clamp, widely accepted as the gold standard method for evaluating IR at present, is cumbersome in a clinical setting. Thus, the development of well-validated, reliable, and affordable biomarkers of IR has attracted considerable attention from the research community. The biomarkers under investigation can be divided into two major categories: (1) indices or ratios, comprising parameters obtained from a basic or comprehensive metabolic panel and/or derived from anthropometric measurements, and (2) circulating molecules implicated in pathophysiological processes associated with IR. Furthermore, numerous novel biomarkers, including markers of β-cell dysfunction, radiographic quantification of excess visceral adipose tissue, T2D prediction models, certain microRNAs and metabolomic biomarkers, have also provided promising preliminary results. This narrative review aims to present current evidence pertaining to the most notable and exciting biomarkers of IR that are under rigorous evaluation.
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Affiliation(s)
- Constantine E Kosmas
- Second Department of Cardiology, National & Kapodistrian University of Athens, Athens, Greece
| | | | | | | | | | - Christina E Kostara
- Laboratory of Clinical Chemistry, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
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11
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Verhoeven JE, Wolkowitz OM, Satz IB, Conklin Q, Lamers F, Lavebratt C, Lin J, Lindqvist D, Mayer SE, Melas PA, Milaneschi Y, Picard M, Rampersaud R, Rasgon N, Ridout K, Veibäck GS, Trumpff C, Tyrka AR, Watson K, Wu GWY, Yang R, Zannas AS, Han LK, Månsson KNT. The researcher's guide to selecting biomarkers in mental health studies. Bioessays 2024; 46:e2300246. [PMID: 39258367 PMCID: PMC11811959 DOI: 10.1002/bies.202300246] [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: 12/25/2023] [Revised: 07/01/2024] [Accepted: 07/03/2024] [Indexed: 09/12/2024]
Abstract
Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability.
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Affiliation(s)
- Josine E. Verhoeven
- Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health program, Amsterdam, The Netherlands
| | - Owen M. Wolkowitz
- Department of Psychiatry and Behavioral Sciences, and Weill Institute for Neurosciences, University of California San Francisco School of Medicine, San Francisco, CA USA 94107
| | - Isaac Barr Satz
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Quinn Conklin
- Center for Mind and Brain, University of California, Davis, Davis, CA 95618, USA
- Center for Health and Community, University of California, San Francisco, San Francisco, CA 94107 USA
| | - Femke Lamers
- Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health program, Amsterdam, The Netherlands
| | - Catharina Lavebratt
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden
- Center for Molecular Medicine, L8:00, Karolinska University Hospital, 17176 Stockholm, Sweden
| | - Jue Lin
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA, 94158, United States
| | - Daniel Lindqvist
- Unit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Office for Psychiatry and Habilitation, Psychiatry Research Skåne, Region Skåne, Lund, Sweden
| | - Stefanie E. Mayer
- Department of Psychiatry and Behavioral Sciences, and Weill Institute for Neurosciences, University of California San Francisco School of Medicine, San Francisco, CA USA 94107
| | - Philippe A. Melas
- Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Yuri Milaneschi
- Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health, Mental Health program, Amsterdam, The Netherlands
- Amsterdam Neuroscience, Complex Trait Genetics, Amsterdam, The Netherlands
| | - Martin Picard
- Department of Psychiatry, Division of Behavioral Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, USA
- Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, USA
- New York State Psychiatric Institute, New York, USA
- Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Ryan Rampersaud
- Department of Psychiatry and Behavioral Sciences, and Weill Institute for Neurosciences, University of California San Francisco School of Medicine, San Francisco, CA USA 94107
| | - Natalie Rasgon
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Kathryn Ridout
- Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA
- Department of Psychiatry, Kaiser Permanente, Santa Rosa Medical Center, Santa Rosa, CA 95403, USA
| | - Gustav Söderberg Veibäck
- Unit for Biological and Precision Psychiatry, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Office for Psychiatry and Habilitation, Psychiatry Research Skåne, Region Skåne, Lund, Sweden
| | - Caroline Trumpff
- Department of Psychiatry, Division of Behavioral Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, USA
| | - Audrey R. Tyrka
- Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI 02885, USA
| | - Kathleen Watson
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
| | - Gwyneth Winnie Y Wu
- Department of Psychiatry and Behavioral Sciences, and Weill Institute for Neurosciences, University of California San Francisco School of Medicine, San Francisco, CA USA 94107
| | - Ruoting Yang
- Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, USA
| | - Anthony S. Zannas
- Department of Psychiatry, University of North Carolina at Chapel Hill, USA; 438 Taylor Hall, 109 Mason Farm Road, Chapel Hill, NC, 27599, USA
- Department of Genetics, University of North Carolina at Chapel Hill
| | - Laura K.M. Han
- Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia
- Orygen, Parkville, VIC, Australia
| | - Kristoffer N. T. Månsson
- Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Psychology and Psychotherapy, Babeș-Bolyai University, Cluj-Napoca, Romania
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12
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Brito Nunes C, Borges MC, Freathy RM, Lawlor DA, Qvigstad E, Evans DM, Moen GH. Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy. Metabolites 2024; 14:508. [PMID: 39330515 PMCID: PMC11434570 DOI: 10.3390/metabo14090508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 09/28/2024] Open
Abstract
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.
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Affiliation(s)
- Caroline Brito Nunes
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
| | - Maria Carolina Borges
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
| | - Rachel M. Freathy
- Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4PY, UK;
| | - Deborah A. Lawlor
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
| | - Elisabeth Qvigstad
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, 0424 Oslo, Norway
| | - David M. Evans
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Frazer Institute, University of Queensland, Brisbane 4102, Australia
| | - Gunn-Helen Moen
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Frazer Institute, University of Queensland, Brisbane 4102, Australia
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway
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13
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Ahern MM, Artegoitia VM, Bosviel R, Newman JW, Keim NL, Krishnan S. Fat burning capacity in a mixed macronutrient meal protocol does not reflect metabolic flexibility in women who are overweight or obese. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.08.29.24312791. [PMID: 39252930 PMCID: PMC11383504 DOI: 10.1101/2024.08.29.24312791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
Introduction Metabolic flexibility, the ability to switch from glucose to fat as a fuel source, is considered a marker of metabolic health. Higher fat oxidation is often associated with greater flexibility and insulin sensitivity, while lower fat oxidation is linked to metabolic inflexibility and insulin resistance. However, our study challenges the universal validity of this relationship, uncovering a more nuanced understanding of the complex interplay between fuel source switching and fat oxidation, especially in the presence of insulin resistance. Methods In an 8-week controlled feeding intervention, overweight to obese women with insulin resistance (as defined by McAuley's index) were randomized to consume either a diet based on the Dietary Guidelines for Americans 2010 (DGA) or a 'Typical' American Diet (TAD), n = 22 each. Participants were given a high-fat mixed macronutrient challenge test (MMCT) (60% fat, 28% carbohydrates, and 12% protein) at weeks 0, 2, and 8. Plasma lipids, metabolome, and lipidome were measured at 0, 0.5, 3, and 6h postprandial (PP); substrate oxidation measures were also recorded at 0,1 3, and 6h PP. Metabolic flexibility was evaluated as the change in fat oxidation from fasting to PP. Mixed model and multivariate analyses were used to evaluate the effect of diet on these outcomes, and to identify variables of interest to metabolic flexibility. Results Intervention diets (DGA and TAD) did not differentially affect substrate oxidation or metabolic flexibility, and equivalence tests indicated that groups could be combined for subsequent analyses. Participants were classified into three groups based on the % of consumed MMCT fat was oxidized in the 6h post meal period at weeks 0, 2 and 8. Low fat burners (LB, n = 6, burned <30% of fat in MMCT) and high fat burners (HB, n = 7, burned > 40% of fat in MMCT) at all weeks. Compared to LB, HB group had higher fat mass, total mass, lean mass, BMI, lower HDLc and lower RER (p < 0.05), but not different % body fat or % lean mass. During week 0, at 1h PP, LB had an increase in % fat oxidation change from 0h compared to HB (p<0.05), suggesting higher metabolic flexibility. This difference disappeared later in the PP phase, and we did not detect this beyond week 0. Partial least squares discriminant analysis (PLSDA (regular and repeated measures (sPLSDA)) models identified that LB group, in the late PP phase, was associated with higher rates of disappearance of acylcarnitines (AC) and lysophosphatidylcholines (LPC) from plasma (Q2: 0.20, R2X: 0.177, R2Y: 0.716). Conclusion In women with insulin resistance, a high fat burning capacity does not imply high metabolic flexibility, and not all women with insulin resistance are metabolically inflexible. LPCs and ACs are promising biomarkers of metabolic flexibility.
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Affiliation(s)
- Mary M. Ahern
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson AZ 85721
| | - Virginia M. Artegoitia
- United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA
| | - Rémy Bosviel
- West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA
| | - John W. Newman
- United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA
- West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, Davis, CA 95616, USA
| | - Nancy L. Keim
- United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA 95616, USA
- Department of Nutrition, University of California, Davis, Davis, CA 95616, USA
| | - Sridevi Krishnan
- School of Nutritional Sciences and Wellness, University of Arizona, Tucson AZ 85721
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14
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Smith EC, Patel JN, Wahba A, Cluckey A, Celedonio J, Park J, Hannah L, Lonce S, Shibao CA, Paranjape SY, Diedrich A, McGuinness O, Wasserman DH, Biaggioni I, Gamboa A. Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity. J Am Heart Assoc 2024; 13:e030775. [PMID: 39119951 DOI: 10.1161/jaha.123.030775] [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: 04/26/2023] [Accepted: 06/05/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.
