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

• Published in: Diabetes/metabolism research and reviews 2018-03, Vol.34 (3), p.n/a
• Main Authors: Rydzon, Brett, Monson, Rebecca S., Oberholzer, Jose, Varady, Krista A., Bellin, Melena D., Danielson, Kirstie K.
• Format: Article
• Language: English
• Subjects: Biomarkers - analysis; Blood Glucose - analysis; Clinical trials; Clinical Trials, Phase I as Topic; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - surgery; exenatide; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin A - analysis; Homeostasis; Humans; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - therapeutic use; Insulin Resistance; insulin sensitivity; islet cell transplantation; Islets of Langerhans Transplantation; Leptin; Ligands; Longitudinal Studies; Male; Metabolism; Middle Aged; Pancreatic islet transplantation; Prognosis; receptor activator of nuclear factor kappa‐B ligand (RANKL); Transplants & implants; type 1 diabetes
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.2972

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