Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes

Background: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. Methods: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SI_is; 95 observations). Results: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P =.02), then stabilized (P =.39); HOMA-IR remained stable posttransplant (P =.92). Adjusting for age and BMI, higher SI_is was associated with lower HbA1c following transplant (P =.03). Greater IS as measured by lower HOMA-IR and higher SI_is was associated with lower fasting C-peptide (both P ≤.04) and also with higher exenatide dose (both P ≤.01). More islets transplanted were associated with higher SI_is (P <.0001). Lower leptin at transplant predicted lower HOMA-IR and higher SI_is after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤.01). Conclusions: Insulin sensitivity measured by SI_is was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.