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Sandforth L, Raverdy V, Sandforth A, Bauvin P, Chatelain E, Verkindt H, Mingrone G, Guidone C, Verrastro O, Zhou K, Archid R, Mihaljevic A, Caiazzo R, Baud G, Marciniak C, Chetboun M, Ganslmeier M, Minelli Faiao V, Heni M, Fritsche L, Moller A, Kantartzis K, Peter A, Lehmann R, Wagner R, Prystupa K, Fritsche A, Stefan N, Preissl H, Birkenfeld AL, Jumpertz von Schwartzenberg R, Pattou F. Subphenotype-Dependent Benefits of Bariatric Surgery for Individuals at Risk for Type 2 Diabetes. Diabetes Care 2025; 48:996-1006. [PMID: 40214701 DOI: 10.2337/dc25-0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/23/2025] [Indexed: 05/22/2025]
Abstract
OBJECTIVE Bariatric surgery is an effective treatment option for individuals with obesity and type 2 diabetes (T2D). However, whether outcomes in subtypes of individuals at risk for T2D and/or comorbidities (Tübingen Clusters) differ, is unknown. Of these, cluster 5 (C5) and cluster 6 (C6) are high-risk clusters for developing T2D and/or comorbidities, while cluster 4 (C4) is a low-risk cluster. We investigated bariatric surgery outcomes, hypothesizing that high-risk clusters benefit most due to great potential for metabolic improvement. RESEARCH DESIGN AND METHODS We allocated participants without T2D but at risk for T2D, defined by elevated BMI, to the Tübingen Clusters. Participants had normal glucose regulation or prediabetes according to American Diabetes Association criteria. Two cohorts underwent bariatric surgery: a discovery (Lille, France) and a replication cohort (Rome, Italy). A control cohort (Tübingen, Germany) received behavioral modification counseling. Main outcomes included alteration of glucose regulation parameters and prediabetes remission. RESULTS In the discovery cohort, 15.0% of participants (n = 121) were allocated to C4, 22.3% (n = 180) to C5, and 62.4% (n = 503) to C6. Relative body weight loss was similar among all clusters; however, reduction of insulin resistance and improvement of β-cell function were strongest in C5. Prediabetes remission rate was lowest in low-risk C4 and highest in high-risk C5. Individuals from high-risk clusters changed to low-risk clusters in both bariatric surgery cohorts but not in the control cohort. CONCLUSIONS Participants in C5 had the highest benefit from bariatric surgery in terms of improvement in insulin resistance, β-cell function, and prediabetes remission. This novel classification might help identify individuals who will benefit specifically from bariatric surgery.
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Affiliation(s)
- Leontine Sandforth
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Violeta Raverdy
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Arvid Sandforth
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Pierre Bauvin
- INSERM, CHU Lille, Institut Pasteur de Lille, U1190-EGID, University Lille, Lille, France
| | - Estelle Chatelain
- CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41-UAR 2014-PLBS, University Lille, Lille, France
| | - Helene Verkindt
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, U.K
| | - Caterina Guidone
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Ornella Verrastro
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Karin Zhou
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Rami Archid
- Department of General, Visceral, and Transplant Surgery, University Hospital of Tübingen, Tübingen, Germany
| | - André Mihaljevic
- Department of General, Visceral, and Transplant Surgery, University Hospital of Tübingen, Tübingen, Germany
| | - Robert Caiazzo
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Gregory Baud
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Camille Marciniak
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Mikael Chetboun
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Marlene Ganslmeier
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Vitória Minelli Faiao
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Martin Heni
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Louise Fritsche
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Anja Moller
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Konstantinos Kantartzis
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Andreas Peter
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf (DDZ), Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Hospital, Düsseldorf, Germany
| | - Katsiaryna Prystupa
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf (DDZ), Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Hospital, Düsseldorf, Germany
| | - Andreas Fritsche
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Norbert Stefan
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Hubert Preissl
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, and Interfaculty Centre for Pharmacogenomics and Pharma Research, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, U.K
| | - Reiner Jumpertz von Schwartzenberg
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Cluster of Excellence EXC 2124 "Controlling Microbes to Fight Infections" (CMFI), University of Tübingen, Tübingen, Germany
- M3 Research Center, Tübingen, Germany
| | - François Pattou
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
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Miletić M, Stević Z, Perić S, Tančić Gajić M, Rakočević J, Stojanović M, Marković B, Žarković M. Adiponectin and Leptin-Considerations in Adult Patients with Spinal Muscular Atrophy Type 3. Diagnostics (Basel) 2025; 15:529. [PMID: 40075777 PMCID: PMC11899018 DOI: 10.3390/diagnostics15050529] [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: 12/27/2024] [Revised: 02/13/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index-HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research.
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Affiliation(s)
- Marija Miletić
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Zorica Stević
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
- Clinic of Neurology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Stojan Perić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
- Clinic of Neurology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | - Milina Tančić Gajić
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Jelena Rakočević
- Institute of Histology and Embryology “Aleksandar Ð. Kostić”, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Miloš Stojanović
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Bojan Marković
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
| | - Miloš Žarković
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (M.T.G.); (M.S.); (B.M.); (M.Ž.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.S.); (S.P.)
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Adams MS, Mensink RP, Plat J, Winkens B, Joris PJ. Long-term egg-protein hydrolysate consumption improves endothelial function: a randomized, double-blind, placebo-controlled trial in older adults with overweight or obesity. Eur J Nutr 2024; 64:54. [PMID: 39718599 DOI: 10.1007/s00394-024-03566-w] [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: 05/21/2024] [Accepted: 11/26/2024] [Indexed: 12/25/2024]
Abstract
PURPOSE The dietary egg-protein hydrolysate Newtricious (NWT)-03 has previously demonstrated improvements in blood pressure and metabolic profiles. However, the long-term effects on vascular function and cardiometabolic risk markers are unknown. METHODS Forty-four older (aged 60-75) adults with overweight/obesity experiencing elevated Subjective Cognitive Failures (SCF) were randomized into a 36-week, double-blind, placebo-controlled trial. Participants either consumed 5.7 g of an egg-protein hydrolysate (NWT-03) or maltodextrin placebo. Endothelial function (brachial artery flow-mediated vasodilation [FMD] and carotid artery reactivity [CAR] responses after a cold pressor test), arterial stiffness (carotid-to-femoral pulse wave velocity [PWVc-f]), retinal microvascular calibers, and cardiometabolic risk markers (insulin sensitivity using a 7-point oral glucose tolerance test, serum lipid profiles, and blood pressure) were evaluated. RESULTS FMD observed a non-significant trend towards a 0.3 percentage point (pp) increase in the intervention compared to the placebo group (95% CI: [0.0, 0.7]; p = 0.08), and a significant intervention effect was observed on CAR responses based on a 0.7 pp improvement after a cold pressor test (95% CI: [0.1, 1.3]; p = 0.03). No significant overall changes were observed for arterial stiffness as measured by PWVc-f. Retinal microvascular calibers and cardiometabolic parameters also did not change. CONCLUSION Long-term supplementation with 5.7 g of the egg-protein hydrolysate NWT-03 for 36 weeks improved vascular endothelial function in older adults with overweight/obesity experiencing elevated SCF, which may benefit cardiovascular disease risk. No overall changes in other vascular function markers, retinal microvascular calibers or cardiometabolic risk markers were observed. CLINICAL TRIAL REGISTRATION The study was registered at ClinicalTrials.gov in January 2021 as NCT04831203: https://clinicaltrials.gov/study/NCT04831203.
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Affiliation(s)
- Micah S Adams
- Department of Nutrition and Movement Sciences, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands.
| | - Ronald P Mensink
- Department of Nutrition and Movement Sciences, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands
| | - Jogchum Plat
- Department of Nutrition and Movement Sciences, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center+, 6200 MD, Maastricht, The Netherlands
| | - Peter J Joris
- Department of Nutrition and Movement Sciences, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands
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Asimakopoulos G, Pergialiotis V, Antsaklis P, Theodora M, Loutradis D, Daskalakis G. Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial. Arch Gynecol Obstet 2024; 310:1895-1903. [PMID: 39141124 DOI: 10.1007/s00404-024-07618-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 06/25/2024] [Indexed: 08/15/2024]
Abstract
PURPOSE Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. METHODS We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. RESULTS The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). CONCLUSION MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. TRIAL REGISTRATION ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.
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Affiliation(s)
- George Asimakopoulos
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
| | - Vasilios Pergialiotis
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Panagiotis Antsaklis
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Mariana Theodora
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Loutradis
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Daskalakis
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Lui DTW, Lee CH, Wong Y, Fong CHY, Tsoi KH, Woo YC, Tan KCB. A Prospective 1-Year Follow-up of Glycemic Status and C-Peptide Levels of COVID-19 Survivors with Dysglycemia in Acute COVID-19 Infection. Diabetes Metab J 2024; 48:763-770. [PMID: 38467385 PMCID: PMC11307110 DOI: 10.4093/dmj.2023.0175] [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: 06/05/2023] [Accepted: 10/13/2023] [Indexed: 03/13/2024] Open
Abstract
BACKGRUOUND We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. METHODS COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. RESULTS Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. CONCLUSION Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.
