Lipoprotein abnormalities in diabetic nephropathy

Abstract

The risk of death from coronary heart disease (CHD) is substantially increased in diabetic nephropathy compared with normal subjects or diabetes without nephropathy. I tried to define abnormal plasma lipoproteins profiles contributing to the increased CHD risk in diabetic nephropathy. This study included: middle-aged to older type 2 diabetic patients with normoalbuminuria, microalbuminuria, and overt albuminuria; nondiabetic patients with primary renal disease; and normal control subjects. Triglyceride (TG) levels were significantly increased in type 2 diabetic patients with microalbuminuria and overt proteinuria. Glycemic control or insulin resistance were not associated with TG levels. Intermediate-density lipoprotein (IDL) and remnant-like particle (RLP) cholesterol in type 2 diabetics were significantly elevated in patients with overt nephropathy. Hepatic TG lipase (HTGL) was significantly decreased in diabetic nephropathy, and their higher IDL levels were inversely related to decreased HTGL. Low-density lipoprotein (LDL) size was significantly smaller in diabetic nephropathy compared with nondiabetics with kidney disease. The TG response after the oral fat load was significantly greater in diabetic nephropathy, and the LDL size was inversely associated with the magnitude of postprandial lipemia. Microalbuminuric diabetic patients had a lower lipoprotein lipase (LPL) mass and a higher von Willebrand factor (vWF), an indicator of endothelial cell damage, than normoalbuminuric patients. The LPL mass was inversely associated with vWF, suggesting that widespread endothelial cell damage results in a reduction in LPL bound to endothelium in diabetic subjects with microalbuminuria. Plasma lipoprotein profiles become more atherogenic in patients with diabetic nephropathy, including the subclinical stage, compared with diabetics without nephropathy or those with nondiabetic kidney disease.