Weight excess and insulin resistance mediate the link between obesity and left ventricular dysfunction. We investigated the effect and mechanisms of lifestyle modification on left ventricular function changes in obese patients.Reduction of body weight and insulin resistance was sought using a behavioural intervention programme including dietary restrictions and exercise training in 261 patients (age 45 +/- 13 years) with BMI >or=30 kg/m(2), no history of cardiac disease and a normal stress echocardiogram. Each patient underwent echocardiographic measurement of myocardial deformation and velocity at baseline and at 6 month follow-up.Improvements in left ventricular systolic and diastolic function were demonstrated only in patients with significant reduction of weight and/or insulin resistance. Left ventricular improvement was less frequent in patients with diabetes than in those without (52% vs 82% for strain, 50% vs 81% for strain rate and 59% vs 80% for peak early diastolic myocardial velocity). The independent predictors of improved left ventricular systolic function (increase in strain) were: weight reduction (beta = 0.14, p < 0.05), decrease in the HOMA insulin resistance index (beta = 0.20, p < 0.005) and absence of diabetes (beta = 0.18, p < 0.02). A decrease in HbA(1c) also predicted improvement of left ventricular diastolic function (beta = 0.26, p < 0.001). There was a parallel increment in exercise capacity with intervention and increase in strain was independently correlated with increase in VO(2) (beta = 0.13, p < 0.04).Effective lifestyle modifications in obese patients improve left ventricular systolic and diastolic function, but appear less effective with co-existing diabetes. The reversal of left ventricular function abnormalities is associated with reduction of both weight and insulin resistance, and is accompanied by an increase in cardiorespiratory fitness.