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Affiliation(s)
- David Tak Wai Lui
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Chi Ho Lee
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Ying Wong
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Carol Ho Yi Fong
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Kimberly Hang Tsoi
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Yu Cho Woo
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Kathryn Choon Beng Tan
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
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Zhou M, Mei L, Jing J, Yang Y, Cai X, Meng X, Jin A, Lin J, Li S, Li H, Wei T, Wang Y, Wang Y, Pan Y. Blood Pressure Partially Mediated the Association of Insulin Resistance and Cerebral Small Vessel Disease: A Community-Based Study. J Am Heart Assoc 2024; 13:e031723. [PMID: 38390815 PMCID: PMC10944068 DOI: 10.1161/jaha.123.031723] [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: 07/14/2023] [Accepted: 01/26/2024] [Indexed: 02/24/2024]
Abstract
BACKGROUND Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects. METHODS AND RESULTS PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study participants underwent brain and vascular imaging techniques and metabolomic risk factors measurements. Insulin resistance was evaluated by the insulin sensitivity index and the Homeostatic Model Assessment for Insulin Resistance based on the standard oral glucose tolerance test. On average, 2752 nondiabetic subjects (47.1% men) aged 60.9 years were included. The multivariable logistic regression model and linear regression model tested the association of insulin resistance with BP components (including systolic BP [SBP], diastolic BP (DBP), and pulse pressure [PP]) and SVD, and of BP components with SVD. In the mediation analysis, SBP, DBP, and PP were found to partially mediate the detrimental effect of insulin resistance (assessed by the insulin sensitivity index) on lacunes (mediation percentage: SBP, 31.15%; DBP, 34.21%; PP, 10.43%), white matter hyperintensity (mediation percentage: SBP, 37.34%; DBP, 44.15%; PP, 9.80%), and SVD total burden (mediation percentage: SBP, 42.07%; DBP, 49.29%; PP, 11.71%) (all P<0.05). The mediation analysis results were not significant when using the Homeostatic Model Assessment for Insulin Resistance to assess insulin resistance. CONCLUSIONS Higher insulin resistance was associated with SVD in this community-dwelling population. The association of insulin resistance with lacunes, white matter hyperintensity, and SVD total burden was explained in part by BP. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03178448.
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Affiliation(s)
- Mengyuan Zhou
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Lerong Mei
- Cerebrovascular Research Lab, Lishui HospitalZhejiang University School of MedicineLishuiChina
| | - Jing Jing
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Yingying Yang
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Xueli Cai
- Department of NeurologyLishui Hospital, Zhejiang University School of MedicineLishuiChina
| | - Xia Meng
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Aoming Jin
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Jinxi Lin
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Shan Li
- Cerebrovascular Research Lab, Lishui HospitalZhejiang University School of MedicineLishuiChina
| | - Hao Li
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
| | - Tiemin Wei
- Department of Cardiology, Lishui HospitalZhejiang University School of MedicineLishuiChina
| | - Yongjun Wang
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
- National Center for Neurological DiseasesBeijingChina
- Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijingChina
| | - Yilong Wang
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
- Chinese Institute for Brain ResearchBeijingChina
- National Center for Neurological DiseasesBeijingChina
- Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijingChina
- Beijing Laboratory of Oral HealthCapital Medical UniversityBeijingChina
| | - Yuesong Pan
- Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
- China National Clinical Research Center for Neurological DiseasesBeijingChina
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7
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Becetti I, Lauze M, Lee H, Bredella MA, Misra M, Singhal V. Changes in Branched-Chain Amino Acids One Year after Sleeve Gastrectomy in Youth with Obesity and Their Association with Changes in Insulin Resistance. Nutrients 2023; 15:3801. [PMID: 37686833 PMCID: PMC10489782 DOI: 10.3390/nu15173801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13-24 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.
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Affiliation(s)
- Imen Becetti
- Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA; (M.M.); (V.S.)
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Meghan Lauze
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Hang Lee
- Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Miriam A. Bredella
- Department of Radiology, Musculoskeletal Imaging and Interventions, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Madhusmita Misra
- Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA; (M.M.); (V.S.)
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Vibha Singhal
- Division of Pediatric Endocrinology, Mass General for Children and Harvard Medical School, Boston, MA 02114, USA; (M.M.); (V.S.)
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Pediatric Program, MGH Weight Center, Massachusetts General Hospital, Boston, MA 02114, USA
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8
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Livadas S, Paparodis R, Anagnostis P, Gambineri A, Bjekić-Macut J, Petrović T, Yildiz BO, Micić D, Mastorakos G, Macut D. Assessment of Type 2 Diabetes Risk in Young Women with Polycystic Ovary Syndrome. Diagnostics (Basel) 2023; 13:2067. [PMID: 37370962 PMCID: PMC10297688 DOI: 10.3390/diagnostics13122067] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
Women with polycystic ovary syndrome (PCOS) are at increased risk for dysglycemia and type 2 diabetes compared to healthy BMI-matched women of reproductive age: robust evidence exists supporting this notion. The presence of altered glycemic status in young women with the syndrome presents a distinct challenge for the clinician for several reasons. Firstly, the reported incidence of this disorder varies among the limited available studies. Furthermore, there is a lack of consensus on the best screening method, which women to screen, at what frequency, and which strategies need to be implemented to reduce the above risk. We provide data regarding the prevalence of dysglycemia in young women suffering from PCOS and the pathophysiological mechanisms underlying the disorder. In addition, we present evidence suggesting universal screening with the oral glucose tolerance test in young women with the syndrome, irrespective of age or BMI status, to identify and manage glycemic abnormalities in a timely manner. Regarding follow-up, oral glucose testing should be carried out at regular intervals if there are initial abnormal findings or predisposing factors. Finally, the efficacy of a well-balanced diet in conjunction with regular exercise and the use of non-pharmacologic agents in this specific population is discussed.
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Affiliation(s)
| | - Rodis Paparodis
- Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA;
| | - Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, 57429 Thessaloniki, Greece;
| | - Alessandra Gambineri
- Unit of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, 40138 Bologna, Italy;
| | - Jelica Bjekić-Macut
- Department of Endocrinology, UMC Bežanijska kosa, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Tijana Petrović
- Department of Endocrinology, UMC Bežanijska kosa, 11080 Belgrade, Serbia;
| | - Bulent O. Yildiz
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of Medicine, Ankara 06100, Turkey;
| | - Dragan Micić
- Department of Medical Sciences, Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia;
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Djuro Macut
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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9
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Huang B, Huang W, Allen JC, Sun L, Goh HJ, Kong SC, Lee D, Ding C, Bosco N, Egli L, Actis-Goretta L, Magkos F, Arigoni F, Leow MKS, Tan SY, Yeo KK. Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index. Front Nutr 2022; 9:979208. [PMID: 36352897 PMCID: PMC9639788 DOI: 10.3389/fnut.2022.979208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/23/2022] [Indexed: 11/20/2022] Open
Abstract
Background Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals. Methods A cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores. Results Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588–0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness. Conclusions The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.
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Affiliation(s)
- Benjamin Huang
- Singapore General Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- *Correspondence: Benjamin Huang
| | - Weiting Huang
- Singapore General Hospital, Singapore, Singapore
- National Heart Center Singapore, Singapore, Singapore
| | | | - Lijuan Sun
- Singapore Institute for Clinical Sciences, Singapore, Singapore
| | - Hui Jen Goh
- Singapore Institute for Clinical Sciences, Singapore, Singapore
| | | | - Dewaine Lee
- National Heart Center Singapore, Singapore, Singapore
| | - Cherlyn Ding
- Nestlé Institute of Health Sciences Singapore, Singapore, Singapore
| | - Nabil Bosco
- Nestlé Institute of Health Sciences Singapore, Singapore, Singapore
- Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
| | - Leonie Egli
- Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
| | | | | | - Fabrizio Arigoni
- Nestlé Institute of Health Sciences Singapore, Singapore, Singapore
| | - Melvin Khee-Shing Leow
- Duke-NUS Medical School, Singapore, Singapore
- Singapore Institute for Clinical Sciences, Singapore, Singapore
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Swee Yaw Tan
- National Heart Center Singapore, Singapore, Singapore
| | - Khung Keong Yeo
- Duke-NUS Medical School, Singapore, Singapore
- National Heart Center Singapore, Singapore, Singapore
- Khung Keong Yeo
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10
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Salvatori B, Linder T, Eppel D, Morettini M, Burattini L, Göbl C, Tura A. TyGIS: improved triglyceride-glucose index for the assessment of insulin sensitivity during pregnancy. Cardiovasc Diabetol 2022; 21:215. [PMID: 36258194 PMCID: PMC9580191 DOI: 10.1186/s12933-022-01649-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/28/2022] [Indexed: 11/21/2022] Open
Abstract
Background The triglyceride-glucose index (TyG) has been proposed as a surrogate marker of insulin resistance, which is a typical trait of pregnancy. However, very few studies analyzed TyG performance as marker of insulin resistance in pregnancy, and they were limited to insulin resistance assessment at fasting rather than in dynamic conditions, i.e., during an oral glucose tolerance test (OGTT), which allows more reliable assessment of the actual insulin sensitivity impairment. Thus, first aim of the study was exploring in pregnancy the relationships between TyG and OGTT-derived insulin sensitivity. In addition, we developed a new version of TyG, for improved performance as marker of insulin resistance in pregnancy. Methods At early pregnancy, a cohort of 109 women underwent assessment of maternal biometry and blood tests at fasting, for measurements of several variables (visit 1). Subsequently (26 weeks of gestation) all visit 1 analyses were repeated (visit 2), and a subgroup of women (84 selected) received a 2 h-75 g OGTT (30, 60, 90, and 120 min sampling) with measurement of blood glucose, insulin and C-peptide for reliable assessment of insulin sensitivity (PREDIM index) and insulin secretion/beta-cell function. The dataset was randomly split into 70% training set and 30% test set, and by machine learning approach we identified the optimal model, with TyG included, showing the best relationship with PREDIM. For inclusion in the model, we considered only fasting variables, in agreement with TyG definition. Results The relationship of TyG with PREDIM was weak. Conversely, the improved TyG, called TyGIS, (linear function of TyG, body weight, lean body mass percentage and fasting insulin) resulted much strongly related to PREDIM, in both training and test sets (R2 > 0.64, p < 0.0001). Bland–Altman analysis and equivalence test confirmed the good performance of TyGIS in terms of association with PREDIM. Different further analyses confirmed TyGIS superiority over TyG. Conclusions We developed an improved version of TyG, as new surrogate marker of insulin sensitivity in pregnancy (TyGIS). Similarly to TyG, TyGIS relies only on fasting variables, but its performances are remarkably improved than those of TyG. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01649-8.
