Association between interleukin-6, suPAR, and hsCRP with subclinical left ventricular dysfunction in type 1 diabetes: The Thousand & 1 study

AIMS: To investigate the association between chronic inflammation and subclinical left ventricular dysfunction in type 1 diabetes (T1D).

METHODS: In a cross-sectional study of individuals with T1D without known heart disease, interleukin-6 (IL-6), soluble-urokinase-plasminogen-activator-receptor (suPAR), and high-sensitivity C-reactive-protein (hsCRP) were examined for associations with echocardiographic E/e' (primary outcome) and global longitudinal strain (GLS) (secondary outcome). We adjusted for several clinical variables in linear regression analysis, including N-terminal pro-B-type natriuretic peptide (NT-proBNP). The biomarkers were categorized as elevated/non-elevated based on their upper quartiles.

RESULTS: Of 962 individuals (52 % male, mean age 49 ± 14 years), mean E/e' was 7 ± 3 and GLS 18 ± 3. In fully adjusted models, all biomarkers were each associated with increased E/e': beta coefficients for IL-6 0.2 (95 % confidence intervals: 0.1-0.3, P = 0.001), suPAR 0.5 (0.1-0.7, P = 0.011), and hsCRP 0.1 (0.0-0.2, P = 0.023). Combining biomarkers showed stronger associations: elevated IL-6 and suPAR 1.3 (0.7-2.0, P < 0.001), elevated all three 1.9 (1.1-2.7, P < 0.001). Results were similar for decreased GLS with IL-6--0.4 (-0.7 to 0.0, P = 0.039), IL6 and hsCRP -1.0 (-1.7 to -0.4, P = 0.007), all three -1.1 (-2.0 to -0.3, P = 0.009).

CONCLUSIONS: Inflammatory biomarkers are independently associated with subclinical left ventricular dysfunction. Chronic inflammation may contribute to the development of myocardial dysfunction in T1D.