The Relationship between Hemoglobin Levels and Endothelial Functions in Diabetes Mellitus

Background and objectives: Hemoglobin (Hb) is the main carrier and buffer of nitric oxide. Evidence has been produced that Hb concentration is inversely related with endothelial function in human diseases. Testing whether this association exists also in diabetic patients stage 1 to 2 chronic kidney disease (CKD) is important because anemia in these patients starts at an earlier stage than in other renal diseases. The relationship was investigated between Hb and flow-mediated dilation (FMD) levels of the patients with diabetic nephropathy in a cross-sectional design. Design, setting, participants, & measurements: Eighty-nine diabetics with mild to moderate proteinuria and normal to mildly reduced GFR who were normotensive, nondyslipidemic, and cardiovascular-events free were enrolled. None of the patients was taking metformin or renin-angiotensin system blockers. Results: FMD was inversely related with Hb levels. Furthermore, there was an inverse link between proteinuria and FMD. However, further analysis of this association showed that the FMD-proteinuria link was confined to patients with proteinuria exceeding 150 mg/d, while no such association existed in patients with proteinuria <150 mg/d. Adjustment of the Hb-FMD relationship for pertinent Framingham risk factors, proteinuria, homeostasis model assessment (HOMA) index, and GFR levels had a modest influence on this association, which remained significant. Conclusions: Endothelial function is inversely associated with Hb levels in diabetic patients with stage 1 to 2 CKD, and proteinuria is an effect modifier of this association. Overall, the observations of this study generate the hypothesis that proteinuria exposes a situation wherein Hb may limit the endothelium-mediated vasoregulation in diabetes.