Apolipoprotein B independently predicts progression of very—low-level albuminuria in insulin-dependent diabetes mellitus

The purpose of the study was to examine the contribution of alterations in lipoprotein metabolism to the progression of very—low-level albuminuria in insulin-dependent diabetes mellitus (IDDM). We measured serum concentrations of lipids, lipoproteins; and apolipoproteins in 53 normoalbuminuric diabetic patients without overt hypertension, whom we restudied after 10 years. Albuminuria was measured as the urinary albumin to creatinine ratio (UAUC) in repeated early-morning samples. Over 10 years, UAUC increased significantly (P < .001), and five patients (9.4%) progressed to microalbuminuria. The increase in albuminuria was significantly and positively related to the baseline serum concentrations of total cholesterol (P < .05), low-density lipoprotein (LDL) cholesterol (P = .05), non-high-density lipoprotein (HDL) cholesterol (P < .05), and apolipoprotein (apo) B (P < .001), but no significant associations were found with triglycerides, HDL cholesterol, apo A-1, or lipoprotein(a) [Lp(a)]. The relative risk of developing microalbuminuria for a serum apo B concentration more than 1.1 g/L was 3.8 (95% confidence interval [CI], 1.9 to 7.7). In multiple linear regression analysis, serum apo B (P < .05) and glycated hemoglobin ([HbA1] P < .05) at baseline were significant independent predictors of the increase in albuminuria, with no significant associations found for sex, smoking, duration of diabetes, mean arterial blood pressure (BP), or family history of cardiovascular disease and hypertension; the regression model predicted 42% of the variation in UAUC at 10 years. The findings suggest that an abnormality in the metabolism of apo B may be independently associated with progression of very—low-level albuminuria and possibly with the development of early nephropathy in IDDM patients.