Umpaichitra V, Bastian W, Taha D, Banerji M A, AvRuskin T W, Castells S
Department of Pediatrics, State University of New York Health Science Center, Brooklyn, New York 11203, USA.
J Clin Endocrinol Metab. 2001 Apr;86(4):1605-9. doi: 10.1210/jcem.86.4.7415.
The present study was conducted to determine the extent of insulin deficiency and glucagon excess in the hyperglycemia of type 2 diabetes in children. The incidence of type 2 diabetes mellitus in children and adolescents has increased substantially over the past several years. Because insulin and glucagon action both regulate blood glucose concentration, we studied their responses to mixed meals in children with type 2 diabetes. Subjects were 24 patients with type 2 diabetes compared with 24 controls, aged 9--20 yr (predominantly African-Americans), matched for body mass index and sexual maturation. All of those with diabetes were negative for antibodies to glutamic acid decarboxylase. Plasma glucose, glucagon, and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body weight; maximum, 360 mL). The area under the curve (AUC) was calculated by trapezoidal estimation. The incremental C-peptide (Delta CP) in response to the mixed meal was calculated (peak -- fasting C-peptide). The plasma glucose AUC was significantly greater in patients than in controls (mean +/- SEM, 1231 +/- 138 vs. 591 +/- 13 mmol/L x min; P < 0.001). The Delta CP was significantly lower in those with diabetes than in controls (1168 +/- 162 vs. 1814 +/- 222 pmol/L; P < 0.02). Glucagon responses did not differ between the two groups. Hyperglycemia is known to inhibit glucagon secretion. Therefore, our patients with substantial hyperglycemia would be expected to have decreased glucagon responses compared with controls and are thus relatively hyperglucagonemic. Patients were divided into poorly and well controlled subgroups (glycosylated hemoglobin A(1c), > or =7.2% and <7.2%, respectively). There were no significant differences in the Delta CP and glucagon responses between these two subgroups. We next analyzed the data in terms of duration of diabetes (long term, > or =1 yr; short term, <1 yr). The CP was significantly lower in long- vs. short-term patients (768 +/- 232 vs. 1407 +/- 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly higher in the long- vs. short-term patients (9029 +/- 976 vs. 6074 +/- 291 ng/L x min; P < 0.001). Hemoglobin A(1c) did not differ between long- vs. short-term patients. Our results indicate that relative hypoinsulinemia and hyperglucagonemia represent the pancreatic beta- and alpha-cell dysfunctions in children with type 2 diabetes. The severity of both beta- and alpha-cell dysfunctions appears to be determined by the duration of diabetes.
本研究旨在确定儿童2型糖尿病高血糖状态下胰岛素缺乏和胰高血糖素过量的程度。在过去几年中，儿童和青少年2型糖尿病的发病率大幅上升。由于胰岛素和胰高血糖素的作用均调节血糖浓度，我们研究了2型糖尿病患儿对混合餐的反应。研究对象为24例2型糖尿病患者和24名对照者，年龄在9至20岁（主要为非裔美国人），根据体重指数和性成熟程度进行匹配。所有糖尿病患者谷氨酸脱羧酶抗体均为阴性。在摄入混合流质餐（Sustacal，7 mL/kg体重；最大量360 mL）后0、30、60、90和120分钟测量血浆葡萄糖、胰高血糖素和血清C肽浓度。通过梯形估计法计算曲线下面积（AUC）。计算混合餐刺激后的增量C肽（ΔCP，峰值减去空腹C肽）。患者的血浆葡萄糖AUC显著高于对照者（均值±标准误，1231±138 vs. 591±13 mmol/L·min；P<0.001）。糖尿病患者的ΔCP显著低于对照者（1168±162 vs. 1814±222 pmol/L；P<0.02）。两组间胰高血糖素反应无差异。已知高血糖会抑制胰高血糖素分泌。因此，与对照者相比，我们的高血糖患者预计胰高血糖素反应会降低，从而相对胰高血糖素血症。患者被分为控制不佳和控制良好的亚组（糖化血红蛋白A1c分别≥7.2%和<7.2%）。这两个亚组的ΔCP和胰高血糖素反应无显著差异。接下来我们根据糖尿病病程（长期，≥1年；短期，<1年）分析数据。长期患者的C肽显著低于短期患者（768±232 vs. 1407±199 pmol/L；P<0.05）。长期患者的血浆胰高血糖素AUC显著高于短期患者（9029±976 vs. 6074±291 ng/L·min；P<0.001）。长期和短期患者的血红蛋白A1c无差异。我们的结果表明，相对胰岛素缺乏和胰高血糖素血症代表了儿童２型糖尿病患者胰岛β细胞和α细胞功能障碍。β细胞和α细胞功能障碍的严重程度似乎由糖尿病病程决定。
