What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Coronary artery disease with and without myocardial ischemia (n=30). Intervention: Ischemic CAD vs. Non-ischemic CAD and non-CAD controls. Primary outcome: Insulin sensitivity, secretion, substrate oxidation, and ectopic fat deposition.

What does this research mean for the field?

In patients with ischemic coronary artery disease, enhanced systemic glucose oxidation inversely correlates with insulin secretion and is accompanied by elevated myocardial fat accumulation, which may represent protective physiological adaptations rather than purely pathogenic processes. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

April 5, 2016Open Access

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

Key Result

Ischemic CAD patients exhibited enhanced systemic glucose oxidation inversely correlated with insulin secretion, and elevated myocardial fat accumulation compared to non-CAD subjects.

Study Design

Type

Cross-Sectional (n=30)

Structured PICO

Population

30 subjects: CAD patients with myocardial ischemia (n=8), CAD patients without myocardial ischemia (n=14), and non-CAD controls (n=8).

Outcome

Insulin sensitivity, insulin secretion, substrate oxidation, and ectopic fat deposition (myocardial, liver, and pancreatic triglyceride contents)surrogate

In ischemic CAD, enhanced glucose oxidation and myocardial fat accumulation may represent physiological adaptations to limited fatty acid oxidative capacity.

Abstract

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. 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. 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. We investigated whether CAD is an independent predictor of insulin resistance, β-cell dysfunction and ectopic fat deposition, and if this interaction is influenced by superimposed myocardial ischemia. We found that in ischemic CAD patients, myocardial fat accumulation and systemic glucose oxidation are enhanced, and the latter correlates inversely with insulin secretion. These can be seen as best-adaptive mechanisms.