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Jalleh RJ, Plummer MP, Marathe CS, Umapathysivam MM, Quast DR, Rayner CK, Jones KL, Wu T, Horowitz M, Nauck MA. Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide. J Clin Endocrinol Metab 2024; 110:1-15. [PMID: 39418085 DOI: 10.1210/clinem/dgae719] [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: 06/10/2024] [Revised: 08/20/2024] [Accepted: 10/10/2024] [Indexed: 10/19/2024]
Abstract
CONTEXT Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. DATA ACQUISITION We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. DATA SYNTHESIS Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. CONCLUSION Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs.
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Affiliation(s)
- Ryan J Jalleh
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Mark P Plummer
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
| | - Chinmay S Marathe
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Mahesh M Umapathysivam
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Southern Adelaide Diabetes and Endocrine Service, Flinders Medical Centre, Bedford Park, SA 5042, Australia
| | - Daniel R Quast
- Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany
| | - Christopher K Rayner
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
| | - Karen L Jones
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Tongzhi Wu
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Michael A Nauck
- Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, Sankt Josef-Hospital, Ruhr-University, D-44791 Bochum, Germany
- Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany
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Fotouhi Ardakani A, Anjom-Shoae J, Sadeghi O, Marathe CS, Feinle-Bisset C, Horowitz M. Association between total, animal, and plant protein intake and type 2 diabetes risk in adults: A systematic review and dose-response meta-analysis of prospective cohort studies. Clin Nutr 2024; 43:1941-1955. [PMID: 39032197 DOI: 10.1016/j.clnu.2024.07.001] [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: 12/26/2023] [Revised: 06/04/2024] [Accepted: 07/03/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND AND AIMS While clinical studies indicate that dietary protein may benefit glucose homeostasis in type 2 diabetes (T2D), the impact of dietary protein, including whether the protein is of animal or plant origin, on the risk of T2D is uncertain. We conducted a systematic review and meta-analysis to evaluate the associations of total, animal, and plant protein intakes with the risk of T2D. METHODS A systematic search was performed using multiple data sources, including PubMed/Medline, ISI Web of Science, Scopus, and Google Scholar, with the data cut-off in May 2023. Our selection criteria focused on prospective cohort studies that reported risk estimates for the association between protein intake and T2D risk. For data synthesis, we calculated summary relative risks and 95% confidence intervals for the highest versus lowest categories of protein intake using random-effects models. Furthermore, we conducted both linear and non-linear dose-response analyses to assess the dose-response associations between protein intake and T2D risk. RESULTS Sixteen prospective cohort studies, involving 615,125 participants and 52,342 T2D cases, were identified, of which eleven studies reported data on intake of both animal and plant protein. Intakes of total (pooled effect size: 1.14, 95% CI: 1.04-1.24) and animal (pooled effect size: 1.18, 95% CI: 1.09-1.27) protein were associated with an increased risk of T2D. These effects were dose-related - each 20-g increase in total or animal protein intake increased the risk of T2D by ∼3% and ∼7%, respectively. In contrast, there was no association between intake of plant protein and T2D risk (pooled effect size: 0.98, 95% CI: 0.89-1.08), while replacing animal with plant protein intake (per each 20 g) was associated with a reduced risk of T2D (pooled effect size: 0.80, 95% CI: 0.76-0.84). CONCLUSIONS Our findings indicate that long-term consumption of animal, but not plant, protein is associated with a significant and dose-dependent increase in the risk of T2D, with the implication that replacement of animal with plant protein intake may lower the risk of T2D.
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Affiliation(s)
- Amirmahdi Fotouhi Ardakani
- Student Research Committee, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran; Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javad Anjom-Shoae
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia
| | - Omid Sadeghi
- Nutrition and Food Security Research Centre and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
| | - Christine Feinle-Bisset
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
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Sun Y, Luo Y, Xiang C, Xie C, Huang W, Sun Z, Jones KL, Horowitz M, Rayner CK, Ma J, Wu T. Gastric emptying in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes and the impact of 4-week insulin pump therapy. Diabetes Obes Metab 2024; 26:3078-3087. [PMID: 38698647 DOI: 10.1111/dom.15626] [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: 03/06/2024] [Revised: 04/05/2024] [Accepted: 04/10/2024] [Indexed: 05/05/2024]
Abstract
AIM To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.
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Affiliation(s)
- Yixuan Sun
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Yong Luo
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chunjie Xiang
- Institute of Diabetes, Southeast University, Nanjing, China
| | - Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Zilin Sun
- Institute of Diabetes, Southeast University, Nanjing, China
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
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Anjom-Shoae J, Feinle-Bisset C, Horowitz M. Impacts of dietary animal and plant protein on weight and glycemic control in health, obesity and type 2 diabetes: friend or foe? Front Endocrinol (Lausanne) 2024; 15:1412182. [PMID: 39145315 PMCID: PMC11321983 DOI: 10.3389/fendo.2024.1412182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 07/17/2024] [Indexed: 08/16/2024] Open
Abstract
It is well established that high-protein diets (i.e. ~25-30% of energy intake from protein) provide benefits for achieving weight loss, and subsequent weight maintenance, in individuals with obesity, and improve glycemic control in type 2 diabetes (T2D). These effects may be attributable to the superior satiating property of protein, at least in part, through stimulation of both gastrointestinal (GI) mechanisms by protein, involving GI hormone release and slowing of gastric emptying, as well as post-absorptive mechanisms facilitated by circulating amino acids. In contrast, there is evidence that the beneficial effects of greater protein intake on body weight and glycemia may only be sustained for 6-12 months. While both suboptimal dietary compliance and metabolic adaptation, as well as substantial limitations in the design of longer-term studies are all likely to contribute to this contradiction, the source of dietary protein (i.e. animal vs. plant) has received inappropriately little attention. This issue has been highlighted by outcomes of recent epidemiological studies indicating that long-term consumption of animal-based protein may have adverse effects in relation to the development of obesity and T2D, while plant-based protein showed either protective or neutral effects. This review examines information relating to the effects of dietary protein on appetite, energy intake and postprandial glycemia, and the relevant GI functions, as reported in acute, intermediate- and long-term studies in humans. We also evaluate knowledge relating to the relevance of the dietary protein source, specifically animal or plant, to the prevention, and management, of obesity and T2D.
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Affiliation(s)
- Javad Anjom-Shoae
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
| | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
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Schumock G, Bandeen-Roche K, Chia CW, Kalyani RR, Ferrucci L, Varadhan R. Nonlinear modeling of oral glucose tolerance test response to evaluate associations with aging outcomes. PLoS One 2024; 19:e0302381. [PMID: 38753665 PMCID: PMC11098391 DOI: 10.1371/journal.pone.0302381] [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: 10/17/2023] [Accepted: 04/02/2024] [Indexed: 05/18/2024] Open
Abstract
As people age, their ability to maintain homeostasis in response to stressors diminishes. Physical frailty, a syndrome characterized by loss of resilience to stressors, is thought to emerge due to dysregulation of and breakdowns in communication among key physiological systems. Dynamical systems modeling of these physiological systems aims to model the underlying processes that govern response to stressors. We hypothesize that dynamical systems model summaries are predictive of age-related declines in health and function. In this study, we analyze data obtained during 75-gram oral-glucose tolerance tests (OGTT) on 1,120 adults older than 50 years of age from the Baltimore Longitudinal Study on Aging. We adopt a two-stage modeling approach. First, we fit OGTT curves with the Ackerman model-a nonlinear, parametric model of the glucose-insulin system-and with functional principal components analysis. We then fit linear and Cox proportional hazards models to evaluate whether usual gait speed and survival are associated with the stage-one model summaries. We also develop recommendations for identifying inadequately-fitting nonlinear model fits in a cohort setting with numerous heterogeneous response curves. These recommendations include: (1) defining a constrained parameter space that ensures biologically plausible model fits, (2) evaluating the relative discrepancy between predicted and observed responses of biological interest, and (3) identifying model fits that have notably poor model fit summary measures, such as [Formula: see text], relative to other fits in the cohort. The Ackerman model was unable to adequately fit 36% of the OGTT curves. The stage-two regression analyses found no associations between Ackerman model summaries and usual gait speed, nor with survival. The second functional principal component score was associated with faster gait speed (p<0.01) and improved survival (p<0.01).
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Affiliation(s)
- Grant Schumock
- Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Karen Bandeen-Roche
- Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Chee W. Chia
- Clinical Research Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
| | - Rita R. Kalyani
- Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Luigi Ferrucci
- Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Ravi Varadhan
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
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Schieren A, Koch S, Pecht T, Simon MC. Impact of Physiological Fluctuations of Sex Hormones During the Menstrual Cycle on Glucose Metabolism and the Gut Microbiota. Exp Clin Endocrinol Diabetes 2024; 132:267-278. [PMID: 38382644 PMCID: PMC11093651 DOI: 10.1055/a-2273-5602] [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: 08/15/2023] [Accepted: 01/18/2024] [Indexed: 02/23/2024]
Abstract
Diabetes mellitus is one of the most prevalent chronic diseases. Previous studies have shown differences in glucose metabolism between males and females. Moreover, difficulties in medication adherence have been reported in females with type 2 diabetes. These observations are believed to be caused by fluctuations in sex hormone concentrations during the menstrual cycle. Furthermore, gut microbiota is linked to female host metabolism and sex hormone production. Understanding the interactions between fluctuating hormone concentrations during the menstrual cycle, gut microbiota, and glucose metabolism in humans is significant because of the increasing prevalence of diabetes and the consequent need to expand preventive efforts. A literature search was performed to determine and summarize the existing evidence, deduce future research needs to maintain female health, and investigate the relationship between the physiological menstrual cycle and glucose metabolism. Studies from 1967 to 2020 have already examined the relationship between variations during the menstrual cycle and glucose metabolism in healthy female subjects using an oral-glucose tolerance test or intravenous glucose tolerance test. However, the overall number of studies is rather small and the results are contradictory, as some studies detected differences in glucose concentrations depending on the different cycle phases, whereas others did not. Some studies reported lower glucose levels in the follicular phase than in the luteal phase, whereas another study detected the opposite. Data on gut microbiota in relation to the menstrual cycle are limited. Conflicting results exist when examining the effect of hormonal contraceptives on the gut microbiota and changes in the course of the menstrual cycle. The results indicate that the menstrual cycle, especially fluctuating sex hormones, might impact the gut microbiota composition.The menstrual cycle may affect the gut microbiota composition and glucose metabolism. These results indicate that glucose tolerance may be the greatest in the follicular phase; however, further well-conducted studies are needed to support this assumption.
