Endothelial function is associated with incident diabetes mellitus: the ELSA-Brasil cohort study

Background Diabetes mellitus (diabetes) is associated with the development of endothelial dysfunction. However, the directionality of this association has been debated. Our primary objective was to evaluate the association of microvascular endothelial function endothelial function with incident diabetes in Brazilian adults. We also assessed whether there was an effect modification according to obesity status. Methods In participants from the ELSA-Brasil cohort study, free of diabetes, and with valid exams for endothelial function at baseline, we evaluated the association between endothelial function and incident diabetes after 8.8 years (SD=2.1) of follow-up. Microvascular endothelial function was assessed by peripheral arterial tonometry (PAT). The variables mean basal pulse amplitude (BPA) representing basal vascular tone, and PAT ratio, the vasodilatory capacity in response to reactive hyperemia, were analyzed in sex-specific quartiles. Higher BPA and lower PAT ratio reflect more impaired endothelial function. Cox proportional hazard models were used for statistical analyses, and multivariable models were adjusted for sex, age, educational level, physical activity level, smoking, alcohol use, and body mass index (BMI) or waist circumference (WC). Results In 1,268 participants, mean age was 51±8 years, with 45% women, and mean BMI of 26.4±4.4 kg/m 2 . After follow-up, we identified 159 new cases of diabetes. The incidence rates varied from 6.5 (95%CI 4.0-10.2) in the first quartile to 19.7 (95%CI 15.1-25.8) in the fourth quartile for BPA and from 7.2 (CI 95% 4.7-11.1) in the fourth quartile to 15.3 (CI 95% 11.4-20.6) in the first quartile of for PAT ratio. After adjustments, we found that the risk of diabetes increased significantly in those with more impaired endothelial function, for both BPA HR 2.13 (95% CI 1.24 – 3.66, p<0.05) and PAT ratio 1.54 (95% CI 0.90 – 2.60, p 0.11). There was no effect modification according to obesity status, evaluated by BMI and WC. Conclusions In Brazilian adults, greater impairment of endothelial function at baseline predicted diabetes after 8.8 years of follow-up, independent of obesity status. These findings may have implications for understanding cardiometabolic diseases in the context of pathophysiology, prognosis and treatment.