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Affiliation(s)
| | - Tina Linder
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Daniel Eppel
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Micaela Morettini
- Department of Information Engineering, Università Politecnica Delle Marche, 60131, Ancona, Italy
| | - Laura Burattini
- Department of Information Engineering, Università Politecnica Delle Marche, 60131, Ancona, Italy
| | - Christian Göbl
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Andrea Tura
- CNR Institute of Neuroscience, Corso Stati Uniti 4, 35127, Padua, Italy.
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11
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Zhou M, Wang S, Jing J, Yang Y, Cai X, Meng X, Mei L, Lin J, Li S, Li H, Wei T, Wang Y, Pan Y, Wang Y. Insulin resistance based on postglucose load measure is associated with prevalence and burden of cerebral small vessel disease. BMJ Open Diabetes Res Care 2022; 10:10/5/e002897. [PMID: 36220196 PMCID: PMC9557259 DOI: 10.1136/bmjdrc-2022-002897] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/25/2022] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION Cerebral small vessel disease (cSVD) is highly prevalent and results in irreversible cognitive impairment and reduced quality of life. Previous studies reported controversial associations between insulin resistance and cSVD. Here, we estimated the association between insulin resistance and cSVD in non-diabetic communities in southeastern China. RESEARCH DESIGN AND METHODS The Polyvascular Evaluation for Cognitive Impairment and Vascular Events study (NCT03178448) recruited 3670 community-dwelling adults. We estimated the association of insulin resistance, assessed by the insulin sensitivity index (ISI0,120) and the homeostatic model assessment for insulin resistance (HOMA-IR) based on the standard oral glucose tolerance test, with cSVD in those without a history of diabetes mellitus. cSVD was measured for both main neuroimaging manifestations of cSVD and total SVD burden scores. RESULTS A total of 2752 subjects were enrolled. In the multivariable logistic regression analysis, the first quartile of ISI0,120 was found to be potentially associated with an increased risk of lacunes (OR 1.96, 95% CI 1.15 to 3.36), severe age-related white matter changes (OR 1.97, 95% CI 1.15 to 3.38), and higher total SVD burden (4-point scale: common OR (cOR) 1.34, 95% CI 1.04 to 1.72; 6-point scale: cOR 1.43, 95% CI 1.14 to 1.79). The associations between HOMA-IR and lacunes (OR 1.90, 95% CI 1.11 to 3.25) and the 4-point scale of total SVD burden (cOR 1.33, 95% CI 1.04 to 1.70) were also significant after adjustment for age, gender, medical history, and medications. However, the associations were not statistically significant after further adjustment for blood pressure/hypertension and body mass index (BMI). CONCLUSIONS A potential association was found between insulin resistance and cSVD, and the ISI0,120 index presented a greater association with increased risk of cSVD as compared with the HOMA-IR. However, these associations were greatly influenced by blood pressure and BMI.
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Affiliation(s)
- Mengyuan Zhou
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Suying Wang
- Cerebrovascular Research Lab, Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Jing Jing
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yingying Yang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xueli Cai
- Department of Neurology, Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Xia Meng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Lerong Mei
- Cerebrovascular Research Lab, Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Jinxi Lin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Shan Li
- Cerebrovascular Research Lab, Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Hao Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Tiemin Wei
- Department of Cardiology, Lishui Hospital, Zhejiang University School of Medicine, Lishui, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yilong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
- Chinese Institute for Brain Research, Beijing, China
- National Center for Neurological Diseases, Beijing, China
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12
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Gastaldelli A. Measuring and estimating insulin resistance in clinical and research settings. Obesity (Silver Spring) 2022; 30:1549-1563. [PMID: 35894085 PMCID: PMC9542105 DOI: 10.1002/oby.23503] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 03/27/2022] [Accepted: 04/21/2022] [Indexed: 11/29/2022]
Abstract
The article discusses how to measure insulin resistance in muscle, liver, and adipose tissue in human participants. The most frequently used methodologies to evaluate insulin resistance are described in detail starting from the gold standard, that is, the euglycemic hyperinsulinemic clamp, to the intravenous glucose tolerance test, surrogate indices based on fasting measurements, or dynamic tests (such as oral glucose or mixed meal tolerance tests). The accuracy, precision, and reproducibility of the tests as well as cutoff values are reported.
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Affiliation(s)
- Amalia Gastaldelli
- National Research Council (CNR)Institute of Clinical Physiology (IFC)PisaItaly
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13
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Ramesh G, Wood AC, Allison MA, Rich SS, Jensen ET, Chen YDI, Rotter JI, Bertoni AG, Goodarzi MO. Associations between adherence to the dietary approaches to stop hypertension (DASH) diet and six glucose homeostasis traits in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Nutr Metab Cardiovasc Dis 2022; 32:1418-1426. [PMID: 35459606 PMCID: PMC9167769 DOI: 10.1016/j.numecd.2022.03.014] [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: 10/14/2021] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components. METHODS AND RESULTS We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) yielded fasting plasma glucose, insulin, C-peptide, and insulin secretion, sensitivity, and disposition index. Habitual dietary intake was assessed by food frequency questionnaire (FFQ). Associations between DASH components and glucose homeostasis traits were examined, controlling for demographics, body mass index (BMI), physical activity, and energy intake. For significant associations, the models were repeated with scores for DASH-P and DASH-NP as predictors in the same model. DASH and DASH-P scores were inversely associated with fasting plasma glucose (DASH:β = -0.036 ± 0.012,P = 0.005; DASH-P: β = -0.04 ± 0.017,P = 0.002), and positively associated with insulin sensitivity (DASH:β = 0.022 ± 0.012,P = 0.042; DASH-P: = 0.036 ± 0.015,P = 0.014). The DASH score was also associated with disposition index (β = 0.026 ± 0.013,P = 0.038), but this association did not reach significance with DASH-P (β = 0.035 ± 0.018,P = 0.051). No associations were observed with DASH-NP score (all P > 0.05). CONCLUSIONS DASH diet is associated with improvement in specific glucose homeostasis traits, likely arising from increased plant-based foods. Such research may help tailor future dietary advice to specific metabolic risk, and to food groups most effective at improving these.
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Affiliation(s)
- Gautam Ramesh
- School of Medicine, University of California, San Diego, La Jolla, CA, 92037, USA
| | - Alexis C Wood
- USDA/ARS Children's Nutrition Research Center, 1100 Bates Avenue, Houston, TX, 77071, USA.
| | - Matthew A Allison
- Division of Preventive Medicine, Department of Family Medicine, University of California, San Diego, La Jolla, CA, 92037, USA
| | - Stephen S Rich
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA
| | - Elizabeth T Jensen
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Yii-Der I Chen
- Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA
| | - Jerome I Rotter
- Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA
| | - Alain G Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Mark O Goodarzi
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
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14
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Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring. Int J Mol Sci 2022; 23:ijms23020999. [PMID: 35055185 PMCID: PMC8780605 DOI: 10.3390/ijms23020999] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/03/2022] [Accepted: 01/06/2022] [Indexed: 11/16/2022] Open
Abstract
Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.
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15
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Livadas S, Anagnostis P, Bosdou JK, Bantouna D, Paparodis R. Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review. World J Diabetes 2022; 13:5-26. [PMID: 35070056 PMCID: PMC8771268 DOI: 10.4239/wjd.v13.i1.5] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 06/30/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.
