The Journal of clinical endocrinology and metabolism 2017 12 13() doi 10.1210/jc.2017-02014
The role of hyperglucagonemia in type 2 diabetes is still debated.
We analyzed glucagon dynamics during oral glucose tolerance testing (oGTT) in young women with 1 out of 3 metabolic phenotypes: healthy control (normoglycemic after a normoglycemic pregnancy); normoglycemic high-risk (normoglycemic after a pregnancy complicated by gestational diabetes); and prediabetes/screening-diagnosed T2D. We asked if glucagon patterns were homogeneous within the metabolic phenotypes.
Design and Setting
5-point oGTT; sandwich ELISA for glucagon; functional data analysis with unsupervised clustering.
Cross-sectional analysis of 285 women from the mono-center observational study PPSDiab ("Prediction, Prevention and Subclassification of gestational and type 2 Diabetes"), recruited between November 2011 and May 2016.
We found 4 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.
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 taken into account in future pathophysiological studies and when testing pharmacotherapies addressing glucagon signaling.