Abstract 19344: Evaluation of the Effects of Diabetes, Insulin Resistance, and Inflammation on Coronary Endothelial Function Assessed by Cardiac Perfusion MRI with Cold Pressor Test

Abstract

OBJECTIVE: To evaluate the effects of diabetes, insulin resistance (IR) and inflammation on coronary endothelial function assessed by cardiac stress perfusion MRI (CMRI) w/ cold pressor test (CPT). METHODS: 20 subjects (14 men, 6 women; mean age: 53.5 - Range: 39-62) w/ T2DM (5-15 years) and 20 healthy controls (age/sex matched) were enrolled in a prospective IRB-approved HIPAA compliant study. Medical history for risk factors was obtained. Subjects w/ known CAD were excluded. Fasting plasma glucose (FPG), insulin, C-peptide, HbA1c, eGFR, lipids and UA/Cr ratio; inflammatory markers: IL-6, TNF-α, hs-CRP and PAI-1 were obtained. 2-hour OGTT was performed on healthy subjects to confirm absence of pre-DM/T2DM. BMI, W/H ratio and HOMA-IR were calculated. To assess vascular tone and myocardial blood flow (MBF) responses to CPT, CMRI w/ CPT was performed w/ gadolinium (Multihance, Bracco) on a 3.0T scanner. Signal slope, myocardial perfusion reserve index (MPRI ), and RPP were calculated. RESULTS: Comparison of MPRI between T2DM ( 1.39 ± 0.10) vs. healthy (2.52 ± 0.36) showed significantly decreased endothelium-dependent change in MBF to CPT in diabetics (p=0.003). Univariate analysis showed that age (p=0.001); HbA1c (p=0.001); FPG (p=0.005); HOMA-IR (p=0.04); IL-6 (p=0.05) and TNF-α (p=0.004) showed significant association w/ MPRI in T2DM. Multivariate analysis, age (p=0.017); FPG (p=0.05); UA/Cr ratio (p=0.001); insulin (p=0.046) and C-peptide (p=0.036) remain statistically significant independent predictors of changes in MBF. Correlative studies showed an inverse relationship w/ MPRI and the following: BMI, W/H ratio, FPG, HOMA-IR, LDL, Triglycerides, PAI-1, IL-6, TNF-α and Hs-CRP as well as a direct relationship w/ HDL and eGFR. CONCLUSIONS: Our results demonstrate that the diabetic state characterized by IR and chronic inflammation is significantly associated w/ low or decreased MPRI that reflects impaired endothelium-related coronary vasomotion, CMRI w/ CPT provides a non-invasive, analytical tool for early detection of endothelial dysfunction. Large scale clinical trials using CMRI w/ CPT for detection of endothelial dysfunction in at-risk populations w/ long term follow-ups, after therapeutic and lifestyle intervention, is warranted.