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Affiliation(s)
- Emily C Smith
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Jay N Patel
- Division of Cardiology Vanderbilt University Medical Center Nashville TN
| | - Amr Wahba
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Andrew Cluckey
- Division of Cardiology Vanderbilt University Medical Center Nashville TN
| | - Jorge Celedonio
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - JinWoo Park
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - LaToya Hannah
- Human Metabolic Physiology Core Vanderbilt University Medical Center Nashville TN
| | - Suzanna Lonce
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Cyndya A Shibao
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Sachin Y Paranjape
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Andre Diedrich
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
| | - Owen McGuinness
- Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN
| | - David H Wasserman
- Department of Molecular Physiology and Biophysics Vanderbilt University Nashville TN
| | - Italo Biaggioni
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
- Department of Pharmacology Vanderbilt University Nashville TN
| | - Alfredo Gamboa
- Division of Clinical Pharmacology, Department of Medicine Vanderbilt University Medical Center Nashville TN
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15
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Tenda ED, Henrina J, Cha JH, Triono MR, Putri EA, Aristy DJ, Tahapary DL. Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes. World J Diabetes 2024; 15:1448-1460. [PMID: 39099813 PMCID: PMC11292334 DOI: 10.4239/wjd.v15.i7.1448] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 05/08/2024] [Accepted: 06/06/2024] [Indexed: 07/08/2024] Open
Abstract
In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.
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Affiliation(s)
- Eric D Tenda
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
- Head of Research Group Artificial Intelligence and Digital Health, Indonesian Medical Education and Research Institute, Faculty of Medicine University of Indonesia, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Joshua Henrina
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Jin H Cha
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Muhammad R Triono
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Ersananda A Putri
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Dahliana J Aristy
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
| | - Dicky L Tahapary
- Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo Hospital, DKI Jakarta, Jakarta Pusat 10430, Indonesia
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16
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Wei Z, Tian L, Xu H, Li C, Wu K, Zhu H, Guan J, Yu Y, Qian D, Li X. Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study. Nutr Metab (Lond) 2024; 21:40. [PMID: 38956564 PMCID: PMC11221003 DOI: 10.1186/s12986-024-00816-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 06/18/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.
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Affiliation(s)
- ZhiCheng Wei
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Ling Tian
- Donghai County Maternal and Child Health Hospital, No. 80, Shanxi Road, Niushan Street, Donghai County, Lianyungang City, 200233, JiangSu, China
| | - Huajun Xu
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Chenyang Li
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Kejia Wu
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Huaming Zhu
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Jian Guan
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China
| | - Yafeng Yu
- Department of Otorhinolaryngology Head and Neck Surgery, First affiliated hospital of Soochow University, Suzhou City, 25006, Jiangsu, China.
| | - Di Qian
- Department of otolaryngology, People's Hospital of Longhua, 38 Jinglong construction Road, Longhua district, Shenzhen, China.
| | - Xinyi Li
- Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, China.
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17
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Zahedi AS, Zarkesh M, Sedaghati-khayat B, Hedayati M, Azizi F, Daneshpour MS. Insulin resistance-related circulating predictive markers in the metabolic syndrome: a systematic review in the Iranian population. J Diabetes Metab Disord 2024; 23:199-213. [PMID: 38932859 PMCID: PMC11196549 DOI: 10.1007/s40200-023-01347-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 11/08/2023] [Indexed: 06/28/2024]
Abstract
Background Specific biomarkers for metabolic syndrome (MetS) may improve diagnostic specificity for clinical information. One of the main pathophysiological mechanisms of MetS is insulin resistance (IR). This systematic review aimed to summarize IR-related biomarkers that predict MetS and have been investigated in Iranian populations. Methods An electronic literature search was done using the PubMed and Scopus databases up to June 2022. The risk of bias was assessed for the selected articles using the instrument suggested by the Joanna Briggs Institute (JBI). This systematic review protocol was registered with PROSPERO (registration number CRD42022372415). Results Among the reviewed articles, 46 studies investigated the association between IR biomarkers and MetS in the Iranian population. The selected studies were published between 2009 and 2022, with the majority being conducted on adults and seven on children and adolescents. The adult treatment panel III (ATP III) was the most commonly used criteria to define MetS. At least four studies were conducted for each IR biomarker, with LDL-C being the most frequently evaluated biomarker. Some studies have assessed the diagnostic potency of markers using the area under the curve (AUC) with sensitivity, specificity, and an optimal cut-off value. Among the reported values, lipid ratios and the difference between non-HDL-C and LDL-C levels showed the highest AUCs (≥ 0.80) for predicting MetS. Conclusions Considering the findings of the reviewed studies, fasting insulin, HOMA-IR, leptin, HbA1c, and visfatin levels were positively associated with MetS, whereas adiponectin and ghrelin levels were negatively correlated with this syndrome. Among the investigated IR biomarkers, the association between adiponectin levels and components of MetS was well established. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-023-01347-6.
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Affiliation(s)
- Asiyeh Sadat Zahedi
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Zarkesh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bahar Sedaghati-khayat
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam S Daneshpour
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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18
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Silva LFR, Garcia BCC, Esteves EA, Mang ZA, Amorim FT, Dias-Peixoto MF, Gripp F, Tricoli V, de Castro Magalhaes F. The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial. PLoS One 2024; 19:e0302480. [PMID: 38805474 PMCID: PMC11132464 DOI: 10.1371/journal.pone.0302480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 04/03/2024] [Indexed: 05/30/2024] Open
Abstract
Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).
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Affiliation(s)
- Luis Filipe Rocha Silva
- Graduate Program in Health Sciences, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
| | - Bruna Caroline Chaves Garcia
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
| | - Elizabethe Adriana Esteves
- Graduate Program in Health Sciences, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
- Department of Nutrition, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
| | - Zachary Aaron Mang
- Post-doctoral Research Associate, Occupational Safety & Health, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America
| | - Fabiano Trigueiro Amorim
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, New Mexico, United States of America
| | - Marco Fabrício Dias-Peixoto
- Graduate Program in Health Sciences, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
| | - Fernando Gripp
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
| | - Valmor Tricoli
- School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Flavio de Castro Magalhaes
- Graduate Program in Health Sciences, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, New Mexico, United States of America
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, Brazil
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19
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Khamseh ME, Malek M, Jahangiri S, Nobarani S, Hekmatdoost A, Salavatizadeh M, Soltanieh S, Chehrehgosha H, Taheri H, Montazeri Z, Attaran F, Ismail-Beigi F, Alaei-Shahmiri F. Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis. Dig Dis Sci 2024; 69:1430-1443. [PMID: 38438774 DOI: 10.1007/s10620-024-08309-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 01/19/2024] [Indexed: 03/06/2024]
Abstract
BACKGROUND Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear. AIMS To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis. METHODS A cross-sectional study was conducted on individuals aged 25-75 years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight. RESULTS A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups. CONCLUSIONS TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status.
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Affiliation(s)
- Mohammad E Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mojtaba Malek
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Soodeh Jahangiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Sohrab Nobarani
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marieh Salavatizadeh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samira Soltanieh
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Haleh Chehrehgosha
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Hoda Taheri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Zeinab Montazeri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Fereshteh Attaran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Faramarz Ismail-Beigi
- Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA
| | - Fariba Alaei-Shahmiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran.
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20
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Wang F, Sun M, Guo R, Wu Z, Wang X, Yang Y, Liu Y, Dong Y, Wang S, Yan S, Li B. The association between vitamin K intake and dyslipidemia in US adults: the mediating effect of insulin resistance. Food Funct 2024; 15:2974-2981. [PMID: 38410907 DOI: 10.1039/d3fo04614a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Background: Dyslipidemia is one of the most common chronic diseases, and is associated with insulin resistance (IR) and inadequate vitamin K intake. We aimed to explore the association between IR, vitamin K intake, and dyslipidemia, and further to explore the mediating role of IR. Materials and methods: 12 860 participants from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were included in this study. Insulin resistance was determined by using the homeostatic model assessment for insulin resistance (HOMA-IR). Weighted multiple logistic regression and mediation analyses were conducted to analyze the associations between IR, vitamin K intake, and dyslipidemia. Results: We found that both vitamin K intake-met Dietary Reference Intake (DRI) and non-IR were protective factors of high triglycerides (with ORs (95% CI) of 0.71 (0.57, 0.87) and 0.36 (0.29, 0.45), respectively) and low high-density lipoprotein cholesterol (with ORs (95% CI) of 0.72 (0.62, 0.82) and 0.39 (0.34, 0.41), respectively). IR-related indicators (HOMA-IR and insulin) partly mediated these effects, and the proportion ranged from 16.36% to 18.52%. Conclusion: Vitamin K intake-met DRI and non-IR were associated with lower risk of dyslipidemia including high TG and low HDL-C. IR partly mediated the association of vitamin K intake with high TG and low HDL-C.
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Affiliation(s)
- Fengdan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Mengzi Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Ruirui Guo
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Zibo Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Xuhan Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Yixue Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Yan Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Yibo Dong
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Sizhe Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
| | - Shoumeng Yan
- School of Nursing, Jilin University, Changchun, China.
| | - Bo Li
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, P. R. China.
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21
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Riccio A, Fortin E, Mellbin L, Norhammar A, Näsman P, Rydén L, Sesti G, Ferrannini G. Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states. Cardiovasc Diabetol 2024; 23:25. [PMID: 38218814 PMCID: PMC10787422 DOI: 10.1186/s12933-023-02093-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 12/11/2023] [Indexed: 01/15/2024] Open
Abstract
BACKGROUND Females are generally less prone to cardiovascular (CV) events than males, but this protection is trumped by diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim to investigate differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index - VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first non-fatal myocardial infarction (MI) across different glycaemic states. METHODS IR indexes were calculated in a population with (n = 696) and without (n = 707) a first non-fatal MI, free from known diabetes. MI cases were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first non-fatal MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. RESULTS Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first non-fatal MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p = 0.06). Females were less insulin resistant than males, especially among cases and with normal glucose tolerance. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9, and 1.9, 1.1-3.4 respectively). CONCLUSIONS These results support the assumption that IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor for non-fatal MI in females, even without glycaemic perturbations.