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Affiliation(s)
| | - Panagiotis Anagnostis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
| | - Julia K Bosdou
- Unit for Human Reproduction, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki 54636, Greece
| | - Dimitra Bantouna
- Department of Pathology and Cytology, University of Patras School of Medicine, Patras 10563, Greece
| | - Rodis Paparodis
- Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, OH 23456, United States
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16
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Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control. Pharmaceuticals (Basel) 2021; 14:ph14080817. [PMID: 34451914 PMCID: PMC8398280 DOI: 10.3390/ph14080817] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/10/2021] [Accepted: 08/17/2021] [Indexed: 12/14/2022] Open
Abstract
The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20–30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.
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17
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Lechner K, Lechner B, Crispin A, Schwarz PEH, von Bibra H. Waist-to-height ratio and metabolic phenotype compared to the Matsuda index for the prediction of insulin resistance. Sci Rep 2021; 11:8224. [PMID: 33859227 PMCID: PMC8050044 DOI: 10.1038/s41598-021-87266-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 03/09/2021] [Indexed: 02/06/2023] Open
Abstract
Current screening algorithms for type 2 diabetes (T2D) rely on fasting plasma glucose (FPG) and/or HbA1c. This fails to identify a sizeable subgroup of individuals in early stages of metabolic dysregulation who are at high risk for developing diabetes or cardiovascular disease. The Matsuda index, a combination of parameters derived from a fasting and postprandial insulin assay, is an early biomarker for metabolic dysregulation (i.e. insulin resistance/compensatory hyperinsulinemia). The aim of this analysis was to compare four widely available anthropometric and biochemical markers indicative of this condition [waist-to-height ratio (WHtR), hypertriglyceridemic-waist phenotype (HTW), triglycerides-to-HDL-C ratio (TG/HDL-C) and FPG] to the Matsuda index. This cross-sectional analysis included 2231 individuals with normal fasting glucose (NFG, n = 1333), impaired fasting glucose (IFG, n = 599) and T2D (n = 299) from an outpatient diabetes clinic in Germany and thus extended a prior analysis from our group done on the first two subgroups. We analyzed correlations of the Matsuda index with WHtR, HTW, TG/HDL-C and FPG and their predictive accuracies by correlation and logistic regression analyses and receiver operating characteristics. In the entire group and in NFG, IFG and T2D, the best associations were observed between the Matsuda index and the WHtR (r = - 0.458), followed by HTW phenotype (r = - 0.438). As for prediction accuracy, WHtR was superior to HTW, TG/HDL-C and FPG in the entire group (AUC 0.801) and NFG, IFG and T2D. A multivariable risk score for the prediction of insulin resistance was tested and demonstrated an area under the ROC curve of 0.765 for WHtR and its interaction with sex as predictor controlled by age and sex. The predictive power increased to 0.845 when FPG and TG/HDL-C were included. Using as a comparator the Matsuda index, WHtR, compared to HTW, TG/HDL-C and FPG, showed the best predictive value for detecting metabolic dysregulation. We conclude that WHtR, a widely available anthropometric index, could refine phenotypic screening for insulin resistance/hyperinsulinemia. This may ameliorate early identification of individuals who are candidates for appropriate therapeutic interventions aimed at addressing the twin epidemic of metabolic and cardiovascular disease in settings where more extended testing such as insulin assays are not feasible.
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Affiliation(s)
- Katharina Lechner
- Kardiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
| | - Benjamin Lechner
- Department of Internal Medicine IV, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Alexander Crispin
- Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Peter E H Schwarz
- Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus, TU, Dresden, Germany
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany
- German Center for Diabetes Research (DZD E.V.), Neuherberg, Germany
| | - Helene von Bibra
- Technical University of Munich, Stelznerstr. 7, 81479, Munich, Germany.
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18
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Mather KJ, Tjaden AH, Hoehn A, Nadeau KJ, Buchanan TA, Kahn SE, Arslanian SA, Caprio S, Atkinson KM, Cree-Green M, Utzschneider KM, Edelstein SL. Precision and accuracy of hyperglycemic clamps in a multicenter study. Am J Physiol Endocrinol Metab 2021; 320:E797-E807. [PMID: 33645253 PMCID: PMC8238133 DOI: 10.1152/ajpendo.00598.2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements. Clamp operators received initial and repeated training with ongoing feedback based on surveillance of clamp performance. The precision and accuracy of the achieved stage-specific glucose targets were evaluated, including differences by study center. We also evaluated robustness of the method to baseline physiologic differences and on-study treatment effects. The RISE approach produced high overall precision (3%-9% variance in achieved plasma glucose from target at various times across the procedure) and accuracy (SD < 10% overall). Statistically significant but numerically small differences in achieved target glucose concentrations were observed across study centers, within the magnitude of the observed technical variability. Variation of the achieved target glucose over time in placebo-treated individuals was low (<3% variation), and the method was robust to differences in baseline physiology (youth vs. adult, IGT vs. diabetes status) and differences in physiology induced by study treatments. The RISE approach to standardization of the hyperglycemic clamp methodology across multiple study centers produced technically excellent standardization of achieved glucose concentrations. This approach provides a reliable method for implementing glucose clamp methodology across multiple study centers.NEW & NOTEWORTHY The Restoring Insulin Secretion (RISE) study centers undertook hyperglycemic clamps using a simplified methodology and a decision guidance algorithm implemented in an easy-to-use spreadsheet. This approach, combined with active management including ongoing central data surveillance and routine feedback to study centers, produced technically excellent standardization of achieved glucose concentrations on repeat studies within and across study centers.
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Affiliation(s)
- Kieren J Mather
- Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana
| | - Ashley H Tjaden
- The Biostatistics Center, Milken Institute School of Public Health, George Washington University, Washington, DC
| | - Adam Hoehn
- College of Osteopathic Medicine, Marian University, Indianapolis, Indiana
| | - Kristen J Nadeau
- Department of Pediatrics, School of Medicine, University of Colorado Denver, Colorado
| | - Thomas A Buchanan
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Steven E Kahn
- Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, Washington
| | - Silva A Arslanian
- Department of Pediatrics, School of Medicine, University of Pittsburgh, Pennsylvania
| | - Sonia Caprio
- Department of Pediatrics, School of Medicine, Yale University, New Haven, Connecticut
| | - Karen M Atkinson
- Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, Washington
| | - Melanie Cree-Green
- Department of Pediatrics, School of Medicine, University of Colorado Denver, Colorado
| | - Kristina M Utzschneider
- Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, Washington
| | - Sharon L Edelstein
- The Biostatistics Center, Milken Institute School of Public Health, George Washington University, Washington, DC
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19
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Smetanina N, Valickas R, Vitkauskiene A, Albertsson-Wikland K, Verkauskienė R. Prevalence of Metabolic Syndrome and Impaired Glucose Metabolism among 10- to 17-Year-Old Overweight and Obese Lithuanian Children and Adolescents. Obes Facts 2021; 14:271-282. [PMID: 33951670 PMCID: PMC8255643 DOI: 10.1159/000514720] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 01/19/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Overweight (Ow) and obesity among adults and children increases the risk of metabolic consequences. Metabolic syndrome (MS) and impaired glucose metabolism are well-known risk factors for cardiovascular diseases and type 2 diabetes. The aim of this study was to evaluate the prevalence of MS and impaired glucose metabolism among Ow and obese (Ob) children and adolescents (aged 10-17 years) in Lithuania, and to evaluate the associations between insulin resistance (IR) indices and anthropometric parameters as well as metabolic disturbances. METHODS The study population consisted of 344 OwOb children and adolescents of all pubertal stages. Oral glucose tolerance tests (OGTTs), IR and β cell function indices, lipid profile, and anthropometric parameters of all subjects were analyzed. MS was defined according to the International Diabetes Federation consensus guidelines. RESULTS MS was found in 21.3% of the OwOb children and adolescents, and 12.1% had impaired glucose metabolism (6.9% with impaired fasting glucose, 4.5% with impaired glucose tolerance, and 0.6% with type 2 diabetes). IR was directly related to body mass index and waist circumference, waist-to-height and waist-to-hip ratios, and sum of skin-fold thicknesses. Children with MS were more insulin-resistant, had higher odds ratio for prediabetes and had a more disturbed lipid profile than subjects without MS. Moreover, total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the more mature OwOb adolescents. CONCLUSION MS and lipid profile disturbances are common in OwOb children and adolescents. MS is directly associated with IR. Therefore, OwOb children and adolescents should be carefully followed up for metabolic abnormalities during late childhood as these can persist into adulthood.
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Affiliation(s)
- Natalija Smetanina
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
- *Natalija Smetanina,
| | - Raimondas Valickas
- Department of Radiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Astra Vitkauskiene
- Department of Laboratory Medicine, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Kerstin Albertsson-Wikland
- Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Rasa Verkauskienė
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
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20
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Ennis GE, Saelzler U, Umpierrez GE, Moffat SD. Prediabetes and working memory in older adults. Brain Neurosci Adv 2020; 4:2398212820961725. [PMID: 33088921 PMCID: PMC7545783 DOI: 10.1177/2398212820961725] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/30/2020] [Indexed: 12/21/2022] Open
Abstract
Insulin sensitivity, pancreatic β-cell function, fasting glucose, and 2-h post-load glucose were related to cognition in cognitively healthy nondiabetic older adults. Thirty-five adults (⩾65 years) underwent a 2-h oral glucose tolerance test and cognitive testing. Seventeen had normal glucose tolerance and 18 had intermediate hyperglycaemia or prediabetes (World Health Organization criteria). Fasting glucose and 2-h post-load glucose and oral glucose tolerance test–derived measures of β-cell function (oral disposition index) and insulin sensitivity were analysed as predictors of four cognitive domains: verbal episodic memory, verbal fluency, executive function, and working memory. The prediabetes group had significantly worse working memory performance than the normal glucose tolerance group. Controlling for age and education, decreased oral disposition index, and increased 2-h post-load glucose were significantly related to worse working memory performance. Prediabetes may worsen working memory in healthy older adults. Reduced pancreatic β-cell function should be investigated as a contributor to age-related cognitive decline.
