Endothelial Function Is Associated With Incident Diabetes Mellitus: The ELSA-Brasil Cohort Study

Diabetes mellitus is associated with endothelial dysfunction, but the bidirectional nature of this relationship remains debated. We aimed to evaluate the association between microvascular endothelial function and incident diabetes in Brazilian adults and to assess potential effect modification by obesity status.

We analysed participants from the ELSA-Brasil cohort without diabetes at baseline and with valid endothelial function measurements. Microvascular endothelial function was assessed by peripheral arterial tonometry (PAT), using mean basal pulse amplitude (BPA), reflecting basal vascular tone and the PAT ratio, indicating vasodilatory capacity. Higher BPA and lower PAT ratio represent worse endothelial function. Sex-specific quartiles were analysed. Incident diabetes was assessed after a mean follow-up of 8.8 years (SD = 2.1). Cox proportional hazards models were adjusted for sex, age, education, physical activity, smoking, alcohol use and body mass index (BMI) or waist circumference.

Among 1268 participants (mean age 51 ± 8 years; 45% women; mean BMI 26.4 ± 4.4 kg/m²), 159 developed diabetes. Incidence rates increased across BPA quartiles and were higher in lower PAT ratio quartiles. After multivariable adjustment, impaired endothelial function was associated with increased diabetes risk, particularly for BPA (HR 2.13; 95% CI 1.24-3.66). The association for PAT ratio was weaker (HR 1.54; 95% CI 0.90-2.60). No effect modification by obesity status was observed.

Impaired endothelial function at baseline was independently associated with incident diabetes in Brazilian adults, regardless of obesity. These findings highlight the role of vascular dysfunction in cardiometabolic disease development.