Brett Rydzon1,2, Rebecca S Monson1, Jose Oberholzer1, Krista A Varady3, Melena D Bellin4, Kirstie K Danielson1,2. 1. Division of Transplant Surgery, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA. 2. Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA. 3. Department of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA. 4. Division of Pediatric Endocrinology, Medical School, University of Minnesota, Minneapolis, MN, USA.
Abstract
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 (SIis ; 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 SIis was associated with lower HbA1c following transplant (P = .03). Greater IS as measured by lower HOMA-IR and higher SIis 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 SIis (P < .0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis 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 SIis 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.
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 (SIis ; 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 SIis was associated with lower HbA1c following transplant (P = .03). Greater IS as measured by lower HOMA-IR and higher SIis 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 SIis (P < .0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis 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 SIis 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.
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