Circulating monocyte chemoattractant protein-1 and early development of nephropathy in type 1 diabetes.
OBJECTIVE
To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes.


METHODS
We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment.


RESULTS
FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values.


CONCLUSIONS
This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.
D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003928:Diabetic Nephropathies / Q000097:blood*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D015227:Lipid Peroxidation; D012016:Reference Values; D012044:Regression Analysis; D013997:Time Factors; D014810:Vitamin E / Q000097:blood
D015415:Biomarkers; D018932:Chemokine CCL2; D006442:Glycated Hemoglobin; D014810:Vitamin E