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Patterns of plasma glucagon dynamics do not match metabolic phenotypes in young women.

Patterns of plasma glucagon dynamics do not match metabolic phenotypes in young women.
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Gar C, Rottenkolber M, Sacco V, Moschko S, Banning F, Hesse N, Popp D, Hübener C, Seissler J, Lechner A,


Gar C, Rottenkolber M, Sacco V, Moschko S, Banning F, Hesse N, Popp D, Hübener C, Seissler J, Lechner A, (click to view)

Gar C, Rottenkolber M, Sacco V, Moschko S, Banning F, Hesse N, Popp D, Hübener C, Seissler J, Lechner A,

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The Journal of clinical endocrinology and metabolism 2017 12 13() doi 10.1210/jc.2017-02014
Abstract
Context
The role of hyperglucagonemia in type 2 diabetes is still debated.

Objective
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.

Participants
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.

Results
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.

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 taken into account in future pathophysiological studies and when testing pharmacotherapies addressing glucagon signaling.

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