Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD

Abstract

Background:Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia.Methods and Results:We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity.Conclusions:In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.

The Gene and Protein Expression of the Main Components of the Lipolytic System in Human Myocardium and Heart Perivascular Adipose Tissue. Effect of Coronary Atherosclerosis

“…In the present study, we did not measure a degree of ischemia but all the participants with CAD were in a stable condition. Nonetheless, our data obtained by direct measurement of the triacylglycerol content in the myocardium of the patients with multivessel coronary artery disease are in line with the above-mentioned report [36].…”

“…Recently, it was shown that myocardial TG content was elevated in patients with ischemic CAD in relation to patients with nonischemic CAD. The degree of ischemia was evaluated with the PET/CT technique [36]. In the present study, we did not measure a degree of ischemia but all the participants with CAD were in a stable condition.…”

Sex-Specific Programming of Cardiac DNA Methylation by Developmental Phthalate Exposure

“…72 Both glucose uptake and insulin signaling are impaired in diseases such as coronary heart disease and heart failure. 71,73 Likewise, additional pathways relevant to cardiac development and function were identified by GREAT analysis, including PI3K pathway function (female, hypomethylated) and embryonic heart tube morphogenesis (male, hypermethylated). The PI3K pathway plays an important role in regulation of cardiac hypertrophy and contractility, and altered function of this pathway is implicated in heart failure and other diseases.…”

Association of latent class analysis-derived subphenotypes of acute kidney injury with mortality in critically ill patients with cardiovascular disease: a retrospective cohort study

“…In addition, patients in class 3 were less likely to have hypertension and diabetes, but their blood pressure and glucose level were significantly higher than those in class 1 and class 2 after admission, indicating that the increase in blood pressure and glucose level might be associated with the stress response. It has been reported that glucose oxidation is enhanced in CAD patients under stress, which could further prevent insulin secretion [17]. AKI in CAD patients after left cardiac catheterization might be associated with contrast nephropathy [18] and ischemic nephropathy [19].…”