1. Two-Year Treatment With Metformin During Puberty Does Not Preserve β-Cell Function in Youth With Obesity
- Author
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Kristina M. Utzschneider, Laura Pyle, Rachael E. Van Pelt, Kristen J. Nadeau, Cameron Severn, Philip Zeitler, Allison M. Hilkin, and Megan M. Kelsey
- Subjects
medicine.medical_specialty ,Waist ,business.industry ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Insulin sensitivity ,Context (language use) ,Type 2 diabetes ,Disease ,medicine.disease ,Biochemistry ,Gastroenterology ,Obesity ,Metformin ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Context Youth-onset type 2 diabetes is a disease of pubertal onset, associated with additional burden of pubertal insulin resistance on the β-cell. Objective 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. Setting Pediatric academic hospital clinical translational research center. Participants Healthy youth in early puberty [Tanner stage (T) 2-3] with normoglycemia and obesity (n = 44). Intervention Double-blinded placebo-control trial of metformin during puberty (until T5). Main Outcome Measures 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. Results 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. Conclusions 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.
- Published
- 2021