Association of endothelial dysfunction with incident prediabetes, type 2 diabetes and related traits: The KORA F4/FF4 study

Abstract

Introduction Peripheral arterial tonometry (PAT) is an operator-independent and non-invasive measurement method to assess microvascular endothelial function in the fingertips. PAT-derived measures of endothelial function were associated with type 2 diabetes in cross-sectional studies. However, longitudinal studies are lacking. The study aims to investigate the association of two PAT-derived endothelial function parameters reactive hyperemia index (RHI) and mean baseline amplitude (MBA) with follow-up glucose and insulin parameters and the development of (pre)diabetes and type 2 diabetes. Research design and methods The study included 673 participants initially without diabetes (328 men and 345 women) aged 52-71 years from the prospective population-based Cooperative Health Research in the Region of Augsburg F4/FF4 cohort study conducted in Southern Germany (baseline examination F4: 2006-2008; follow-up FF4: 2013-2014). An oral glucose tolerance test was performed at baseline and follow-up to define type 2 diabetes, prediabetes, fasting glucose, fasting insulin, 2-hour glucose, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function and hemoglobin A1c. Results In multivariable adjusted logistic/linear regression models, a 1 SD increase in baseline RHI was inversely associated with incident type 2 diabetes (OR 0.69 (95% CI 0.48 to 0.97)) as well as with fasting insulin (β -0.069 (95% CI -0.131 to -0.007)) and HOMA-IR (β -0.072 (95% CI -0.133 to -0.010)) at follow-up in participants with initial normoglycemia. A 1 SD increase in baseline MBA was positively associated with incident (pre)diabetes (OR 1.62 (95% CI 1.25 to 2.11)) and fasting glucose (β 0.096 (95% CI 0.047 to 0.146)) at follow-up in participants with initial normoglycemia. Conclusions Microvascular endothelial dysfunction seems to be involved in the development of early derangements in glucose metabolism and insulin resistance and could thereby trigger the development of prediabetes and type 2 diabetes.