Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Division of Biostatistics and Epidemiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
J Pediatr. 2015 Mar;166(3):672-8. doi: 10.1016/j.jpeds.2014.11.029. Epub 2014 Dec 31.
To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents.
Obese adolescents with normal glucose tolerance (n = 41) were studied longitudinally over the course of 4 years with serial measure of the acute insulin response to glucose (AIRg) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with the homeostatic model assessment of insulin resistance (HOMA-IR), the disposition index (DI) computed as AIRg × 1/HOMA-IR, and intravenous glucose tolerance estimated as the glucose disappearance constant.
Four adolescents developed diabetes mellitus (DM) during the study, and the rest of the cohort remained nondiabetic. Baseline PI exceeded the IQR of the nondiabetic group in 3 of 4 subjects with DM, and all had >85% reduction from baseline AIRg, and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study, but these changes paralleled those for the nondiabetic group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis but was comparable with baseline in the other 3. The DI and glucose disappearance constant of the subjects with DM was less than the 10th percentile of the nondiabetic group before and after diagnosis.
Conversion from normal glucose tolerance to T2DM in adolescents can occur rapidly, and the onset of T2DM is heralded by a substantial decrease in AIRg and DI, as well as increased release of PI. These results support loss of β-cell function as the proximate step in the development of T2DM in this age group.
确定导致青少年 2 型糖尿病（T2DM）发病的病理生理变化。
对 41 名糖耐量正常的肥胖青少年进行了 4 年的纵向研究，连续测量葡萄糖刺激下的急性胰岛素反应（AIRg）和胰岛素原（PI）浓度。用稳态模型评估胰岛素抵抗（HOMA-IR）估计胰岛素抵抗，用胰岛素分泌指数（DI）计算 AIRg×1/HOMA-IR，用静脉葡萄糖耐量估计葡萄糖清除常数。
在研究期间，有 4 名青少年发展为糖尿病（DM），其余队列仍为非糖尿病。DM 组中 3 例患者的基线 PI 超过非糖尿病组的 IQR，且所有患者在诊断后 6 个月内的 AIRg 和 DI 均从基线下降了>85%。所有 DM 患者在研究过程中体重增加，但这些变化与非糖尿病组相似。DM 组中有 1 例患者在诊断时的 HOMA-IR 显著升高，但与基线相比，其他 3 例患者的 HOMA-IR 与基线相比无明显差异。DM 患者的 DI 和葡萄糖清除常数在诊断前后均低于非糖尿病组的第 10 百分位数。
青少年从糖耐量正常到 T2DM 的转变可能很快发生，T2DM 的发生伴随着 AIRg 和 DI 的显著下降，以及 PI 的释放增加。这些结果支持β细胞功能丧失是该年龄段 T2DM 发展的直接步骤。