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Affiliation(s)
- Alessia Riccio
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden.
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
| | - Elena Fortin
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
| | - Linda Mellbin
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
- Heart, Vascular and Neuro Theme, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Norhammar
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
- Capio St Görans Hospital, Stockholm, Sweden
| | - Per Näsman
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
- Center for safety research, KTH Royal Institute of Technology, Stockholm, Sweden
| | - Lars Rydén
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
- Heart, Vascular and Neuro Theme, Karolinska University Hospital, Stockholm, Sweden
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Giulia Ferrannini
- Cardiology Unit, Department of Medicine Solna, Karolinska Institute Stockholm, Stockholm, Sweden
- Internal Medicine Unit, Södertälje hospital, Södertälje, Sweden
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22
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Hosseinkhani S, Forouzanfar K, Hadizadeh N, Razi F, Darzi S, Bandarian F. Insight into the Predictive Power of Surrogate Diagnostic Indices for Identifying Individuals with Metabolic Syndrome. Endocr Metab Immune Disord Drug Targets 2024; 24:1291-1302. [PMID: 38258774 DOI: 10.2174/0118715303264620231106105345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 09/05/2023] [Accepted: 09/23/2023] [Indexed: 01/24/2024]
Abstract
BACKGROUND This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations. METHODS Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences. RESULTS The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals. CONCLUSION The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.
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Affiliation(s)
- Shaghayegh Hosseinkhani
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Katayoon Forouzanfar
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nastaran Hadizadeh
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farideh Razi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Darzi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Bandarian
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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23
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Belay KE, Ayalew BL, Meherete Etana A, Ashrafi Mahabadi M. Extremely high-dose insulin requirement in a diabetic patient with psychiatric illness: A case report. SAGE Open Med Case Rep 2023; 11:2050313X231220834. [PMID: 38130913 PMCID: PMC10734350 DOI: 10.1177/2050313x231220834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023] Open
Abstract
Severe insulin resistance is defined as the need of insulin requirement of more than two units per kilogram of body weight. It is rarely seen in diabetic patients. Common causes of severe insulin resistance include severe insulin resistance syndromes, drugs, endocrine disorders, factitious causes, lipodystrophy, increased insulin clearance, and impaired insulin absorption. Here, we describe a diabetic patient with major depressive disorder who was prescribed a maximum of 282 units (4.9 units/kg) of insulin a day. However, the cause in this patient was pseudo-resistance to insulin due to the inappropriate use of insulin by the patient. The ability to maintain her glycemia in the target range with lower doses of insulin was confirmed after the patient was admitted to the hospital. It is, therefore, crucial to systematically address any patient who requires an exceptionally high dose of exogenous insulin, starting with technical issues (injection technique, site of administration, or insulin storage), medication adherence, or medication errors.
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Affiliation(s)
- Kibret Enyew Belay
- Department of Internal Medicine, Endocrinology and Metabolism Unit, Bahirdar University, Bahirdar, Ethiopia
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Jebasingh FK, Anoop S, Dasgupta R, Kurian ME, Joseph A, Rebekah G, Mohan V, Thomas N. Understanding the predictive accuracy of the InsuTAG index over other surrogate indices in normoglycaemic, non-obese males from Southern India. Sci Rep 2023; 13:19497. [PMID: 37945732 PMCID: PMC10636180 DOI: 10.1038/s41598-023-45880-z] [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: 04/17/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023] Open
Abstract
We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson's correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r - 0.23, p = 0.01), McAuley index (r - 0.65, p < 0.01), QUICKI (r - 0.34, p < 0.01) and FGIR (r - 0.35, p < 0.01). Significant positive correlations of InsuTAG index were observed for BMI and waist circumference. The ROC-AUC was higher for InsuTAG index (0.75) than FGIR (0.30), QUICKI (0.31), and McAuley index (0.20). The InsuTAG cut-off value ≥ 19.13 showed 66.7% sensitivity and 69.2% specificity in this study group.
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Affiliation(s)
- Felix K Jebasingh
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India
| | - Shajith Anoop
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India
| | - Riddhi Dasgupta
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India
| | - Mathews Edatharayil Kurian
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India
| | - Aneez Joseph
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India
| | - Grace Rebekah
- Department of Biostatistics, Christian Medical College, Vellore, India
| | - Venkataraghava Mohan
- Department of Community Health and Development, Christian Medical College, Vellore, India
| | - Nihal Thomas
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, Ida Scudder Road, Vellore, Tamilnadu, 632004, India.
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Kassab HS, Osman NA, Elrahmany SM. Assessment of Triglyceride-Glucose Index and Ratio in Patients with Type 2 Diabetes and Their Relation to Microvascular Complications. Endocr Res 2023; 48:94-100. [PMID: 37565769 DOI: 10.1080/07435800.2023.2245909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/12/2023]
Abstract
OBJECTIVE Triglyceride-based indices have gained much attention over the past few years. Relation of triglyceride - glucose (TyG) index with insulin resistance and diabetic macrovascular complications was thoroughly studied; nevertheless its relation to microvascular complications is still unclear. This provoked us to carry out the present study. METHODS This cross-sectional study included 500 patients with type 2 diabetes (T2DM), who were enrolled from the outpatient clinic of the Diabetes and Metabolism Unit at Alexandria Main University Hospital. The equations utilized to calculate triglycerides-related indices were: TyG ratio = fasting triglycerides (mg/dL)/fasting glucose (mg/dL), and TyG index = logarithm of [fasting triglyceride (mg/dl) x fasting glucose (mg/dl)/2]. The diagnostic criteria set by the American Diabetes Association were followed to diagnose diabetic microvascular complications. RESULTS In patients with T2DM, TyG index was significantly higher in patients with diabetic retinopathy, diabetic kidney disease, and diabetic peripheral neuropathy compared to those without complications (p < 0.001). TyG index was significantly positively correlated to diabetes duration, as well as triglyceride/high density lipoprotein ratio in the total sample (p < 0.001). CONCLUSION TyG index is an easy, cheap, and available marker for detection of microvascular complications in patients with T2DM.
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Affiliation(s)
- Heba S Kassab
- Lecturer of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Nermin A Osman
- Lecturer of Biomedical Informatics and Medical Statistics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Shimaa M Elrahmany
- Lecturer of Internal Medicine (Diabetes and Metabolism Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Tsilingiris D, Schimpfle L, von Rauchhaupt E, Sulaj A, Seebauer L, Bartl H, Herzig S, Szendroedi J, Kopf S, Kender Z. Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development. J Clin Endocrinol Metab 2023; 108:e979-e988. [PMID: 37139855 PMCID: PMC10505541 DOI: 10.1210/clinem/dgad248] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/03/2023] [Accepted: 05/02/2023] [Indexed: 05/05/2023]
Abstract
AIM To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. METHODS A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. RESULTS Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). CONCLUSION We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.
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Affiliation(s)
- Dimitrios Tsilingiris
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Schimpfle
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Ekaterina von Rauchhaupt
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Alba Sulaj
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Seebauer
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Hannelore Bartl
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany
| | - Stephan Herzig
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
- Helmholtz Center Munich, Institute for Diabetes and Cancer, 85764 Munich-Neuherberg, Germany
| | - Julia Szendroedi
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
| | - Stefan Kopf
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Zoltan Kender
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
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Hammel MC, Stein R, Kratzsch J, Vogel M, Eckert AJ, Triatin RD, Colombo M, Meigen C, Baber R, Stanik J, Spielau U, Stoltze A, Wirkner K, Tönjes A, Snieder H, Holl RW, Stumvoll M, Blüher M, Kiess W, Körner A. Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs. THE LANCET REGIONAL HEALTH. EUROPE 2023; 30:100652. [PMID: 37465325 PMCID: PMC10350850 DOI: 10.1016/j.lanepe.2023.100652] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 04/25/2023] [Accepted: 04/27/2023] [Indexed: 07/20/2023]
Abstract
Background Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. Methods We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5-80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. Findings There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1-3.21)), fasting insulin HR 1.89 (95% CI 1.11-3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62-1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. Interpretation The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. Funding German Research Foundation (DFG)-through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union-European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.
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Affiliation(s)
- Maximiliane Chiara Hammel
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
| | - Robert Stein
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Germany
| | - Jürgen Kratzsch
- Medical Faculty, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University of Leipzig, Leipzig, Germany
| | - Mandy Vogel
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Alexander J. Eckert
- University of Ulm, Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Rima Destya Triatin
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Marco Colombo
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
| | - Christof Meigen
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Ronny Baber
- Medical Faculty, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnosis, University of Leipzig, Leipzig, Germany
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Juraj Stanik
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
- Medical Faculty, Department of Pediatrics, and DIABGENE Laboratory, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Comenius University, Bratislava, Slovakia
| | - Ulrike Spielau
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
| | - Anette Stoltze
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
| | - Kerstin Wirkner
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Anke Tönjes
- Department of Endocrinology, Nephrology und Rheumatic Diseases, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Harold Snieder
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Reinhard W. Holl
- University of Ulm, Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Michael Stumvoll
- Department of Endocrinology, Nephrology und Rheumatic Diseases, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Germany
- Department of Endocrinology, Nephrology und Rheumatic Diseases, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Wieland Kiess
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Antje Körner
- Medical Faculty, University Hospital for Children and Adolescents, Center for Pediatric Research, University of Leipzig, Leipzig, Germany
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Germany
- LIFE Child Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
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Westphal-Nardo G, Chaput JP, Faúndez-Casanova C, Fernandes CAM, de Andrade Gonçalves EC, Utrila RT, Oltramari K, Grizzo FMF, Nardo-Junior N. Exploring New Tools for Risk Classification among Adults with Several Degrees of Obesity. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:6263. [PMID: 37444110 PMCID: PMC10341139 DOI: 10.3390/ijerph20136263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/27/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023]
Abstract
The epidemic of obesity worldwide has been recognized as a very important challenge. Within its complexity, the identification of higher-risk patients is essential, as it is unsustainable to offer access to treatment to all people with obesity. Several new approaches have recently been presented as important tools for risk stratification. In this research, we applied several of these tools in a cross-sectional study involving adults with obesity classes I, II, III, and super-obesity. The participants had their cardiometabolic risk profiles assessed. The study included adults with obesity aged 18 to 50 years (n = 404), who were evaluated using anthropometric, body composition, hemodynamic, physical fitness, and biochemical assessments. These variables were used to identify the prevalence of risk factors for cardiometabolic diseases according to the classes of obesity by gender and age group. The results showed high prevalence of risk factors, especially among the upper classes of obesity (BMI > 35 kg/m2) using single parameters as the waist circumference, with almost 90% above the cut-off point. For smaller numbers such as Glycated Hemoglobin, however, the prevalence was around 30%. Indexes such as the atherogenic index of plasma (AIP) had the highest prevalence, with 100% of the male participants identified as being at increased risk for cardiovascular disease.
