University of Colorado School of Medicine, Department of Pediatrics, Aurora, CO, USA.
University of Colorado School of Medicine, Department of Biostatistics, Aurora, CO, USA.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2622-e2632. doi: 10.1210/clinem/dgab170.
Youth-onset type 2 diabetes is a disease of pubertal onset, associated with additional burden of pubertal insulin resistance on the β-cell.
Evaluate the impact of metformin treatment during puberty, a critical window of cardiometabolic change, on insulin sensitivity (Si) and compensatory β-cell response in youth with obesity.
Pediatric academic hospital clinical translational research center.
Healthy youth in early puberty [Tanner stage (T) 2-3] with normoglycemia and obesity (n = 44).
Double-blinded placebo-control trial of metformin during puberty (until T5).
Insulin sensitivity (Si), insulin response [acute insulin response to glucose (AIRg)], and disposition index (DI), estimated from frequently sampled intravenous glucose tolerance testing; body fat (dual X-ray absorptiometry); and other laboratory parameters, collected at baseline, T4, and T5. Placebo-subtracted treatment effect was calculated using linear mixed models.
At T5, metformin treatment, adjusting for sex, race, and baseline value, was associated with improved BMI z-score (-0.44 ± 0.16, P = 0.02), percentage body fat (%body fat; -3.4 ± 1.2%, P = 0.06), and waist circumference (-11.3 ± 3.2cm, P = 0.003). There were no significant treatment effects at T5 on Si or secretion: Si (0.85 ± 0.87 × 10-4/min-1/μIU/mL, P = 0.34), AIRg (-259 ± 386 μIU/mL, P = 0.51), or DI (508 ± 802 × 10-4/min-1, P = 0.53). High baseline DI predicted longitudinal decline in DI.
Two years of metformin treatment in obese youth during puberty improved BMI and body fat, but not Si or β-cell function. Of note, high DI in early puberty may be predictive of later decline in DI. Further studies are needed to develop strategies for preservation of β-cell function in youth at risk for type 2 diabetes.
青少年 2 型糖尿病是一种青春期发病的疾病，与青春期胰岛素抵抗对β细胞的额外负担有关。
评估在青春期（心脏代谢变化的关键窗口）期间使用二甲双胍治疗对肥胖青少年的胰岛素敏感性（Si）和β细胞反应的代偿作用。
儿科学术医院临床转化研究中心。
健康的青春期前期青少年（Tanner 分期 2-3 期），血糖正常且肥胖（n=44）。
青春期期间（直到 T5）进行二甲双胍双盲安慰剂对照试验。
通过多次采样静脉葡萄糖耐量试验估算胰岛素敏感性（Si）、胰岛素反应[急性葡萄糖诱导的胰岛素反应（AIRg）]和胰岛功能指数（DI）；体脂（双能 X 线吸收法）；以及其他实验室参数，在基线、T4 和 T5 时收集。使用线性混合模型计算经安慰剂校正的治疗效果。
在 T5 时，与性别、种族和基线值调整后的二甲双胍治疗相关的指标有改善的 BMI z 评分（-0.44±0.16，P=0.02）、体脂百分比（%body fat；-3.4±1.2%，P=0.06）和腰围（-11.3±3.2cm，P=0.003）。T5 时，Si 或分泌无显著的治疗作用：Si（0.85±0.87×10-4/min-1/μIU/mL，P=0.34）、AIRg（-259±386 μIU/mL，P=0.51）或 DI（508±802×10-4/min-1，P=0.53）。较高的基线 DI 预测 DI 的纵向下降。
肥胖青少年在青春期接受二甲双胍治疗 2 年可改善 BMI 和体脂，但不能改善 Si 或β细胞功能。值得注意的是，青春期早期的高 DI 可能预示着以后 DI 的下降。需要进一步的研究来制定策略，以保护处于 2 型糖尿病风险的青少年的β细胞功能。
