Atherogenic lipoprotein changes in diabetic nephropathy

Cardiovascular risk is increased in patients with diabetic nephropathy. The aim of this study was to examine the relative impacts of albuminuria and renal failure, the two important features of diabetic nephropathy, on potentially atherogenic lipoprotein changes in this condition. The subjects were 160 non-diabetic healthy controls and a total of 200 type 2 diabetes patients with various degrees of nephropathy. The diabetic patients were divided into four groups by urinary albumin/creatinine ratio (U-ACR) and serum creatinine (S-Cr) levels: DM-1 (U-ACR<30 mg/g, N=85), DM-2 (U-ACR=30–300 mg/g, N=48), DM-3 (U-ACR>300 mg/g, N=29) and DM-4 (S-Cr>177 μmol/l or 2.0 mg/dl, N=38). Lipids in very low (VLDL), intermediate (IDL), low (LDL), and high density (HDL) lipoproteins were measured following ultracentrifugation. VLDL-cholesterol (VLDL-C) was elevated (by 73–100%) in diabetic patients and it did not differ among the stages of nephropathy. IDL-C was higher as the nephropathy stage was advanced, and the elevation was significant in the DM-3 (by 75%) and DM-4 (by 131%) groups. LDL-C was not elevated in diabetic patients and was not different among the stages of nephropathy. Reduction of HDL-C was significant in DM-1, DM-2 and DM-3 (by 12–16%) and it was more exaggerated in DM-4 (by 35%). Multiple regression analyses indicated that elevated S-Cr, but not U-ACR, was an independent factor associated with raised IDL-C and lowered HDL-C in diabetic patients. These results indicate that diabetic patients with nephropathy show multiple lipoprotein changes, and that renal failure has greater impact than albuminuria on abnormalities in IDL and HDL. These lipoprotein alterations may contribute to an increased cardiovascular risk in diabetic nephropathy, especially in diabetic renal failure.