Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes

J Clin Endocrinol Metab. 2016 Mar;101(3):1181-9. doi: 10.1210/jc.2015-3885. Epub 2016 Jan 8.


Context: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).

Objective: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.

Design: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).

Setting: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.

Patients and participants: Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included.

Main outcome measures: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.

Results: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001).

Conclusions: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Child
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glicentin / blood*
  • Glucagon / blood*
  • Glucagon-Like Peptide 1 / blood*
  • Glucose Intolerance / blood
  • Glucose Intolerance / complications
  • Glucose Intolerance / epidemiology
  • Glucose Tolerance Test
  • Humans
  • Male
  • Pediatric Obesity / blood*
  • Pediatric Obesity / complications
  • Pediatric Obesity / epidemiology
  • Sweden / epidemiology


  • Blood Glucose
  • Glicentin
  • Glucagon-Like Peptide 1
  • Glucagon