# Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication
## 3 Biomarkers in Diabetics with Known HF  
Biomarkers have been posed as promising surrogate indicators of pathologic changes in target organs (myocardium, kidney, vessels, and skeletal muscles) and metabolic homeostasis, particularly having diagnostic and predictive capabilities for patients with T2 DM and HF [47]. Current clinical guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) and European Cardiology Society (ESC) have proposed the use of biomarkers in personalized medical care of HF patients, regardless of T2 DM, to diagnose HF and stratify patients at higher risk of poor prognosis, despite some differences in recommendations for practical use [6; 48; 49]. Table 1 reports the use of biomarkers in the management of HF according to 2016 ESC and 2017 ACC/AHA clinical guidelines [6; 48]. Although biomarkers of biomechanical stress (natriuretic peptides) and myocardial injury (high-sensitivity cardiac troponin (hs-cTn)), which are commonly used in HFrEF \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**Strategy**} & \multirow{2}{*}{**Biomarkers**} & \multicolumn{4}{c}{**ESC, 2016**} & \multicolumn{4}{c}{**ACC/AHA/HFSA, 2017**} \\ \cline{2-9}  & & **COR** & **LOE** & **Phenotype of HF** & **COR** & **LOE** & **Phenotype of HF** \\ \hline Diagnosis & BNP/NT-proBNP/MR-proBNP & I & A &
\begin{tabular}{c} AHF, HFpEF, \\ HFrEF \\ \end{tabular} & I & A & AHF, CHF \\ \hline \multirow{2}{*}{Risk of in-hospital death} & BNP/NT-proBNP & I & C & AHF & I & A & AHF, CHF \\ \cline{2-9}  & hs-cTr & I & C & AHF & I & A & AHF, CHF \\ \hline Risk of recurrent & \multirow{2}{*}{BNP/NT-proBNP} & \multirow{2}{*}{-} & \multirow{2}{*}{I} & \multirow{2}{*}{A} & \multirow{2}{*}{AHF, CHF} & \multirow{2}{*}{I} & \multirow{2}{*}{A} & \multirow{2}{*}{AHF, CHF} \\ \cline{2-9}  & hospital admission & & & & & & & \\ \hline \multirow{4}{*}{Risk of post-discharged death} & BNP/NT-proBNP & I & A & AHF, CHF & I & A & AHF, CHF \\ \cline{2-9}  & hs-cTr & I & C & AHF, CHF & I & IIa & AHF, CHF \\ \cline{2-9}  & Galectin-3 & & - & & IIb & B & AHF, CHF \\ \cline{2-9}  & sST2 & & - & IIb & B & AHF, CHF \\ \hline Prevention of HF onset & BNP/NT-proBNP & - & IIa & B & AHF, CHF \\ \hline Guided therapy & BNP/NT-proBNP & - & I & A & HFrEF/HFpEF \\ \hline \hline \end{tabular}
\end{table} 
Table 1: 2016 ESC and 2017 ACC/AHA/HFSA recommendations for the use of biomarkers in the management of HF. and to help to diagnose HFpEF, have high predictive utility in T2 DM, they are markers of general pathological processes and consequently are not specific for T2 DM-induced HF [50]. Conventional and alternative biomarkers of HF in T2 DM patients are reported in Figure 2.  
Novel biomarkers of fibrosis and inflammation (soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3)) are included in the ACC/AHA/HFSA HF guidelines as an alternative tool for CVD prediction and HF risk stratification, but their clinical utility in T2 DM has not yet been proven and requires thorough elucidation. However, they were surrogate biomarkers for hard endpoints, such as all-cause and CV mortality and hospitalization in several large clinical trials in T2 DM [51]. Other alternative HF biomarkers, such as oxidative stress, inflammation, and collagen turn-over biomarkers, have been investigated in the context of offering add-on information for prognoses and personalized risk management among patients with T2 DM-induced HF [52; 53; 54; 55]. Table 2 reports the advantages and disadvantages of HF biomarkers in patients with T2 DM. Figure 2: Conventional and alternative biomarkers of HF in T2 DM patients.