Endothelial Function Assessed by Digital Volume Plethysmography Predicts the Development and Progression of Type 2 Diabetes Mellitus.

Abstract

BackgroundEndothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development.Methods and ResultsIn a population‐based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35–74 years at enrollment in 2007–2012), we identified 1610 cases of incident pre–diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A1c (HbA1c) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow‐mediated dilation and digital volume plethysmography–derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate β coefficients of HbA1c levels at follow‐up and relative risks of incident (pre–)diabetes mellitus. Reactive hyperemia index was independently associated with HbA1c after multivariable adjustment for baseline HbA1c, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack‐years of smoking, non–high‐density lipoprotein/high‐density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C‐reactive protein (β=−0.020; P=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02–1.15; P=0.012) for incident pre–diabetes mellitus and 1.16 (95% CI, 1.01–1.34; P=0.041) for incident type 2 diabetes mellitus. Flow‐mediated dilation independently increased the relative risk for developing pre–diabetes mellitus by 8% (95% CI, 1.02–1.14; P=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86–1.19; P=0.92) and with HbA1c (β=−0.003; P=0.59).ConclusionsEndothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre–)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.