Longitudinal Predictors of Insulin Sensitivity and Secretion during Puberty

Abstract

All youth experience a transient reduction in Si during puberty, but little is known about the associated physiology. We previously demonstrated cross-sectionally that insulin-like growth factor 1 (IGF-1) and leptin are associated with Si early in puberty. We now aim to evaluate longitudinal predictors of Si and acute insulin response to glucose (AIRg) during puberty. Methods: Forty-five (47% female) normal-weight (mean BMI %ile 44±22%) ethnically mixed youth entered the study in early puberty (Tanner [T] 2-3). Study visits, including an IV glucose tolerance test (IVGTT), fasting laboratory studies, and DXA, were performed at T2-3, T4, and T5, based on breast development and testicular volume. Physical activity (PA) was assessed by the 3DPAR (3-Day PA Recall). Repeated measures models were used to test if changes over time in potential predictors (IGF-1, leptin, estradiol, total testosterone, dehydroepiandrosterone-sulfate, PA, and urinary gonadotropins) were associated with changes over time in the outcomes, with and without adjustment for sex and % body fat. Results: Si (p=0.04) decreased and AIRg increased (p=0.12) from T2/3-T5. IGF-1 and leptin were the only significant predictors of change in Si and AIRg over time. IGF-1 was associated with both Si (β=-0.016, p=0.0004) and AIRg (β=1.40, p=0.002), and remained so after adjusting for sex and % fat (p=0.0007 and 0.004, respectively). Leptin was associated with Si in univariate analysis (p=0.003) and with both Si (β=-0.238, p=0.003) and AIRg (β=38.4, p=0.043) after adjustment for sex and % fat. Conclusions: This is the first study to show a longitudinal relationship between leptin and Si and AIRg during puberty independent of sex and body fat, and confirms previous reports of associations between IGF-1 and Si and AIRg. These results suggest that leptin and IGF-1 may be driving factors for changes in Si and AIRg during puberty. Knowledge of normal pubertal metabolism may contribute to understanding of diseases of pubertal onset, such as type 2 diabetes. Disclosure M.M. Kelsey: Other Relationship; Self; Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp.. L. Pyle: None. A.M. Hilkin: None. A. Johnson: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH.