ApoE polymorphism and albuminuria in diabetes mellitus: a role for LDL in the development of nephropathy in NIDDM?

Abstract

Chronic hyperglycaemia stands with diabetes duration as the main predicting factor for the development of nephropathy in insulin dependent diabetes mellitus (IDDM). In contrast, nephropathy in non-insulin-dependent diabetes mellitus (NIDDM) presents with a different natural history and, as well as atherosclerosis, can precede diabetes diagnosis and even the onset of patent hyperglycaemia. The role of lipid abnormalities in this matter remains debated. We studied the prevalence of nephropathy (N+ = urinary albumin excretion rate (UAE) > 20 mg/d) in 134 Caucasian NIDDM patients ranked according to alipoprotein E (apoE) genotype (same distribution in 132 controls). Age, diabetes duration and sex ratio did not differ between N+ and N-. A patient with E2E4 (n = 1) was excluded from the analysis. The prevalence of nephropathy was significantly reduced in E2 allele carriers (36%, 8/22) vs 69% (77/111) in E2 non-carriers (P < 0.01). Relative risk (RR) of E2 carriers developing nephropathy was 0.52 (95% CI = 0.35-0.80). Both groups were comparable in terms of age (55 +/- 11 vs 57 +/- 11 years), diabetes duration (15 +/- 9 vs 14 +/- 10 years) and prevalence of retinopathy (59 vs 48%). Similar results were observed when patients with diabetes duration longer than 8 years were studied (n = 94). It has been largely established that low-density lipoprotein (LDL)-cholesterol level in E2 allele carriers (whether diabetic or not) was lower than in E2 non-carriers. The 2-fold increase of nephropathy in E2 non-carriers with NIDDM argues for a role for LDL in the development of human nephropathy in NIDDM patients. This result is in agreement with previous data established both in vitro and in vivo in animal models. These findings support evidence for the pathogenic and morphologic similarities between kidney disease and atherosclerosis in NIDDM patients.