Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes
MR Rickels, SM Kong, C Fuller… - The Journal of …, 2013 - academic.oup.com
MR Rickels, SM Kong, C Fuller, C Dalton-Bakes, JF Ferguson, MP Reilly, KL Teff, A Naji
The Journal of Clinical Endocrinology & Metabolism, 2013•academic.oup.comContext: Islet transplantation can improve metabolic control for type 1 diabetes (T1D), an
effect anticipated to improve insulin sensitivity. However, current immunosuppression
regimens containing tacrolimus and sirolimus have been shown to induce insulin resistance
in rodents. Objective: The objective of the study was to evaluate the effect of islet
transplantation on insulin sensitivity in T1D using euglycemic clamps with the isotopic
dilution method to distinguish between effects at the liver and skeletal muscle. Design …
effect anticipated to improve insulin sensitivity. However, current immunosuppression
regimens containing tacrolimus and sirolimus have been shown to induce insulin resistance
in rodents. Objective: The objective of the study was to evaluate the effect of islet
transplantation on insulin sensitivity in T1D using euglycemic clamps with the isotopic
dilution method to distinguish between effects at the liver and skeletal muscle. Design …
Context
Islet transplantation can improve metabolic control for type 1 diabetes (T1D), an effect anticipated to improve insulin sensitivity. However, current immunosuppression regimens containing tacrolimus and sirolimus have been shown to induce insulin resistance in rodents.
Objective
The objective of the study was to evaluate the effect of islet transplantation on insulin sensitivity in T1D using euglycemic clamps with the isotopic dilution method to distinguish between effects at the liver and skeletal muscle.
Design, Setting, and Participants
Twelve T1D subjects underwent evaluation in the Clinical and Translational Research Center before and between 6 and 7 months after the transplant and were compared with normal control subjects.
Intervention
The intervention included intrahepatic islet transplantation according to a Clinical Islet Transplantation Consortium protocol under low-dose tacrolimus and sirolimus immunosuppression.
Main Outcome Measures
Total body (M/Δinsulin), hepatic (1/endogenous glucose production ·basal insulin) and peripheral [(Rd − endogenous glucose production)/Δinsulin] insulin sensitivity assessed by hyperinsulinemic (1 mU·kg−1·min−1) euglycemic (∼90 mg/dL) clamps with 6,6-2H2-glucose tracer infusion were measured.
Results
Glycosylated hemoglobin was reduced in the transplant recipients from 7.0% ± 0.3% to 5.6% ± 0.1% (P < .01). There were increases in total (0.11 ± 0.01 to 0.15 ± 0.02 dL/min·kg per microunit per milliliter), hepatic [2.3 ± 0.1 to 3.7 ± 0.4 × 102 ([milligrams per kilogram per minute]−1·(microunits per milliliter)−1)], and peripheral (0.08 ± 0.01 to 0.12 ± 0.02 dL/min·kg per microunit per milliliter) insulin sensitivity from before to after transplantation (P < .05 for all). All insulin sensitivity measures were less than normal in T1D before (P ≤ .05) and not different from normal after transplantation.
Conclusions
Islet transplantation results in improved insulin sensitivity mediated by effects at both the liver and skeletal muscle. Modern dosing of glucocorticoid-free immunosuppression with low-dose tacrolimus and sirolimus does not induce insulin resistance in this population.
Oxford University Press