Circulating markers of endothelial dysfunction in type 2 diabetic patients with microalbuminuria

Background: Progressive nephropathy represents a substantial source of morbidity and mortality in type 2 diabetes. Increasing albuminuria is a strong predictor of progressive renal dysfunction and heightened cardiovascular risk. Endothelial damage is associated with albuminuria. VonWillebrand factor (vWf) and Thrombomodulin (TM) are possible markers of endothelial dysfunction and damage.

Objectives: We studied the relationship between plasma vWf, TM, and urinary albumin excretion.

Methods: We conducted on 90 diabetic patients fulfilled the WHO criteria for type 2 diabetes. Diabetic patients were placed into three groups according to urinary albumin concentration (UAC) in a 24-hour urine collection. Group I: included 30 patients with normal urinary albumin concentration (without nephropathy); microalbumin/24 hour urine less than 30 mg. Group II: included 30 patients with microalbuminuria (incipient diabetic nephropathy), microalbumin/24 hour urine from 30 to 299 mg. Group III: included 30 patients with macroalbuminuria (overt diabetic nephropathy); microalbumin/24 hour urine greater than 300 mg. We measured plasma levels of vonWillebrand factor (vWf) and Thrombomodulin (TM) as markers of endothelial dysfunction, to evaluate their relationship to urinary albumin excretion in patients with type 2 diabetes mellitus.

Results: There were significant increase in the levels of cholesterol and triglyceride, and significant decrease in HDL in group III compared to the control group, while it was highly significant with group II and III. TM levels showed no significant difference between control group and group I while it was highly significant with group II and III (p <0.01), also there was highly significant difference between group I and III (p <0.01). TM index showed no significant difference between control group and group I and II, while there was highly significant difference between control group and group III (p <0.01) and highly significant difference between group II and III (p <0.01). Albumin concentration in 24 hours urine showed no significant difference between control group and group I, while there were highly significant difference between control group and group II and III (p <0.01), also there was significant difference between group II and III (p <0.01). There were highly significant positive correlation between vWF, TM levels and all studied variables. Multivariate analysis which showed that total cholesterol, urinary albumin and age retained significant influence on the plasma vWF and TM.

Conclusions: These results suggested that generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage. Hence, plasma vWF and TM represents valuable markers of endothelial dysfunction that could be used for early detection of diabetic microvascular complications.