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Affiliation(s)
- Greice Westphal-Nardo
- Department of Physical Education, Associate Graduate Program in Physical Education UEM/UEL, Health Sciences Center, State University of Maringa, Maringa 87020-900, Parana, Brazil; (C.F.-C.); (N.N.-J.)
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada;
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Jean-Philippe Chaput
- Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada;
| | - César Faúndez-Casanova
- Department of Physical Education, Associate Graduate Program in Physical Education UEM/UEL, Health Sciences Center, State University of Maringa, Maringa 87020-900, Parana, Brazil; (C.F.-C.); (N.N.-J.)
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
- Faculty of Education Sciences, Catholic University of Maule, Talca 34809112, Maule, Chile
| | - Carlos Alexandre Molena Fernandes
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Eliane Cristina de Andrade Gonçalves
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Raquel Tomiazzi Utrila
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Karine Oltramari
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Felipe Merchan Ferraz Grizzo
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
| | - Nelson Nardo-Junior
- Department of Physical Education, Associate Graduate Program in Physical Education UEM/UEL, Health Sciences Center, State University of Maringa, Maringa 87020-900, Parana, Brazil; (C.F.-C.); (N.N.-J.)
- Center for Multiprofessional Studies on Obesity—NEMO/HUM/UEM, University Hospital of Maringa, State University of Maringa, Maringa 87083-240, Parana, Brazil; (C.A.M.F.); (E.C.d.A.G.); (R.T.U.); (K.O.); (F.M.F.G.)
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Jena S, Mishra I, Baliarsinha AK, Jena D, Debata M. Variation in Clinical Presentation, Metabolic Profile, Hormonal Parameters and Inflammatory Markers in Polycystic Ovary Syndrome Women with and without Polycystic Ovary Morphology Appearance. J Hum Reprod Sci 2023; 16:132-139. [PMID: 37547087 PMCID: PMC10404011 DOI: 10.4103/jhrs.jhrs_60_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 08/08/2023] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with a spectrum of presentation. Studies have reported considerably different rates in terms of the incidence of polycystic ovary morphology (PCOM) in patients with PCOS with inconsistent results regarding the effects of PCOM in them. Aims The aim of this study was to determine the differences in clinical presentation, metabolic profile, hormonal parameters and inflammatory markers in PCOS women with and without PCOM on ultrasonography (USG). Settings and Design A total of 70 PCOS women were recruited. To analyse the differences between various parameters, the patients were divided into two groups based on the presence or absence of PCOM on USG of the pelvis as per the Rotterdam criteria. Materials and Methods A total of 37 patients had PCOM as per the diagnostic criteria for PCOS (Group 1), while 33 patients did not have PCOM on USG and were designated as Group 2. All participants underwent a detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein, serum adiponectin, luteinising hormone, follicle-stimulating hormone, total testosterone and serum anti-Mullerian hormone. The homeostasis model assessment of IR (HOMA-IR) was calculated using standard equations. Statistical Analysis Used The mean and Standard deviation were computed for all continuous variables. Frequencies and proportions were calculated for categorical variables. Comparisons of the mean scores between the study groups were assessed using the Unpaired Student's t-test. The mean score of the subgroups was also compared using the unpaired Student's t-test. P < 0.05 was considered significant for all statistical inferences. Results The mean LDL and mean triglyceride were higher in Group 2, which was statistically significant (P = 0.004 and P ≤ 0.001, respectively). The mean hs-CRP was found to be higher in Group 2, which was statistically significant (P = 0.005). The mean AMH was higher in Group 1, which was statistically significant (P = 0.002). Group 1 had higher adiponectin levels, which was statistically significant (P = 0.04). Conclusion The above findings suggest that patients without diagnostic PCO morphology have a worse metabolic profile compared to those with PCO morphology on USG. Obese patients without PCO morphology probably have a higher cardiovascular risk compared to obese patients with PCO morphology.
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Affiliation(s)
- Sweekruti Jena
- Department of Endocrinology, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Ipsita Mishra
- Department of Endocrinology, SCB Medical College and Hospital, Cuttack, Odisha, India
| | | | - Debarchan Jena
- Department of Endocrinology, SCB Medical College and Hospital, Cuttack, Odisha, India
| | - Madhumita Debata
- Department of Radiology, SCB Medical College and Hospital, Cuttack, Odisha, India
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Association between hepcidin and type 2 diabetes markers in indigenous Argentinean children living at high altitude. Clin Chim Acta 2022; 537:194-198. [DOI: 10.1016/j.cca.2022.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/19/2022] [Accepted: 08/22/2022] [Indexed: 01/08/2023]
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Ferreira PPR, Silva LFR, Dias-Peixoto MF, Cassilhas RC, Gripp F, Amorim FT, Mang ZA, Esteves EA, Tricoli VA, Ferraresi C, Magalhães FDC. Effects of the association of different volumes of strength training with photobiomodulation therapy on insulin resistance: A protocol for a randomized, triple-blind, placebo-controlled trial. Contemp Clin Trials Commun 2022; 29:100984. [PMID: 36052175 PMCID: PMC9424937 DOI: 10.1016/j.conctc.2022.100984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 08/08/2022] [Accepted: 08/11/2022] [Indexed: 10/27/2022] Open
Abstract
Background Insulin resistance (IR) is the main risk factor for developing type 2 diabetes. Both strength training (ST) and photobiomodulation therapy (PBMt) reduce IR, but the effect of combining different volumes of ST with PBMt is unknown. Methods Overweight/obese individuals will be assigned to 4 groups (n = 12/group): ST with volume following international guidelines (3 sets per exercise - high volume) or one-third of this volume (1 set per exercise - low volume), combined with PBMt or placebo. ST will be performed for 20 sessions over 10 weeks and will consist of 7 exercises. The PBMt will be applied after training sessions using blankets with light emitters (LEDs) placed over the skin on the frontal and the posterior region of the body, following the parameters recommended by the literature. The placebo group will undergo an identical procedure, but blankets will emit insignificant light. To measure plasma glucose and insulin concentrations, oral glucose tolerance tests (OGTT) will be performed before and after the training period. Thereafter, IR, the area under the curve of glucose and insulin, and OGTT-derived indices of insulin sensitivity/resistance will be calculated. Expected impact on the field This study will determine the effects of different ST volumes on IR and whether the addition of PBMt potentiates the effects of ST. Because previously sedentary, obese, insulin-resistant individuals might not comply with recommended volumes of exercise, the possibility that adding PBMt to low-volume ST enhances ST effects on IR bears practical significance.
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Affiliation(s)
- Pedro Paulo Ribeiro Ferreira
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Luís Filipe Rocha Silva
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Marco Fabrício Dias-Peixoto
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Ricardo Cardoso Cassilhas
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Fernando Gripp
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Fabiano Trigueiro Amorim
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, NM, USA
| | - Zachary A. Mang
- Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, NM, USA
| | - Elizabethe Adriana Esteves
- Department of Nutrition, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
| | - Valmor A. Tricoli
- School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, SP, Brazil
| | - Cleber Ferraresi
- Deparment of Physical Therapy, Federal University of Sao Carlos, Sao Carlos, SP, Brazil
| | - Flávio de Castro Magalhães
- Department of Physical Education, Federal University of the Jequitinhonha and Mucuri Valleys, Campus JK, Diamantina, MG, Brazil
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Yang CD, Pan WQ, Feng S, Quan JW, Chen JW, Shu XY, Aihemaiti M, Ding FH, Shen WF, Lu L, Zhang RY, Wang XQ. Insulin Resistance Is Associated With Heart Failure With Recovered Ejection Fraction in Patients Without Diabetes. J Am Heart Assoc 2022; 11:e026184. [PMID: 36129062 DOI: 10.1161/jaha.122.026184] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2-IR). The median HOMA2-IR level was 1.05 (interquartile range [IQR], 0.67-1.63) in our cohort of patients with HF who were nondiabetic. During follow-up, 121 (odds ratio [OR], 46.2% [95% CI 40.2-52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2-IR levels (0.92 [IQR, 0.61-1.37] versus 1.14 [IQR, 0.75-1.78], P=0.007), especially in nonischemic HF. Log2-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson's r=-0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2-IR was associated with a 42.8% decreased likelihood of HFrecEF (OR, 0.572 [95% CI, 0.385-0.827]). Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.
