One of the pathophysiological components of T2D is adipocyte insulin resistance. We demonstrated diminished insulin suppression of lipolysis, using the hyperinsulinemic-euglycemic clamp combined with [2H5]glycerol tracer, in obese IGT vs. NGT youth (Diabetes 66: 2017). Herein we examined a surrogate index of adipose tissue insulin resistance (AT-IR= fasting insulin x FFA) to test the hypothesis that AT-IR increases from normal weight (NW) to obese NGT to IGT to T2D. A total of 2youth (70 M/135 F; Tanner IV-V) had body composition, visceral adipose tissue (VAT), fasting glucose, insulin and free fatty acids (FFA), and AT-IR evaluated. Despite hyperinsulinemia in obese IGT youth, fasting FFA was higher compared with NW and obese NGT peers (Table). AT-IR was 2.2 fold higher in obese NGT, 4.3 fold higher in IGT and 4.6 fold higher in T2D compared with NW before and after adjusting for sex, Tanner stage, BMI and VAT.

In conclusion, the surrogate index of AT-IR reflects pathophysiological alterations in adipose tissue insulin sensitivity showing progressive increase in AT-IR in youth from normal weight to obese, and from NGT to IGT to T2D. This AT-IR, derived from fasting blood samples, could be used in epidemiological, observational and/or interventional studies investigating changes in adipocyte insulin sensitivity in obese youth with IGT and T2D.

Variables, mean ± SEM NW (n=49) Obese-NGT (n=89) Obese-IGT (n=38) Obese-T2D (n=29) P, ANCOVA 
Age (years) 14.4 ± 0.3 14.6 ± 0.2 14.9 ± 0.4 15.2 ± 0.3 NS 
BMI (kg/m2) 20.6 ± 0.3 33.9 ± 0.7 36.8 ± 1.0 36.8 ± 1.0 <0.0001 
Visceral adipose tissue (cm2) 24.4 ± 2.2 60.8 ± 4.1 85.1 ± 5.1 83.6 ± 7.7 <0.0001 
Fasting glucose (mg/dL) 95.1 ± 0.8 95.4 ± 0.6 96.8 ± 1.2 121.5 ± 4.8 <0.0001 
Fasting insulin (µU/mL) 16.2 ± 0.8 31.3 ± 1.5 50.4 ± 4.9 57.6 ± 9.6 <0.0001 
Fasting FFA (mmol/L) 0.25 ± 0.02 0.28 ± 0.01 0.35 ± 0.02 0.32 ± 0.02 0.001 
AT-IR (µU/mL x mmol/L) 4.± 0.38 8.98 ± 0.69 17.51 ± 1.99 18.59 ± 3.00 <0.0001 
Variables, mean ± SEM NW (n=49) Obese-NGT (n=89) Obese-IGT (n=38) Obese-T2D (n=29) P, ANCOVA 
Age (years) 14.4 ± 0.3 14.6 ± 0.2 14.9 ± 0.4 15.2 ± 0.3 NS 
BMI (kg/m2) 20.6 ± 0.3 33.9 ± 0.7 36.8 ± 1.0 36.8 ± 1.0 <0.0001 
Visceral adipose tissue (cm2) 24.4 ± 2.2 60.8 ± 4.1 85.1 ± 5.1 83.6 ± 7.7 <0.0001 
Fasting glucose (mg/dL) 95.1 ± 0.8 95.4 ± 0.6 96.8 ± 1.2 121.5 ± 4.8 <0.0001 
Fasting insulin (µU/mL) 16.2 ± 0.8 31.3 ± 1.5 50.4 ± 4.9 57.6 ± 9.6 <0.0001 
Fasting FFA (mmol/L) 0.25 ± 0.02 0.28 ± 0.01 0.35 ± 0.02 0.32 ± 0.02 0.001 
AT-IR (µU/mL x mmol/L) 4.± 0.38 8.98 ± 0.69 17.51 ± 1.99 18.59 ± 3.00 <0.0001 
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Disclosure

J. Kim: None. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. H. Tfayli: None. S. Michaliszyn: None. S.A. Arslanian: None.

© 2018 by the American Diabetes Association.
2018
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