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Affiliation(s)
- Gilda E Ennis
- School of Psychology, College of Sciences, Georgia Institute of Technology, Atlanta, GA, USA.,Division of Geriatrics and Gerontology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Ursula Saelzler
- School of Psychology, College of Sciences, Georgia Institute of Technology, Atlanta, GA, USA
| | - Guillermo E Umpierrez
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA
| | - Scott D Moffat
- School of Psychology, College of Sciences, Georgia Institute of Technology, Atlanta, GA, USA
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21
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Insulin sensitivity in male sheep born to ewes treated with testosterone during pregnancy. J Dev Orig Health Dis 2020; 12:456-464. [PMID: 32662387 DOI: 10.1017/s2040174420000665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
In animal models, exposure to excess testosterone during gestation induces polycystic ovary syndrome (PCOS)-like reproductive and metabolic traits in female offspring, suggesting that the hyperandrogenemic intrauterine environment may have a role in the etiology of PCOS. Additionally, few studies have also addressed metabolic and reproductive outcomes in male offspring. In the present study, the intravenous glucose tolerance test (IGTT) was used to assess the insulin-glucose homeostasis at various ages during sexual development in male sheep born to testosterone-treated ewes. To further analyze the programming effect of testosterone on insulin-glucose homeostasis, indexes of insulin sensitivity were assessed in orchidectomized post-pubertal males born to testosterone-treated ewes (Torq-males) and orchidectomized post-puberal controls (Corq-males) before and 48 h after a testosterone injection. There was no difference in insulin sensitivity indexes between males born to testosterone-treated ewes (T-males) and control males born to control ewes (C-males) at 5, 10, 20 and 30 weeks of age, representing the infantile, early and late pre-pubertal, and early post-pubertal stage of sexual development, respectively. In orchidectomized males, basal levels of insulin and glucose were not different between both groups before and after the testosterone injection; however, Torq-males released more insulin before and after T challenge during the first 20 min of the test. Despite this, plasma glucose concentrations were not different in both groups during IVGTT, resulting in an insulin sensitivity index composite similar between groups. We concluded that the effect of prenatal exposure to excess testosterone may reprogram the pancreatic β-cells insulin release in ovine males, with effects more evident in castrated males versus intact males.
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22
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Mayerhofer E, Ratzinger F, Kienreich NE, Stiel A, Witzeneder N, Schrefl E, Greiner G, Wegscheider C, Graf I, Schmetterer K, Marculescu R, Szekeres T, Perkmann T, Fondi M, Wagner O, Esterbauer H, Mayerhofer M, Holocher-Ertl S, Wojnarowski C, Hoermann G. A Multidisciplinary Intervention in Childhood Obesity Acutely Improves Insulin Resistance and Inflammatory Markers Independent From Body Composition. Front Pediatr 2020; 8:52. [PMID: 32154197 PMCID: PMC7047334 DOI: 10.3389/fped.2020.00052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 02/03/2020] [Indexed: 12/21/2022] Open
Abstract
Childhood obesity is an increasing health care problem associated with insulin resistance and low-level systemic inflammation, which can ultimately lead to diabetes. Evidence for efficacy of therapeutic intervention programs on the early development of obesity associated sequelae is moderate. This paper investigates the effect of a multidisciplinary short-term intervention program on insulin resistance and metaflammation in childhood obesity. Two hundred and 36 overweight or obese children and adolescents between the ages of 10 and 14 were included in a prospective 5 months intervention study, which included sports, psychotherapy, and nutritional counseling. Primary endpoints were the effects on body mass index standard deviation score (BMI-SDS) and homeostatic model assessment of insulin resistance (HOMA-IR), key secondary endpoints were the levels of C-reactive protein (CRP), leptin, and adiponectin. At baseline, a substantial proportion of participants showed signs of insulin resistance (mean HOMA-IR 5.5 ± 3.4) despite not meeting the diagnostic criteria for diabetes, and low-level inflammation (mean CRP 3.9 mg/l ± 3.8 mg/l). One hundred and 95 participants (83%) completed the program resulting in a significant reduction in BMI-SDS, HOMA-IR, CRP, and leptin and a significant increase in adiponectin (mean change compared to baseline -0.14, -0.85, -1.0 mg/l, -2.8 ng/ml, and 0.5 μg/ml, respectively; p < 0.001 each). Effects on BMI-SDS, HOMA-IR, CRP, and adiponectin were largely independent whereas leptin was positively correlated with BMI-SDS and total fat mass before and after intervention (r = 0.56 and 0.61, p < 0.001 each). Short-term multidisciplinary intervention successfully improved body composition, insulin sensitivity, low-level systemic inflammation, and the adipokine profile in childhood obesity. Our findings highlight the immediate connection between obesity and the pathophysiology of its sequelae, and emphasize the importance of early intervention. Continued lifestyle modification is likely necessary to consolidate and augment the long-term effects.
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Affiliation(s)
- Ernst Mayerhofer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.,Department of Neurology and Neurophysiology, Medical Center, University of Freiburg, Freiburg, Germany
| | - Franz Ratzinger
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Annika Stiel
- Austrian Social Health Insurance Fund, Vienna, Austria
| | - Nadine Witzeneder
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Eva Schrefl
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.,FH Wien, University of Applied Sciences, Vienna, Austria
| | - Georg Greiner
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Irene Graf
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.,Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Klaus Schmetterer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Rodrig Marculescu
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Szekeres
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Martina Fondi
- FH Wien, University of Applied Sciences, Vienna, Austria
| | - Oswald Wagner
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Harald Esterbauer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Stefana Holocher-Ertl
- Psychology Institute of the University Outpatient Department for Children and Adolescents, Sigmund Freud Private University, Vienna, Austria
| | | | - Gregor Hoermann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.,Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Innsbruck, Innsbruck, Austria
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23
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Smith EVL, Dyson RM, Berry MJ, Gray C. Fructose Consumption During Pregnancy Influences Milk Lipid Composition and Offspring Lipid Profiles in Guinea Pigs. Front Endocrinol (Lausanne) 2020; 11:550. [PMID: 32849314 PMCID: PMC7431635 DOI: 10.3389/fendo.2020.00550] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 07/06/2020] [Indexed: 12/31/2022] Open
Abstract
Excess dietary fructose is a major public health concern (1-4). Evidence shows increased fructose intake can cause insulin resistance, hepatic de novo lipogenesis, hypertriglyceridemia, obesity and non-alcoholic fatty liver disease (NAFLD) (5-9). However, little is known about the effects of fructose during pregnancy and its influence on offspring development and predisposition to later-life disease. To determine whether moderately increased maternal fructose intake could have health consequences on offspring, we have investigated the effects of 10% w/v fructose water intake during preconception and pregnancy. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD;10% kcal from fructose) ad-libitum 60 days prior to mating and throughout gestation. Offspring were culled at weaning, day 21 (d21). Compared to CD dams, FD dams had altered glucose metabolism and increased milk free fatty acid content. Matsuda-DeFronzo insulin sensitivity index (M-ISI) from OGTT plasma showed no significant difference in whole-body insulin sensitivity between FD and CD dams 60 days post-dietary intervention and during midgestation. Fetal exposure to increased maternal fructose resulted in offspring with significantly altered serum free fatty acids at days 0, 7, 14, and 21 [including pentadecanoic acid (15:0), dma16:0, margaric acid (17:0) palmitoleic acid, total omega-7 and total saturates], increased levels of uric acid and triglycerides were also observed at d21. We have demonstrated that increased fructose intake during pregnancy can cause significant changes in maternal metabolic function and milk composition, which alters offspring metabolism. Taken together, these changes in pregnancy outcomes and feto-maternal condition may underlie their offspring's predisposition to metabolic dysfunction during later-life.