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Affiliation(s)
- Alina Schieren
- University of Bonn, Institute of Nutrition and Food Sciences, Nutrition
and Microbiota, Bonn, Germany
| | - Sandra Koch
- University of Bonn, Institute of Nutrition and Food Sciences, Nutrition
and Microbiota, Bonn, Germany
| | - Tal Pecht
- University of Bonn, Life & Medical Sciences (LIMES) Institute,
Department for Genomics and Immunoregulation, Bonn, Germany
- German Center for Neurodegenerative Diseases (DZNE), Systems Medicine,
Bonn, Germany
| | - Marie-Christine Simon
- University of Bonn, Institute of Nutrition and Food Sciences, Nutrition
and Microbiota, Bonn, Germany
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Xiang C, Sun Y, Luo Y, Xie C, Huang W, Sun Z, Jones KL, Horowitz M, Rayner CK, Ma J, Wu T. Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes. Nutr Diabetes 2024; 14:13. [PMID: 38589353 PMCID: PMC11001856 DOI: 10.1038/s41387-024-00264-8] [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: 11/26/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.
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Affiliation(s)
- Chunjie Xiang
- School of Medicine, Southeast University, Nanjing, 210009, China
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Yixuan Sun
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Yong Luo
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China
| | - Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Zilin Sun
- School of Medicine, Southeast University, Nanjing, 210009, China
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China.
| | - Tongzhi Wu
- School of Medicine, Southeast University, Nanjing, 210009, China.
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia.
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Ha J, Chung ST, Springer M, Kim JY, Chen P, Chhabra A, Cree MG, Diniz Behn C, Sumner AE, Arslanian SA, Sherman AS. Estimating insulin sensitivity and β-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model. Am J Physiol Endocrinol Metab 2024; 326:E454-E471. [PMID: 38054972 PMCID: PMC11639675 DOI: 10.1152/ajpendo.00189.2023] [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: 06/23/2023] [Revised: 11/27/2023] [Accepted: 11/27/2023] [Indexed: 12/07/2023]
Abstract
Efficient and accurate methods to estimate insulin sensitivity (SI) and β-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and β-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.
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Affiliation(s)
- Joon Ha
- Department of Mathematics, Howard University, Washington, District of Columbia, United States
| | - Stephanie T Chung
- Section on Pediatric Diabetes, Obesity, and Metabolism, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States
| | - Max Springer
- Department of Mathematics, University of Maryland, College Park, Maryland, United States
| | - Joon Young Kim
- Department of Exercise Science, David B. Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York, United States
| | | | - Aaryan Chhabra
- Department of Biology, Indian Institute of Science Education and Research, Pune, India
| | - Melanie G Cree
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Cecilia Diniz Behn
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, Colorado, United States
| | - Anne E Sumner
- Intramural Research Program, National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health, Bethesda, Maryland, United States
- Section on Ethnicity and Health, Diabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland, United States
- Hypertension in Africa Research Team, North-West University, Potchefstroom, South Africa
| | - Silva A Arslanian
- Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Center for Pediatric Research in Obesity and Metabolism, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States
| | - Arthur S Sherman
- Laboratory of Biological Modeling, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States
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Steinert RE, Mueller M, Serra M, Lehner-Sigrist S, Frost G, Gero D, Gerber PA, Bueter M. Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study. Nutr Diabetes 2024; 14:9. [PMID: 38448413 PMCID: PMC10918168 DOI: 10.1038/s41387-024-00267-5] [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: 07/10/2023] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.
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Affiliation(s)
- R E Steinert
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland.
| | - M Mueller
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - M Serra
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - S Lehner-Sigrist
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - G Frost
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - D Gero
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - P A Gerber
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - M Bueter
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
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10
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Salman UA, Schwartz JG, McMahan AC, Michalek JE, Phillips WT. Rapid Gastric emptying in spontaneously hypertensive rats. J Hypertens 2024; 42:572-578. [PMID: 38088427 DOI: 10.1097/hjh.0000000000003640] [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: 02/01/2024]
Abstract
OBJECTIVE To assess the rate of gastric emptying in spontaneously hypertensive rats (SHR) and to evaluate rapid gastric emptying as a possible predisposing factor for hypertension. Rapid gastric emptying of carbohydrates, known to elevate postprandial serum glucose, has been reported to occur in many insulin-resistant states, including hypertension. SHR exhibit insulin resistance similar to human hypertensive patients. No prior studies have assessed gastric emptying of an oral glucose solution in SHR as compared with control Wistar Kyoto rats (WKY). METHODS Using scintigraphic imaging, gastric emptying of a physiologic, orally consumed glucose solution was assessed in 12 SHR and 12 control WKY at 5 weeks of age, prior to the development of hypertension, and at 12 weeks of age after hypertension was fully established. RESULTS At 5 weeks, the gastric half-emptying time (GHET) was 67.8 ± 9.8 min for the SHR vs. 109.3 ± 18 ( P = 0.042) minutes for the WKY controls. At 12 weeks, the GHET was 37.29 ± 10.3 min for the SHR vs. 138.53 ± 37.6 ( P = 0.016) min for the WKY controls. CONCLUSION Gastric emptying was significantly more rapid in the SHR before and after the development of hypertension. Even though SHR are known to have increased sympathetic activity associated with their development of hypertension, this increased sympathetic activity does not inhibit gastric emptying. SHR are a promising animal model for investigating therapeutic agents for treating hypertension aimed at slowing the rate of gastric emptying.
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Affiliation(s)
| | | | | | - Joel E Michalek
- Department of Population Health Sciences, UT Health San Antonio, San Antonio, Texas, USA
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11
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Caturano A, Cavallo M, Nilo D, Vaudo G, Russo V, Galiero R, Rinaldi L, Marfella R, Monda M, Luca G, Sasso FC. Diabetic Gastroparesis: Navigating Pathophysiology and Nutritional Interventions. GASTROINTESTINAL DISORDERS 2024; 6:214-229. [DOI: 10.3390/gidisord6010016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Diabetic gastroparesis (DGP) delays gastric emptying in diabetes patients, notably impacting those with type 1 and long-standing type 2 diabetes. Symptoms include early satiety, fullness, appetite loss, bloating, abdominal pain, and vomiting, arising from slow stomach-to-intestine food movement. DGP’s unpredictable nature complicates diagnosis and blood glucose management, leading to severe complications like dehydration, malnutrition, and bezoar formation. Understanding DGP’s mechanisms is crucial for effective management. Vagal dysfunction, disturbances in the interstitial cells of Cajal, reduced neural nitric oxide synthase, and increased oxidative stress contribute to the complex pathophysiology. Accurate diagnosis demands a comprehensive approach, utilizing tools like gastric scintigraphy and the Gastric Emptying Breath Test. Considering the complex relationship between DGP and glycemia, managing blood glucose levels becomes paramount. Nutritional interventions, tailored to each patient, address malnutrition risks, emphasizing smaller, more frequent meals and liquid consistency. DGP’s complex nature necessitates collaborative efforts for enhanced diagnostic strategies, improved pathophysiological understanding, and compassionate management approaches. This comprehensive approach offers hope for a future where individuals with DGP can experience improved well-being and quality of life.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Massimiliano Cavallo
- Internal Medicine Unit, Santa Maria Terni Hospital, I-05100 Terni, Italy
- Medical Andrology and Reproductive Endocrinology Unit, Santa Maria Hospital, I-05100 Terni, Italy
| | - Davide Nilo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Gaetano Vaudo
- Internal Medicine Unit, Santa Maria Terni Hospital, I-05100 Terni, Italy
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Luca Rinaldi
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, I-86100 Campobasso, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Marcellino Monda
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Giovanni Luca
- Medical Andrology and Reproductive Endocrinology Unit, Santa Maria Hospital, I-05100 Terni, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
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12
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Jensen MM, Pedersen HE, Clemmensen KKB, Ekblond TS, Ried-Larsen M, Færch K, Brock C, Quist JS. Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity. J Nutr 2024; 154:41-48. [PMID: 37315794 DOI: 10.1016/j.tjnut.2023.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. OBJECTIVE The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. METHODS 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. RESULTS Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. CONCLUSIONS More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. TRIAL REGISTRATION Clinicaltrials.gov IDs (NCT03894670, NCT03854656).
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Affiliation(s)
- Marie M Jensen
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Hanne E Pedersen
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Kim K B Clemmensen
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Trine S Ekblond
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Mathias Ried-Larsen
- the Center of Inflammation and Metabolism and the Center for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Denmark; Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Denmark
| | - Kristine Færch
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christina Brock
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Jonas S Quist
- Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; School of Psychology, University of Leeds, Leeds, UK.
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13
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Salman UA, McMahan CA, Schwartz JG, Michalek JE, Phillips WT. Rapid gastric emptying during pregnancy in a rat model. Eur J Obstet Gynecol Reprod Biol 2023; 289:74-78. [PMID: 37639818 DOI: 10.1016/j.ejogrb.2023.08.370] [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: 01/21/2023] [Revised: 05/13/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND/AIMS The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations. MATERIALS AND METHODS 24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy. RESULTS The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats. CONCLUSION These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia.
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De Fano M, Porcellati F, Fanelli CG, Corio S, Mazzieri A, Lucidi P, Bolli GB, Bassotti G. The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime? Diabetes Res Clin Pract 2023; 203:110828. [PMID: 37481116 DOI: 10.1016/j.diabres.2023.110828] [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: 04/09/2023] [Revised: 06/30/2023] [Accepted: 07/11/2023] [Indexed: 07/24/2023]
Abstract
Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine. A bidirectional relationship between GE and glycemia has been established: GE may explain the up to 30-40 % variance in glycemic response following a carbohydrate-rich meal. In addition, acute and chronic hyperglycemia induce deceleration of GE after meals. Hypoglycemia accelerates GE, but its role in counterregulation has been poorly investigated. The role of GE as a counterregulatory mechanism has been confirmed in pathophysiological conditions, such as gastroparesis or following recurrent hypoglycemia. Therefore, it could represent an "ancestral" mechanism, highly conservative and effective in all individuals, conditions and clinical contexts. Recent guidelines recommend GLP-1 receptor agonists (GLP-1RAs) either as the first injectable therapy for type 2 diabetes mellitus or in combination with insulin. Considering the potential impact on GE, it would be important to study subjects on GLP-1 RAs during hypoglycemia, to establish whether a possible deceleration of GE impairs glucose counterregulation.
