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January 18, 2016

Altered Levels of Glucagon and Glicentin in Adolescents With Obesity and Type 2 Diabetes

Proglucagon-derived hormones are important for glucose metabolism but little is known about them in pediatric obesity and T2DM. Therefore, Manell and co-workers from Uppsala University, Sweden, investigated fasting and post-prandial levels of glucagon, GLP-1 and glicentin in obese adolescents, age 10–18 years, with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or T2DM. As a control group, age-matched lean adolescents were chosen. Plasma insulin, glucagon and glicentin were quantified by ELISA from Mercodia.

The results showed that adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT. Moreover, adolescents with obesity and T2DM had higher fasting glucagon levels than those with NGT. Ratios of glicentin/glucagon were lower in adolescents with obesity and NGT than in lean adolescents and even lower in IGT and T2DM.

The study concluded that obese adolescents with IGT had lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, while GLP-1 and glicentin levels are maintained low. During an OGTT, obese adolescents have more proglucagon-derived products from the pancreas than the intestines, i.e. more glucagon and less GLP-1 in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.  This suggests that elevating incretin hormones and suppressing glucagon are treatment strategies worth exploring in this patient group.

Manell H et al. (2016) Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes. J Clin Endocrinol Metab In press.

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