Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction

• DOI: 10.1161/circulationaha.116.023446
• Publication Date: 2016-09-28T02:18:56Z
• Authors: Ben M. Sörensen; Alfons J. H. M. H...; Tos T. J. M. Bere...; Jan S. A. G. Scho...; Abraham A. Kroon; Carla J. H. van d...; Ronald M. A. Henry; Annemarie Koster; Simone J. S. Sep; Pieter C. Dagnelie; Nicolaas C. Schaper; Miranda T. Schram; Coen D. A. Stehouwer
• Keywords: Prediabetes; Reactive hyperemia

Background: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes (“ticking clock hypothesis”). Whether a similar phenomenon also applies to microvascular dysfunction not known. We therefore tested the hypothesis that present and more severe T2DM. To do so, we investigated associations prediabetes, T2DM, measures hyperglycemia function measured as flicker light-induced retinal arteriolar dilation heat-induced skin hyperemia. Methods: In Maastricht Study, T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), determined %-dilation (Dynamic Vessel Analyzer), %-hyperemia (laser-Doppler flowmetry), glucose metabolism status (oral tolerance test; normal [n=1269], [n=335], or T2DM [n=609]). Differences were assessed multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, use lipid-modifying pressure-lowering medication, prior Results: Retinal was (mean±standard deviation) 3.4±2.8 metabolism, 3.0±2.7 2.3±2.6 Adjusted showed lower (B=–0.20, 95% confidence interval –0.56 0.15) further deterioration (B=–0.61 [–0.97 –0.25]) versus ( P trend=0.001). Skin 1235±810 1109±748 937±683 (B=–46 [–163 72]) (B=–184 [–297 –71]) addition, higher glycohemoglobin A1c fasting plasma fully models (for A1c, standardized B=–0.10 [–0.15 –0.05], <0.001 B=–0.13 [–0.19 –0.07], <0.001, respectively; glucose, B=–0.09 –0.04], =0.002, respectively). Conclusion: Prediabetes, are independently impaired retina skin. These findings support concept precedes thus may contribute T2DM-associated disease other complications, part have origin such cognition heart failure.