title: Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes.
abstract: 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 (ρ = -0.20;p < 0.0001) and E/E' ratio (ρ = 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.
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal. fontes.carvalho@gmail.com.|Cardiology Department, Gaia Hospital Center, Vila Nova Gaia, Portugal. fontes.carvalho@gmail.com.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. fontes.carvalho@gmail.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fontes-Carvalho
authors.affiliation: Cardiology Department, Gaia Hospital Center, Vila Nova Gaia, Portugal. ricardoladeiraslopes@gmail.com.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. ricardoladeiraslopes@gmail.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ladeiras-Lopes
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal. pbettfer@med.up.pt.|Department of Internal Medicine, Centro Hospitalar São João, Porto, Portugal. pbettfer@med.up.pt.
authors.forename: Paulo
authors.initials: P
authors.lastname: Bettencourt
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. amoreira@med.up.pt.|Department of Cardiothoracic Surgery, Centro Hospitalar São João, Porto, Portugal. amoreira@med.up.pt.
authors.forename: Adelino
authors.initials: A
authors.lastname: Leite-Moreira
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal. azevedana@gmail.com.|Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal. azevedana@gmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Azevedo
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D003971:Diastole; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D008875:Middle Aged; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*