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Affiliation(s)
- Chen Die Yang
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Wen Qi Pan
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Shuo Feng
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Jin Wei Quan
- Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Jia Wei Chen
- Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Xin Yi Shu
- Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Muladili Aihemaiti
- Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Feng Hua Ding
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Wei Feng Shen
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China.,Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Lin Lu
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China.,Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Rui Yan Zhang
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
| | - Xiao Qun Wang
- Department of Cardiovascular Medicine, Ruijin Hospital Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China.,Institute of Cardiovascular Disease Shanghai Jiao-Tong University School of Medicine Shanghai P. R. China
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Chocair PR, de Menezes Neves PDM, Sato VAH, Mohrbacher S, Oliveira ÉS, Pereira LVB, Bales AM, da Silva FP, Duley JA, Cuvello-Neto AL. Proposal for standardizing normal insulin ranges in Brazilian patients and a new classification of metabolic syndrome. Front Med (Lausanne) 2022; 9:984001. [PMID: 36160146 PMCID: PMC9500149 DOI: 10.3389/fmed.2022.984001] [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: 07/01/2022] [Accepted: 08/23/2022] [Indexed: 11/29/2022] Open
Abstract
Background Insulin resistance and/or hyperinsulinemia are closely linked to adiposity, metabolic syndrome (MetS) and prolonged inflammatory processes. Methods We retrospectively analyzed 1,018 adult individuals with a mean age of 46 years (74% male) and classified them as: Metabolically normal: without any of the five criteria of the International Diabetes Federation (IDF) used for the diagnosis of MetS, plus normal fasting insulin (Men < 8 mU/L, Women < 10 mU/L); Level 1 MetS: with one or two IDF criteria, plus hyperinsulinemia (Men: ≥ 8 mU/L), and Women: ≥ 10 mU/L); Level 2 MetS: with three or more IDF criteria, plus hyperinsulinemia. Results The mean values for fasting insulinemia in metabolically normal individuals was 4.6 ± 1.8 mU/L and 5.6 ± 2.3 mU/L, while their means for the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were 1.0 and 1.2 for men and women, respectively. In addition, the mean values for insulin (and HOMA-IR) for individuals with two normal anthropometric parameters (body mass index and waist girth), or two normal anthropometric parameters plus no IDF criteria, were similar to the metabolically normal group. Based on the obtained mean + 2 SD, we established the following insulin (and HOMA-IR) values as diagnostic cut-offs for hyperinsulinemia: Men: ≥ 8 mU/L (≥ 1.5), and Women: ≥ 10 mU/L (≥ 2.0). The mean serum insulin was significantly higher for individuals with Level 1 MetS (approx. 9 mU/L for both genders) compared with metabolically normal individuals, as was the prevalence of hepatic steatosis, which was more evident in men. Thus, the presence of one or two abnormal IDF criteria, combined with hyperinsulinemia and/or raised HOMA-IR, suggests the presence of MetS and insulin resistance. Patients of both genders with Level 2 MetS had higher serum insulin and/or HOMA-IR values than Level 1, as well as a higher prevalence of hypertension and hepatic steatosis, being more pronounced among men. The process was progressive and proportional to the degree of hyperinsulinemia. Conclusion It is proposed that intervention against MetS progression should be started in individuals with Level 1 MetS, rather than waiting for more criteria for diagnostic confirmation, which this should help to reduce the occurrence of known complications such as type 2 diabetes, atherosclerosis, hypertension, and chronic kidney disease, among others.
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Affiliation(s)
- Pedro Renato Chocair
- Internal Medicine and Nephrology Service, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
- *Correspondence: Pedro Renato Chocair,
| | | | | | - Sara Mohrbacher
- Internal Medicine and Nephrology Service, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - Érico Souza Oliveira
- Internal Medicine and Nephrology Service, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | | | | | | | - John A. Duley
- School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
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The insulin sensitivity Mcauley index (MCAi) is associated with 40-year cancer mortality in a cohort of men and women free of diabetes at baseline. PLoS One 2022; 17:e0272437. [PMID: 35921366 PMCID: PMC9348742 DOI: 10.1371/journal.pone.0272437] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 07/19/2022] [Indexed: 12/24/2022] Open
Abstract
Background The association between insulin resistance and cancer-mortality is not fully explored. We investigated the association between several insulin sensitivity indices (ISIs) and cancer-mortality over 3.5 decades in a cohort of adult men and women. We hypothesized that higher insulin resistance will be associated with greater cancer-mortality risk. Methods A cohort of 1,612 men and women free of diabetes during baseline were followed since 1979 through 2016 according to level of insulin resistance (IR) for cause specific mortality, as part of the Israel study on Glucose Intolerance, Obesity and Hypertension (GOH). IR was defined according to the Mcauley index (MCAi), calculated by fasting insulin and triglycerides, the Homeostatic Model Assessment (HOMA), the Matsuda Insulin Sensitivity Index (MISI), and the Quantitative Insulin Sensitivity Check Index (QUICKI), calculated by plasma glucose and insulin. Results Mean age at baseline was 51.5 ± 8.0 years, 804 (49.9%) were males and 871 (54.0%) had prediabetes. Mean follow-up was 36.7±0.2 years and 47,191 person years were accrued. Cox proportional hazard model and competing risks analysis adjusted for age, sex, country of origin, BMI, blood pressure, total cholesterol, smoking and glycemic status, revealed an increased risk for cancer-mortality, HR = 1.5 (95% CI: 1.1–2.0, p = 0.005) for the MCAi Q1 compared with Q2-4. No statistically significant associations were observed between the other ISIs and cancer-mortality. Conclusion The MCAi was independently associated with an increased risk for cancer-mortality in adult men and women free of diabetes and should be further studied as an early biomarker for cancer risk.
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35
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Gastaldelli A. Measuring and estimating insulin resistance in clinical and research settings. Obesity (Silver Spring) 2022; 30:1549-1563. [PMID: 35894085 PMCID: PMC9542105 DOI: 10.1002/oby.23503] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 03/27/2022] [Accepted: 04/21/2022] [Indexed: 11/29/2022]
Abstract
The article discusses how to measure insulin resistance in muscle, liver, and adipose tissue in human participants. The most frequently used methodologies to evaluate insulin resistance are described in detail starting from the gold standard, that is, the euglycemic hyperinsulinemic clamp, to the intravenous glucose tolerance test, surrogate indices based on fasting measurements, or dynamic tests (such as oral glucose or mixed meal tolerance tests). The accuracy, precision, and reproducibility of the tests as well as cutoff values are reported.
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Affiliation(s)
- Amalia Gastaldelli
- National Research Council (CNR)Institute of Clinical Physiology (IFC)PisaItaly
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36
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Gottlieb S, Rand JS, Ishioka K, Dias DA, Boughton BA, Roessner U, Ramadan Z, Anderson ST. Measures of insulin sensitivity, leptin, and adiponectin concentrations in cats in diabetic remission compared to healthy control cats. Front Vet Sci 2022; 9:905929. [PMID: 35968003 PMCID: PMC9372504 DOI: 10.3389/fvets.2022.905929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/04/2022] [Indexed: 12/03/2022] Open
Abstract
Objectives Firstly, to compare differences in insulin, adiponectin, leptin, and measures of insulin sensitivity between diabetic cats in remission and healthy control cats, and determine whether these are predictors of diabetic relapse. Secondly, to determine if these hormones are associated with serum metabolites known to differ between groups. Thirdly, if any of the hormonal or identified metabolites are associated with measures of insulin sensitivity. Animals Twenty cats in diabetic remission for a median of 101 days, and 21 healthy matched control cats. Methods A casual blood glucose measured on admission to the clinic. Following a 24 h fast, a fasted blood glucose was measured, and blood sample taken for hormone (i.e., insulin, leptin, and adiponectin) and untargeted metabolomic (GC-MS and LC-MS) analysis. A simplified IVGGT (1 g glucose/kg) was performed 3 h later. Cats were monitored for diabetes relapse for at least 9 months (270 days). Results Cats in diabetic remission had significantly higher serum glucose and insulin concentrations, and decreased insulin sensitivity as indicated by an increase in HOMA and decrease in QUICKI and Bennett indices. Leptin was significantly increased, but there was no difference in adiponectin (or body condition score). Several significant correlations were found between insulin sensitivity indices, leptin, and serum metabolites identified as significantly different between remission and control cats. No metabolites were significantly correlated with adiponectin. No predictors of relapse were identified in this study. Conclusion and clinical importance Insulin resistance, an underlying factor in diabetic cats, persists in diabetic remission. Cats in remission should be managed to avoid further exacerbating insulin resistance.
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Affiliation(s)
- Susan Gottlieb
- The Cat Clinic, Brisbane, QLD, Australia
- School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia
- *Correspondence: Susan Gottlieb
| | - Jacquie S. Rand
- School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia
- Australian Pet Welfare Foundation, Kenmore, QLD, Australia
| | - Katsumi Ishioka
- School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan
| | - Daniel A. Dias
- Discipline of Laboratory Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, VIC, Australia
| | - Berin A. Boughton
- School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia
- Australian National Phenome Centre, Murdoch University, Murdoch, WA, Australia
| | - Ute Roessner
- School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia
| | - Ziad Ramadan
- Nestlé Purina Research, St Louis, MO, United States
| | - Stephen T. Anderson
- School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, Australia
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Gołacki J, Matuszek M, Matyjaszek-Matuszek B. Link between Insulin Resistance and Obesity—From Diagnosis to Treatment. Diagnostics (Basel) 2022; 12:diagnostics12071681. [PMID: 35885586 PMCID: PMC9321808 DOI: 10.3390/diagnostics12071681] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/29/2022] [Accepted: 07/09/2022] [Indexed: 11/25/2022] Open
Abstract
Insulin resistance (IR) has become a common health issue in medical practice. There are no detailed data on IR prevalence, but it is an increasing problem due to its close association with obesity. However, IR is not considered as a separate nosological entity and the diagnostic criteria are not well defined, which leads to overdiagnosis of IR and an inappropriate approach. This review aims to summarize the available literature on IR pathophysiology, its relationship with obesity, as well as diagnostic methods, clinical presentation and treatment. Excessive energy intake results in cell overload that triggers mechanisms to protect cells from further energy accumulation by reducing insulin sensitivity. Additionally, hypertrophied adipocytes and macrophage infiltration causes local inflammation that may result in general inflammation that induces IR. The clinical picture varies from skin lesions (e.g., acanthosis nigricans) to metabolic disorders such as diabetes mellitus or metabolic-associated fatty liver disease. There are numerous IR laboratory markers with varying sensitivities and specificities. Nutrition changes and regular physical activity are crucial for IR management because a reduction in adipose tissue may reverse the inflammatory state and consequently reduce the severity of insulin resistance. In cases of obesity, anti-obesity medications can be used.
