EFFECTS OF PANCREAS TRANSPLANTATION ON DISTRIBUTION AND COMPOSITION OF PLASMA-LIPOPROTEINS

In type I (insulin-dependent) diabetic patients, peripheral hyperinsul inemia due to subcutaneous insulin treatment is associated with increa sed high-density lipoprotein (HDL) cholesterol, and also with an alter ed surface composition of HDL. Pancreas grafts also release insulin in to the systemic rather than into the portal venous system, giving rise to pronounced peripheral hyperinsulinemia. We hypothesized that if pe ripheral hyperinsulinemia is responsible for high HDL cholesterol and/ or altered surface composition of HDL in diabetic subjects, similar ch anges in the lipid profile should be present in pancreas-kidney transp lant recipients (PKT-R). Using zonal ultracentrifugation, we isolated HDL(2), HDL(3), very-low-density lipoprotein (VLDL), intermediate-dens ity lipoprotein (IDL), and low-density lipoprotein (LDL) from fasting plasma of 14 type I diabetic PKT-R, eight nondiabetic kidney transplan t recipients (KT-R), and 14 healthy control subjects and determined th e level and composition of the above lipoproteins. HDL(2) cholesterol was increased in PKT-R as compared with KT-R and healthy controls (bot h P < .05), whereas HDL(3) cholesterol was unchanged. However, an alte red lipoprotein surface composition was evident in PKT-R: HDL(2), HDL( 3), and LDL were enriched in unesterified cholesterol ([UC] PKT-R v KT -R, P = .13, P < .005, and P < .05, respectively; PKT-R v controls, al l P < .005); HDL was enriched in phospholipids; and LDL was depleted o f phospholipid. KT-R, in contrast, showed no changes in lipoprotein su rface composition but a substantial triglyceride enrichment of HDL(2) as compared with PKT-R and healthy controls (both P < .05). LDL size a s determined by gradient gel electrophoresis was increased in PKT-R co mpared with controls (P < .005). The plasma concentration of cholester yl ester (CE) transfer protein (CETP), involved also in phospholipid t ransfer, was increased in both transplant groups compared with healthy controls (both P < .05). Insulin concentrations in fasting plasma wer e directly related to CETP levels and to the weight-percentage of UC i n HDL(3), and inversely to the weight-percentage of phospholipids in L DL (all P < .05). We explain the increase in HDL(2) cholesterol and LD L size in PKT-R by their high lipoprotein lipase (LPL) activity confer ring an excellent capacity to clear chylomicron triglycerides. Effecti ve handling of postprandial triglycerides, high HDL(2) cholesterol, an d predominance of LDL pattern A, respectively, are established indicat ors of a low risk of atherosclerosis. However, it is presently unclear what effects the compositional changes on the surface of HDL and LDL may have on cardiovascular risk in clinically stable PKT-R. Copyright (C) 1996 by W.B. Saunders Company