Effect of steroid-therapy on insulin sensitivity in insulin-dependent diabetic patients after kidney transplantation

Abstract

Little information is available on glucose and energy metabolism in insulin-dependent diabetes mellitus (IDDM) patients receiving immunosuppression after kidney transplantation. We therefore measured insulin sensitivity (euglycemic insulin clamp in combination with indirect calorimetry and infusion of tritiated glucose) in (a) eight steroid-treated IDDM patients after kidney transplantation, (b) ten IDDM patients without nephropathy, (c) ten nondiabetic patients after kidney transplantation, and (d) ten healthy control subjects. Hepatic glucose production was enhanced in both steroid-treated transplanted IDDM patients [4.8 ± 0.6 mg/kg lean body mass (LBM)·min] and IDDM patients without complications (3.8 ± 0.2 mg/kg LBM·min) compared with nondiabetic renal graft recipients and with healthy controls (2.8 ± 0.2 and 2.7 ± 0.1 mg/kg LBM·min; p < 0.01). Insulin-stimulated glucose disposal was reduced in transplanted and non-transplanted IDDM patients and nondiabetic transplanted patients versus healthy controls (6.6 ± 0.8, 5.7 ± 0.7, and 7.5 ± 0.6 versus 9.3 ± 0.6 mg/kg LBM·min; p < 0.05). This reduction was mainly due to an impairment in nonoxidative glucose metabolism, i.e., glycogen synthesis (3.1 ± 0.6, 2.7 ± 0.4, and 3.3 ± 0.5 versus 5.0 ± 0.5 mg/kg LBM·min; p < 0.05 versus healthy controls). It is concluded that IDDM patients without nephropathy show both hepatic and peripheral insulin resistance. In IDDM patients a further increase of insulin resistance caused by treatment with corticosteroids can be corrected by increased insulin doses. However, nondiabetic steroid-treated renal graft recipients show insulin resistance comparable to IDDM patients.