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Affiliation(s)
- Jakub Gołacki
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
- Correspondence:
| | - Małgorzata Matuszek
- Student’s Scientific Society at the Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, 20-954 Lublin, Poland;
| | - Beata Matyjaszek-Matuszek
- Department of Endocrinology, Diabetology and Metabolic Diseases, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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38
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Venojärvi M, Lindström J, Aunola S, Nuutila P, Atalay M. Improved Aerobic Capacity and Adipokine Profile Together with Weight Loss Improve Glycemic Control without Changes in Skeletal Muscle GLUT-4 Gene Expression in Middle-Aged Subjects with Impaired Glucose Tolerance. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19148327. [PMID: 35886175 PMCID: PMC9320448 DOI: 10.3390/ijerph19148327] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/01/2022] [Accepted: 07/04/2022] [Indexed: 11/26/2022]
Abstract
(1) Objective: The aim of this study was to clarify the role of adipokines in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance in response to a long-term exercise and dietary intervention. (2) Methods: Skeletal muscle, plasma and serum samples were examined in 22 subjects from an exercise−diet intervention study aiming to prevent type 2 diabetes. The subjects were further divided into two subgroups (non-responders n = 9 and responders n = 13) based on their achievement in losing at least 3 kg. (3) Results: The two-year exercise−diet intervention reduced leptin levels and increased adiponectin levels in responders; the changes in leptin levels were significantly associated with changes in their weights (r = 0.662, p < 0.01). In responders, insulin sensitivity (Bennett and McAuley index) increased and was associated with changes in maximal oxygen uptake (VO2peak) (r = 0.831, p < 0.010 and r = 0.890, p < 0.01). In addition, the VO2peak and oxidative capacity of skeletal muscle improved in responders, but not in non-responders. However, there were no changes between the two groups in expressions of the glucose transporter protein-4 (GLUT-4) gene or of AMP-activated protein kinase (AMPK)-α1 or AMPK-α2 proteins. (4) Conclusions: The exercise−diet intervention decreased serum leptin and increased serum adiponectin concentrations, improved glucose control without affecting GLUT-4 gene expression in the skeletal muscle in responders.
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Affiliation(s)
- Mika Venojärvi
- Institute of Biomedicine, Sport and Exercise Medicine, University of Eastern Finland, 70210 Kuopio, Finland
- Correspondence:
| | - Jaana Lindström
- Population Health Unit, Department of Public Health and Welfare, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland;
| | - Sirkka Aunola
- Functional Capacity Unit, Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, 20740 Turku, Finland;
| | - Pirjo Nuutila
- PET Centre, University of Turku, 20500 Turku, Finland;
| | - Mustafa Atalay
- Institute of Biomedicine, Physiology, University of Eastern Finland, 70210 Kuopio, Finland;
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Dinh Le T, Minh Bui T, Hien Vu T, Phi Thi Nguyen N, Thanh Thi Tran H, Nguyen ST, Ho Thi Nguyen L, Van Ngo M, Huy Duong H, Thanh Vu B, Dinh HT, Nhu Do B, Le DC, Thi Nguyen H, Trung Nguyen K. Insulin Resistance in Gestational Diabetes Mellitus and Its Association With Anthropometric Fetal Indices. Clin Med Insights Endocrinol Diabetes 2022; 15:11795514221098403. [PMID: 35601878 PMCID: PMC9121510 DOI: 10.1177/11795514221098403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 04/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background: In pregnant women with gestational diabetes mellitus (GDM), insulin
resistance (IR) increases the risk of developing manifest type 2 diabetes
mellitus and is associated with complications in both mother and fetus. Objectives: This research aimed to evaluate the associations between IR evaluated by 3
indices (namely updated homeostasis model assessment model (HOMA2), QUICKI,
and McAuley’s index) and the diabetes risk factors and the fetal growth
indices in Vietnamese women with GDM. Methods: A cross-sectional descriptive study was conducted on 370 women with GDM and
40 healthy pregnant women from January 2015 to May 2019. IR was calculated
by HOMA2 (HOMA2-IR), QUICKI, and McAuley’s index. Fetal anthropometric
measurements were assessed via ultrasound which was performed and
interpreted by ultrasound experts. Results: In the simple regression analysis, McAuley’s index illustrated had
statistically significant correlations to the highest number of risk factors
of diabetes mellitus compared with HOMA2-IR and QUICKI indices. Moreover,
McAuley’s index correlated statistically significantly to the highest number
of fetal ultrasound measurements factors such as including biparietal
diameter (BPD) (r = −0.271, P < .001),
head circumference (HC) (r = −0.225,
P < .001), abdominal circumference (AC)
(r = −0.214, P < .001), femur
length (FL) (r = −0.231, P < .001),
estimated fetal weight (EFW) (r = −0.239,
P < .001) and fetal estimated age
(r = −0.299, P < .001). In the
multivariable analysis, the McAuley’s index contributed the greatest to AC
(Standardized B of −0.656, P < .001). Conclusion: The McAuley’s index was significantly associated with a higher number of more
risk factors for diabetes mellitus as well as fetal ultrasound sonography
findings measurements than compared with HOMA2-IR and QUICKI indices.
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Affiliation(s)
- Tuan Dinh Le
- Center of Emergency, Critical Care Medicine and Clinical Toxicology, Military Hospital 103, Ha Noi, Vietnam.,Department of Rheumatology and Endocrinology, Military Hospital 103, Ha Noi, Vietnam.,Vietnam Military Medical University, Ha Noi, Vietnam
| | - Tien Minh Bui
- Department of Obstetrics and Gynecology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | | | - Nga Phi Thi Nguyen
- Department of Rheumatology and Endocrinology, Military Hospital 103, Ha Noi, Vietnam.,Vietnam Military Medical University, Ha Noi, Vietnam
| | | | - Son Tien Nguyen
- Department of Rheumatology and Endocrinology, Military Hospital 103, Ha Noi, Vietnam.,Vietnam Military Medical University, Ha Noi, Vietnam
| | | | - Manh Van Ngo
- Postgraduate Training Management Department, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Hoang Huy Duong
- Department of Neurology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Binh Thanh Vu
- Department of Internal Medicine, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Hoa Trung Dinh
- Departmen of Requested Treatment, National Hospital of Endocrinology, Ha Noi, Vietnam
| | - Binh Nhu Do
- Division of Military Science, Military Hospital 103, Vietnam Military Medical University, Ha Noi, Vietnam
| | - Duc-Cuong Le
- Department of Epidemiology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Hien Thi Nguyen
- Department of Physiology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
| | - Kien Trung Nguyen
- Department of Obstetrics and Gynecology, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam
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Lockard B, Mardock M, Oliver JM, Byrd M, Simbo S, Jagim AR, Kresta J, Baetge CC, Jung YP, Koozehchian MS, Khanna D, Rasmussen C, Kreider RB. Comparison of Two Diet and Exercise Approaches on Weight Loss and Health Outcomes in Obese Women. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:4877. [PMID: 35457744 PMCID: PMC9032860 DOI: 10.3390/ijerph19084877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 04/08/2022] [Accepted: 04/13/2022] [Indexed: 11/16/2022]
Abstract
AIM To compare the efficacy of two popular weight loss approaches on weight loss, body composition, and markers of health in sedentary obese women. METHODS In total, 51 sedentary women (age 34.5 ± 7.7 yrs.; weight 90.0 ± 14.5 kg; BMI 34.0 ± 5.1 kg/m2; 46.5 ± 7.0% fat) were matched and randomized to participate in the Weight Watchers® Momentum™ (WW) or Curves® (CV) Fitness and Weight Management program for 16 weeks. Participants in the WW group (n = 27) were provided a point-based diet program, received weekly progress checks and counseling, and were encouraged to exercise. Participants in the CV group (n = 24) followed a menu-based higher protein/low-fat diet (1200 kcal/d) for 1 week; 1500 kcal/d diet for 3 weeks; and 2000-2500 kcals/d for 2 weeks that was repeated three times (except the last segment) while participating in a supervised circuit-style resistance training program (3 d/wk). A general linear model (GLM) with repeated measures was used to analyze data and are presented as mean changes from baseline (mean [UL, LL]). RESULTS Supervised CV training resulted in greater amounts of vigorous and total physical activity. After 16 weeks, both groups lost weight (WW -6.1 [-7.8, -4.6], CV -4.9 [-6.2, -3.2] kg, p = 0.264). Participants in the CV group observed greater reductions in fat mass (WW -2.9 [-6.7, -0.2], CV -6.4 [-9.2, -3.6] kg, p = 0.081) and increases in lean mass (WW -2.5 [-4.3, -0.7], CV 1.3 [-0.6, 3.2] kg, p = 0.005) resulting in more favorable changes in percent body fat (WW -1.4 [-4.1, 1.2], CV -4.7 [-7.5, -1.8]%, p = 0.098). Both groups observed improvements in peak aerobic capacity and muscular endurance, although bench press lifting volume was greater in the CV group. Those in the CV group experienced a greater increase in HDLc and reduction in the CHL-HDLc ratio and triglycerides. CONCLUSION Both interventions promoted weight loss and improvements in fitness and markers of health. The CV program, which included supervised resistance training and higher protein diet menus, promoted greater fat loss, increases in lean mass, and improvements in percent body fat and blood lipids. TRIAL REGISTRATION clinicaltrials.gov, #NCT04372771, registered retrospectively 1 May 2020.
