期刊
DIABETES CARE
卷 31, 期 12, 页码 2338-2343出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc08-0277
关键词
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资金
- National Institutes of Health (NIH) [K08 DK066246]
- Juvenile Diabetes Research Foundation [1-2000-646]
- Earle P. Charlton, Jr. Charitable Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
OBJECTIVE - Progressive nephropathy represents a substantial source of morbidity and mortality in type 1 diabetes. Increasing albuminuria is a strong predictor of progressive renal dysfunction and heightened cardiovascular risk. Early albuminuria probably reflects vascular endothelial dysfunction, which may be mediated in part by chronic inflammation. RESEARCH DESIGN AND METHODS - We measured baseline levels of four inflammatory biomarkers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1, and soluble tumor necrosis factor-alpha receptor-1) in stored blood samples from the 1,441 participants of the Diabetes Control and Complication Trial (DCCT). We used mixed-effects regression models to determine the average annual change in urinary albumin excretion rate (AER) by tertiles of each biomarker. We also used Cox proportional hazards models to estimate the relative risk of incident sustained microalbuminuria according to levels of each biomarker. RESULTS - After adjustment for baseline age, sex, duration of diabetes, AlC, and randomized treatment assignment, we observed a significantly higher 5.9 mu g.min(-1).year(-1) increase in AER among those in the highest compared with the lowest tertile of baseline sICAM-1 (P = 0.04). Those in the highest tertile of sICAM-1 had an adjusted relative risk of 1.67 (95% CI 0.96-2.92) of developing incident sustained microalbuminuria (P-treand = 0.03). CONCLUSIONS - Higher baseline sICAM-1 levels predicted an increased risk of progressive nephropathy in type I diabetes and may represent an early risk marker that reflects the important role of vascular endothelial dysfunction in this long-term complication.
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