There is evidence that IGF-1 enhances both renal blood flow and GFR by stimulating IGF-1 receptors (25). Moreover, in vivo studies in animal models have shown that renal vasodilation induced by IGF-1 infusion was http://www.selleckchem.com/products/U0126.html blocked by co-administration of NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide (NO) biosynthesis (26). In endothelial cells, IGF-1, interacting with its receptor, induces NO biosynthesis and upregulates expression of endothelial NO synthase (27). In human aortic endothelial cells and human dermal microvascular endothelial cells, IGF-1 receptors are more abundant than insulin receptors (28). It is therefore possible that the reduced eGFR that was observed in individuals with 1hPG ��155 mg/dl may be partially attributed to reduced activation of NO biosynthesis in renal vasculature as a consequence of lower IGF-1 levels.

Accordingly, we observed that the association between 1-hour postload hyperglycemia and CKD was abrogated after adjustment for IGF-1 levels, suggesting that kidney dysfunction may reflect an impairment in IGF-1 action. Finally, acute hyperglycemia 1 hour after oral glucose loading is closely associated with oxidative stress, which could promote renal damage via decreased production and availability of NO and accelerated formation of glycoxidation and lipid peroxidation products (28,29). The relatively large sample size, the inclusion of both genders, the homogeneity of the sample with detailed characterization of cardiometabolic variables, and the use of the new CKD-EPI equation to estimate GFR, which is more accurate at a higher GFR, are major strengths of this study.

Nevertheless, this study has certain limitations that require consideration. First, serum creatinine levels and estimated GFR were used to identify kidney function. Although gold standard methods to measure GFR (isotope clearance measurements) may provide a more sensitive estimate of renal function, they are very expensive procedures which are not feasible in large-scale studies. Thus, we believe that eGFR based on serum creatinine, as modified by the CKD-EPI group, and used in large epidemiologic studies for estimation of renal function (13), is reliable with relatively large data sets such as that analyzed in this study. Furthermore, it is possible that hyperfiltration associated with IGT may have masked declines in eGFR; however, that our results were unchanged when we excluded from the analysis individuals with IGT makes this possibility unlikely.

Unfortunately, we did not have information on microalbuminuria, which might have been a better marker of mild kidney disease. In addition, a single 75-g OGTT was used to measure glucose levels. These measures are subject to intraindividual variability, and this may have introduced some imprecision in the classification of participants that may affect the Drug_discovery results.