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Affiliation(s)
- Brittanie Lockard
- School of Nursing and Health Professions, University of the Incarnate Word, San Antonio, TX 78209, USA;
| | - Michelle Mardock
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
| | - Jonathan M. Oliver
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
| | - Mike Byrd
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
- Byrd’s Eye Enterprises, Inc., Forney, TX 75126, USA
| | - Sunday Simbo
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
- Center for Translational Research in Aging & Longevity, Human Clinical Research Facility, Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843, USA
| | - Andrew R. Jagim
- Department of Sports Medicine, Mayo Clinic Health System, Onalaska, WI 54650, USA;
| | - Julie Kresta
- College of Education and Human Development, Texas A&M University Central-Texas, Killeen, TX 76549, USA;
| | - Claire C. Baetge
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
| | | | - Majid S. Koozehchian
- Department of Kinesiology, Jacksonville State University, Jacksonville, AL 36265, USA;
| | - Deepesh Khanna
- Department of Foundational Sciences, Nova Southeastern University, Clearwater, FL 33759, USA;
| | - Chris Rasmussen
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
| | - Richard B. Kreider
- Exercise & Sport Nutrition Lab, Human Clinical Research Facility, Department of Health and Kinesiology, Texas A & M University, College Station, TX 77843, USA; (M.M.); (J.M.O.); (M.B.); (S.S.); (C.C.B.); (C.R.)
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Kårhus ML, Sonne DP, Thomasen M, Ellegaard AM, Holst JJ, Rehfeld JF, Chávez-Talavera O, Tailleux A, Staels B, Nielsen DS, Krych L, Dragsted LO, Vilsbøll T, Brønden A, Knop FK. Enterohepatic, Gluco-metabolic, and Gut Microbial Characterization of Individuals With Bile Acid Malabsorption. GASTRO HEP ADVANCES 2022; 1:299-312. [PMID: 39131668 PMCID: PMC11307667 DOI: 10.1016/j.gastha.2021.12.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 12/14/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims Bile acid malabsorption (BAM) is a debilitating disease characterized by loose stools and high stool frequency. The pathophysiology of BAM is not well-understood. We investigated postprandial enterohepatic and gluco-metabolic physiology, as well as gut microbiome composition and fecal bile acid content in patients with BAM. Methods Twelve participants with selenium-75 homocholic acid taurine test-verified BAM and 12 healthy controls, individually matched on sex, age, and body mass index, were included. Each participant underwent 2 mixed meal tests (with and without administration of the bile acid sequestrant colesevelam) with blood sampling and evaluation of gallbladder motility; bile acid content and microbiota composition were evaluated in fecal specimens. Results Patients with BAM were characterized by increased bile acid synthesis as assessed by circulating 7-alpha-hydroxy-4-cholesten-3-one, fecal bile acid content, and postprandial concentrations of glucose, insulin, C-peptide, and glucagon. The McAuley index of insulin sensitivity was lower in patients with BAM than that in healthy controls. In patients with BAM, colesevelam co-administered with the meal reduced postprandial concentrations of bile acids and fibroblast growth factor 19 and increased 7-alpha-hydroxy-4-cholesten-3-one concentrations but did not affect postprandial glucagon-like peptide 1 responses or other gluco-metabolic parameters. Patients with BAM were characterized by a gut microbiome with low relative abundance of bifidobacteria and high relative abundance of Blautia, Streptococcus, Ruminococcus gnavus, and Akkermansia muciniphila. Conclusion Patients with BAM are characterized by an overproduction of bile acids, greater fecal bile acid content, and a gluco-metabolic profile indicative of a dysmetabolic prediabetic-like state, with changes in their gut microbiome composition potentially linking their enterohepatic pathophysiology and their dysmetabolic phenotype. ClinicalTrials.gov number NCT03009916.
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Affiliation(s)
- Martin L. Kårhus
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - David P. Sonne
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Pharmacology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Martin Thomasen
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
| | - Anne-Marie Ellegaard
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
| | - Jens J. Holst
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens F. Rehfeld
- Department of Clinical Biochemistry, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Oscar Chávez-Talavera
- University of Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - Anne Tailleux
- University of Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - Bart Staels
- University of Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - Dennis S. Nielsen
- Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Lukasz Krych
- Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Lars O. Dragsted
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
| | - Tina Vilsbøll
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Andreas Brønden
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Pharmacology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Filip K. Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital – Herlev and Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
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Amisi CA. Markers of insulin resistance in Polycystic ovary syndrome women: An update. World J Diabetes 2022; 13:129-149. [PMID: 35432749 PMCID: PMC8984569 DOI: 10.4239/wjd.v13.i3.129] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 09/14/2021] [Accepted: 02/22/2022] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.
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Affiliation(s)
- Chantal Anifa Amisi
- Endocrinology and Diabetes Unit, Department of Medicine, Universita Campus Bio-medico di Rome, Rome 00128, Italy
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Gao H, Yang J, Pan W, Yang M. Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study. Diabetes Metab J 2022; 46:307-318. [PMID: 35249273 PMCID: PMC8987685 DOI: 10.4093/dmj.2020.0287] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 03/17/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference. METHODS Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes. RESULTS According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes. CONCLUSION IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.
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Affiliation(s)
- He Gao
- Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinying Yang
- Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenfei Pan
- Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Yang
- Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Corresponding author: Min Yang https://orcid.org/0000-0001-9487-6828 Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, 866 Yu-hang-tang Road, Hangzhou, Zhejiang 310058, China E-mail:
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Milluzzo A, Manuella L, Cannata E, Russo G, La Vignera S, Purrello F, Di Cataldo A, Sciacca L. Influence of Body Mass Index, Cancer Type and Treatment on Long-Term Metabolic and Liver Outcomes in Childhood Cancer Survivors. J Clin Med 2022; 11:878. [PMID: 35160329 PMCID: PMC8836510 DOI: 10.3390/jcm11030878] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/04/2022] [Accepted: 02/05/2022] [Indexed: 11/25/2022] Open
Abstract
In the last decade, the survival of subjects affected by cancer in childhood has significantly improved. The increased lifespan of childhood cancer survivors (CCS) led to a greater risk for long-term, therapy-related morbidity. To identify the clinical predictors of metabolic adverse outcomes in CCS (average off-therapy period: 12 years), we recruited 126 survivors of different childhood cancers (86.5% hematological cancers) who received at least anticancer chemotherapy, consecutively approached during their annual oncohematological outpatient visit. At examination, anthropometric measures and cancer-related history were collected. Moreover, a fasting venous sample was carried out for measuring fasting plasma glucose and insulin, glycated hemoglobin, lipid panel, and transaminases. We calculated the indexes of insulin resistance (HOMA-IR, McAuley, and QUICKI) and secretion (HOMA-β), liver steatosis (Hepatic Steatosis Index) and fibrosis (FIB-4 and NAFLD fibrosis score), and visceral fat dysfunction (Visceral Adiposity Index). More than one-third of the subjects (37.3%) did not have normal weight, with 11.1% of them affected by obesity. At recruitment, obese subjects were at significantly higher risk for impaired fasting glucose, metabolic syndrome, visceral adipose dysfunction, and liver steatosis/fibrosis. Subjects who received bone marrow transplantation were prone to insulin resistance, while survivors of lymphoma presented a visceral adipose dysfunction These results suggest a carefully metabolic monitoring of CCS, particularly in subgroups at higher risk, to early detect these conditions, promptly begin therapeutic interventions, and mitigate the dysmetabolic-related health burden.
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Affiliation(s)
- Agostino Milluzzo
- Department of Clinical and Experimental Medicine, Endocrinology, University of Catania Medical School, 95122 Catania, Italy; (A.M.); (L.M.)
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95122 Catania, Italy
| | - Lucia Manuella
- Department of Clinical and Experimental Medicine, Endocrinology, University of Catania Medical School, 95122 Catania, Italy; (A.M.); (L.M.)
| | - Emanuela Cannata
- Department of Clinical and Experimental Medicine, Paediatric Oncohematology Unit, University of Catania Medical School, 95122 Catania, Italy; (E.C.); (G.R.); (A.D.C.)
| | - Giovanna Russo
- Department of Clinical and Experimental Medicine, Paediatric Oncohematology Unit, University of Catania Medical School, 95122 Catania, Italy; (E.C.); (G.R.); (A.D.C.)
| | - Sandro La Vignera
- Department of Clinical and Experimental Medicine, University of Catania, Policlinico “G. Rodolico”, 95123 Catania, Italy;
| | - Francesco Purrello
- Department of Clinical and Experimental Medicine, Internal Medicine, Garibaldi-Nesima Hospital, University of Catania, 95123 Catania, Italy;
| | - Andrea Di Cataldo
- Department of Clinical and Experimental Medicine, Paediatric Oncohematology Unit, University of Catania Medical School, 95122 Catania, Italy; (E.C.); (G.R.); (A.D.C.)
| | - Laura Sciacca
- Department of Clinical and Experimental Medicine, Endocrinology, University of Catania Medical School, 95122 Catania, Italy; (A.M.); (L.M.)
