Decreased activated protein C levels are inversely associated with the urinary albumin excretion rate in patients with type 2 diabetes.

ABSTRACT

BACKGROUND: Activated protein C (APC) plays a vital renoprotective role against diabetic nephropathy in STZ-induced diabetic mice by inhibiting endothelial cell and podocyte apoptosis. This study aimed to examine the relationship between the degree of albuminuria and APC levels in patients with type 2 diabetes. METHODS: Ninety-four patients with type 2 diabetes and 38 healthy subjects were recruited into this study. The urinary albumin concentrations of urine collected over 24 hours were measured by ELISA to evaluate the mean urinary albumin excretion rate (UAER). The HbA1c levels were determined using an HPLC assay. RESULTS: There was no significant difference in the APC levels between diabetic patients with normoalbuminuria and controls, although APC levels were significantly lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) or macroalbuminuria (8.06 +/- 10.09 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) as compared to control subjects. In addition, in comparison to diabetic patients with normoalbuminuria, APC levels were lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 55.69 +/- 31.98 pg/mL, p < 0.05) and they were the lowest in diabetic patients with macroalbuminuria (8.06 +/- 10.09 vs. 55.69 +/- 31.98 pg/mL, p < 0.05). Multivariate regression and ROC analysis found that the levels of APC and HbA1c were independent risk factors for UAER levels (R2(ad) = 0.61, f = 25.69, p < 0.01) and the value of APC < or = 41.588 pg/mL indicated elevated albuminuria in patients with type 2 diabetes. CONCLUSIONS: Decreased APC levels in patients with type 2 diabetes may serve as a biomarker to indicate the early development of diabetic nephropathy.