DIFFERING EFFECTS OF PANCREAS-KIDNEY TRANSPLANTATION WITH SYSTEMIC VERSUS PORTAL VENOUS DRAINAGE ON CHOLESTERYL ESTER TRANSFER IN IDDM SUBJECTS

OBJECTIVE - Cholesteryl ester transfer (CET) is accelerated in patient s with IDDM treated with conventional (subcutaneous) insulin therapy ( CIT) and a number of other disorders associated with premature cardiov ascular disease. We have shown that in IDDM this disturbance is closel y linked to iatrogenic hyperinsulinemia (HI), because it was reversed when insulin was administered by the intraportal (IP) route. In this s tudy, we sought to determine whether HI after successful pancreas-kidn ey transplantation (PKT) has the same adverse effect on CET. RESEARCH DESIGN AND METHODS - CET was measured by both mass and isotopic assays and compared in two groups of euglycemic non-insulin-requiring IDDM P KT patients with either systemically draining allografts and persisten t HI or grafts with portal vein anastomoses that were normoinsulinemic (PK-P). A third group of eight nondiabetic kidney transplant (KT) pat ients receiving the same immunosuppressive drugs served as control sub jects. RESULTS - CET in pancreas-kidney transplantation subjects with systemic venous drainage (PK-S) was increased (P < 0.001) to the same level we have reported previously in IDDM patients receiving CIT and w as significantly higher (P < 0.001) than in those subjects with PK-P. CET in the PK-P group did not differ from that of the KT control patie nts. CONCLUSIONS - CET is affected by variations in systemic insulin l evels in pancreas transplant patients with allografts that have differ ing Venous drainage, Because high systemic insulin levels are linked t o the activation of CET, euglycemic HI IDDM pancreas allograft recipie nts may continue to be at high risk For macrovascular complications.