BACKGROUND Duchenne muscular dystrophy (DMD) is known to impact the subepicardial layer of the myocardium through chronic inflammation. Recent animal studies have shown predominant subendocardial involvement in rats with DMD. The primary outcome parameter was to determine by cardiovascular MRI (CMR) if two differential patterns of myocardial involvements exist in DMD; the secondary outcome parameters were to correlate the observed pattern with metabolic markers such as insulin resistance measures. METHODS Forty patients with DMD were screened using CMR to determine which of them had predominantly subendocardial dysfunction (SENDO group), or subepicardial/midmyocardial involvement (SEPMI group). Patients were subjected to body mass index measurement, serum creatinine kinase, serum lactate dehydrogenase enzyme, fasting glucose-insulin ratio (FGIR), full lipid profile, left ventricular ejection fraction (LVEF), left ventricle E/E´ ratio (the ratio of early mitral inflow velocity to average early diastolic velocities of the basal septum and mitral annulus) for left ventricle diastolic function, and myocardial layer strain discriminating echocardiography (MLSD-STE). Results: 26 patients displayed SENDO while 34 displayed SEPMI. SENDO group displayed overt insulin resistance; (FGIR (SENDO: 7 ± 1 vs. SEPMI: 5 ± 1, P < 0.001). FGIR was negatively correlated with Subendocardial Global Longitudinal Strain (ENDO-LS) with r = -0.75. CONCLUSIONS DMD does not seem to influence the heart uniformly; DMD cardiomyopathy probably has two separate phenotypes with different mechanisms. Insulin resistance might be implicated in its pathogenesis and its reversal may help to slow disease progression.