Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients

Abstract

Diabetic nephropathy is associated with cardiovascular morbidity and mortality [1,2]. It is also associated with increased concentrations of serum total and LDL-cholesterol, triglyceride and apolipoprotein (apo)B [3,4,5,6]. In macroalbuminuria HDL-cholesterol is reduced but in microalbuminuric patients HDL-cholesterol has been reported to be reduced [3,4], unchanged [7,8] Abstract Aims/hypothesis. To examine whether the HDL-cholesterol:apoA-I + apoA-II ratio and the e2 allele are related to albuminuria at baseline and whether they are risk factors for progression of albuminuria in a cohort study of patients with Type I (insulin-dependent) diabetes mellitus. Methods. At baseline, the study cohort comprised 617 patients, aged 15±60 years, from seven European diabetic centres of the EURODIAB study. Albumin excretion rate, measured in a central laboratory, was categorised as normoalbuminuria at 20 mg/min or less, microalbuminuria between 20 and 200 mg/min or macroalbuminuria at 200 mg/min or over. Of the 250 patients who were normoalbuminuric at baseline and had follow-up albuminuria measurements, 34 patients were defined as early progressors. Results. At baseline, the mean HDL-cholesterol:apoA-I + apoA-II ratio was lower in macroalbuminuric patients (0.79, 95 % CI:0.74±0.83) compared with normoalbuminuric (0.88, 95 % CI:0.87±0.90) patients (p = 0.0002, adjusted for age and sex). At follow-up, 34 patients who progressed from normoalbuminuria to microalbuminuria or macroalbuminuria also had a slightly lower baseline ratio (0.85, 95 % CI:0.80±0.89) than those 216 who remained normoalbuminuric (0.89, 95 % CI:0.87±0.92) (adjusted p = 0.08). Neither of these relations were independent of LDL-cholesterol or fasting triglyceride. There was no association of the e2 allele with albuminuria either at baseline (OR = 1.4, 95 % CI:0.7±2.8) or with progression of albuminuria (OR = 0.4, 95 % CI:0.1±3.5). Conclusion/interpretation. There is an inverse relation of HDL-cholesterol:apoA-I + apoA-II ratio with albuminuria at baseline. This lower ratio in microalbuminuric or macroalbuminuric patients could contribute to the increased risk of cardiovascular disease associated with nephropathy. There is weak evidence that HDL-composition is a risk factor for progression of albuminuria and no association of the e2 allele with diabetic nephropathy. [Diabetologia 2000

Influence of Apolipoprotein E Genotype on Progression of Diabetic Nephropathy

“…One study reported an increase in progression from normalbuminuria to microalbuminuria to macroalbuminuria in patients with the apoE2 allele; however, the decline in renal function was not examined [21]. This is in contrast to a European study which failed to find an association between E2 and either baseline albuminuria, or progression to albuminuria in type 1 diabetes [22]. There has been one previous study showing that the apoE4 allele is associated with a faster rate of decline in glomerular filtration rate in patients with diabetic nephropathy [23].…”

A Retrospective Study on the Influence of Apolipoprotein E and Serum Lipids in Progressive Renal Failure

“…This finding is in agreement with the results of other studies in which triglycerides were part of multiple lipoprotein abnormalities in type 1 diabetic patients with nephropathy [19,20]. The apolipoprotein e2 allele has been reported to be a positive predictive factor for progression of renal failure in diabetes type 1 [21,22], while others could not find such association [23]. Because of the small number of patients, we analyzed progression rate by comparing e4 allele positivity vs. the rest.…”

Role of apolipoprotein E variants in lipoprotein glomerulopathy and other renal lipidoses

“…[4][5][6][7] However, the influence of apoE2 in diabetic nephropathy has been denied by other authors. [53][54][55][56] At present, the controversy has not been resolved, because these studies depend on statistical evaluation in casecontrol studies only. Because many essential factors promote the development of diabetic nephropathy, such statistical methods may not be sufficient to confirm the role of apoE.…”