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Affiliation(s)
- Michelantonio De Fano
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Francesca Porcellati
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - Carmine G Fanelli
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Sofia Corio
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Alessio Mazzieri
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Paola Lucidi
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Geremia B Bolli
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Gabrio Bassotti
- Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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15
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Lee JS, Sohn M, Kim K, Yoon YS, Lim S. Glucose Regulation after Partial Pancreatectomy: A Comparison of Pancreaticoduodenectomy and Distal Pancreatectomy in the Short and Long Term. Diabetes Metab J 2023; 47:703-714. [PMID: 37349082 PMCID: PMC10555545 DOI: 10.4093/dmj.2022.0205] [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: 06/16/2022] [Accepted: 09/07/2022] [Indexed: 06/24/2023] Open
Abstract
BACKGRUOUND Long term quality of life is becoming increasingly crucial as survival following partial pancreatectomy rises. The purpose of this study was to investigate the difference in glucose dysregulation after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). METHODS In this prospective observational study from 2015 to 2018, 224 patients who underwent partial pancreatectomy were selected: 152 (67.9%) received PD and 72 (32.1%) received DP. Comprehensive assessment for glucose regulation, including a 75 g oral glucose tolerance test was conducted preoperatively, and 1, 12, and 52 weeks after surgery. Patients were further monitored up to 3 years to investigate development of new-onset diabetes mellitus (NODM) in patients without diabetes mellitus (DM) at baseline or worsening of glucose regulation (≥1% increase in glycosylated hemoglobin [HbA1c]) in those with preexisting DM. RESULTS The disposition index, an integrated measure of β-cell function, decreased 1 week after surgery in both groups, but it increased more than baseline level in the PD group while its decreased level was maintained in the DP group, resulting in a between-group difference at the 1-year examination (P<0.001). During follow-up, the DP group showed higher incidence of NODM and worsening of glucose regulation than the PD group with hazard ratio (HR) 4.29 (95% confidence interval [CI], 1.49 to 12.3) and HR 2.15 (95% CI, 1.09 to 4.24), respectively, in the multivariate analysis including dynamic glycemic excursion profile. In the DP procedure, distal DP and spleen preservation were associated with better glucose regulation. DP had a stronger association with glucose dysregulation than PD. CONCLUSION Proactive surveillance of glucose dysregulation is advised, particularly for patients who receive DP.
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Affiliation(s)
- Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Minji Sohn
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Kyuho Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Soo Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Xie C, Huang W, Sun Y, Xiang C, Trahair L, Jones KL, Horowitz M, Rayner CK, Wu T. Disparities in the Glycemic and Incretin Responses to Intraduodenal Glucose Infusion Between Healthy Young Men and Women. J Clin Endocrinol Metab 2023; 108:e712-e719. [PMID: 36987568 PMCID: PMC10438868 DOI: 10.1210/clinem/dgad176] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 02/23/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023]
Abstract
CONTEXT Premenopausal women are at a lower risk of type 2 diabetes (T2D) compared to men, but the underlying mechanism(s) remain elusive. The secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), from the small intestine is a major determinant of glucose homeostasis and may be influenced by sex. OBJECTIVES This study compared blood glucose and plasma insulin and incretin responses to intraduodenal glucose infusions in healthy young males and females. DESIGN In Study 1, 9 women and 20 men received an intraduodenal glucose infusion at 2 kcal/min for 60 minutes. In Study 2, 10 women and 26 men received an intraduodenal glucose at 3 kcal/min for 60 minutes. Venous blood was sampled every 15 minutes for measurements of blood glucose and plasma insulin, GLP-1 and GIP. RESULTS In response to intraduodenal glucose at 2 kcal/min, the incremental area under the curve between t = 0-60 minutes (iAUC0-60min) for blood glucose and plasma GIP did not differ between the 2 groups. However, iAUC0-60min for plasma GLP-1 (P = 0.016) and insulin (P = 0.011) were ∼2-fold higher in women than men. In response to intraduodenal glucose at 3 kcal/min, iAUC0-60min for blood glucose, plasma GIP, and insulin did not differ between women and men, but GLP-1 iAUC0-60min was 2.5-fold higher in women (P = 0.012). CONCLUSION Healthy young women exhibit comparable GIP but a markedly greater GLP-1 response to intraduodenal glucose than men. This disparity warrants further investigations to delineate the underlying mechanisms and may be of relevance to the reduced risk of diabetes in premenopausal women when compared to men.
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Affiliation(s)
- Cong Xie
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
| | - Yixuan Sun
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
| | - Chunjie Xiang
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- School of Medicine, Southeast University, Nanjing 210009, China
| | - Laurence Trahair
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide 5000, Australia
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, Australia
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17
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Smedegaard S, Kampmann U, Ovesen PG, Støvring H, Rittig N. Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis. Am J Clin Nutr 2023; 118:391-405. [PMID: 37536867 DOI: 10.1016/j.ajcnut.2023.05.012] [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: 11/22/2022] [Revised: 04/19/2023] [Accepted: 05/02/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate. OBJECTIVES The objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)]. METHODS We searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022. RESULTS Whey protein premeals lowered peak glucose concentration by -1.4 mmol/L [-1.9 mmol/L; -0.9 mmol/L], and the area under the curve for glucose was -0.9 standard deviation (SD) [-1.2 SD; -0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects. CONCLUSIONS In conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.
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Affiliation(s)
- Stine Smedegaard
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
| | - Ulla Kampmann
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Per G Ovesen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik Støvring
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Nikolaj Rittig
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
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Smith K, Taylor GS, Walker M, Brunsgaard LH, Bowden Davies KA, Stevenson EJ, West DJ. Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing β-Cell Function and Reducing Insulin Clearance in T2D. J Clin Endocrinol Metab 2023; 108:e603-e612. [PMID: 36734166 PMCID: PMC10807909 DOI: 10.1210/clinem/dgad069] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/12/2022] [Accepted: 02/01/2023] [Indexed: 02/04/2023]
Abstract
CONTEXT Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear. OBJECTIVE To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function. METHODS This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS β-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146.
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Affiliation(s)
- Kieran Smith
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Human Nutrition and Exercise Research Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Guy S Taylor
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Human Nutrition and Exercise Research Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Mark Walker
- Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Lise H Brunsgaard
- Health and Performance Nutrition, Arla Foods Ingredients Group P/S, Viby J 8260, Denmark
| | - Kelly A Bowden Davies
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Sport and Exercise Sciences, Manchester Metropolitan University, Manchester M1 7EL, UK
| | - Emma J Stevenson
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Human Nutrition and Exercise Research Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Daniel J West
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
- Human Nutrition and Exercise Research Centre, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
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Jalleh RJ, Trahair LG, Wu T, Standfield S, Feinle‐Bisset C, Rayner CK, Horowitz M, Jones KL. Effect of gastric distension with concurrent small intestinal saline or glucose infusion on incretin hormone secretion in healthy individuals: A randomized, controlled, crossover study. Diabetes Obes Metab 2023; 25:1849-1854. [PMID: 36864654 PMCID: PMC10947269 DOI: 10.1111/dom.15042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/16/2023] [Accepted: 02/27/2023] [Indexed: 03/04/2023]
Abstract
AIM To evaluate the effect of gastric distension, induced using a gastric 'barostat', on the secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the presence and absence of small intestinal nutrients in healthy individuals. MATERIALS AND METHODS Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m2 ) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. RESULTS Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P = 1.00 for saline infusion and P = .99 for glucose infusion). CONCLUSIONS Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans.
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Affiliation(s)
- Ryan J. Jalleh
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
- Diabetes and Endocrine ServicesNorthern Adelaide Local Health NetworkAdelaideAustralia
| | - Laurence G. Trahair
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
| | - Tongzhi Wu
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
| | - Scott Standfield
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
| | - Christine Feinle‐Bisset
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
| | - Christopher K. Rayner
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
- Department of Gastroenterology and HepatologyRoyal Adelaide HospitalAdelaideAustralia
| | - Michael Horowitz
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
| | - Karen L. Jones
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
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20
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Arunachala Murthy T, Chapman M, Jones KL, Horowitz M, Marathe CS. Inter-relationships between gastric emptying and glycaemia: Implications for clinical practice. World J Diabetes 2023; 14:447-459. [PMID: 37273253 PMCID: PMC10236995 DOI: 10.4239/wjd.v14.i5.447] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/09/2022] [Accepted: 04/07/2023] [Indexed: 05/15/2023] Open
Abstract
Gastric emptying (GE) exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes; the rise in blood glucose following oral carbohydrate is greater when GE is relatively more rapid and more sustained when glucose tolerance is impaired. Conversely, GE is influenced by the acute glycaemic environment acute hyperglycaemia slows, while acute hypoglycaemia accelerates it. Delayed GE (gastroparesis) occurs frequently in diabetes and critical illness. In diabetes, this poses challenges for management, particularly in hospitalised individuals and/or those using insulin. In critical illness it compromises the delivery of nutrition and increases the risk of regurgitation and aspiration with consequent lung dysfunction and ventilator dependence. Substantial advances in knowledge relating to GE, which is now recognised as a major determinant of the magnitude of the rise in blood glucose after a meal in both health and diabetes and, the impact of acute glycaemic environment on the rate of GE have been made and the use of gut-based therapies such as glucagon-like peptide-1 receptor agonists, which may profoundly impact GE, in the management of type 2 diabetes, has become commonplace. This necessitates an increased understanding of the complex inter-relationships of GE with glycaemia, its implications in hospitalised patients and the relevance of dysglycaemia and its management, particularly in critical illness. Current approaches to management of gastroparesis to achieve more personalised diabetes care, relevant to clinical practice, is detailed. Further studies focusing on the interactions of medications affecting GE and the glycaemic environment in hospitalised patients, are required.
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Affiliation(s)
- Tejaswini Arunachala Murthy
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
| | - Marianne Chapman
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
| | - Karen L Jones
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
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21
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Teong XT, Liu K, Vincent AD, Bensalem J, Liu B, Hattersley KJ, Zhao L, Feinle-Bisset C, Sargeant TJ, Wittert GA, Hutchison AT, Heilbronn LK. Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nat Med 2023; 29:963-972. [PMID: 37024596 DOI: 10.1038/s41591-023-02287-7] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 03/02/2023] [Indexed: 04/08/2023]
Abstract
Intermittent fasting appears an equivalent alternative to calorie restriction (CR) to improve health in humans. However, few trials have considered applying meal timing during the 'fasting' day, which may be a limitation. We developed a novel intermittent fasting plus early time-restricted eating (iTRE) approach. Adults (N = 209, 58 ± 10 years, 34.8 ± 4.7 kg m-2) at increased risk of developing type 2 diabetes were randomized to one of three groups (2:2:1): iTRE (30% energy requirements between 0800 and 1200 hours and followed by a 20-h fasting period on three nonconsecutive days per week, and ad libitum eating on other days); CR (70% of energy requirements daily, without time prescription); or standard care (weight loss booklet). This open-label, parallel group, three-arm randomized controlled trial provided nutritional support to participants in the iTRE and CR arms for 6 months, with an additional 12-month follow-up. The primary outcome was change in glucose area under the curve in response to a mixed-meal tolerance test at month 6 in iTRE versus CR. Glucose tolerance was improved to a greater extent in iTRE compared with CR (-10.10 (95% confidence interval -14.08, -6.11) versus -3.57 (95% confidence interval -7.72, 0.57) mg dl-1 min-1; P = 0.03) at month 6, but these differences were lost at month 18. Adverse events were transient and generally mild. Reports of fatigue were higher in iTRE versus CR and standard care, whereas reports of constipation and headache were higher in iTRE and CR versus standard care. In conclusion, incorporating advice for meal timing with prolonged fasting led to greater improvements in postprandial glucose metabolism in adults at increased risk of developing type 2 diabetes. ClinicalTrials.gov identifier NCT03689608 .
