TNFa and Serum Galectin-3 in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction, Insulin Resistance and Type 2 Diabetes Mellitus

Abstract

Background: Proinflammatory cytokines may modulate insulin signaling and contribute to systemic insulin resistance (IR). Galectin-3 (Gal-3) is a marker of myocardial fibrosis. Purpose: To investigate the relation between serum Gal-3 levels (sGal3), THF-alpha(TNFa), Nt-proBNP, HOMA index and insulin in patients with heart failure with preserved left ventricular ejection fraction (HFpEF), IR and type 2 diabetes mellitus (T2DM). Methods: Seventy four patients (40 males and 34 females; mean age 62.2768.7 years) with HFpEF with and without concomitant T2DM were examined. The sGal3, Nt-proBNP, TNF-alpha and insulin were measured in serum by ELISA, according to manufacturer’s instructions. HOmeostasis Model Assessment (HOMA) index was calculated as a measure of IR at fasting state (IR5fasting glucose fasting insulin/ 22.5), after what patients were divided into three groups: 30 patients with HFpEF and IR, 31 patients with HFpEF and T2DM and 11 patients with HFpEF and without T2DM and IR. Spearman’s correlation analysis and Kruskal-Wallis test were used. All statistical tests were 2-tailed, and p!0.05 was considered statistically significant. Results: IR was diagnosed in 31 (43.6%) patients without a history of diabetes. In the group with HFpEF and IR the level of sGal3, TNF-alpha and insulin were significantly higher compared to the HFpEF patients with T2DM and HFpEF patients without IR and T2DM (p!0.05, p!0.05 and p!0.0001 respectively) (Table 1). Therewith analyses detected that increasing of sGal3 levels associated with increasing TNFa levels (r50.610; p ! 0.001), insulin levels (r 5 0.33; p !0.01) and HOMA index (r 5 0.29; p !0.05). In addition, our data showed that the strength of relation of sGal3 and TNFa levels increased from HFpEF patients with IR (r 5 0.520) to HFpEF patients with T2DM (r 5 0.709) (p !0.05). Multiple linear regression analysis suggested a significant dependence between sGal3 and TNFa (HFpEF patients with IR and without T2DM group: r 5 0.23, p ! 0.01, HFpEF patients with T2DM group: r 5 0.76, p ! 0.0001), but the dependences between TNF and Nt-proBNP (r 5 0.37, p ! 0.01), and between sGal3 and Nt-proBNP (r 5 0.82, p ! 0.0001) was significant only in patients with IR and without T2DM. Conclusions: Our results clearly show that sGal3, TNF-alpha and insulin are significantly increased in HFpEF patients with IR and without T2DM. Our findings show the association between sGal3 levels and TNFa levels in the presence of impaired glucose tolerance in HFpEF patients. This dependence increases with the progression of IR.