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Affiliation(s)
- Erin Vanessa LaRae Smith
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
- Centre for Translational Physiology, University of Otago, Wellington, New Zealand
| | - Rebecca Maree Dyson
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
- Centre for Translational Physiology, University of Otago, Wellington, New Zealand
| | - Mary Judith Berry
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
- Centre for Translational Physiology, University of Otago, Wellington, New Zealand
| | - Clint Gray
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
- Centre for Translational Physiology, University of Otago, Wellington, New Zealand
- *Correspondence: Clint Gray
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24
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Zhu Z, Cao F, Li X. Epigenetic Programming and Fetal Metabolic Programming. Front Endocrinol (Lausanne) 2019; 10:764. [PMID: 31849831 PMCID: PMC6901800 DOI: 10.3389/fendo.2019.00764] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 10/21/2019] [Indexed: 12/30/2022] Open
Abstract
Fetal metabolic programming caused by the adverse intrauterine environment can induce metabolic syndrome in adult offspring. Adverse intrauterine environment introduces fetal long-term relatively irreversible changes in organs and metabolism, and thus causes fetal metabolic programming leading metabolic syndrome in adult offspring. Fetal metabolic programming of obesity and insulin resistance plays a key role in this process. The mechanism of fetal metabolic programming is still not very clear. It is suggested that epigenetic programming, also induced by the adverse intrauterine environment, is a critical underlying mechanism of fetal metabolic programming. Fetal epigenetic programming affects gene expression changes and cellular function through epigenetic modifications without DNA nucleotide sequence changes. Epigenetic modifications can be relatively stably retained and transmitted through mitosis and generations, and thereby induce the development of metabolic syndrome in adult offspring. This manuscript provides an overview of the critical role of epigenetic programming in fetal metabolic programming.
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Affiliation(s)
- Ziqiang Zhu
- Children's Hospital of Soochow University, Suzhou, China
- Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University, Changzhou, China
| | - Fang Cao
- Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University, Changzhou, China
| | - Xiaozhong Li
- Children's Hospital of Soochow University, Suzhou, China
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25
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Newman AA, Grimm NC, Wilburn JR, Schoenberg HM, Trikha SRJ, Luckasen GJ, Biela LM, Melby CL, Bell C. Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training. J Clin Endocrinol Metab 2019; 104:1953-1966. [PMID: 30597042 DOI: 10.1210/jc.2018-01741] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 12/21/2018] [Indexed: 12/11/2022]
Abstract
CONTEXT The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.
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Affiliation(s)
- Alissa A Newman
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - Nathan C Grimm
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - Jessie R Wilburn
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - Hayden M Schoenberg
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - S Raj J Trikha
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - Gary J Luckasen
- Medical Center of the Rockies Foundation, University of Colorado Health, Loveland, Colorado
| | - Laurie M Biela
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
| | - Christopher L Melby
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado
| | - Christopher Bell
- Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado
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26
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Rosenbaum M, Hall KD, Guo J, Ravussin E, Mayer LS, Reitman ML, Smith SR, Walsh BT, Leibel RL. Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet. Obesity (Silver Spring) 2019; 27:971-981. [PMID: 31067015 PMCID: PMC6922028 DOI: 10.1002/oby.22468] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 02/22/2019] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The objective of this study was to measure changes in glucose, lipid, and inflammation parameters after transitioning from a baseline diet (BD) to an isocaloric ketogenic diet (KD). METHODS Glucose homeostasis, lipid homeostasis, and inflammation were studied in 17 men (BMI: 25-35 kg/m2 ) during 4 weeks of a BD (15% protein, 50% carbohydrate, 35% fat) followed by 4 weeks of an isocaloric KD (15% protein, 5% carbohydrate, 80% fat). Postprandial responses were assessed following mixed-meal tests matched to compositions of the BD (control meal [CM]) and KD (ketogenic meal). RESULTS Fasting ketones, glycerol, free fatty acids, glucagon, adiponectin, gastric inhibitory peptide, total and low-density lipoprotein cholesterol, and C-reactive protein were significantly increased on the KD. Fasting insulin, C-peptides, triglycerides, and fibroblast growth factor 21 were significantly decreased. During the KD, the glucose area under the curve was significantly higher with both test meals, and the insulin area under the curve was significantly higher only for the CM. Analyses of glucose homeostasis suggested that the KD insulin sensitivity decreased during the CM but increased during the ketogenic meal. Insulin-mediated antilipolysis was decreased on the KD regardless of meal type. CONCLUSIONS Switching to the KD was associated with increased cholesterol and inflammatory markers, decreased triglycerides, and decreased insulin-mediated antilipolysis. Glucose homeostasis parameters were diet dependent and test meal dependent.
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Affiliation(s)
- Michael Rosenbaum
- Departments of Pediatrics and Medicine, Division of Molecular Genetics, Columbia University Irving Medical Center, New York, New York, USA
| | - Kevin D Hall
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Juen Guo
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
| | - Laurel S Mayer
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, New York, USA
| | - Marc L Reitman
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Steven R Smith
- The Translational Research Institute for Metabolism and Diabetes, Orlando, Florida, USA
| | - B Timothy Walsh
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, New York, USA
| | - Rudolph L Leibel
- Departments of Pediatrics and Medicine, Division of Molecular Genetics, Columbia University Irving Medical Center, New York, New York, USA
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27
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Kwon J, Kim W, Lee SA, Choi D, Park EC. Effects of different types and frequencies of physical activity on the homeostatic model assessment of insulin resistance. J Investig Med 2019; 67:841-849. [PMID: 30659090 DOI: 10.1136/jim-2018-000885] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2018] [Indexed: 01/01/2023]
Abstract
This study analyzed the type and frequency of physical activity that most effectively reduces the homeostatic model assessment of insulin resistance (HOMA2-IR) among adults (≥19 years) in Asia. We used national representative data from 1645 men and 2272 women who participated in the Korea National Health and Nutrition Examination Survey in 2015 were included in the analysis. The effects of different types and frequencies of physical activity on HOMA2-IR were investigated using a multiple regression analysis. Compared with no activity, moderate-to-vigorous physical activity (MVPA) ≥5 times per week (β: -0.214, p≤0.0198) and walking and MVPA ≥5 times per week (β: -0.183, p≤0.0049) were negatively associated with HOMA2-IR. In the subgroup analysis, the strongest effect was observed among overweight men. Additionally, walking plus MVPA ≥5 times per week had the strongest effect on men with a higher-than-recommended daily calorie intake (β: -0.350, p≤0.0030). Therefore, in conclusion, the appropriate type and frequency of physical activity can help reduce HOMA2-IR in South Korean men, especially those who are overweight and/or have a higher-than-recommended daily calorie intake.
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Affiliation(s)
- Junhyun Kwon
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Woorim Kim
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Sang Ah Lee
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Dongwoo Choi
- Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea
| | - Eun-Cheol Park
- Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea.,Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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28
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Cree-Green M, Cai N, Thurston JE, Coe GV, Newnes L, Garcia-Reyes Y, Baumgartner AD, Pyle L, Nadeau KJ. Using simple clinical measures to predict insulin resistance or hyperglycemia in girls with polycystic ovarian syndrome. Pediatr Diabetes 2018; 19:1370-1378. [PMID: 30246333 PMCID: PMC6400639 DOI: 10.1111/pedi.12778] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 08/09/2018] [Accepted: 09/09/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Polycystic ovarian syndrome (PCOS) includes insulin resistance (IR) and impaired glucose tolerance (IGT) in youth, and a greatly elevated risk of type 2 diabetes in adulthood. Identifying IR is challenging and documenting IGT requires an oral glucose tolerance test (OGTT). OBJECTIVE Identify easily applied surrogate measures for IR and IGT in girls with PCOS. METHODS We studied 28 girls with PCOS (body mass index [BMI] percentile 98 (83.99); 15.5 (14.5,16.6) years of age) and 20 with normal menses [BMI percentile (97 (88.99); 15.5 (13.3,16.1) years]. Hyperinsulinemic-euglycemic clamps (insulin dose of 80 μU/ml/min) to determine glucose infusion rate (GIR) and a 75 g OGTT were performed. Surrogates for IR including fasting insulin, homeostatic model assessment-insulin resistant (HOMA-IR), Matsuda index, and estimate of insulin sensitivity (e-IS) were compared to IGT status and GIR. Spearman correlations were performed between surrogates and GIR or IGT, and receiver operator curve (ROC) analysis to predict GIR below the median or IGT status. RESULTS GIR was lower in PCOS (12.9 ± 4.6 vs 17.1 ± 5.1 mg/kg fat-free mass·min; P = 0.01). Within PCOS, HOMA-IR (r = -0.78, P < 0.0001), e-IS (r = 0.70, P < 0.001), and Matsuda (r = 0.533, P < 0.001) correlated with GIR. e-IS provided a good sensitivity (100%) and specificity (71%) to identify IR (e-IS cutoff: <6.3, ROC-area under curve = 0.898). Fasting insulin >22 IU/mL had the best sensitivity (88%), specificity (78%), and ROC (0.760) for IGT status. CONCLUSIONS Girls with PCOS have significant IR, and IGT is common. Both e-IS and fasting insulin are obtainable without an OGTT or clamp and could be used clinically to guide treatment in PCOS.