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Affiliation(s)
- Xiao Tong Teong
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Kai Liu
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Andrew D Vincent
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Julien Bensalem
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Bo Liu
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Kathryn J Hattersley
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Lijun Zhao
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | | | - Timothy J Sargeant
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Gary A Wittert
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Amy T Hutchison
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Leonie K Heilbronn
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
- Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
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22
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Gursan A, Hendriks AD, Welting D, de Jong PA, Klomp DWJ, Prompers JJ. Deuterium body array for the simultaneous measurement of hepatic and renal glucose metabolism and gastric emptying with dynamic 3D deuterium metabolic imaging at 7 T. NMR IN BIOMEDICINE 2023:e4926. [PMID: 36929629 DOI: 10.1002/nbm.4926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 06/18/2023]
Abstract
Deuterium metabolic imaging (DMI) is a novel noninvasive method to assess tissue metabolism and organ (patho)physiology in vivo using deuterated substrates, such as [6,6'-2 H2 ]-glucose. The liver and kidneys play a central role in whole-body glucose homeostasis, and in type 2 diabetes, both hepatic and renal glucose metabolism are dysregulated. Diabetes is also associated with gastric emptying abnormalities. In this study, we developed a four-channel 2 H transmit/receive body array coil for DMI in the human abdomen at 7 T and assessed its performance. In addition, the feasibility of simultaneously measuring gastric emptying, and hepatic and renal glucose uptake and metabolism with dynamic 3D DMI upon administration of deuterated glucose, was investigated. Simulated and measured B1 + patterns were in good agreement. The intrasession variability of the natural abundance deuterated water signal in the liver and right kidney, measured in nine healthy volunteers, was 5.6% ± 0.9% and 4.9% ± 0.7%, respectively. Dynamic 3D DMI scans with oral administration of [6,6'-2 H2 ]-glucose showed similar kinetics of deuterated glucose appearance and disappearance in the liver and kidney. The measured gastric emptying half time was 80 ± 10 min, which is in good agreement with scintigraphy measurements. In conclusion, DMI with oral administration of [6,6'-2 H2 ]-glucose enables simultaneous assessment of gastric emptying and liver and kidney glucose uptake and metabolism. When applied in patients with diabetes, this approach may advance our understanding of the interplay between disturbances in liver and kidney glucose uptake and metabolism and gastric emptying, at a detail that cannot be achieved by any other method.
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Affiliation(s)
- Ayhan Gursan
- Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Arjan D Hendriks
- Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Dimitri Welting
- Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Pim A de Jong
- Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Dennis W J Klomp
- Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jeanine J Prompers
- Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands
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23
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Nadia J, Olenskyj AG, Stroebinger N, Hodgkinson SM, Estevez TG, Subramanian P, Singh H, Singh RP, Bornhorst GM. Cooked rice- and wheat-based food structure influenced digestion kinetics and glycemic response in growing pigs. J Nutr 2023; 153:1373-1388. [PMID: 36906148 DOI: 10.1016/j.tjnut.2023.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 03/01/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND How starch-based food structure can impact the rate and extent of digestion in the small intestine and resulting glycemic response is not properly understood. One possible explanation is that food structure influences gastric digestion, which subsequently determines digestion kinetics in the small intestine and glucose absorption. However, this possibility has not been investigated in detail. OBJECTIVES Using growing pigs as a digestion model for adult humans, this study aimed to investigate how physical structure of starch-rich foods impacts small intestinal digestion and glycemic response. METHODS Male growing pigs (21.7 ± 1.8 kg, Large White × Landrace) were fed one of six cooked diets (250-g starch equivalent) with varying initial structures (rice grain, semolina porridge, wheat or rice couscous, or wheat or rice noodle). The glycemic response, small intestinal content particle size and hydrolyzed starch content, ileal starch digestibility, and portal vein plasma glucose were measured. Glycemic response was measured as plasma glucose collected from an in-dwelling jugular vein catheter for up to 390 min postprandial. Portal vein blood samples and small intestinal content were measured after sedation and euthanasia of the pigs at 30, 60, 120, or 240 min postprandial. Data were analyzed with a mixed-model ANOVA. RESULTS The plasma glucose Δmaxoverall and iAUCoverall for couscous and porridge diets (smaller-sized diets) were higher than intact grain and noodle diets (larger-sized diets); 29.0 ± 3.2 vs. 21.7 ± 2.6 mg/dL and 5659 ± 727 vs. 2704 ± 521 mg/dL.min, for the smaller- and larger-sized diets, respectively (p < 0.05). Ileal starch digestibility was not significantly different between diets (p ≥ 0.05). The iAUCoverall was inversely related to the starch gastric emptying half-time of the diets (r = -0.90, p = 0.015). CONCLUSIONS Starch-based food structure affected the glycemic response and starch digestion kinetics in the small intestine of growing pigs.
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Affiliation(s)
- Joanna Nadia
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand; School of Food and Advanced Technology, Massey University, Private Bag 11222, Palmerston North, New Zealand
| | - Alexander G Olenskyj
- Department of Biological and Agricultural Engineering, University of California, Davis, CA 95618, USA
| | - Natascha Stroebinger
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand
| | - Suzanne M Hodgkinson
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand
| | - Talia G Estevez
- Department of Biological and Agricultural Engineering, University of California, Davis, CA 95618, USA
| | | | - Harjinder Singh
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand
| | - R Paul Singh
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand; Department of Biological and Agricultural Engineering, University of California, Davis, CA 95618, USA
| | - Gail M Bornhorst
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North, New Zealand; Department of Biological and Agricultural Engineering, University of California, Davis, CA 95618, USA.
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24
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Lesgards JF. Benefits of Whey Proteins on Type 2 Diabetes Mellitus Parameters and Prevention of Cardiovascular Diseases. Nutrients 2023; 15:nu15051294. [PMID: 36904293 PMCID: PMC10005124 DOI: 10.3390/nu15051294] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/27/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality, and it is a major risk factor for the early onset of cardiovascular diseases (CVDs). More than genetics, food, physical activity, walkability, and air pollution are lifestyle factors, which have the greatest impact on T2DM. Certain diets have been shown to be associated with lower T2DM and cardiovascular risk. Diminishing added sugar and processed fats and increasing antioxidant-rich vegetable and fruit intake has often been highlighted, as in the Mediterranean diet. However, less is known about the interest of proteins in low-fat dairy and whey in particular, which have great potential to improve T2DM and could be used safely as a part of a multi-target strategy. This review discusses all the biochemical and clinical aspects of the benefits of high-quality whey, which is now considered a functional food, for prevention and improvement of T2DM and CVDs by insulin- and non-insulin-dependent mechanisms.
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Affiliation(s)
- Jean-François Lesgards
- Ingénierie des Peptides Thérapeutiques, Ambrilia-Cellpep, Faculté de Médecine Nord, Aix-Marseille University, Boulevard Pierre Dramard, 13015 Marseille, France
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25
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Huang W, Xie C, Wewer Albrechtsen NJ, Jones KL, Horowitz M, Rayner CK, Wu T. The 'early' postprandial glucagon response is related to the rate of gastric emptying in type 2 diabetes. Peptides 2023; 161:170941. [PMID: 36623554 DOI: 10.1016/j.peptides.2023.170941] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/15/2022] [Accepted: 01/02/2023] [Indexed: 01/09/2023]
Abstract
Gastric emptying (GE) is a major determinant of the postprandial glycemic and insulinemic responses in health and type 2 diabetes (T2D). However, the effect of GE on the postprandial glucagon response, which is characteristically augmented in T2D, is unknown. This study examined the relationship between plasma glucagon and GE of a standardized mixed meal in individuals with well-controlled T2D. 89 individuals with T2D (HbA1c 6.6 ± 0.1%) consumed a mashed potato meal labeled with 100 µL 13C-octanoic acid between 0 and 5 min. Venous blood was sampled frequently over 4 h for measurements of blood glucose and plasma glucagon. The gastric half-emptying time (T50) was calculated by quantification of 13C in the breath. Blood glucose peaked at t = 90 min after the meal. Plasma glucagon increased to a peak at t = 30 min and then decreased to a nadir at t = 180 min. The T50 was 68.3 ± 1.6 min. The incremental area under the plasma glucagon curve between t = 0-30 min (glucagon iAUC0-30 min) was related inversely to the T50 (r = -0.23, P = 0.029), while the increase in blood glucose at t = 30 min was related directly to the plasma glucagon iAUC0-30 min (r = 0.25, P = 0.018). Accordingly, individuals with relatively faster GE exhibited higher postprandial glucagon and glucose levels (ANOVA: P<0.01 for each). In well-controlled T2D, the early postprandial glucagon response to a mixed meal is related to the rate of GE, and predictive of the initial glycemic response. These observations suggest that a reduction in plasma glucagon may contribute to the effect of dietary and pharmacological strategies which reduce postprandial glycemia in T2D by slowing GE.
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Affiliation(s)
- Weikun Huang
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia
| | - Cong Xie
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia
| | | | - Karen L Jones
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia
| | - Michael Horowitz
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, Australia
| | - Christopher K Rayner
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Australia
| | - Tongzhi Wu
- Centre for Research Excellence in Translating Nutritional Sciences to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide 5000, Australia.
