1959-LB: An Insulin-Modified Oral Glucose Tolerance Test (OGTT) to Assess Insulin Resistance (IR) in Type 1 Diabetes (T1D)

IR is a key contributor to cardiovascular disease in T1D and increasingly so with increased rates of obesity in T1D. IR is difficult to measure in T1D due to absent insulin secretion. The hyperinsulinemic euglycemic clamp (HEC) is the gold-standard method for assessing IR in T1D, but is cumbersome, especially in youth. We thus adapted the simpler and more physiologic OGTT to T1D and assessed its performance vs. the HEC in T1D adolescents who use insulin pumps. Each youth underwent admission with variable overnight intravenous insulin infusion, followed by an AM HEC with 80mU/m2/min insulin infusion paired with a variable glucose infusion rate (GIR, 20% dextrose infusion). IR was assessed by end-HEC steady-state GIR. On a separate day, each youth underwent an OGTT. The participant’s insulin pump basal rate was left running with autocorrection mode suspended, and a subcutaneous injection of regular insulin given using the participant’s home insulin:carbohydrate ratio and blood glucose correction factor. 30 minutes later, a 75-gram Glucola was consumed (T=0). Blood samples were taken at T=-30, -20, -5, 0, +10, +20, +30, +45, +60, +75, +90, +120, and IR calculated via the Matsuda Index, which correlates well with HEC in non-T1D populations. Spearman correlations between GIR and Matsuda Index were performed. Descriptive statistics were examined for normality, then expressed as median (25th,75th) or mean ± SD. 17 pubertal youth (10 girls, 7 boys) 14-17 yrs of age (15.8 ± 0.9 yrs) were enrolled (BMI 20.0 19.4, 24.8 kg/m2, HbA1c 7.6 ± 1.1%). Mean HEC GIR was 10.0 ± 4.6 mg/kg/min; Matsuda was 4.9 ± 4.0 (unitless). GIR correlated with Matsuda Index (r=0.54, p=0.025). In T1D youth, HEC-assessed IR correlated well with insulin-augmented OGTT Matsuda Index. Future work will compare different methods of calculating IR from an OGTT to determine the optimal method and incorporate isotope tracers to allow tissue-specific IR measures. An insulin-modified OGTT is a viable option to assess IR in T1D. Disclosure K.J. Nadeau: None. A. Bernard: None. A. Baumgartner: None. A. Hines: None. A. Bailey: None. G. Carey: None. L. Pyle: None. C. Diniz Behn: Research Support; Lumos Tech. J.K. Snell-Bergeon: None. M.G. Cree: Consultant; Pollie, Inc. Research Support; Amino Co. Funding JDRF (2-SRA-2022-1144-M-B)