Background: The epidemic of obesity is growing in the U.S. due to changes in diet and lifestyle. Similar trends are also now occurring in T1D youth and may worsen IR and associated cardiovascular risk. However, the impact of obesity on IR in each tissue is unknown in T1D. Thus, we evaluated adipose, hepatic and muscle IR in obese youth with T1D, compared to BMI-similar control or T2D youth.

Methods: 20 youth with T1D (age 16.0±2.3 years; % female 55; BMI%ile 95th [97, 98]; HbA1c 8.7±1.6%), 20 youth with T2D (age 15.4±2.3; % female 52; BMI%ile 95th [98, 99]; HbA1c 8.5±2.4%) and 16 controls (age 14.8±1.8; % female 55; BMI%ile 97th [98, 99]) were included. In those with diabetes, glucose was controlled overnight by IV insulin to a target of ∼100 mg/dL. A 4-phase hyperinsulinemic-euglycemic clamp (basal, 10, 16 and 80 mU/m2/min of insulin [I]) with isotopic tracers was performed the following AM to assess adipose, hepatic and muscle IR, respectively. Free fatty acids (FFA), glucose rate of disappearance (Rd) and glycerol and glucose rate of appearance (Ra) and %suppression (basal to 80 phase) were calculated.

Results: Participant age, sex, BMI and Tanner stage were similar between groups. HbA1c was similar in groups with diabetes. During the basal phase, glycerol Ra/I and glucose Ra/I were similar between groups, but FFA/I was highest in obese controls (p<0.001). At phase 10, glycerol Ra/I was similar between groups but FFA/I at phase 10 and 16 were similarly higher in T1D and T2D vs. controls (p=0.004, p<0.001). At phase 16, glucose Ra/I and glycerol Ra/I were highest in T1D (p<0.001, p<0.001). At phase 80, T1D vs. T2D had similarly lower %glycerol Ra suppression than controls (p<0.001) but higher glycerol Ra/I and glucose Rd in T1D vs. T2D (p=0.003, p=0.042). T1D youth and controls had similar glucose Rd (p=0.25).

Conclusion: Obese youth with T1D have similar to worse adipose, worse hepatic, and less muscle IR than those with T2D. Treatment targeting obesity and IR is critically needed in T1D youth.


P. Wiromrat: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. B.C. Bergman: Consultant; Spouse/Partner; Novo Nordisk Inc., Sanofi US. Research Support; Self; Eli Lilly and Company. Speaker’s Bureau; Spouse/Partner; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. K.L. Tommerdahl: None. A. Baumgartner: None. L. Pyle: None. K.J. Nadeau: None.


American Diabetes Association (7-11-CD-08 to K.J.N.); National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; JDRF

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at