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26
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Pedersen K, Andersen H, Fledelius C, Holst JJ, Hjuler ST, Kuhre RE. Standard procedures for blood withdrawal in conscious male rats induce stress and profoundly affect glucose tolerance and secretion of glucoregulatory hormones. Mol Metab 2023; 69:101689. [PMID: 36739969 PMCID: PMC9950954 DOI: 10.1016/j.molmet.2023.101689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/24/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE A fundamental difference between physiological and pharmacological studies in rats and humans is that withdrawal of blood from conscious rats necessitates restraint which inevitably inflicts a higher level of stress. We investigated the impact of handling on acute glucose regulation and secretion of glucoregulatory hormones in rats. METHODS Fasted male Sprague Dawley rats (375-400 g, n = 11) were given an oral glucose tolerance test (OGTT) by gavage (2 g/kg). Blood was sampled frequently until 90 min after challenge by handheld sampling (HS) or by automated sampling (AS). In the HS experiment, blood was withdrawn by restraint and sublingual vein puncture; two weeks later, samples were obtained by AS through an implanted catheter in a carotid artery, allowing sampling without disturbing the animals. RESULTS On the day of HS, post challenge glucose AUCs were ∼17% higher (P < 0.0001), despite gastric emptying (AUC) being reduced by ∼30% (P < 0.0001). Plasma insulin AUC was 3.5-fold lower (P < 0.001), and glucose-dependent insulinotropic peptide (GIP) AUC was reduced by ∼36% but glucagon-like peptide-1 concentrations were not affected. Glucagon concentrations were higher both before and after challenge (fold difference in AUCs = 3.3). Adrenocorticotropin (ACTH) and corticosterone AUCs were 2.4-fold and 3.6-fold higher (P < 0.001), respectively. DISCUSSION AND CONCLUSION Our study highlights that sampling of blood from conscious rats by sublingual vein puncture inflicts stress which reduces glucose absorption and glucose tolerance and blunts secretion of insulin and GIP. As blood sampling in humans are less stressful, standard procedures of conducting OGTT's in rats by HS presumably introduce an interspecies difference that may have negative consequences for translatability of test results.
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Affiliation(s)
- Kent Pedersen
- Integrated Physiology Research, Department of Obesity and NASH Pharmacology, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark
| | - Helle Andersen
- Integrated Physiology Research, Department of Obesity and NASH Pharmacology, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark
| | - Christian Fledelius
- Integrated Physiology Research, Department of Diabetes Pharmacology, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark
| | - Jens Juul 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
| | - Sara Toftegaard Hjuler
- Integrated Physiology Research, Department of Obesity and NASH Pharmacology, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark
| | - Rune Ehrenreich Kuhre
- Integrated Physiology Research, Department of Obesity and NASH Pharmacology, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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Subramanian V, Bagger JI, Holst JJ, Knop FK, Vilsbøll T. A glucose-insulin-glucagon coupled model of the isoglycemic intravenous glucose infusion experiment. Front Physiol 2022; 13:911616. [PMID: 36148302 PMCID: PMC9485803 DOI: 10.3389/fphys.2022.911616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 07/19/2022] [Indexed: 11/13/2022] Open
Abstract
Type 2 diabetes (T2D) is a pathophysiology that is characterized by insulin resistance, beta- and alpha-cell dysfunction. Mathematical models of various glucose challenge experiments have been developed to quantify the contribution of insulin and beta-cell dysfunction to the pathophysiology of T2D. There is a need for effective extended models that also capture the impact of alpha-cell dysregulation on T2D. In this paper a delay differential equation-based model is developed to describe the coupled glucose-insulin-glucagon dynamics in the isoglycemic intravenous glucose infusion (IIGI) experiment. As the glucose profile in IIGI is tailored to match that of a corresponding oral glucose tolerance test (OGTT), it provides a perfect method for studying hormone responses that are in the normal physiological domain and without the confounding effect of incretins and other gut mediated factors. The model was fit to IIGI data from individuals with and without T2D. Parameters related to glucagon action, suppression, and secretion as well as measures of insulin sensitivity, and glucose stimulated response were determined simultaneously. Significant impairment in glucose dependent glucagon suppression was observed in patients with T2D (duration of T2D: 8 (6-36) months) relative to weight matched control subjects (CS) without diabetes (k1 (mM)-1: 0.16 ± 0.015 (T2D, n = 7); 0.26 ± 0.047 (CS, n = 7)). Insulin action was significantly lower in patients with T2D (a1 (10 pM min)-1: 0.000084 ± 0.0000075 (T2D); 0.00052 ± 0.00015 (CS)) and the Hill coefficient in the equation for glucose dependent insulin response was found to be significantly different in T2D patients relative to CS (h: 1.4 ± 0.15; 1.9 ± 0.14). Trends in parameters with respect to fasting plasma glucose, HbA1c and 2-h glucose values are also presented. Significantly, a negative linear relationship is observed between the glucagon suppression parameter, k1, and the three markers for diabetes and is thus indicative of the role of glucagon in exacerbating the pathophysiology of diabetes (Spearman Rank Correlation: (n = 12; (-0.79, 0.002), (-0.73,.007), (-0.86,.0003)) respectively).
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Affiliation(s)
- Vijaya Subramanian
- Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, United States
| | - Jonatan I. Bagger
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Jens J. Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Filip K. Knop
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Pasmans K, Meex RCR, van Loon LJC, Blaak EE. Nutritional strategies to attenuate postprandial glycemic response. Obes Rev 2022; 23:e13486. [PMID: 35686720 PMCID: PMC9541715 DOI: 10.1111/obr.13486] [Citation(s) in RCA: 6] [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: 04/25/2022] [Accepted: 05/27/2022] [Indexed: 11/29/2022]
Abstract
Maintaining good glycemic control to prevent complications is crucial in people with type 2 diabetes and in people with prediabetes and in the general population. Different strategies to improve glycemic control involve the prescription of blood glucose-lowering drugs and the modulation of physical activity and diet. Interestingly, lifestyle intervention may be more effective in lowering hyperglycemia than pharmaceutical intervention. Regulation of postprandial glycemia is complex, but specific nutritional strategies can be applied to attenuate postprandial hyperglycemia. These strategies include reducing total carbohydrate intake, consuming carbohydrates with a lower glycemic index, the addition of or substitution by sweeteners and fibers, using food compounds which delay or inhibit gastric emptying or carbohydrate digestion, and using food compounds which inhibit intestinal glucose absorption. Nevertheless, it must be noted that every individual may respond differently to certain nutritional interventions. Therefore, a personalized approach is of importance to choose the optimal nutritional strategy to improve postprandial glycemia for each individual, but this requires a better understanding of the mechanisms explaining the differential responses between individuals.
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Affiliation(s)
- Kenneth Pasmans
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Ruth C R Meex
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Luc J C van Loon
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Ellen E Blaak
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
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Jalleh RJ, Wu T, Jones KL, Rayner CK, Horowitz M, Marathe CS. Relationships of Glucose, GLP-1, and Insulin Secretion With Gastric Emptying After a 75-g Glucose Load in Type 2 Diabetes. J Clin Endocrinol Metab 2022; 107:e3850-e3856. [PMID: 35608823 PMCID: PMC9387705 DOI: 10.1210/clinem/dgac330] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT The relationships of gastric emptying (GE) with the glycemic response at 120 minutes, glucagon-like peptide-1 (GLP-1), and insulin secretion following a glucose load in type 2 diabetes (T2D) are uncertain. OBJECTIVE We evaluated the relationship of plasma glucose, GLP-1, and insulin secretion with GE of a 75-g oral glucose load in T2D. DESIGN Single-center, cross-sectional, post hoc analysis. SETTING Institutional research center. PARTICIPANTS 43 individuals with T2D age 65.6 ± 1.1 years, hemoglobin A1c 7.2 ± 1.0%, median duration of diabetes 5 years managed by diet and/or metformin. INTERVENTION Participants consumed the glucose drink radiolabeled with 99mTc-phytate colloid following an overnight fast. GE (scintigraphy), plasma glucose, GLP-1, insulin, and C-peptide were measured between 0 and 180 minutes. MAIN OUTCOME MEASURES The relationships of the plasma glucose at 120 minutes, plasma GLP-1, and insulin secretion (calculated by Δinsulin0-30/ Δglucose0-30 and ΔC-peptide0-30/Δglucose0-30) with the rate of GE (scintigraphy) were evaluated. RESULTS There were positive relationships of plasma glucose at 30 minutes (r = 0.56, P < 0.001), 60 minutes (r = 0.57, P < 0.001), and 120 minutes (r = 0.51, P < 0.001) but not at 180 minutes (r = 0.13, P = 0.38), with GE. The 120-minute plasma glucose and GE correlated weakly in multiple regression models adjusting for age, GLP-1, and insulin secretion (P = 0.04 and P = 0.06, respectively). There was no relationship of plasma GLP-1 with GE. Multiple linear regression analysis indicated that there was no significant effect of GE on insulin secretion. CONCLUSION In T2D, while insulin secretion is the dominant determinant of the 120-minute plasma glucose, GE also correlates. Given the relevance to interpreting the results of an oral glucose tolerance test, this relationship should be evaluated further. There appears to be no direct effect of GE on either GLP-1 or insulin secretion.
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Affiliation(s)
- Ryan J Jalleh
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Tongzhi Wu
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Karen L Jones
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
- Adelaide Medical School, The University of Adelaide, Adelaide, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Chinmay S Marathe
- Correspondence: Chinmay S. Marathe, MBBS, PhD, FRACP, Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide Medical School, The University of Adelaide, Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia. ; Level 5, Adelaide Health and Medical Science building, North Terrace, Adelaide SA 5000, Australia
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Collins KA, Ross LM, Slentz CA, Huffman KM, Kraus WE. Differential Effects of Amount, Intensity, and Mode of Exercise Training on Insulin Sensitivity and Glucose Homeostasis: A Narrative Review. SPORTS MEDICINE - OPEN 2022; 8:90. [PMID: 35834023 PMCID: PMC9283590 DOI: 10.1186/s40798-022-00480-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 06/18/2022] [Indexed: 11/29/2022]
Abstract
As type 2 diabetes remains a leading cause of morbidity and mortality, identifying the most appropriate preventive treatment early in the development of disease is an important public health matter. In general, lifestyle interventions incorporating exercise and weight loss via caloric restriction improve cardiometabolic risk by impacting several key markers of insulin sensitivity and glucose homeostasis. However, variations in the effects of specific types of exercise interventions on these markers have led to conflicting results surrounding the optimal amount, intensity, and mode of exercise for optimal effects. Moreover, the addition of weight loss via caloric restriction to exercise interventions appears to differentially impact changes in body composition, metabolism, and insulin sensitivity compared to exercise alone. Determining the optimal amount, intensity, and mode of exercise having the most beneficial impact on glycemic status is both: (1) clinically important to provide guidelines for appropriate exercise prescription; and (2) physiologically important to understand the pathways by which exercise-with and without weight loss-impacts glycemic status to enhance precision lifestyle medicine. Thus, the purposes of this narrative review are to: (1) summarize findings from the three Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) randomized trials regarding the differential effects of exercise amount, intensity, and mode on insulin action and glucose homeostasis markers; and (2) compare the STRRIDE findings to other published dose-response exercise trials in order to piece together the various physiologic pathways by which specific exercise interventions-with or without weight loss-impact glycemic status.
