1931-P: Skeletal Muscle (SM) Insulin Resistance (IR) in Coronary Artery Disease (CAD) in Type 1 Diabetes (T1D)

IR in T1D may contribute to CAD risk. We recently reported that SM IR in T1D primarily involves oxidative SM while glycolytic SM is comparable to healthy controls. This study compared systemic glucose disposal (GD) and SM IR in T1D with and without CAD. Insulin-infusion glucose clamps measured systemic GD concurrent with positron emission tomography (PET) imaging of SM glucose uptake with [¹⁸F]fluorodeoxyglucose (FDG) to profile glucose transport and phosphorylation, rate-limiting steps for GD. PET images were co-registered with MRI of the calf to determine FDG uptake (Patlak K) in soleus (SO) SM (largely oxidative muscle, type 1 fibers) vs. tibialis anterior (TA) SM (largely glycolytic muscle, type 2 fibers). Subjects with (n=9) and without (n=10) CAD were from the Epidemiology of Diabetes Complications (EDC) study, a 30-year prospective study of childhood onset T1D. Those CAD+ were older (52.4 vs. 43.1 years, p <0.01), heavier (BMI 28.0 vs. 24.3 kg/m², p<0.05), and had higher systolic blood pressure (137 vs. 116 mmHg, p <0.05), each a factor disposing to IR. Groups did not differ in HbA_1c (7.6 vs. 7.6%), insulin dose (0.59 vs. 0.59 U/kg), waist circumference (91.7 vs. 85.2 cm, p=0.07 controlled for sex), creatinine (1.0 vs. 0.9 mg/dL), CKD-EPI (78.9 vs. 93.1 mL/minute/1.73m²), or lipids. Those CAD+ did not differ from CAD- in systemic GD (5.40 vs. 4.95 mg/kg-FFM, p=0.59). In SM, FDG uptake in SO did not differ in T1D CAD+ vs. CAD- (0.0080 vs. 0.0075 mL/cm³-minute), though these values were reduced by 40% compared to controls (n=13). FDG uptake in TA SM was greater in T1D CAD+ vs. CAD- (0.0133 vs. 0.0077 mL/cm³-minute, p<0.01), and was also higher than in controls. Neither systemic nor SM IR were more severe in T1D with CAD compared to T1D without CAD. SM IR in T1D is present in oxidative type SM regardless of CAD, yet IR in T1D is not evident in glycolytic SM. Moreover, insulin-stimulated glucose transport/phosphorylation is increased in TA SM of T1D with CAD, perhaps as a compensatory heightening of insulin action in glycolytic SM.