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Insulin Sensitivity, Glucose Effectiveness, and Free Fatty Acid Dynamics after Human Islet Transplantation for Type 1 Diabetes

Department of Medicine (M.R.R., K.L.T.), Division of Endocrinology, Diabetes, and Metabolism, Department of Surgery (A.N.), Division of Transplantation, and the Monell Chemical Senses Center (K.L.T.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149

Address all correspondence and requests for reprints to: Michael R. Rickels, M.D., University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, 778 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149. E-mail: rickels{at}mail.med.upenn.edu.

Context: Islet transplantation results in impaired insulin secretion, but whether defects in insulin sensitivity contribute to impaired glucose disposal after islet transplantation under modern immunosuppression is not known.

Objective: Our objective was to evaluate insulin sensitivity after islet transplantation performed under tacrolimus-based immunosuppression that used minimal steroids.

Setting: This study was conducted at the University of Pennsylvania General Clinical Research Center.

Participants: Eight islet transplant recipients, six type 1 diabetic (T1D), and 10 nondiabetic control subjects participated.

Intervention: We performed an insulin-modified frequently sampled iv glucose tolerance test to measure insulin sensitivity (S_I), glucose effectiveness, and free fatty acid (FFA) dynamics.

Results: S_I was significantly greater in the islet transplant and control groups, compared with the T1D group (P < 0.05 for both comparisons). Glucose effectiveness was not significantly different across all three groups but was lower by trend in the T1D and islet transplant groups, compared with the control group (P = 0.07 overall ANOVA). FFA levels suppressed normally in the transplant recipients, but the timing and magnitude of FFA suppression were significantly impaired in the T1D group, compared with the islet transplant and control groups (P < 0.05 for all comparisons). The acute insulin response to glucose and the disposition index (D_I = acute insulin response to glucose x S_I) were significantly lower in the islet transplant group, compared with the control group (P < 0.05 for all comparisons).

Conclusions: These data suggest that even modest restoration of insulin secretion in islet transplant recipients may result in improved insulin sensitivity and FFA dynamics.

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