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Affiliation(s)
- Katherine A Collins
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Leanna M Ross
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.
| | - Cris A Slentz
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - Kim M Huffman
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
| | - William E Kraus
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
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Stevens JE, Jalleh RJ, Trahair LG, Marathe CS, Horowitz M, Jones KL. Comparative effects of low-carbohydrate, full-strength and low-alcohol beer on gastric emptying, alcohol absorption, glycaemia and insulinaemia in health. Br J Clin Pharmacol 2022; 88:3421-3427. [PMID: 35246999 PMCID: PMC9314679 DOI: 10.1111/bcp.15297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 01/26/2022] [Accepted: 02/12/2022] [Indexed: 02/05/2023] Open
Abstract
AIMS The aim of this study was to evaluate the comparative effects of low-carbohydrate (LC), full-strength (FS), and low-alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health. METHODS Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m2 ) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc-calcium phytate, in random order. RESULTS There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = -0.87, P < .01) and a trend for inverse relationships after LC (r = -0.67, P = .07) and FS (r = -0.69, P = .06). The AUC 0-180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0). CONCLUSION In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response.
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Affiliation(s)
- Julie E. Stevens
- Pharmacy, School of Health and Biomedical SciencesRMIT UniversityBundooraAustralia
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaideAustralia
- Clinical and Health SciencesUniversity of South AustraliaAdelaideAustralia
| | - Ryan J. Jalleh
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
| | | | - Chinmay S. Marathe
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
| | - Michael Horowitz
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
| | - Karen L. Jones
- Adelaide Medical SchoolThe University of AdelaideAdelaideAustralia
- Centre of Research Excellence in Translating Nutritional Science to Good HealthThe University of AdelaideAdelaideAustralia
- Clinical and Health SciencesUniversity of South AustraliaAdelaideAustralia
- Endocrine and Metabolic UnitRoyal Adelaide HospitalAdelaideAustralia
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Response of blood glucose and GLP-1 to different food temperature in normal subject and patients with type 2 diabetes. Nutr Diabetes 2022; 12:28. [PMID: 35624116 PMCID: PMC9142530 DOI: 10.1038/s41387-022-00208-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 05/05/2022] [Accepted: 05/23/2022] [Indexed: 11/16/2022] Open
Abstract
Background Eating behavior is a major factor in type 2 diabetes. We investigated the different responses of glucose-regulating hormones to cold and hot glucose solutions in normal subjects and patients with type 2 diabetes. Methods In this crossover, self-controlled study, normal subjects (N = 19) and patients with type 2 diabetes (N = 22) were recruited and randomly assigned to a hot (50 °C) or a cold (8 °C) oral glucose-tolerance test (OGTT). The subsequent day, they were switched to the OGTT at the other temperature. Blood glucose, insulin, GIP, glucagon-like peptide-1 (GLP-1), and cortisol were measured at 0, 5, 10, 30, 60, and 120 min during each OGTT. After the hot OGTT, all subjects ingested hot (>42 °C) food and water for that day, and ingested food and water at room temperature (≤24 °C) for the day after cold OGTT. All participants had continuous glucose monitoring (CGM) throughout the study. Results Compared to cold OGTT, blood glucose was significantly higher with hot OGTT in both groups (both P < 0.05). However, insulin and GLP-1 levels were significantly higher in hot OGTT in normal subjects only (both P < 0.05). The GIP and cortisol responses did not differ with temperature in both groups. CGM showed that normal subjects had significantly higher 24-h mean glucose (MBG) (6.11 ± 0.13 vs. 5.84 ± 0.11 mmol/L, P = 0.021), and standard deviation of MBG with hot meals (0.59 ± 0.06 vs. 0.48 ± 0.05 mmol/L, P = 0.043), T2DM patients had higher MBG only (8.46 ± 0.38 vs. 8.88 ± 0.39 mmol/L, P = 0.022). Conclusions Food temperature is an important factor in glucose absorption and GLP-1 response. These food temperatures elicited differences are lost in type 2 diabetes.
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L’intestin un organe endocrine : de la physiologie aux implications thérapeutiques en nutrition. NUTR CLIN METAB 2022. [DOI: 10.1016/j.nupar.2021.12.179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Hajishafiee M, McVeay C, Lange K, Rehfeld JF, Horowitz M, Feinle-Bisset C. Effects of intraduodenal infusion of lauric acid and L-tryptophan, alone and combined, on glucoregulatory hormones, gastric emptying and glycaemia in healthy men. Metabolism 2022; 129:155140. [PMID: 35065080 DOI: 10.1016/j.metabol.2022.155140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 12/28/2021] [Accepted: 01/14/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM In healthy men, intraduodenal administration of the fatty acid, lauric acid ('C12') and the amino acid, L-tryptophan ('TRP'), at loads that individually do not affect energy intake, reduce energy intake substantially when combined. C12 and TRP may also stimulate cholecystokinin and glucagon-like peptide-1 (GLP-1), which both slow gastric emptying, a key determinant of postprandial blood glucose. Accordingly, combination of C12 and TRP has the potential to reduce post-meal glycaemia more than either nutrient alone. METHODS Twelve healthy, lean men (age (mean ± SD): 28 ± 7 years) received, on 4 separate occasions, 45-min intraduodenal infusions of C12 (0.3 kcal/min), TRP (0.1 kcal/min), C12 + TRP (0.4 kcal/min), or 0.9% saline (control), in a randomised, double-blind fashion. 30 min after commencement of the infusion a mixed-nutrient drink was consumed and gastric emptying measured (13C breath-test) for 3 h. Blood samples were obtained at baseline, in response to treatments alone, and for 2 h post-drink for measurements of plasma glucose, cholecystokinin, GLP-1, C-peptide, insulin and glucagon. 'Early' (first 30 min) and 'overall' glycaemic and hormone responses were evaluated. RESULTS C12 + TRP and C12 delayed the rise in, but did not affect the overall glycaemic response to the drink, compared with control and TRP (all P < 0.05). C12 + TRP slowed gastric emptying compared with control and TRP (both P < 0.005), and C12 non-significantly slowed gastric emptying compared with control (P = 0.090). C12 + TRP and C12 delayed the rise in C-peptide and insulin, and also stimulated CCK and glucagon, compared with control and TRP (all P < 0.05). Only C12 + TRP stimulated early and overall GLP-1 compared with control (P < 0.05). CONCLUSIONS In healthy men, C12 + TRP and C12, in the loads administered, had comparable effects to delay the rise in glucose following a nutrient drink, probably primarily by slowing of gastric emptying, as a result of CCK and GLP-1 stimulation, while TRP had no effect.
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Affiliation(s)
- M Hajishafiee
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - C McVeay
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - K Lange
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - J F Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
| | - M Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - C Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
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Camastra S, Palumbo M, Santini F. Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation. Eat Weight Disord 2022; 27:449-461. [PMID: 33895917 PMCID: PMC8933374 DOI: 10.1007/s40519-021-01194-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/10/2021] [Indexed: 01/19/2023] Open
Abstract
Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB-less after SG-bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.
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Affiliation(s)
- Stefania Camastra
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy. .,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
| | - Maria Palumbo
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy
| | - Ferruccio Santini
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy
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Wittstock M, Kästner M, Kolbaske S, Sellmann T, Porath K, Patejdl R. Serial Measurements of Refractive Index, Glucose and Protein to Assess Gastric Liquid Nutrient Transport—A Proof-of-Principal Study. Front Nutr 2022; 8:742656. [PMID: 35187015 PMCID: PMC8850719 DOI: 10.3389/fnut.2021.742656] [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: 07/16/2021] [Accepted: 12/29/2021] [Indexed: 11/22/2022] Open
Abstract
Delayed gastric emptying contributes to complications as aspiration or malnutrition. Among patients suffering from acute neurological diseases, motility disorders are prevalent but poorly understood. Thus, methods to measure gastric emptying are required to allow for appropriate adaptions of individual enteral nutrition algorithms. For enterally fed patients repetitive concentration measurements of gastric content have been proposed to assess gastric emptying. This approach can be used to calculate the gastric residual volume (GRV) and transport of nutrition formula (NF), but it has not yet been implemented in clinical routine. The aim of this study was to investigate whether refractometry or other likewise straightforward analytical approaches produce the best results under in vitro conditions mimicking the gastric milieu. We measured NF in different known concentrations, either diluted in water or in simulated gastric fluid (SGF), with each of the following methods: refractometer, handheld glucose meter, and Bradford protein assay. Then, in enterally fed patients suffering from acute neurological disease, we calculated GRVs and nutrition transport and tested possible associations with clinical parameters. In water dilution experiments, NF concentrations could be assessed with the readout parameters of all three methods. Refractometry yielded the most precise results over the broadest range of concentrations and was biased least by the presence of SGF (detection range for Fresubin original fibre, given as volume concentration/normalized error of regression slope after incubation with water or SGF: 0–100 vs. 0–100%/0.5 vs. 3.9%; glucose-measurement: 5–100 vs. 25–100%/7.9 vs. 6.1%; Bradford-assay: 0–100 vs. 0–100%/7.8 vs. 15.7%). Out of 28 enterally fed patients, we calculated significant slower nutrition transport in patients with higher blood glucose (Rho −0.391; p = 0.039) and in patients who received high-dose sufentanil (Rho −0.514; p = 0.005). Also, the calculated nutrition transport could distinguish patients with and without feeding intolerance (Median 6 vs. 17 ml/h; Mann-Whitney test: p = 0.002). The results of our study prove that serial refractometry is a suitable and cost-effective method to assess gastric emptying and to enhance research on gastrointestinal complications of stroke.
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Affiliation(s)
- Matthias Wittstock
- Department of Neurology, University Medical Center Rostock, Rostock, Germany
| | - Matthias Kästner
- Department of Neurology, University Medical Center Rostock, Rostock, Germany
| | - Stephan Kolbaske
- Department of Neurology, University Medical Center Rostock, Rostock, Germany
| | - Tina Sellmann
- Oscar Langendorff Institute of Physiology, University Medical Center Rostock, Rostock, Germany
| | - Katrin Porath
- Oscar Langendorff Institute of Physiology, University Medical Center Rostock, Rostock, Germany
| | - Robert Patejdl
- Oscar Langendorff Institute of Physiology, University Medical Center Rostock, Rostock, Germany
- *Correspondence: Robert Patejdl
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Harray AJ, Binkowski S, Keating BL, Horowitz M, Standfield S, Smith G, Paramalingam N, Jones T, King BR, Smart CEM, Davis EA. Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes. J Clin Endocrinol Metab 2022; 107:e205-e213. [PMID: 34410410 DOI: 10.1210/clinem/dgab614] [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: 04/01/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.
