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Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes
Author(s) -
Rydzon Brett,
Monson Rebecca S.,
Oberholzer Jose,
Varady Krista A.,
Bellin Melena D.,
Danielson Kirstie K.
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2972
Subject(s) - medicine , insulin resistance , endocrinology , type 2 diabetes , exenatide , islet , insulin , diabetes mellitus , transplantation , homeostatic model assessment , leptin , type 2 diabetes mellitus , obesity
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.