Christina Gar1,2,3, Marietta Rottenkolber1,2,3, Vanessa Sacco1,2,3, Sarah Moschko1,2,3, Friederike Banning1,2,3, Nina Hesse4, Daniel Popp4, Christoph Hübener5, Jochen Seissler1,2,3, Andreas Lechner1,2,3. 1. Diabetes Research Group, Medizinische Klinik IV, Medical Center of the University of Munich (Klinikum der Universitaet Muenchen), Munich, Germany. 2. Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum Muenchen, Neuherberg, Germany. 3. German Center for Diabetes Research, Neuherberg, Germany. 4. Department of Clinical Radiology, Medical Center of the University of Munich (Klinikum der Universitaet Muenchen), Munich, Germany. 5. Department of Gynecology and Obstetrics, Medical Center of the University of Munich (Klinikum der Universitaet Muenchen), Munich, Germany.
Abstract
Context: The role of hyperglucagonemia in type 2 diabetes is still debated. Objective: We analyzed glucagon dynamics during oral glucose tolerance tests (oGTTs) in young women with one out of three metabolic phenotypes: healthy control (normoglycemic after a normoglycemic pregnancy), normoglycemic high-risk (normoglycemic after a pregnancy complicated by gestational diabetes), and prediabetes/screening-diagnosed type 2 diabetes. We asked if glucagon patterns were homogeneous within the metabolic phenotypes. Design and Setting: Five-point oGTT, sandwich enzyme-linked immunosorbent assay for glucagon, and functional data analysis with unsupervised clustering. Participants: Cross-sectional analysis of 285 women from the monocenter observational study Prediction, Prevention, and Subclassification of gestational and type 2 Diabetes, recruited between November 2011 and May 2016. Results: We found four patterns of glucagon dynamics that did not match the metabolic phenotypes. Elevated fasting glucagon and delayed glucagon suppression was overrepresented with prediabetes/diabetes, but this was only detected in 21% of this group. It also occurred in 8% of the control group. Conclusions: We conclude that hyperglucagonemia may contribute to type 2 diabetes in a subgroup of affected individuals but that it is not a sine qua non for the disease. This should be considered in future pathophysiological studies and when testing pharmacotherapies addressing glucagon signaling.
Context: The role of hyperglucagonemia in type 2 diabetes is still debated. Objective: We analyzed glucagon dynamics during oral glucose tolerance tests (oGTTs) in young women with one out of three metabolic phenotypes: healthy control (normoglycemic after a normoglycemic pregnancy), normoglycemic high-risk (normoglycemic after a pregnancy complicated by gestational diabetes), and prediabetes/screening-diagnosed type 2 diabetes. We asked if glucagon patterns were homogeneous within the metabolic phenotypes. Design and Setting: Five-point oGTT, sandwich enzyme-linked immunosorbent assay for glucagon, and functional data analysis with unsupervised clustering. Participants: Cross-sectional analysis of 285 women from the monocenter observational study Prediction, Prevention, and Subclassification of gestational and type 2 Diabetes, recruited between November 2011 and May 2016. Results: We found four patterns of glucagon dynamics that did not match the metabolic phenotypes. Elevated fasting glucagon and delayed glucagon suppression was overrepresented with prediabetes/diabetes, but this was only detected in 21% of this group. It also occurred in 8% of the control group. Conclusions: We conclude that hyperglucagonemia may contribute to type 2 diabetes in a subgroup of affected individuals but that it is not a sine qua non for the disease. This should be considered in future pathophysiological studies and when testing pharmacotherapies addressing glucagon signaling.
Authors: Robert Wagner; Sabine S Eckstein; Louise Fritsche; Katsiaryna Prystupa; Sebastian Hörber; Hans-Ulrich Häring; Andreas L Birkenfeld; Andreas Peter; Andreas Fritsche; Martin Heni Journal: Front Endocrinol (Lausanne) Date: 2022-06-29 Impact factor: 6.055
Authors: Micaela Morettini; Laura Burattini; Christian Göbl; Giovanni Pacini; Bo Ahrén; Andrea Tura Journal: Front Endocrinol (Lausanne) Date: 2021-03-22 Impact factor: 5.555