Increased Glucagon, but Reduced GIP Secretion, in Adolescents with Obesity and T2DM

Abstract

We have previously reported that insulin and glucagon levels at fasting and during OGTT are increased in obese adolescents as glucose intolerance develops. In adults incretin hormone GIP has been coupled with enhanced glucagon secretion. We hypothesized that the observed elevated glucagon levels in obese adolescents were associated with increased levels of GIP. Total GIP in plasma samples from obese (NGT=7, IGT=9, T2DM=4) and lean (n=8) adolescents was measured at fasting and during OGTT with a newly developed ELISA (Mercodia AB, Uppsala, Sweden). Newly secreted GIP and glucagon were defined as GIP and glucagon area under curve AUC during the first 30 min, AUC30. Ethical approval was obtained from the Uppsala Ethical Review Board. Fasting GIP levels ± SEM were 4.7 ± 2.8, 3.6 ± 2.0, 2.9 ± 1.7 and 2.2 ± 0.9 pM in lean, obese NGT, obese IGT and obese T2DM adolescents, respectively. During OGTT GIP concentrations peaked at 30 min for all groups (Figure). Highest concentrations were observed throughput the OGTT in lean, followed by obese NGT, obese IGT and obese T2DM adolescents. GIP AUC30 ± SEM was 1181 ± 197, 920 ± 22, 707 ± 146 and 699 ± 211 pmol/L *min in lean, obese NGT, obese IGT and obese T2DM, respectively. For the same groups glucagon AUC30 ± SEM was -73 ± 21, -39 ± 43, -3 ± 30 and 91 ± 80 pmol/L *min. Hyperglucagonemia in adolescents developing T2DM does not seem to be driven by enhanced GIP secretion. Disclosure H. Kristinsson: None. H. Manell: None. M. Vilhelmsson: Employee; Self; Mercodia AB. J. Presto: Employee; Self; Mercodia AB. C. Gäredal: None. H. Ritzén: None. A.H. Forslund: None. P. Bergsten: None.