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Patterns of Plasma Glucagon Dynamics Do Not Match Metabolic Phenotypes in Young Women
Christina Gar1,2,3, Marietta Rottenkolber1,2,3, Vanessa Sacco1,2,3
1Diabetes Research Group, Medizinische Klinik IV, Medical Center of the University of Munich (Klinikum der Universitaet Muenchen), Munich, Germany.
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.
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