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Affiliation(s)
- Melanie Cree-Green
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO.,Center for Women’s Health Research, Aurora, CO
| | - Ninghe Cai
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Jessica E. Thurston
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | - Gregory V. Coe
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Lindsay Newnes
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Yesenia Garcia-Reyes
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Amy D. Baumgartner
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Laura Pyle
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO,Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO
| | - Kristen J. Nadeau
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO.,Center for Women’s Health Research, Aurora, CO
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29
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Zhou W, Ye S. Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy. Cell Biol Int 2018; 42:1282-1291. [PMID: 29908010 DOI: 10.1002/cbin.11015] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 05/27/2018] [Indexed: 12/11/2022]
Abstract
Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This study aimed to explore the effects of rapamycin, a specific inhibitor of kinase mammalian target of rapamycin (mTOR), on IR in T2DM rats, and to validate whether the underlying mechanism was associated with autophagy. In this study, the model of T2DM rats was established by feeding the animals with a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). Diabetic rats were randomly divided into model of T2DM control group (DM-C, n = 15), metformin group (DM-M, n = 15), rapamycin group (DM-Rapa, n = 15), 3-methyladenine (3-MA) group (DM-3-MA, n = 15), and rapamycin + 3-MA group (DM-Rapa-3-MA, n = 15). Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile, normal control group was established (n = 10). As expected, HFD- and STZ- induced T2DM rats exhibited significantly impaired glucose tolerance, reduced insulin sensitivity, dysglycemia and dyslipidemia, aggravated hepatic steatosis, enhanced hepatic inflammation, elevated p-mTOR, and suppressed hepatic autophagy. Importantly, rapamycin and metformin significantly ameliorated IR, relieved disorders of glucose and lipid metabolism, reduced inflammatory level, inhibited mTOR, and promoted autophagy. Importantly, the autophagy inhibitor 3-MA significantly reversed the effects exerted by rapamycin. Collectively, our study suggests that rapamycin improved IR and hepatic steatosis in T2DM rats via activation of autophagy.
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Affiliation(s)
- Wan Zhou
- Department of Endocrinology, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei, Anhui 230001, China
| | - Shandong Ye
- Department of Endocrinology, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei, Anhui 230001, China
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30
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Wang J, Yan R, Wen J, Kong X, Li H, Zhou P, Zhu H, Su X, Ma J. Association of lower body mass index with increased glycemic variability in patients with newly diagnosed type 2 diabetes: a cross-sectional study in China. Oncotarget 2017; 8:73133-73143. [PMID: 29069856 PMCID: PMC5641199 DOI: 10.18632/oncotarget.17111] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 04/03/2017] [Indexed: 01/19/2023] Open
Abstract
Previous studies have indicated that the pathogenesis of diabetes differs between obese and lean patients. We investigated whether newly diagnosed Chinese diabetic patients with different body mass indices (BMIs) have different glycemic variability, and we assessed the relationship between BMI and glycemic variability. This was a cross-sectional study that included 169 newly diagnosed and drug-naïve type 2 diabetic patients (mean age, 51.33 ± 9.83 years; 110 men). The clinical factors and results of the 75-g oral glucose tolerance test were all recorded. Glycemic variability was assessed using continuous glucose monitoring. Compared with overweight or obese patients (BMI ≥ 24 kg/m2), underweight or normal-weight patients (BMI < 24 kg/m2) had higher levels of blood glucose fluctuation parameters, particularly in terms of mean amplitude of glycemic excursion (MAGE 6.64 ± 2.38 vs. 5.67 ± 2.05; P = 0.007) and postprandial glucose excursions (PPGEs) (PPGE at breakfast, 7.72 ± 2.79 vs. 6.79 ± 2.40, P = 0.028; PPGE at lunch, 5.53 ± 2.70 vs. 5.07 ± 2.40, P = 0.285; PPGE at dinner, 5.96 ± 2.24 vs. 4.87 ± 2.50, P = 0.008). BMI was negatively correlated with glycemic variability (r = -0.243, P = 0.002). On multiple linear regression analyses, BMI (β = -0.231, P = 0.013) and Insulin Secretion Sensitivity Index-2 (β = -0.204, P = 0.048) were two independent predictors of glycemic variability. In conclusion, lower BMI was associated with increased glycemic variability, characterized by elevated PPGEs, in newly diagnosed Chinese type 2 diabetic patients.
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Affiliation(s)
- Jian Wang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Rengna Yan
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Juan Wen
- Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Xiaocen Kong
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Huiqin Li
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Peihua Zhou
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Honghong Zhu
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaofei Su
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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31
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Westwood S, Liu B, Baird AL, Anand S, Nevado-Holgado AJ, Newby D, Pikkarainen M, Hallikainen M, Kuusisto J, Streffer JR, Novak G, Blennow K, Andreasson U, Zetterberg H, Smith U, Laakso M, Soininen H, Lovestone S. The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology. ALZHEIMERS RESEARCH & THERAPY 2017; 9:31. [PMID: 28441961 PMCID: PMC5405532 DOI: 10.1186/s13195-017-0258-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 03/24/2017] [Indexed: 01/26/2023]
Abstract
Background Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer’s disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD. Methods Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE ε4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland. CSF AD biomarkers (amyloid β-peptide (Aβ), total tau and tau phosphorylated at the Thr181 epitope) were examined with respect to IR. Targeted proteomics using ELISA and Luminex xMAP assays were performed to assess the influence of IR on previously identified CSF and plasma protein biomarker candidates of AD pathology. Furthermore, CSF and plasma SOMAscan was performed to discover proteins that associate with IR and CSF AD biomarkers. Results CSF AD biomarkers did not differ between IR and non-IR groups, although plasma insulin correlated with CSF Aβ/tau across the whole cohort. In total, 200 CSF and 487 plasma proteins were differentially expressed between IR and non-IR subjects, and significantly enriched pathways, many of which have been previously implicated in AD, were identified. CSF and plasma proteins significantly associated with CSF AD biomarkers were also discovered, and those sensitive to both IR and AD were identified. Conclusions These data indicate that IR is not directly related to the level of CSF AD pathology in cognitively healthy men. Proteins that associated with both AD and IR are potential markers indicative of shared pathology. Electronic supplementary material The online version of this article (doi:10.1186/s13195-017-0258-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sarah Westwood
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK
| | - Benjamine Liu
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK
| | - Alison L Baird
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK
| | - Sneha Anand
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK
| | | | - Danielle Newby
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK
| | - Maria Pikkarainen
- Institute of Clinical Medicine, Neurology, University of Eastern Finland, 70211, Kuopio, Finland
| | - Merja Hallikainen
- Institute of Clinical Medicine, Neurology, University of Eastern Finland, 70211, Kuopio, Finland
| | - Johanna Kuusisto
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, 70211, Kuopio, Finland
| | - Johannes R Streffer
- Janssen Research and Development, Janssen Pharmaceutics NV, Turnhoutseweg 30, 2340, Beerse, Belgium
| | - Gerald Novak
- Janssen Pharmaceutical Research and Development, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Kaj Blennow
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, SE-431 80, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80, Mölndal, Sweden
| | - Ulf Andreasson
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, SE-431 80, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80, Mölndal, Sweden
| | - Henrik Zetterberg
- Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, SE-431 80, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 80, Mölndal, Sweden.,Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK
| | - Ulf Smith
- Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy at the University of Gothenburg, 405 30, Gothenburg, Sweden
| | - Markku Laakso
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, 70211, Kuopio, Finland
| | - Hilkka Soininen
- Institute of Clinical Medicine, Neurology, University of Eastern Finland, 70211, Kuopio, Finland.,Neurocenter, Neurology, Kuopio University Hospital, 70211, Kuopio, Finland
| | - Simon Lovestone
- Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, UK.
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32
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Pan Y, Jing J, Chen W, Zheng H, Jia Q, Mi D, Li H, Zhao X, Liu L, Wang C, Gaisano HY, He Y, Wang Y, Wang Y. Post-Glucose Load Measures of Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke. J Am Heart Assoc 2017; 6:JAHA.116.004990. [PMID: 28108466 PMCID: PMC5523645 DOI: 10.1161/jaha.116.004990] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Background Insulin resistance is associated with an increased risk of cardiovascular events in the general population. This study aimed to estimate the association between post–glucose load measures of insulin resistance and prognosis of nondiabetic patients with ischemic stroke. Methods and Results Data were derived from the ACROSS‐China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry. Patients with ischemic stroke without a history of diabetes mellitus were included. Two post–glucose load measures of insulin sensitivity, the insulin sensitivity indices ISI(composite) and the ISI0,120, were calculated. Outcomes included stroke recurrence, all‐cause death, and poor functional outcome at 12 months. Among 1203 patients, 63.3% were male with an average age of 62.1 years. At 12 months, 168 (14.4%) patients had recurrent stroke, 111 (9.2%) had died, and 288 (24.4%) had poor outcome. After adjustment for potential covariates, the first quartile of the ISI(composite) was associated with increased 12‐month stroke recurrence (adjusted hazard ratio 2.02, 95% CI 1.28–3.18, P=0.003), death (adjusted hazard ratio 2.78, 95% CI 1.59–4.86, P<0.001), and poor outcome (adjusted odds ratio 2.67, 95% CI 1.69–4.21, P<0.001) compared with the fourth quartile. Similar results were observed for the ISI0,120 but with a larger magnitude of association. Using a multivariable regression model with restricted cubic spline, we found an L‐shaped association between the insulin sensitivity indices and the risk of each end point. Conclusions In this large‐scale registry, post–glucose load measures of insulin resistance with the ISI(composite) and the ISI0,120 were associated with 12‐month poor outcomes of nondiabetic patients with ischemic stroke.
