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C-reactive protein is associated with high- normal urinary albumin excretion in normotensive and normoalbuminuric type 1 diabetic patients

An association of low-grade inflammatory markers with diabetic nephropathy has been proven in type 1 diabetic patients. As it is well known that the degree of albuminuria is closely related to the progression of nephropathy, we aimed to determine whether C- reactive protein and homocysteine value significantly differs between type 1 diabetic patients with high normal and low normal urinary albumin excretion. Patients and Methods. Two hundred and ten normoalbuminuric (urinary albumin excretion < 30mg/24h measured at three occasions, ) and normotensive (casual BP <130/80 mmHg at three occasions) type 1 diabetics were included. They were divided upon the albumin excretion median (16, 2mg/24h) into low-normoalbuminuric (n=116) and high- normoalbuminuric group (n=94). None showed signs of renal or cardiovascular disease and received antihypertensive or other drugs that could attenuate low-grade inflammation. Urinary albumin concentration was determined by an immunoturbidimetric assay. C reactive protein was measured by radioimmunoassay. Homocysteine was measured by chemiluminiscence. Results. The low-normoalbuminuric (UAE= 8, 02± ; ; ; 4, 56) and high-normoalbuminuric group (UAE= 23, 41± ; ; ; 6, 16, p=0.0001) did not differ regarding age, gender, BMI, HbA1c, systolic and diastolic blood pressure, HDL cholesterol, triglycerides, creatinine clearance, smoking status. High- normoalbuminuric in comparison to low- normoalbuminuric group showed significantly higher duration of diabetes (18, 2 ± ; ; ; 9, 18 ; 14± ; ; ; 8, 98 ; p=0.003) and C- reactive protein value (2, 17± ; ; ; 4, 94 ; 1, 17 ± ; ; ; 2 mg/l ; p=0.04). Homocysteine was also higher in the high-normoalbuminuric compared to low-normoalbuminuric group, but the level did not reach the statistical significance (9, 53± ; ; ; 7, 64 ; 9 ± ; ; ; 2, 89 μ mol/l ; p=0.56). Urinary albumin excretion was positively correlated with diabetes duration, BMI, triglycerides, C-reactive protein, homocysteine, diastolic blood pressure and inversly with HDL. C- reactive protein was positively correlated with diabetes duration, BMI, triglycerides, urinary albumin excretion, homocysteine and inversely to HDL. In a multiple regression analysis with diabetes duration, BMI, HDL, triglycerides, urinary albumin excretion, homocysteine and HDL cholesterol in a model, C-reactive protein was independently associated with urinary albumin excretion (β =0, 103), homocysteine (β =0, 259) and diabetes duration (β =0, 63 ; p=0.001). Conclusion. C reactive protein, a low-grade inflammatory marker, is associated with high- normal urinary albumin excretion in type 1 diabetic patients. The independent relation of diabetes duration with C-recative protein suggests that chronic exposure to glucose may stimulate its production already at the normoalbuminuric stage. Whether the detection of increased C-reactive protein value in normoalbuminuric type 1 diabetics has predictive value for development of microalbuminuria needs to be assessed.

C-reactive protein ; homocysteine ; normoalbuminuria ; type 1 diabetes

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