Puberty and Insulin Resistance: A Longitudinal Examination of Hyperglycemic Clamp-Derived Insulin Sensitivity and Insulin Secretion Among Non-Hispanic Black and Non-Hispanic White Children

Presentation Number: OR30-3
Date of Presentation: April 4th, 2017

Shannon E Marwitz1, Megan Gaines2, Sheila M Brady1, James C Reynolds2, Miranda Marguerite Broadney3, Ovidiu A Galescu4, Susan Z Yanovski5 and Jack Adam Yanovski*1
1Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 2National Institutes of Health, Bethesda, MD, 3National Institutes of Health, Betheda, MD, 4Center for Drug Evaluation and Research (CDER) Food and Drug Administration, Silver Spring, MD, 5National Institutes of Health NIDDK, Bethesda, MD

Abstract

Background:

Some studies have suggested children experience a transient decrease in insulin sensitivity (SI) during puberty, but few longitudinal studies using criterion measures of SI or insulin secretion (IS) have been conducted. We hypothesized that longitudinal assessments of SI and IS by hyperglycemic clamps would demonstrate that pre- and early-pubertal children exhibit worsened SI during late puberty, but there would be improved SI and IS among adolescents who were studied again as adults.

Methods:

First phase and steady state insulin concentrations and SI to glucose were measured via hyperglycemic clamps (200 mg/dL for 2h) in a sample of non-Hispanic Black and non-Hispanic White children evaluated at age 6-12y and at 5y intervals into adulthood (maximum age 27y) as part of participation in the NIH Children’s Growth Study. The associations of pubertal stage with SI and IS were assessed cross-sectionally in 129 participants at the five Tanner stages of puberty (as assessed by physical examination) and in adulthood (18-27y). Longitudinal changes in SI (ΔSI) and IS (ΔIS) were compared among available participants who underwent repeated clamps from 3 groups defined by changes in pubertal stage: Prepubertal (Tanner I) at baseline and Tanner IV or V at follow-up (n=28), Early Pubertal (Tanner II) at baseline and Tanner IV or V at follow-up (n=24), and Late Pubertal (Tanner V) at baseline and adult at follow-up (n=26). Analyses accounted for race, sex, fat percentage, and (in longitudinal analyses) change in fat percentage.

Results:

Cross-sectionally, SI was highest in Tanner I and II (p’s<0.001 vs. Tanner III, IV or V), lowest in Tanner III, and significantly greater in adults compared to Tanner V adolescents (p=0.02). Longitudinally, SI decreased significantly from Tanner I/II to IV/V, and increased significantly for Tanner V adolescents restudied as adults (p’s<0.007). Cross-sectionally, steady state IS was highest in Tanner stage IV and V (p’s<0.027 vs. Tanner II and adults). Longitudinally, first phase IS increased from Tanner I/II to IV/V and decreased for Tanner V adolescents restudied as adults. Additionally, first phase IS, steady state IS, and SI were associated with adiposity (p’s<0.001) and race (IS greater in NHB, SI greater in NHW; p’s≤0.032).

Conclusion:

There is a transient decrease in SI and increase in IS during puberty that resolves in adulthood.

 

Disclosure: JAY: Principal Investigator, Rhythm Pharmaceuticals Inc, Principal Investigator, Zafgen, Inc. Nothing to Disclose: SEM, MG, SMB, JCR, MMB, OAG, SZY