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Affiliation(s)
- Amelia J Harray
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
- School of Population Health, Curtin University, Bentley, Perth, Western Australia, Australia
| | - Sabrina Binkowski
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| | - Barbara L Keating
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia
| | | | | | - Grant Smith
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| | - Nirubasini Paramalingam
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia
- Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia
| | - Timothy Jones
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia
- Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia
| | - Bruce R King
- John Hunter Children's Hospital, New Lambton Heights, New South Wales, Australia
- Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Carmel E M Smart
- John Hunter Children's Hospital, New Lambton Heights, New South Wales, Australia
- Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Elizabeth A Davis
- Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
- Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia
- Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia
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Heiran A, Bagheri Lankarani K, Bradley R, Simab A, Pasalar M. Efficacy of herbal treatments for functional dyspepsia: A systematic review and meta-analysis of randomized clinical trials. Phytother Res 2021; 36:686-704. [PMID: 34851546 DOI: 10.1002/ptr.7333] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 09/20/2021] [Accepted: 10/23/2021] [Indexed: 02/05/2023]
Abstract
Functional dyspepsia (FD) is a very common condition globally. Relevant keywords were searched for in title and abstract of selected databases, that is, Medline/PubMed, Scopus, Embase, Web of knowledge, and Google Scholar. Placebo and active-control trials on herbal remedies amongst adults who were diagnosed with FD were included. Dichotomous outcomes were presented as relative risk (RR) with 95% confidence interval (CI) and continuous outcomes were presented as pooled standardized mean difference (SMD) with 95% CI. Forty-nine randomized controlled trials (RCTs) were entered into meta-analysis (6,987 subjects). Herbal remedies resulted in a higher improvement in FD symptoms in comparison with the placebo (SMD = -0.58 [-0.66- -0.51], p < .00001 and RR = 1.73 [1.62-1.85], p < .00001). No significant difference between herbal remedies and placebo in the incidence of adverse events was observed (12.27 vs. 8.41%, RR = 1.06 [0.91-1.23], p = .45). Also, herbal remedies resulted in a higher improvement in quality of life in comparison with placebo (SMD = -0.64 [-0.73- -0.55], p < .00001). When comparing herbal remedies with conventional medicine through sensitivity analysis, no outcomes were significantly different (p > .05). Herbal remedies might be efficacious and safe in treating FD, and demonstrate comparable effect sizes for efficacy to conventional treatments. Further high-quality studies are warranted to firmly establish the clinical efficacy of the herbal remedies.
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Affiliation(s)
- Alireza Heiran
- Non-communicable Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Ryan Bradley
- Helfgott Research Institute, National University of Natural Medicine, Portland, USA
| | - Alireza Simab
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Pasalar
- Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Holst JJ, Gasbjerg LS, Rosenkilde MM. The Role of Incretins on Insulin Function and Glucose Homeostasis. Endocrinology 2021; 162:6199910. [PMID: 33782700 PMCID: PMC8168943 DOI: 10.1210/endocr/bqab065] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Indexed: 12/14/2022]
Abstract
The incretin effect-the amplification of insulin secretion after oral vs intravenous administration of glucose as a mean to improve glucose tolerance-was suspected even before insulin was discovered, and today we know that the effect is due to the secretion of 2 insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). But how important is it? Physiological experiments have shown that, because of the incretin effect, we can ingest increasing amounts of amounts of glucose (carbohydrates) without increasing postprandial glucose excursions, which otherwise might have severe consequences. The mechanism behind this is incretin-stimulated insulin secretion. The availability of antagonists for GLP-1 and most recently also for GIP has made it possible to directly estimate the individual contributions to postprandial insulin secretion of a) glucose itself: 26%; b) GIP: 45%; and c) GLP-1: 29%. Thus, in healthy individuals, GIP is the champion. When the action of both incretins is prevented, glucose tolerance is pathologically impaired. Thus, after 100 years of research, we now know that insulinotropic hormones from the gut are indispensable for normal glucose tolerance. The loss of the incretin effect in type 2 diabetes, therefore, contributes greatly to the impaired postprandial glucose control.
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Affiliation(s)
- Jens Juul Holst
- Department of Biomedical Sciences and the NovoNordisk Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, The Panum Institute, Copenhagen N, DK-2200 Denmark
- Correspondence: Jens Juul Holst, MD, University of Copenhagen, Department of Biomedical Sciences, The Panum Institute, 3 Blegdamsvej, Copenhagen, DK-2200 Denmark.
| | - Lærke Smidt Gasbjerg
- Department of Biomedical Sciences and the NovoNordisk Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, The Panum Institute, Copenhagen N, DK-2200 Denmark
| | - Mette Marie Rosenkilde
- Department of Biomedical Sciences and the NovoNordisk Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, The Panum Institute, Copenhagen N, DK-2200 Denmark
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Albarazanji K, Nawrocki AR, Gao B, Wang X, Wang Y(J, Xiao YF. Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates. Sci Rep 2021; 11:11866. [PMID: 34088949 PMCID: PMC8178340 DOI: 10.1038/s41598-021-91027-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/12/2021] [Indexed: 02/05/2023] Open
Abstract
Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.
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Affiliation(s)
- Kamal Albarazanji
- grid.497530.c0000 0004 0389 4927Janssen Research & Development, Cardiovascular and Metabolism, 1400 McKean Rd., Spring House, PA 19477 USA
| | - Andrea R. Nawrocki
- grid.497530.c0000 0004 0389 4927Janssen Research & Development, Cardiovascular and Metabolism, 1400 McKean Rd., Spring House, PA 19477 USA
| | - Bin Gao
- grid.497530.c0000 0004 0389 4927Janssen Research & Development, Cardiovascular and Metabolism, 1400 McKean Rd., Spring House, PA 19477 USA
| | - Xiaoli Wang
- Cardiovascular and Metabolic Diseases, Crown Bioscience, Inc., 6 Beijing West Road, Taicang, Jiangsu Province 215400 People’s Republic of China
| | - Yixin (Jim) Wang
- Cardiovascular and Metabolic Diseases, Crown Bioscience, Inc., 6 Beijing West Road, Taicang, Jiangsu Province 215400 People’s Republic of China
| | - Yong-Fu Xiao
- Cardiovascular and Metabolic Diseases, Crown Bioscience, Inc., 6 Beijing West Road, Taicang, Jiangsu Province 215400 People’s Republic of China
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Elovaris RA, Bitarafan V, Agah S, Ullrich SS, Lange K, Horowitz M, Feinle-Bisset C. Comparative Effects of the Branched-Chain Amino Acids, Leucine, Isoleucine and Valine, on Gastric Emptying, Plasma Glucose, C-Peptide and Glucagon in Healthy Men. Nutrients 2021; 13:nu13051613. [PMID: 34064996 PMCID: PMC8150294 DOI: 10.3390/nu13051613] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/04/2023] Open
Abstract
(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using 13C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0–30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.
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Affiliation(s)
- Rachel A. Elovaris
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
| | - Vida Bitarafan
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
| | - Shahram Agah
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
| | - Sina S. Ullrich
- Clinical Trials Unit, University Hospital Basel, 4031 Basel, Switzerland;
| | - Kylie Lange
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
| | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide 5005, Australia; (R.A.E.); (V.B.); (S.A.); (K.L.); (M.H.)
- Correspondence: ; Tel.: +61-8-8313-6053
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Nadia J, Bronlund J, Singh RP, Singh H, Bornhorst GM. Structural breakdown of starch-based foods during gastric digestion and its link to glycemic response: In vivo and in vitro considerations. Compr Rev Food Sci Food Saf 2021; 20:2660-2698. [PMID: 33884751 DOI: 10.1111/1541-4337.12749] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 02/19/2021] [Accepted: 03/08/2021] [Indexed: 01/10/2023]
Abstract
The digestion of starch-based foods in the small intestine as well as factors affecting their digestibility have been previously investigated and reviewed in detail. Starch digestibility has been studied both in vivo and in vitro, with increasing interest in the use of in vitro models. Although previous in vivo studies have indicated the effect of mastication and gastric digestion on the digestibility of solid starch-based foods, the physical breakdown of starch-based foods prior to small intestinal digestion is often less considered. Moreover, gastric digestion has received little attention in the attempt to understand the digestion of solid starch-based foods in the digestive tract. In this review, the physical breakdown of starch-based foods in the mouth and stomach, the quantification of these breakdown processes, and their links to physiological outcomes, such as gastric emptying and glycemic response, are discussed. In addition, the physical breakdown aspects related to gastric digestion that need to be considered when developing in vitro-in vivo correlation in starch digestion studies are discussed. The discussion demonstrates that physical breakdown prior to small intestinal digestion, especially during gastric digestion, should not be neglected in understanding the digestion of solid starch-based foods.
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Affiliation(s)
- Joanna Nadia
- School of Food and Advanced Technology, Massey University, Palmerston North, New Zealand.,Riddet Institute, Massey University, Palmerston North, New Zealand
| | - John Bronlund
- School of Food and Advanced Technology, Massey University, Palmerston North, New Zealand.,Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Rajinder Paul Singh
- Riddet Institute, Massey University, Palmerston North, New Zealand.,Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California, USA
| | - Harjinder Singh
- Riddet Institute, Massey University, Palmerston North, New Zealand
| | - Gail M Bornhorst
- Riddet Institute, Massey University, Palmerston North, New Zealand.,Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California, USA
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Rezaie P, Bitarafan V, Horowitz M, Feinle-Bisset C. Effects of Bitter Substances on GI Function, Energy Intake and Glycaemia-Do Preclinical Findings Translate to Outcomes in Humans? Nutrients 2021; 13:1317. [PMID: 33923589 PMCID: PMC8072924 DOI: 10.3390/nu13041317] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/07/2021] [Accepted: 04/15/2021] [Indexed: 12/25/2022] Open
Abstract
Bitter substances are contained in many plants, are often toxic and can be present in spoiled food. Thus, the capacity to detect bitter taste has classically been viewed to have evolved primarily to signal the presence of toxins and thereby avoid their consumption. The recognition, based on preclinical studies (i.e., studies in cell cultures or experimental animals), that bitter substances may have potent effects to stimulate the secretion of gastrointestinal (GI) hormones and modulate gut motility, via activation of bitter taste receptors located in the GI tract, reduce food intake and lower postprandial blood glucose, has sparked considerable interest in their potential use in the management or prevention of obesity and/or type 2 diabetes. However, it remains to be established whether findings from preclinical studies can be translated to health outcomes, including weight loss and improved long-term glycaemic control. This review examines information relating to the effects of bitter substances on the secretion of key gut hormones, gastric motility, food intake and blood glucose in preclinical studies, as well as the evidence from clinical studies, as to whether findings from animal studies translate to humans. Finally, the evidence that bitter substances have the capacity to reduce body weight and/or improve glycaemic control in obesity and/or type 2 diabetes, and potentially represent a novel strategy for the management, or prevention, of obesity and type 2 diabetes, is explored.