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Schaupp CM, Botta D, White CC, Scoville DK, Srinouanprachanh S, Bammler TK, MacDonald J, Kavanagh TJ. Persistence of improved glucose homeostasis in Gclm null mice with age and cadmium treatment. Redox Biol 2022; 49:102213. [PMID: 34953454 PMCID: PMC8715110 DOI: 10.1016/j.redox.2021.102213] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 12/23/2022] Open
Abstract
Antioxidant signaling/communication is among the most important cellular defense and survival pathways, and the importance of redox signaling and homeostasis in aging has been well-documented. Intracellular levels of glutathione (GSH), a very important endogenous antioxidant, both govern and are governed by the Nrf2 pathway through expression of genes involved in its biosynthesis, including the subunits of the rate-limiting enzyme (glutamate cysteine ligase, GCL) in GSH production, GCLC and GCLM. Mice homozygous null for the Gclm gene are severely deficient in GSH compared to wild-type controls, expressing approximately 10% of normal GSH levels. To compensate for GSH deficiency, Gclm null mice have upregulated redox-regulated genes, and, surprisingly, are less susceptible to certain types of oxidative damage. Furthermore, young Gclm null mice display an interesting lean phenotype, resistance to high fat diet-induced diabetes and obesity, improved insulin and glucose tolerance, and decreased expression of genes involved in lipogenesis. However, the persistence of this phenotype has not been investigated into old age, which is important in light of studies which suggest aging attenuates antioxidant signaling, particularly in response to exogenous stimuli. In this work, we addressed whether aging compromises the favorable phenotype of increased antioxidant activity and improved glucose homeostasis observed in younger Gclm null mice. We present data showing that under basal conditions and in response to cadmium exposure (2 mg/kg, dosed once via intraperitoneal injection), the phenotype previously described in young (<6 months) Gclm null mice persists into old age (24+ months). We also provide evidence that transcriptional activation of the Nrf2, AMPK, and PPARγ pathways underlie the favorable metabolic phenotype observed previously in young Gclm null mice.
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Affiliation(s)
- Christopher M Schaupp
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - Dianne Botta
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - Collin C White
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - David K Scoville
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - Sengkeo Srinouanprachanh
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - Theo K Bammler
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - James MacDonald
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA
| | - Terrance J Kavanagh
- Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, 98195, USA.
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Stamm E, Marques-Vidal P, Rodriguez EG, Vollenweider P, Hans D, Lamy O. Association of adiposity evaluated by anthropometric, BIA, and DXA measures with cardiometabolic risk factors in nonobese postmenopausal women: the CoLaus/OsteoLaus cohort. Menopause 2022; 29:450-459. [PMID: 35357367 DOI: 10.1097/gme.0000000000001930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/12/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE After menopause, body composition changes with body fat accumulation, and an increase in cardiometabolic risk factors. Total fat mass, regional fat mass, and visceral adipose tissue (VAT) may be estimated with anthropometric measures, bioelectrical impedance analysis (BIA), and dual-energy X-ray absorptiometry (DXA). The aim of our study was to assess which measurement correlated best with cardiometabolic risk factors in healthy nonobese postmenopausal women. METHODS The CoLaus/OsteoLaus cohort included 1,500 postmenopausal women (age range 50-80). We analyzed correlations between: 1) measurements of body composition assessed by anthropometric measures, BIA, and DXA and 2) these measurements and different selected cardiometabolic risk factors, such as blood pressure, lipid markers (cholesterol subtypes and triglycerides), and metabolic markers (glucose, insulin, adiponectin, and leptin). Spearman correlation coefficient, stepwise forward regression, and linear regression analyses were used to determine association between anthropometric measurements and cardiometabolic risk factors. RESULTS In the 803 included participants (mean age 62.0 ± 7.1 y, mean body mass index 25.6 kg/m2 ± 4.4), correlations between total fat mass measured by BIA and total fat mass, android fat, gynoid fat, or VAT measured by DXA are very strong (from r = 0.531, [99% confidence interval (CI), 0.443-0.610] to r = 0.704, [99% CI, 0.640-0.758]). Body mass index and waist circumference have a higher correlation with VAT (r = 0.815, [99% CI, 0.772-0.851] and r = 0.823 [99% CI, 0.782-0.858], respectively) than BIA (r = 0.672 [99% CI, 0.603-0.731]). Among the anthropometric measurement and the measurements derived from DXA and BIA, VAT is the parameter most strongly associated with cardiometabolic risk factors. VAT better explains the variation of most of the cardiometabolic risk factors than age and treatment. For example, nearly 5% of the variability of the diastolic blood pressure (9.9 vs 4.9), nearly 15% of the variability of high-density lipoprotein cholesterol (20.3 vs 3.8) and triglyceride (21.1 vs 6.5), 25.3% of the variability of insulin (33.3 vs 8.1), and 37.5% of the variability of leptin (37.7 vs 1.1) were explained by VAT. CONCLUSIONS BIA seems not to be a good tool to assess VAT. At the population level, waist circumference and body mass index seem to be good tools to estimate VAT. VAT measured by DXA is the parameter most correlated with cardiometabolic risk factors and could become a component of the cardiometabolic marker on its own.
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Affiliation(s)
- Elisabeth Stamm
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; and
| | - Pedro Marques-Vidal
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; and
| | - Elena Gonzalez Rodriguez
- Bone Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Peter Vollenweider
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; and
| | - Didier Hans
- Bone Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Olivier Lamy
- Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; and
- Bone Unit, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
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Al-Naemi A. Establishing a Reference Interval for an Estimate of Peripheral Insulin Resistance in a Group of Iraqi People. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.7928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background and aims: Insulin resistance (IR) is the cornerstone in pathophysiology of T2DM. Identifying people with IR can slow the progress to diabetes. Triglyceride and glucose index (TyG index) is a simple tool to assess IR without insulin measurement. This study aims at establishing the reference interval for TyG index in apparently healthy Iraqis. Material and method: This study involved (77) apparently healthy adults (41 men and 36 women) in Mosul, Iraq. Fasting Serum lipids, glucose and insulin were measured and BMI was calculated. The modified TyG index was calculated and compared to other surrogate measures of IR and its reference interval was calculated. Results: TyG index values were normally distributed and significantly correlated with HOMA-IR, Mc-Auley index, QUICKI, and triglycerides/ HDL-c index (r= 0.322, p= 0.004; r=-0.68, p<0001; r= -0.29, p=0.01; r=0.84, p<0.0001respectively). ANOVA and PostHoc Duncan’s analyses revealed significant differences in mean TyG between (lean people) and (overweight and obese subjects), (p=0.02). BMI- based TyG reference intervals were calculated as (4.11- 4.91) and (4.25- 5.05) respectively. This is the first study in Iraq to set a reference interval for TyG index. Values should be interpreted according to BMI.
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Lian K, Feng H, Liu S, Wang K, Liu Q, Deng L, Wang G, Chen Y, Liu G. Insulin quantification towards early diagnosis of prediabetes/diabetes. Biosens Bioelectron 2022; 203:114029. [DOI: 10.1016/j.bios.2022.114029] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/13/2022] [Accepted: 01/20/2022] [Indexed: 12/19/2022]
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A New Method for Estimating Diagnostic Parameters in the Dynamics Model of Modified Glucose-Insulin Homeostasis from the Oral Glucose Tolerance Test Using a Gravitational Search Algorithm. ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING 2022. [DOI: 10.1007/s13369-021-05945-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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50
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Fatima S, Gerasimidis K, Wright C, Malkova D. Impact of high energy oral nutritional supplements consumed in the late afternoon on appetite, energy intake and cardio-metabolic risk factors in females with lower BMI. Eur J Clin Nutr 2022; 76:811-818. [PMID: 34773094 PMCID: PMC9187517 DOI: 10.1038/s41430-021-01042-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 10/11/2021] [Accepted: 10/20/2021] [Indexed: 12/04/2022]
Abstract
BACKGROUND/OBJECTIVE Morning consumption of a single dose of high-energy oral nutritional supplement (ONS) in females with a lower BMI displaces some of the food eaten at breakfast but increases overall daily energy intake. This study investigated the effectiveness of ONS intake in the late afternoon and for longer duration. SUBJECTS/METHODS Twenty-one healthy females (mean ± SD, age 25 ± 5 years; BMI 18.7 ± 1.2 kg/m2) participated in a randomised, crossover study with two experimental trials. In the afternoon of days 1-5, participants consumed either ONS (2.510 MJ) or low-energy PLACEBO drink (0.377 MJ) and recorded food eaten at home. On day six, energy intake was measured during buffet meals, and energy expenditure, appetite measurements and blood samples were collected throughout the day. RESULT Over the 5-day period, in the ONS trial energy intake from evening meals was lower (ONS, 2.7 ± 0.25 MJ; Placebo, 3.6 ± 0.25 MJ, P = 0.01) but averaged total daily energy intake was higher (ONS, 9.2 ± 0.3 MJ; PLACEBO, 8.2 ± 0.4 MJ, P = 0.03). On day six, energy intake, appetite scores, plasma GLP-1 and PYY, and energy expenditure were not significantly different between the two trials but fasting insulin concentration and HOMAIR, were higher (P < 0.05) and insulin sensitivity score based on fasting insulin and TAG lower (P < 0.05) in ONS trial. CONCLUSION Late afternoon consumption of ONS for five consecutive days by females with a lower BMI has only a partial and short-lived energy intake suppression and thus increases daily energy intake but reduces insulin sensitivity.
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Affiliation(s)
- Sadia Fatima
- grid.8756.c0000 0001 2193 314XHuman Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK ,grid.444779.d0000 0004 0447 5097Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Konstantinos Gerasimidis
- grid.8756.c0000 0001 2193 314XHuman Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Charlotte Wright
- grid.8756.c0000 0001 2193 314XHuman Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Dalia Malkova
- Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
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