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Affiliation(s)
- Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jing Jing
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Weiqi Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Huaguang Zheng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Qian Jia
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Donghua Mi
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Hao Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Liping Liu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Chunxue Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | | | - Yan He
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China .,Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Yilong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China .,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China .,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
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Ursini F, D’Angelo S, Russo E, Nicolosi K, Gallucci A, Chiaravalloti A, Bruno C, Naty S, De Sarro G, Olivieri I, Grembiale RD. Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis. PLoS One 2016; 11:e0163464. [PMID: 27656896 PMCID: PMC5033360 DOI: 10.1371/journal.pone.0163464] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 09/08/2016] [Indexed: 12/20/2022] Open
Abstract
Objectives To evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients. Methods For the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT. Results In our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7–1.8), mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients. Conclusions In conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.
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Affiliation(s)
- Francesco Ursini
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
- * E-mail:
| | - Salvatore D’Angelo
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
| | - Emilio Russo
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
| | - Kassandra Nicolosi
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
| | | | | | - Caterina Bruno
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
| | - Saverio Naty
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
| | | | - Ignazio Olivieri
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy
| | - Rosa Daniela Grembiale
- Department of Health Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy
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Isaksen VT, Larsen MA, Goll R, Florholmen JR, Paulssen EJ. Hepatic steatosis, detected by hepatorenal index in ultrasonography, as a predictor of insulin resistance in obese subjects. BMC OBESITY 2016; 3:39. [PMID: 27672441 PMCID: PMC5028973 DOI: 10.1186/s40608-016-0118-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Accepted: 09/06/2016] [Indexed: 02/06/2023]
Abstract
Background The metabolic syndrome is a worldwide health issue, with non-alcoholic fatty liver disease (liver steatosis) being one of its features, particularly closely related to insulin resistance. This study aims to investigate whether quantification of hepatic steatosis by abdominal ultrasonography, using hepatorenal index, is a feasible tool for the prediction of insulin resistance, and thus the metabolic syndrome. Methods Patients were recruited from the Centre of Obesity at the University Hospital of North Norway, and among participants from the Sixth Tromsø Study. Homeostasis Model Assessment of Insulin Resistance (HOMA1-IR) was measured, body mass index (BMI, kg/m2) calculated, and hepatorenal index (HRI), i.e. the ratio of liver to kidney optical densities, was measured by transabdominal ultrasonography. Receiver operating characteristic (ROC) analyses were performed, detecting insulin resistance at HOMA1-IR cut-off values >2.3 and >2.5. Results Ninety participants were included in the study, of which 46 (51 %) had BMI ≥30 and 27 (30 %) had BMI ≥35. Overall, HRI at level 1.17 had sensitivity 0.90 and specificity 0.70 for predicting insulin resistance (HOMA1-IR >2.3) in all participants. For participants with BMI ≥30, HRI at level 1.17 had sensitivity 0.94 and specificity 0.70, and for BMI ≥35, HRI at level 1.17 had sensitivity 0.93 and specificity 0.75 for predicting HOMA1-IR >2.3. Setting the HRI limit at 1.42 gave low sensitivities and high specificities in all BMI groups. In the analysis predicting HOMA1-IR >2.5, sensitivity values were almost the same as in the analysis predicting HOMA1-IR >2.3, but specificity values were lower in this analysis. Conclusion Detection and quantification of hepatic steatosis by ultrasound and the hepatorenal index is a feasible screening tool for identifying patients with low risk of having insulin resistance (IR, HRI <1.17), patients at risk of having IR (HRI 1.17-1.41) and patients with likely IR (HRI ≥1.42), especially in obese individuals.
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Affiliation(s)
- Victoria T Isaksen
- Research group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway ; Victoria Therese Isaksen, Faculty of Health Sciences, UiT The Arctic University of Tromsø, P. O. Box 6050 Langnes, N-9037 Tromsø, Norway
| | - Maria A Larsen
- Research group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
| | - Rasmus Goll
- Research group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway ; Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Jon R Florholmen
- Research group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway ; Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
| | - Eyvind J Paulssen
- Research group of Gastroenterology and Nutrition, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway ; Department of Gastroenterology, University Hospital of North Norway, Tromsø, Norway
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Schooneman MG, Napolitano A, Houten SM, Ambler GK, Murgatroyd PR, Miller SR, Hollak CEM, Tan CY, Virtue S, Vidal-Puig A, Nunez DJ, Soeters MR. Assessment of plasma acylcarnitines before and after weight loss in obese subjects. Arch Biochem Biophys 2016; 606:73-80. [PMID: 27444119 DOI: 10.1016/j.abb.2016.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 07/14/2016] [Accepted: 07/17/2016] [Indexed: 12/22/2022]
Abstract
Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention. We measured plasma acylcarnitines in 60 obese subjects before and after a 12 week weight loss intervention. These samples originated from three different interventions (diet alone (n = 20); diet and exercise (n = 21); diet and drug treatment (n = 19)). Acylcarnitine profiles were analysed in relation to clinical parameters of glucose metabolism, insulin sensitivity and energy expenditure. Conclusions were drawn from all 60 subjects together. Despite amelioration of HOMA-IR, plasma acylcarnitines levels increased during weight loss. HOMA-IR, energy expenditure and respiratory exchange ratio were not related to plasma acylcarnitines. However non-esterified fatty acids correlated strongly with several acylcarnitines at baseline and during the weight loss intervention (p < 0.001). Acylcarnitines did not correlate with clinical parameters of glucose metabolism during weight loss, questioning their role in insulin resistance and type 2 diabetes mellitus.
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Affiliation(s)
- Marieke G Schooneman
- Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.
| | - Antonella Napolitano
- GlaxoSmithKline Research and Development, Research Triangle Park, NC, 27709, USA
| | - Sander M Houten
- Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, NY, USA
| | - Graeme K Ambler
- Institute of Metabolic Science, Metabolic Research Laboratories, Cambridge University Hospital NHS Trust, Cambridge, UK
| | - Peter R Murgatroyd
- NIHR Wellcome Trust Clinical Research Facility, Cambridge University Hospital NHS Trust, Cambridge, UK
| | - Sam R Miller
- GlaxoSmithKline Research and Development, Research Triangle Park, NC, 27709, USA
| | - Carla E M Hollak
- Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Chong Y Tan
- Institute of Metabolic Science, Metabolic Research Laboratories, Cambridge University Hospital NHS Trust, Cambridge, UK
| | - Samuel Virtue
- Institute of Metabolic Science, Metabolic Research Laboratories, Cambridge University Hospital NHS Trust, Cambridge, UK
| | - Antonio Vidal-Puig
- Institute of Metabolic Science, Metabolic Research Laboratories, Cambridge University Hospital NHS Trust, Cambridge, UK
| | - Derek J Nunez
- GlaxoSmithKline Research and Development, Research Triangle Park, NC, 27709, USA
| | - Maarten R Soeters
- Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Institute of Metabolic Science, Metabolic Research Laboratories, Cambridge University Hospital NHS Trust, Cambridge, UK. http://www.metabolism.maartensoeters.nl/
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Peng X, Nie Y, Wu J, Huang Q, Cheng Y. Juglone prevents metabolic endotoxemia-induced hepatitis and neuroinflammation via suppressing TLR4/NF-κB signaling pathway in high-fat diet rats. Biochem Biophys Res Commun 2015; 462:245-50. [PMID: 25964086 DOI: 10.1016/j.bbrc.2015.04.124] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 04/26/2015] [Indexed: 12/21/2022]
Abstract
Juglone as a natural production mainly extracted from green walnut husks of Juglans mandshurica has been defined as the functional composition among a series of compounds. It showed powerful protective effect in various diseases by inhibiting inflammation and tumor cells growth. However, studies on its anti-inflammatory effect based on high-fat diet-induced hepatitis and neuroinflammation are still not available. In this regard, we first investigated whether juglone suppresses high-fat diet-stimulated liver injury, hypothalamus inflammation and underlying mechanisms by which they may recover them. SD rats were orally treated with or without high-fat diet, 0.25 mg/kg or 1 mg/kg juglone for 70 days. Subsequently, blood, hypothalamus and liver tissue were collected for different analysis. Also, the primary astrocytes were isolated and used to analyze the inhibitory effect of juglone in vitro. Analysis of inflammatory cytokines declared that the inhibition of TNF-α, IL-1β and IL-6 could be carried by juglone in response to high-fat diet rats. Meanwhile, TLR4 expression and NF-kappa activity also have been confirmed to be the key link in the development of hepatitis and nerve inflammation. The activation was significantly suppressed in treatment group as compared with model. These results indicated that juglone prevents high-fat diet-induced liver injury and nerve inflammation in mice through inhibition of inflammatory cytokine secretion, NF-kappa B activation and endotoxin production.
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Affiliation(s)
- Xiaohui Peng
- College of Aerospace Science and Engineering, National Univ. of Defense Technology, Changsha, Hunan 430000, China.
| | - Yao Nie
- College of Aerospace Science and Engineering, National Univ. of Defense Technology, Changsha, Hunan 430000, China
| | - Jianjun Wu
- College of Aerospace Science and Engineering, National Univ. of Defense Technology, Changsha, Hunan 430000, China
| | - Qiang Huang
- College of Aerospace Science and Engineering, National Univ. of Defense Technology, Changsha, Hunan 430000, China
| | - Yuqiang Cheng
- College of Aerospace Science and Engineering, National Univ. of Defense Technology, Changsha, Hunan 430000, China
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