Bettina Nowotny1, Sabine Kahl1, Birgit Klüppelholz2, Barbara Hoffmann3, Guido Giani2, Roshan Livingstone4, Peter J Nowotny4, Valerie Stamm4, Christian Herder4, Andrea Tura5, Giovanni Pacini5, Jong-Hee Hwang4, Michael Roden6. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany. 2. German Center for Diabetes Research, München-Neuherberg, Germany; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany. 3. IUF - Leibniz Research Institute for Environmental Medicine, Institute for Occupational, Social and Environmental Medicine, Heinrich-Heine University, Düsseldorf, Germany. 4. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany. 5. Metabolic Unit, Institute of Neuroscience, CNR, Padova, Italy. 6. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research, München-Neuherberg, Germany. Electronic address: michael.roden@ddz.uni-duesseldorf.de.
Abstract
BACKGROUND: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion. SUBJECTS/ METHODS: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and 1H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas. RESULTS: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; β=-0.403, p=0.0003 and β=-0.237, p=0.01, respectively) and adaptation index (AI; β=-0.210, p=0.006 and β=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (β=0.375, p<0.0001) and AI (β=0.192, p=0.003). Similar results were obtained for the disposition index (DI). CONCLUSIONS: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans.
BACKGROUND: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion. SUBJECTS/ METHODS: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and 1H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas. RESULTS: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; β=-0.403, p=0.0003 and β=-0.237, p=0.01, respectively) and adaptation index (AI; β=-0.210, p=0.006 and β=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (β=0.375, p<0.0001) and AI (β=0.192, p=0.003). Similar results were obtained for the disposition index (DI). CONCLUSIONS: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans.
Authors: Robert Wagner; Sabine S Eckstein; Hajime Yamazaki; Felicia Gerst; Jürgen Machann; Benjamin Assad Jaghutriz; Annette Schürmann; Michele Solimena; Stephan Singer; Alfred Königsrainer; Andreas L Birkenfeld; Hans-Ulrich Häring; Andreas Fritsche; Susanne Ullrich; Martin Heni Journal: Nat Rev Endocrinol Date: 2021-10-20 Impact factor: 43.330
Authors: Ivana R Sequeira; Wilson C Yip; Louise W W Lu; Yannan Jiang; Rinki Murphy; Lindsay D Plank; Garth J S Cooper; Carl N Peters; Jun Lu; Kieren G Hollingsworth; Sally D Poppitt Journal: Front Physiol Date: 2022-03-31 Impact factor: 4.566