Continued insulin dependence despite normal range insulin sensitivity and insulin connecting peptide levels in a...

The majority of islet transplant recipients remain insulin-requiring, although many have near-normal connecting peptide (CP) levels. Insulin resistance may be one possible cause of the continuing need for exogenous insulin in islet transplant recipients. To assess this, we have studied the insulin sensitivity index (S1) in one patient with near-normal CP levels after islet transplant who remained insulin-requiring.

The islet transplant recipient is a 36-year-old woman with no residual CP who received a kidney transplant, followed 7 days later by an islet transplant. The islets were infused into the liver via the umbilical vein. Induction immunosuppression consisted of OKT3, prednisone, cyclosporin A, and azathioprine, with maintenance on the latter three.

Maximum CP levels after a standardized Sustacal meal were 2.09, 1.18, 0.85, and 0.81 nmol/l at 1,6,18, and 24 months posttransplant, respectively. Insulin requirements at the same times were 0.27, 0.45, 0.49, and 0.62 U.kg(-1).d(-1), while S1 was 36.3, 53.3, and 13.2 min (-1).nmol(-1).ml at 6,18, and 24 months, respectively. This compares with S1 values of 43.3+/- 10.0 min (-1).nmol(-1).ml for normal subjects.

This patient had near-normal S1 and CP levels, but she was unable to discontinue insulin therapy, suggesting that other factors are critical. Despite this, she maintained normal or near-normal glycated hemoglobins, indicating metabolic benefit from the islet transplant.