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.
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.
Authors: Sara E Stinson; Anna E Jonsson; Morten A V Lund; Christine Frithioff-Bøjsøe; Louise Aas Holm; Oluf Pedersen; Lars Ängquist; Thorkild I A Sørensen; Jens J Holst; Michael Christiansen; Jens-Christian Holm; Bolette Hartmann; Torben Hansen Journal: J Clin Endocrinol Metab Date: 2021-05-13 Impact factor: 5.958
Authors: Sara E Stinson; Anna E Jonsson; Ierai Fernández de Retana Alzola; Morten A V Lund; Christine Frithioff-Bøjsøe; Louise Aas Holm; Cilius E Fonvig; Oluf Pedersen; Lars Ängquist; Thorkild I A Sørensen; Jens J Holst; Michael Christiansen; Jens-Christian Holm; Bolette Hartmann; Torben Hansen Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134
Authors: Steven E Kahn; Kieren J Mather; Silva A Arslanian; Elena Barengolts; Thomas A Buchanan; Sonia Caprio; David A Ehrmann; Tamara S Hannon; Santica Marcovina; Kristen J Nadeau; Kristina M Utzschneider; Anny H Xiang; Sharon L Edelstein Journal: Diabetes Care Date: 2021-06-15 Impact factor: 17.152