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Biomarkers in the progression of nephropathy in type 2DM


There is a growing recognition that dyslipidemia and elevated inflammatory biomarkers are associated with nephropathy as well as with the insulin-resistant state characteristic of type 2 diabetes. Most investigations, however, have examined these biomarkers and kidney function only in those with severe chronic kidney disease or end-stage renal disease in a cross-sectional manner. A few recent studies suggest that dyslipidemia and inflammation may contribute to subsequent glomerular filtration rate (GFR) decline, but only baseline biomarkers have been examined in this context. The effects of how alterations in lipids and inflammation over time affect kidney function over time are not known. This prospective study seeks to expand on currently funded work that focuses on identifying predictors of progressive nephropathy in type 2 diabetes, which is the leading cause of kidney failure in the world. The central hypothesis is that increasing or sustained high levels of dyslipidemia and inflammation over 11 years (1989 to 2000) will be independently associated with progressive nephropathy, as measured by estimated GFR decline and increased albuminuria over a subsequent eight years of follow-up (2000 to 2008), in 500 women with confirmed type 2 diabetes who are participating in the Nurses' Health Study (NHS). Biomarkers of interest in this investigation include total cholesterol, low-density lipoprotein, triglycerides, high-density lipoproteins, soluble tumor necrosis factor-(, fibrinogen, and C-reactive protein. Several of these biomarkers are significantly inversely associated with estimated GFR in preliminary cross-sectional studies in this NHS cohort. Multivariable regression will be used to adjust for important covariates such as age, duration of diabetes, body mass index, hypertension, cigarette smoking and other medication use, which may confound associations between biomarkers and progressive nephropathy in type 2 diabetes. Data on how these modifiable biomarkers are related to kidney function decline could have an important and beneficial impact on treatment and monitoring of nephropathy in type 2 diabetes in the near future.


Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.