# Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication
## 3 Biomarkers in Diabetics with Known HF
### Biomarkers of Inflammation and Fibrosis
#### 3.2.4 Galectin-3  
Galectin-3 is a \(\beta\)-galactosidase-binding lectin, which belongs to the galectin family [119]. Its biological functions include the modulation of cell growth, proliferation, differentiation, suppression of apoptosis, pre-mRNA splicing, attenuation of angiogenesis, reduction in inflammation, and fibrosis [120; 121; 122]. It has been established that a deficiency of galectin-3 mediates tissue injury, whereas the over-expression of galectin-3 was associated with tissue protection [123]. In addition, galectin-3 serves as a prognostic cardiac biomarker with promising therapeutic potency [123].  
The Dallas Heart Study showed that levels of galectin-3 were associated with T2 DM prevalence, incident T2 DM, and fat compartments [124]. In addition, galectin-3 levels were positively correlated with levels of hs-CRP, IL-18, monocyte chemoattractant protein 1, soluble TNF receptor 1A, myeloperoxidase, C-peptide, and homeostatic model assessment for insulin resistance [124]. Moreover, serum galectin-3 is independently related to progressive renal disease in T2 DM, CVD and increased risk of all-cause mortality [125; 126].  
Serum levels of galectin-3 have been shown to increase in HF patients, and were associated with myocardial fibrosis, adverse cardiac remodeling, atrial fibrillation, and CAD [127; 128]. Furthermore, galectin-3 is considered not only as a powerful predictive biomarker of incident HF, but also as a mediator of T2 DM progression [129; 130]. Among HFpEF patients, the levels of galectin-3 were significantly positively associated with age, creatinine clearance, arterial stiffness (determined by the measurement of carotid femoral pulse wave velocity), aldosteroneone and BNP levels, and inversely correlated with LV ejection fraction [131; 132; 133]. Among 1386 patients with a \(\geq\)1 risk factor for HF (e.g., hypertension, T2 DM, and atherosclerotic CVD) or previously suspected HF, that were enrolled in the DIAST-CHF study, galectin-3 levels of >313.57 ng/mL (sensitivity = 0.61 and specificity = 0.73) predicted incident HFpEF, adjusted all-cause mortality, and the adjusted composite of CV hospitalization and death [134]. [PERSON] et al. (2019) [135] concluded that galectin-3 concentrations were positively associated with HF severity and negatively correlated with left ventricular ejection fraction.  
Elevated levels of galectin-3 substantially predicted mortality in acute HF, as well as in both phenotypes of chronic HF [136]. Although recent investigations found that galectin-3 was not superior to NT-proBNP, sST2, GDF-15, and hs-CRP as a predictor of mortality, the combination of galectin-3 and NPs had better discriminative capacity for predicting mortality when compared with either of the biomarkers alone [137; 138]. Overall, galectin-3 has shown the ability to predict HF regardless of T2 DM beyond the conventional biomarkers, such as NPs and cardiac troponin, but its role in the point-of-care of HF patients still needs investigation and future studies.