Vol 10, Issue 5, 2022 ISSN - 2321-4406 BNP AND NT-PRO BNP AS INDEPENDENT DIAGNOSTIC BIOMARKERS FOR CARDIOVASCULAR DISEASE IN TYPE 2 DIABETES MELLITUS Balaji Vijayam 1 *, Taarika Balaji 2 , Madhuri S Balaji 3 , Seshiah Veerasamy 1 , Vinoth Kumar Ganesan 3 1 Department of Diabetology, Dr. V Balaji Diabetes Care and Research Institute, Chennai, Tamil Nadu, India. 2 Department of Medicine, Saveetha Institute of Technical and Medical Sciences, Chennai, Tamil Nadu, India. 3 Department of Medical Research, Dr. V Balaji Diabetes ABSTRACT The risk of developing heart failure (HF) with a reduced and preserved ejection fraction is known to increase with pre-diabetes and diabetic mellitus (DM). Natriuretic peptides (NPs) have been shown to be an important tool for assessing the risk of cardiovascular diseases (CVD) in people with pre- diabetes and Type 2 diabetes (T2DM), regardless of HF characteristics. Elevated levels of NPs were associated with an increased risk of readmission for HF, all-cause mortality, CVD mortality, HF progression, and readmission due to HF, according to earlier clinical investigations. In pre-diabetes and T2DM populations, the discriminative power of NPs for CVD death and HF-related clinical events has not been established beyond conventional CVD risk variables. The purpose of the review is to gather details regarding the predictive value of circulating NPs based on pre-diabetes and established T2DM presentation. Researchers have found that HFrEF or HFpEF in T2DM patients may necessitate a change in NP cutoff values to diagnose primary HF and identify HF-related risks. The relationship between clinical outcomes and the dynamic of circulating levels of NPs in diabetics treated with glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors has to be clarified in big clinical trials in the future. Keywords: T2DM, CVD, Biomarker, BNP, NT-proBNP. BACKGROUND Biomarkers have become crucial diagnostic, risk-based, and therapeutic decision-making tools for cardiovascular illnesses in recent years [1,2]. Particularly, cardiac troponins have become the cornerstone of the diagnostic process for patients with acute coronary syndromes. The scientific community is currently studying a number of intriguing novel biomarkers. Except for B-type natriuretic peptide (BNP) and its N-terminal fragment, most of these novel biomarkers are not yet appropriate for therapeutic use (NT-proBNP) [3]. Both markers have advanced from the laboratory bench to clinical application as a result of numerous research demonstrating their diagnostic value. The goal of the present studies is to provide a comprehensive review of the literature on BNP and NT-proBNP measurements in Type 2 diabetic mellitus (T2DM) patients with cardiovascular disease (CVD) and their therapeutic implications [4]. PHYSIOLOGY OF BNP AND NT-PROBNP BNP, also known as brain-type natriuretic peptide, was isolated from pig brain in 1988 and was originally characterized in same year. However, it was quickly discovered that it is mostly a cardiac hormone that comes from the heart. The natriuretic peptide family includes BNP and additional peptides including atrial natriuretic peptide, C-type natriuretic peptide, and urodilatin that have structurally similar features [5]. A ring of 17 amino acids and a disulfide bridge connecting two cysteine molecules make up the comparable and distinctive structural structure of the natriuretic peptides. The primary site of BNP synthesis and secretion is the ventricular myocardium. Only little amounts of BNP are stored in granules, and the process controlling BNP secretion relies on rapid gene expression and de novo peptide synthesis. Atrial natriuretic peptide, in contrast, is kept in granules and can be released immediately after stimulation. BNP, a prohormone made up of 108 amino acids, is produced (proBNP) [6]. On release into circulation, ProBNP is cleaved in equal proportions into the biologically inactive 76 amino acid N-terminal fragment and the physiologically active 32 amino acid BNP, which is the C-terminal fragment (NT-proBNP) [7]. Both molecules are continuously released and are visible in blood. Myocardial wall stress is the primary trigger for increased BNP and NT-proBNP production and secretion. In addition, elements like myocardial ischemia and endocrine and paracrine regulation by other neurohormones and cytokines, respectively, are significant [4,7]. Numerous biological processes in systemic circulation are mediated by the interaction between BNP and the natriuretic peptide receptor Type A, which leads to the production of intracellular cyclic GMP. BNP has a number of physiological effects, including natriuresis, diuresis, peripheral vasodilation, and inhibition of the sympathetic nervous system and renin-angiotensin-aldosterone system. BNP is taken out of the plasma by binding to natriuretic peptide receptor Type C and being proteolyzed by neutral endopeptidases [8]. The main mode of NT-proBNP clearance, however, is renal excretion. The idea that NT-proBNP might be eliminated through more important pathways is raised by recent studies, nevertheless. Although both molecules are released in equimolar proportions, NT-proBNP serum levels are around 6 times higher than BNP levels. This difference can be attributed to NT-proBNP, which has a half-life of 120 min as opposed to BNP’s 20 min [4,9]. TYPE 2 DIABETES MELLITUS WITH CARDIOVASCULAR DISEASE The most prevalent metabolic illness in the world, DM, is the eighth greatest cause of mortality [5]. According to DM data, 500 million people worldwide will have the condition by 2030 [10]. In 2013, 382 million people worldwide were estimated to have it. The Reduction of Atherothrombosis for Continued Health registry found that people with T2DM had a higher risk of cardiovascular death, nonfatal myocardial infarction, or non-fatal stroke compared to those without T2DM [11]. Thus, T2DM was independently associated with a 33% increased risk of heart failure (HF), HF-related events, and CVD death [12,13]. In addition, T2DM and CVD illnesses frequently coexist, and CVD risk factors have a considerable impact on both conditions’ onset Review Article © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijms.2022v10i5.45992. Journal homepage: https://innovareacademics.in/journals/index.php/ijms Care and Research Institute, Chennai, Tamil Nadu, India. E-mail: balajivijayam@gmail.com Received: 28 July 2022, Revised and Accepted: 28 August 2022