Manell Hannes, Staaf Johan, Manukyan Levon, Kristinsson Hjalti, Cen Jing, Stenlid Rasmus, Ciba Iris, Forslund Anders, Bergsten Peter
Department of Medical Cell Biology (H.M., J.S., L.M., H.K., J.C., R.S., P.B.), Uppsala University, 75123 Uppsala, Sweden; Department of Women's and Children's Health (H.M., J.S., J.C., R.S., I.C., A.F.), Uppsala University Hospital, Uppsala, Sweden.
J Clin Endocrinol Metab. 2016 Mar;101(3):1181-9. doi: 10.1210/jc.2015-3885. Epub 2016 Jan 8.
Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).
Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.
This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).
This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.
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.
Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.
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).
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.
胰高血糖素原衍生激素对葡萄糖代谢很重要，但在儿童肥胖症和2型糖尿病（T2DM）中人们对它们了解甚少。
研究糖耐量范围内肥胖青少年中胰高血糖素原衍生肽胰高血糖素、GLP - 1和肠促胰素的空腹及餐后水平。
这是一项横断面研究，在空腹及口服葡萄糖耐量试验（OGTT）期间对血浆激素水平进行定量分析。
本研究在瑞典乌普萨拉大学医院的儿科肥胖诊所进行。
纳入了年龄在10 - 18岁、糖耐量正常（NGT，n = 23）、糖耐量受损（IGT，n = 19）或T2DM（n = 4）的肥胖青少年以及年龄匹配的瘦青少年（n = 19）。
观察指标为空腹及OGTT时血浆胰岛素、胰高血糖素、活性GLP - 1和肠促胰素水平。
肥胖且IGT的青少年空腹GLP - 1和肠促胰素水平低于糖耐量正常的青少年（0.25对0.53 pM，P <.05；18.2对23.6 pM，P <.01），肥胖且T2DM的青少年空腹胰高血糖素水平高于糖耐量正常的青少年（18.1对10.1 pM，P <.01）。在OGTT期间，肥胖且糖耐量正常的青少年的肠促胰素/胰高血糖素比值低于瘦青少年（P <.01），在IGT（P <.05）和T2DM（P <.001）中更低。
肥胖且IGT的青少年空腹GLP - 1和肠促胰素水平降低。在T2DM中，空腹胰高血糖素水平升高，而GLP - 1和肠促胰素水平维持在低水平。在OGTT期间，肥胖青少年血浆中胰高血糖素原经胰腺裂解产生的产物比经肠道裂解产生的产物更多（即胰高血糖素更多，GLP - 1更少）。当糖耐量恶化时，这种转变会更加明显。
