Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: Effect of kidney and pancreas transplantation

Abstract

Chronic renal failure (CRF) in nondiabetics is associated with a number of lipoprotein abnormalities that place these patients at high risk for atherosclerosis. This study compared the lipoprotein composition of nondiabetic controls (n = 68) with that of patients with insulin-dependent diabetes mellitus ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], high-density lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC]) and lipid (by enzymatic assays) composition of each subfraction was determined. The only abnormalities found in IDDM patients were increases in IDL and HDL-L triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC) level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG, apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2) elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid (PL) levels (with an increased CE TG ratio in VLDL only); (3) decreased HDL-M apo A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4) decreased lecithin: cholesterol acyltransferase (LCAT) activity. Twenty-five of the IDDM + CRF patients underwent combined pancreas and kidney (P + K) transplantation, and 12 patients received only a kidney transplant. Lipoprotein composition was determined at 3, 6, and 12 months posttransplant. Both types of transplantation resulted in similar alterations in lipoprotein composition, even though there was essential normalization of blood glucose levels in most of the patients who received a pancreas transplant (hemoglobin A 1C [HbA 1C], 9.1% ± 1.1% v 5.7% ± 0.3% at 12 months, P < .01). These posttransplant changes included (1) no improvement in the elevated TG level in any lipid subfraction even though there was some reduction in apo C-III levels in VLDL; (2) reductions in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL apo C-III and FC concentrations despite an increase in LCAT activity; and (4) increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins. This is probably because the difference in glycemic control between the P + K group and the kidney-alone group is usually not associated with substantial abnormalities in lipoprotein composition. This study is too short to address the issue of whether pancreas transplantation can reduce the risk of atherosclerosis associated with IDDM and CRF. The immunosuppressive drugs and persistently abnormal renal function following transplantation probably adversely affected the lipoproteins. This is unfortunate because of the added urgency for lipoprotein normalization in these patients, since they are very likely to have advanced atherosclerotic disease, having typically experienced at least one cycle of renal failure and dialysis.