What is the clinical evidence from this study?

Study design: Case-Control. Population: Coronary Heart Disease (n=21). Intervention: Euglycemic hyperinsulinemia (insulin clamp) vs. Healthy age- and weight-matched subjects. Primary outcome: Myocardial glucose uptake (μmol/min/g) (p=0.0005).

November 1, 1996Open Access

Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography.

Key Result

Patients with coronary heart disease exhibited a 46% reduction in myocardial glucose uptake compared to healthy controls, demonstrating flow-independent cardiac insulin resistance.

Study Design

Type

Case-Control (n=21)

Multicenter

Structured PICO

Do patients with coronary artery disease and regional wall motion abnormalities exhibit impaired myocardial and skeletal muscle glucose uptake independent of blood flow compared to healthy controls?

Population

15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities (history of myocardial infarction and low ejection fraction), and 6 age- and weight-matched healthy controls (total n=21).

Intervention

Measurement of regional glucose uptake and blood flow using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG) and H2(15)O during euglycemic hyperinsulinemia (insulin clamp).

Comparator

Age- and weight-matched healthy subjects.

Outcome

Heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia.surrogate

Patients with coronary artery disease and low ejection fraction exhibit both myocardial and skeletal muscle insulin resistance that is independent of regional blood flow.

Main Result

Absolute Event Rate: 0.38% vs 0.7%

p-value: p=0.0005

Limitations

Small sample size of 15 patients and 6 controls.
Values of the lumped constant and the rate of FDG-6-phosphate dephosphorylation are not known in man, which is a limitation of the PET technique.
Medical therapy was not standardized among the patients.
Differences in physical fitness between patients and controls could potentially contribute to the observed skeletal muscle insulin resistance.

Abstract

Patients with coronary artery disease or heart failure have been shown to be insulin resistant. Whether in these patients heart muscle participates in the insulin resistance, and whether reduced blood flow is a mechanism for such resistance is not known. We measured heart and skeletal muscle blood flow and glucose uptake during euglycemic hyperinsulinemia (insulin clamp) in 15 male patients with angiographically proven coronary artery disease and chronic regional wall motion abnormalities. Six age- and weight-matched healthy subjects served as controls. Regional glucose uptake was measured by positron emission tomography using 18F2-fluoro-2-deoxy-D-glucose (FDG), blood flow was measured by the H2(15)O method. Myocardial glucose utilization was measured in regions with normal perfusion and wall motion as assessed by radionuclide ventriculography. Whole-body glucose uptake was 37+/-4 micromol x min(-1) x kg(-1) in controls and 14+/-2 mciromol x min(-1) x kg(-1) in patients (P = 0.001). Myocardial blood flow (1.09+/-0.06 vs. 0.97+/-0.04 ml x min(-1) x g(-1), controls vs. patients) and skeletal muscle (arm) blood flow (0.046+/-0.012 vs. 0.043+/-0.006 ml x min(-1) x g(-1)) were similar in the two groups (P = NS for both). In contrast, in patients both myocardial (0.38+/-0.03 vs. 0.70+/-0.03 micromol x min(-1) x g(-1), P = 0.0005) and muscle glucose uptake (0.026+/-0.004 vs. 0.056+/-0.006 micromol x min(-1) x g(-1), P = 0.005) were markedly reduced in comparison with controls. In the whole dataset, a direct relationship existed between insulin-stimulated glucose uptake in heart and skeletal muscle. Patients with a history of myocardial infarction and a low ejection fraction are insulin resistant. This insulin resistance affects both the myocardium and skeletal muscle and is independent of blood flow.

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