Ethnic Disparities in Endothelial Function and Its Cardiometabolic Correlates: The Pathobiology of Prediabetes in A Biracial Cohort Study.

Ibiye Owei,Sotonte Ebenibo,Jim Wan,Sam Dagogo-Jack,Nkiru Umekwe,Hanan Mohamed

doi:10.3389/fendo.2018.00094

Ibiye Owei, Sotonte Ebenibo + Show 4 more

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https://doi.org/10.3389/fendo.2018.00094

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Abstract

Endothelial function (EF) reflects the balance between vasodilatory and vasoconstrictive factors produced by (or acting on) the innermost lining of blood vessels. Endothelial dysfunction, an imbalance between these factors that favors vasoconstriction, has been associated with increased risk for cardiovascular disease. However, the influence of race/ethnicity and glycemic status on association between EF and cardiovascular risk factors remain to be clarified. We assessed EF in relation to glycemia and cardiometabolic profile in African-American (AA) and European-American (EA) offspring of parents with type 2 diabetes (T2D), who are participants in the prospective pathobiology and reversibility of prediabetes in a biracial cohort (PROP-ABC) study. Assessments at enrollment included a 75 g oral glucose tolerance test (OGTT), blood pressure, anthropometry, body composition (DEXA), and lipid profile. Other assessments were insulin sensitivity and resting energy expenditure. EF was measured using flow-mediated vasodilation (EndoPAT 2000) and expressed as reactive hyperemia index (RHI). We studied 190 subjects (100 AA, 90 C), mean age (±SD) 53.1 ± 9.1 years, and body mass index 30.6 ± 6.8 kg/m2. Based on OGTT data, 96 subjects (52 AA, 44 EA) had prediabetes and 94 subjects were normoglycemic (48 AA and 46 EA). The RHI was lower in AA than EA (2.17 ± 0.55 vs. 2.36 ± 0.72, P = 0.05) and in prediabetic than normoglycemic subjects (2.14 ± 0.62 vs. 2.38 ± 0.65, P = 0.013). Using RHI ≤ 1.68 as diagnostic cut-off, 19% of participants with prediabetes and 10% of normoglycemic participants had endothelial dysfunction (P = 0.04). In univariate models, RHI was positively associated with age and HDL cholesterol levels, and inversely associated with adiposity, diastolic blood pressure, and 2hr plasma glucose. The association between RHI and adiposity was stronger in men than women. The association between RHI and age, glucose and HDL cholesterol displayed marked ethnic disparities. In our biracial cohort comprising offspring of parents with T2D, prediabetes increased the risk of endothelial dysfunction. However, the association between EF and cardiometabolic risk factors was significantly modified by ethnicity and gender. Our findings support current understanding of endothelial dysfunction as an early sensitive indicator of cardiometabolic risk.

Highlights

Endothelium, the largest end organ in the body by surface area, is the target of numerous noxious stimuli, including proinflammatory cytokines, oxidative stress, shear stress from blood pressure, glycemia, and lipidemia, among others [1]
The pathobiology of prediabetes in a biracial cohort (POP-ABC) study was a longitudinal study in which normoglycemic AA and EA offspring of individuals with T2DM were followed for the occurrence of incident prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) using American Diabetes Association criteria [17]
In AA than EA participants, but there was no difference in fasting plasma glucose (FPG), 2-hour plasma glucose (2hrPG), or Resting energy expenditure (REE) between the two groups (Table 1)

Summary

Introduction

Endothelium, the largest end organ in the body by surface area, is the target of numerous noxious stimuli, including proinflammatory cytokines, oxidative stress, shear stress from blood pressure, glycemia, and lipidemia, among others [1]. Endothelial function (EF) reflects the balance between vasodilatory and vasoconstrictive factors produced by (or acting on) the innermost lining of blood vessels, and is traditionally assessed by methodologies based on measurement of flow-mediated vasodilation [2]. Endothelial dysfunction, is a pathological state that shifts the balance among the various vasoactive factors toward increased vasoconstrictive tone [2]. Several reports have demonstrated that endothelial dysfunction is an early marker of cardiovascular disease in patients with diabetes [1,2,3,4,5,6]. Endothelial function (EF) reflects the balance between vasodilatory and vasoconstrictive factors produced by (or acting on) the innermost lining of blood vessels. Endothelial dysfunction, an imbalance between these factors that favors vasoconstriction, has been associated with increased risk for cardiovascular disease. EF was measured using flow-mediated vasodilation (EndoPAT 2000) and expressed as reactive hyperemia index (RHI)

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