Systemic microvascular response to insulin is associated with risk of heart failure with preserved ejection fraction in women with type 2 diabetes

Abstract Background Endothelial microvascular dysfunction (MD) is a key pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Comorbidities such as type 2 diabetes (T2D) indeed can affect the endothelium of both peripheral and coronary microcirculation, thereby triggering systemic derangements well left ventricular diastolic (LVDD). Altered response to insulin common in T2D but its clinical relevance association cardiovascular risk particularly HFpEF remains unclear. Likewise, involvement MD early LVDD uncertain. Finally, influence sex on needs further investigation help understand female predominance HFpEF. Purpose We aimed characterize T2D, investigate echocardiographic markers LVDD/HFpEF. Further, we test effect modification by between Methods 152 prospectively enrolled participants (77 men, 75 women) from Hoorn Diabetes Care System Cohort underwent vivo evaluation MD, echocardiography blood sampling. was assessed laser speckle contrast analysis combined iontophoresis (Ins), acetylcholine (ACh) sodium nitroprusside (SNP). The indices LVDD/HFpEF multivariable linear regression adjusted confounders. defined presence cardiac structural functional abnormalities, according current recommendation. Probability estimated H2PEFF score. Results Mean age 65±6y, mean HbA1c 7.5±1.2%, 70.6% were asymptomatic. Comorbidity burden biomarkers did not significantly differ sexes. Women had smaller LV mass index (82.8±18.1 vs 99.2±20.3 g/m2) higher E/E' (13.4±4.4 11.3±2.8) compared men. Skin perfusion plateau after application each substance women than men no significant differences sexes observed terms relative change, calculated 100% × ([Perfusion − Baseline flow] / flow) any substances. change due Ins associated score, independently factors drug use (1% increase 0.07% decrease score). Stratified sex, this present only 0.10% No associations ACh SNP score or markers. Conclusions Impaired endothelial-mediated vasodilation confers T2D. In measures could represent novel markers, refined prediction Funding Acknowledgement Type funding sources: Private grant(s) and/or Sponsorship. Main source(s): Young Investigator award grant, Early ShePredicts programs, Hartstichting, Netherlands.