Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes

Background: Diabetes increases the risk of heart failure but the underlying mechanisms leading to diabetic cardiomyopathy are poorly understood. Left ventricle diastolic dysfunction (LVDD) is one of the earliest cardiac changes in these patients. We aimed to evaluate the association between LVDD with insulin resistance, metabolic syndrome (MS) and diabetes, across the diabetic continuum. Methods: Within a population-based study (EPIPorto), a total of 1063 individuals aged >= 45 years (38% male, 61.2 +/- 9.6 years) were evaluated. Diastolic function was assessed by echocardiography, using tissue Doppler analysis (E' velocity and E/E' ratio) according to the latest consensus guidelines. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score. Results: The HOMA-IR score correlated to E' velocity (rho = -0.20; p < 0.0001) and E/E' ratio (rho = 0.20; p < 0.0001). There was a progressive worsening in E' velocity (p for trend < 0.001) and in E/E' ratio across HOMA-IR quartiles (p for trend < 0.001). Individuals in the highest HOMA-IR quartile were more likely to have LVDD, even after adjustment for age, sex, blood pressure and body mass index (adjusted OR: 1.82; 95% CI: 1.09-3.03). From individuals with no MS, to patients with MS and no diabetes, to patients with diabetes, there was a progressive decrease in E' velocity (11.2 +/- 3.3 vs 9.7 +/- 3.1 vs 9.2 +/- 2.8 cm/s; p < 0.0001), higher E/E' (6.9 +/- 2.3 vs 7.8 +/- 2.7 vs 9.0 +/- 3.6; p < 0.0001) and more diastolic dysfunction (adjusted OR: 1.62; 95% CI: 1.12-2.36 and 1.78; 95% CI: 1.09-2.91, respectively). Conclusions: HOMA-IR score and metabolic syndrome were independently associated with LVDD. Changes in diastolic function are already present before the onset of diabetes, being mainly associated with the state of insulin resistance.