1311-P: Insulin Resistance in Non-obese Young Adults with Type 1 Diabetes

Abstract

Insulin resistance has been noted in youth and adults with type 1 diabetes (T1D) and is associated with higher levels of cardiovascular and kidney complications. Obesity is increasing in populations with T1D, and the degree of insulin resistance in younger adults with T1D who are free from complications and non-obese isn’t clear. We performed hyperinsulinemic euglycemic clamps in non-obese adults aged 20-45 with and without T1D. Inclusion criteria included diabetes duration > 5 years and HbA1c <9% among people with T1D, or no diabetes based on fasting glucose and HbA1c among controls; Body mass index (BMI) < 30 kg/m2, no use of statins or other medication affecting insulin sensitivity, non-smokers and normal thyroid function. Participants were given a fixed macronutrients study diet for 2 days and were asked to refrain from vigorous exercise for 72 hours. Clamps were performed by a single investigator after an overnight stay. A sliding scale insulin infusion was used overnight for participants with T1D. Arterial stiffness (brachial artery distensibility, pulse wave velocity and reactive hyperemia index) was assessed. There were 47 participants, 24 with T1D and 23 without diabetes. 53% were women (25/47), and the average age did not differ between controls and people with T1D (31 ± 6 years vs. 28 ± 6 years, p=0.12). Whole body insulin sensitivity estimated by glucose infusion rate (GIR) per kg fat free mass was reduced by more than half in adults with T1D (LS mean ± SE =5.4 ± 1.0 mg/kg FFM/min) compared to adults without diabetes (12.7 ± 1.0 mg/kg FFM/min, p<0.0001). In contrast, there were no differences in BMI, body fat, urinary albumin, or measures of arterial stiffness by diabetes status. Young, non-obese adults with T1D are profoundly insulin resistant compared to nondiabetic adults, even when no differences in vascular stiffness or kidney complications are apparent. These results suggest that insulin resistance may occur earlier than vascular or kidney complications in people with T1D and is independent of obesity. Disclosure C.J. Chartier-Logan: None. I.E. Schauer: None. M. Cree-Green: Consultant; Pollie Inc. Research Support; Amino Corp LLC. L. Pyle: None. B.C. Bergman: Research Support; Eli Lilly and Company. J.K. Snell-Bergeon: None. Funding JDRF (2-SRA-2019-849-S-B)