Insulin Resistance in Type 1 Diabetes: Determinants and Clinical Consequences

Insulin resistance (IR) is well documented in type 1 diabetes (T1D) and is theorized to relate to diabetes complications, including renal and coronary artery disease (CAD). The hyperinsulinemic-euglycemic clamp technique provides accurate assessment of IR, yet the laborious, costly, and invasive nature of this technique is often inappropriate for large investigations. Increasing use of the Estimated Glucose Disposal (eGDR) equation in T1D makes further examination of this equation desirable as it may be improved with additional assessments. Leg adiposity has been favorably associated with IR and cardiovascular risk, but whether this protective tendency is similar in T1D populations is unknown. This dissertation examines whether diabetes complications or additional clinical factors (i.e. regional adiposity distribution) contributes to the estimation of IR in T1D. Differences in regional adiposity, and the extent to which these differences influence IR, were examined in T1D and individuals without diabetes. Associations between CAD risk factors and regional adiposity were also investigated in individuals with T1D. No differences in IR were observed between T1D individuals with CAD or renal disease. All adiposity measures were detrimentally associated with IR, however, general obesity most strongly predicted IR in this population. Despite lower levels of adiposity, more severe IR was observed in individuals with T1D compared to non-diabetic individuals. Leg adiposity was favorably associated with presence of CAD, even after controlling for general obesity, but this association was only observed in non-diabetes and in T1D individuals who were obese. Trunk and leg fat displayed equal yet opposite associations with CAD risk factors and increasing leg adiposity was associated with decreased risk for the presence of CAD in females with T1D. This dissertation thus yields significant Public Health findings by providing evidence that IR is a prominent feature in T1D, is largely driven by adiposity, and can be estimated using clinical measures. Furthermore, the finding that leg adiposity was favorably associated with presence of CAD in individuals with T1D provides impetus to further study and underscores the complex association of adiposity with morbidity in T1D