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Affiliation(s)
| | | | | | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide 5005, Australia; (P.R.); (V.B.); (M.H.)
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Chiavaroli L, Di Pede G, Dall'Asta M, Cossu M, Francinelli V, Goldoni M, Scazzina F, Brighenti F. The importance of glycemic index on post-prandial glycaemia in the context of mixed meals: A randomized controlled trial on pasta and rice. Nutr Metab Cardiovasc Dis 2021; 31:615-625. [PMID: 33229200 DOI: 10.1016/j.numecd.2020.09.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 08/28/2020] [Accepted: 09/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Post-prandial glycemic response (PPGR) depends on the intrinsic characteristic of the carbohydrate-rich foods as well as on the amount and type of other nutrients. This study aimed to explore whether the addition of condiments can affect the difference in PPGR between a low and a medium-high Glycemic Index (GI) food. METHODS AND RESULTS Spaghetti (S) and rice ® were consumed plain and after adding tomato sauce and extra virgin olive oil (TEVOO), or pesto sauce (P). The GI of R (63 ± 3) was statistically higher than that of S (44 ± 7) (p = 0.003). The Incremental Area Under the Curve (IAUC) for R was significantly greater than S (124.2 ± 12.1 and 82.1 ± 12.9 mmol∗min/L respectively) (p = 0.016) for blood glucose but not for insulin (1192.6 ± 183.6 and 905.2 ± 208.9 mU∗min/L, respectively) (p = 0.076). There were no significant differences after the addition of either TEVOO or P. The postprandial peaks of blood glucose and insulin for R (6.7 ± 0.3 mmol/L and 36.4 ± 4.9 mU/L, respectively) were significantly higher compared to S (6.0 ± 0.2 mmol/L and 26.7 ± 3.6 mU/L, respectively) (p = 0.033 and p = 0.025). The postprandial peak for insulin remained significantly higher with P (36.8 ± 3.7 and 28.6 ± 2.9 mU/L for R + P and S + P, p = 0.045) but not with EVOO (p = 0.963). Postprandial peaks for blood glucose were not significantly different with condiment. CONCLUSIONS The differences in PPGR were significant between spaghetti and rice consumed plain, they reduced or disappeared with fat adding, depending on the type of condiment used. REGISTRATION NUMBER: (www.clinicaltrial.gov):NCT03104712.
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Affiliation(s)
- Laura Chiavaroli
- Department of Food and Drugs, University of Parma, Parma, 43125, Italy; Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Toronto, ON, M5C 2T2, Canada; Clinical Nutrition and Risk Factor Modification Center, St. Michael's Hospital, Toronto, ON M5C 2T2, Canada; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Giuseppe Di Pede
- Department of Food and Drugs, University of Parma, Parma, 43125, Italy
| | - Margherita Dall'Asta
- Department of Food and Drugs, University of Parma, Parma, 43125, Italy; Department of Animal Science, Food and Nutrition, Università Cattolica del Sacro Cuore, 29122, Piacenza, Italy
| | - Marta Cossu
- Department of Food and Drugs, University of Parma, Parma, 43125, Italy
| | | | - Matteo Goldoni
- Medical Statistics, Department of Medicine and Surgery, University of Parma, Parma, 43126, Italy
| | | | - Furio Brighenti
- Department of Food and Drugs, University of Parma, Parma, 43125, Italy
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Murthy TA, Grivell J, Hatzinikolas S, Chapple LAS, Chapman MJ, Stevens JE, Malbert CH, Rayner CK, Horowitz M, Jones KL, Marathe CS. Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia. J Clin Endocrinol Metab 2021; 106:364-371. [PMID: 33230553 DOI: 10.1210/clinem/dgaa854] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Indexed: 02/07/2023]
Abstract
CONTEXT Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown. OBJECTIVE To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health. DESIGN, SETTING, AND SUBJECTS Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. RESULTS Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia. CONCLUSION In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.
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Affiliation(s)
- Tejaswini Arunachala Murthy
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | | | - Seva Hatzinikolas
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
| | - Lee-Anne S Chapple
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Marianne J Chapman
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | | | | | - Christopher K Rayner
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Karen L Jones
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
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Dimitriadis GD, Maratou E, Kountouri A, Board M, Lambadiari V. Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients 2021; 13:E159. [PMID: 33419065 PMCID: PMC7825450 DOI: 10.3390/nu13010159] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/18/2020] [Accepted: 12/24/2020] [Indexed: 12/18/2022] Open
Abstract
Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.
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Affiliation(s)
- George D. Dimitriadis
- Sector of Medicine, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Eirini Maratou
- Department of Clinical Biochemistry, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece;
- Department of Clinical Biochemistry, Medical School, “Attikon” University Hospital, Rimini 1, 12462 Chaidari, Greece
| | - Aikaterini Kountouri
- Research Institute and Diabetes Center, 2nd Department of Internal Medicine, “Attikon” University Hospital, 1 Rimini Street, 12542 Haidari, Greece; (A.K.); (V.L.)
| | - Mary Board
- St. Hilda’s College, University of Oxford, Cowley, Oxford OX4 1DY, UK;
| | - Vaia Lambadiari
- Research Institute and Diabetes Center, 2nd Department of Internal Medicine, “Attikon” University Hospital, 1 Rimini Street, 12542 Haidari, Greece; (A.K.); (V.L.)
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Elovaris RA, Hajishafiee M, Ullrich SS, Fitzgerald PCE, Lange K, Horowitz M, Feinle-Bisset C. Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes. Diabetes Res Clin Pract 2021; 171:108618. [PMID: 33310174 DOI: 10.1016/j.diabres.2020.108618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 12/02/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
AIMS In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D). METHODS 14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10 g leucine, 10 g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74 g carbohydrates, 18 g protein, 15 g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured. RESULTS Leucine and isoleucine stimulated insulin, both before and after the drink (all P < 0.05; peak (mU/L): control: 70 ± 15; leucine: 88 ± 17; isoleucine: 74 ± 15). Isoleucine stimulated (P < 0.05), and leucine tended to stimulate (P = 0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P = 0.031; peak (pg/mL): control: 62 ± 5; leucine: 70 ± 9; isoleucine: 69 ± 6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0 ± 0.5; leucine: 12.5 ± 0.7; isoleucine: 12.0 ± 0.6). CONCLUSIONS In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.
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Affiliation(s)
- Rachel A Elovaris
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Maryam Hajishafiee
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Sina S Ullrich
- Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Penelope C E Fitzgerald
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Kylie Lange
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia
| | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
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Smith K, Taylor GS, Allerton DM, Brunsgaard LH, Bowden Davies KA, Stevenson EJ, West DJ. The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial. Front Endocrinol (Lausanne) 2021; 12:696977. [PMID: 34220720 PMCID: PMC8253223 DOI: 10.3389/fendo.2021.696977] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 05/19/2021] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. METHODS In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. RESULTS WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. CONCLUSION Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. CLINICAL TRIAL REGISTRATION ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.
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Affiliation(s)
- Kieran Smith
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Guy S. Taylor
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Dean M. Allerton
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Lise Hoej Brunsgaard
- Health and Performance Nutrition, Arla Foods Ingredients Group P/S, Viby J., Denmark
| | - Kelly A. Bowden Davies
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
- School of Sport and Exercise Sciences, Manchester Metropolitan University, Manchester, United Kingdom
| | - Emma J. Stevenson
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Daniel J. West
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
- *Correspondence: Daniel J. West,
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Amin A, Frampton J, Liu Z, Franco-Becker G, Norton M, Alaa A, Li JV, Murphy KG. Differential effects of L- and D-phenylalanine on pancreatic and gastrointestinal hormone release in humans: A randomized crossover study. Diabetes Obes Metab 2021; 23:147-157. [PMID: 32991046 DOI: 10.1111/dom.14204] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 09/11/2020] [Accepted: 09/25/2020] [Indexed: 12/16/2022]
Abstract
AIM To investigate the effects of L-phenylalanine on gastroenteropancreatic hormone release, glucose levels, subjective appetite and energy intake in humans, and to determine whether these effects were stereoisomer-specific by comparing them with D-phenylalanine. MATERIALS AND METHODS A dose-finding, non-randomized, unblinded, crossover study was conducted during October-December 2017 at the NIHR Imperial Clinical Research Facility in five participants, in which the tolerability of escalating doses of oral L-phenylalanine was assessed (0, 3, 6 and 10 g). Also, an acute, randomized, double-blind, placebo-controlled crossover study was conducted during January-May 2018 at the NIHR Imperial Clinical Research Facility in 11 participants, in which the effects of oral 10 g L-phenylalanine relative to D-phenylalanine and placebo on gastroenteropancreatic hormone (insulin, glucagon, glucose-dependent insulinotropic polypeptide [GIP], peptide tyrosine tyrosine [PYY], glucagon-like peptide-1) and glucose concentrations, visual analogue scales for subjective appetite and energy intake at an ad libitum meal served 70 minutes postingestion, were investigated. RESULTS L-phenylalanine was well-tolerated and increased insulin and glucagon concentrations prior to meal ingestion at several time points relative to placebo and D-phenylalanine (P < .05). L-phenylalanine also increased GIP concentrations relative to D-phenylalanine (P = .0420) and placebo (P = .0249) 70 minutes following ingestion. L-phenylalanine reduced postprandial glucose area under the curve (AUC)70-150mins relative to placebo (P = .0317) but did not affect subjective appetite or energy intake (P > .05). D-phenylalanine increased postprandial PYY AUC70-150mins concentrations relative to placebo (P = .0002). CONCLUSIONS Ingestion of L-phenylalanine, but not D-phenylalanine, increases insulin, glucagon and GIP concentrations without appearing to have a marked effect on appetite.
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Affiliation(s)
- Anjali Amin
- Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - James Frampton
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Zhigang Liu
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Georgia Franco-Becker
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Mariana Norton
- Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Aos Alaa
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Jia V Li
- Section for Nutrition Research, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Kevin G Murphy
- Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
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50
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Xie C, Huang W, Wang X, Trahair LG, Pham HT, Marathe CS, Young RL, Jones KL, Horowitz M, Rayner CK, Wu T. Gastric emptying in health and type 2 diabetes: An evaluation using a 75 g oral glucose drink. Diabetes Res Clin Pract 2021; 171:108610. [PMID: 33301790 DOI: 10.1016/j.diabres.2020.108610] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 10/14/2020] [Accepted: 12/03/2020] [Indexed: 02/07/2023]
Abstract
AIM Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls. METHODS T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min. RESULTS The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects. CONCLUSIONS Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM.
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Affiliation(s)
- Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Xuyi Wang
- Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China
| | - Laurence G Trahair
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Hung T Pham
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Chinmay S Marathe
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Richard L Young
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
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