The Impact of Obesity On Insulin Sensitivity and Secretion During Pubertal Progression: A Longitudinal Study

J Clin Endocrinol Metab. 2020 May 1;105(5):e2061-e2068. doi: 10.1210/clinem/dgaa043.


Context: Physiologic changes in glucose metabolism are well-described to occur during puberty. However, there are important gaps in understanding the interaction between obesity and the normal physiologic changes during puberty, as well as how these changes could contribute to the increased risk of comorbidities, such as type 2 diabetes and dyslipidemia, in youth with obesity.

Objective: The objective of this study was to compare longitudinal changes in insulin sensitivity (Si) and secretion during pubertal progression in youth with obesity versus those with normal weight.

Design: Longitudinal observational study evaluating youth from early puberty (Tanner [T]2-T3) until puberty completion (T5).

Setting: Pediatric academic hospital Clinical Translational Research Center.

Participants: Pubertal youth with normal weight (n = 47; 22 female, 25 male) and obesity (n = 37; 23 female, 14 male).

Main outcome measures: Si, insulin response (acute insulin response to glucose, AIRg) and disposition index (DI) by intravenous glucose tolerance test at baseline (T2-T3), T4, and T5.

Results: Youth with obesity had significantly lower Si and higher AIRg at each time point (P < 0.001), but DI was similar between the groups. There were no group differences in trajectory of Si, AIRg or DI over time. Leptin, insulin-like growth factor-1, and obesity were most strongly associated with Si and AIRg at all time points.

Conclusions: Obesity significantly impacts Si during puberty, even at the earliest stages. However, in general, obese youth have adequate β-cell compensation for the significantly reduced Si of puberty. Future studies are needed to better predict the subset of youth who fail to maintain β-cell compensation during puberty.

Trial registration: NCT01775813.

Keywords: beta-cell function; insulin sensitivity; intravenous glucose tolerance testing; obesity; puberty.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Glucose / metabolism
  • Child
  • Colorado / epidemiology
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Insulin Secretion / physiology*
  • Longitudinal Studies
  • Male
  • Pediatric Obesity / epidemiology
  • Pediatric Obesity / metabolism*
  • Puberty / physiology*
  • Time Factors


  • Blood Glucose
  • Insulin

Associated data