Myocardial steatosis, cardiac remodelling and fitness in insulin-sensitive and insulin-resistant obese women

BACKGROUND: Obesity predisposes to heart failure and premature cardiovascular death, particularly in sedentary women. In animal models and in men with type 2 diabetes mellitus, impaired cardiac function is associated with myocardial triglyceride (MTG) accumulation. Lipotoxic injury from altered myocardial metabolism may be causative. Whether such association also exists in obese, non-diabetic women is unknown. OBJECTIVE: To explore the relation between MTG content, cardiac remodelling and cardiorespiratory fitness in obese, insulin-sensitive and insulin-resistant non-diabetic women. DESIGN: Cross-sectional investigation. SETTING: Academic clinical research centre. PATIENTS: 65 Overweight/obese and sedentary, but otherwise healthy women (body mass index 33±4 kg/m(2); age 45±10 years). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Cardiac structure and function measured by cardiovascular magnetic resonance imaging and MTG content of the interventricular septum by (1)H MR spectroscopy. Additional outcomes were cardiopulmonary fitness and insulin sensitivity during oral glucose tolerance testing. RESULTS: Insulin resistance (composite insulin sensitivity index (C-ISI) <4.6) was present in 29 women. MTG content was higher (0.83±0.30 vs 0.61±0.23, p=0.002) and left ventricular diastolic (p<0.01), but not systolic function was reduced in women with insulin resistance compared with insulin-sensitive women. The remodelling index defined as left ventricular mass divided by end-diastolic volume was increased in women with impaired glucose tolerance (p=0.006). Furthermore, cardiopulmonary fitness was equal in both groups, but was inversely correlated with MTG (r=-0.28, p=0.02). CONCLUSIONS: In overweight and obese women, insulin resistance is associated with increased MTG content, cardiac remodelling and reduced diastolic function. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00956566.