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Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 50 citations

PubMed: 30020457 DOI: 10.1210/jc.2018-00433

Youth With Type 1 Diabetes Have Adipose, Hepatic, and Peripheral Insulin Resistance.

J Clin Endocrinol Metab 103(10):3647-3657

Authors: Melanie Cree-Green, Jacob J Stuppy, Jessica Thurston, Bryan C Bergman, Gregory V Coe, Amy D Baumgartner, Samantha Bacon, Ann Scherzinger, Laura Pyle, Kristen J Nadeau

Affiliations

  • Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Department of Biomedical Sciences and Biotechnology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado.
  • Department of Medicine, Division of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Abstract

Context

Adolescents with type 1 diabetes (T1D) have difficulty obtaining optimal glucose control, which may relate to insulin resistance (IR), especially during puberty. Moreover, IR increases the risk for cardiovascular disease, the leading cause of death in T1D. However, the tissue specificity of IR in adolescents with T1D has not been fully phenotyped.

Objective

To assess adipose, hepatic, and peripheral insulin sensitivity in adolescents with and without T1D.

Design and Setting

Thirty-five youth with T1D [median age, 16 (first and third quartiles, 14, 17) years; 53% female; median body mass index (BMI) percentile, 82nd (55th, 96th); late puberty; median hemoglobin A1c, 8.3% (7.3%, 9.4%)] and 22 nondiabetic youth of similar age, BMI, pubertal stage, and level of habitual physical activity were enrolled. Insulin action was measured with a four-phase hyperinsulinemic euglycemic clamp (basal and 10, 16, and 80 mU/m2/min) with glucose and glycerol isotope tracers.

Results

Adolescents with T1D had a significantly higher rate of lipolysis (P < 0.0001) and endogenous glucose production (P < 0.001) and lower peripheral glucose uptake (glucose rate of disappearance, 6.9 ± 2.9 mg/kg/min for patients with T1D vs 11.3 ± 3.3 for controls; P < 0.0001) during hyperinsulinemia compared with controls. In youth with T1D, glucose rate of disappearance correlated with free fatty acid at the 80-mU/m2/min phase (P = 0.005), markers of inflammation (IL-6; P = 0.012), high-sensitivity C-reactive protein (P = 0.001), and leptin (P = 0.008)], but not hemoglobin A1c.

Conclusions

Adolescents with T1D have adipose, hepatic and peripheral IR. This IR occurs regardless of obesity and metabolic syndrome features. Youth with T1D may benefit from interventions directed at improving IR in these tissues, and this area requires further research.

MeSH

Diabetes Mellitus, Endocrinology, Hemoglobins, Insulin Resistance, Insulin, Puberty, C-Reactive Protein, Adolescent, Tissues, Diabetes Mellitus, Type 1

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