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Background and Aims: Regenerating islet-derived protein 3-beta (Reg3β) and oncostatin-M (OSM), an inducer of Reg3β, are important for the recruitment of macrophages, tissue repair and survival after myocardial infarction. The study was planned to elucidate the diagnostic utility of serum Reg3β and OSM levels for the acute coronary syndrome (ACS)., Methods: Forty-two type 2 diabetes mellitus (T2DM) patients with ACS as cases and forty-two T2DM patients as controls were recruited. Routine biochemical investigations, creatine kinase-total (CK-T), and creatine kinase-MB (CK-MB) levels were estimated. Serum Reg3β and OSM levels were analysed by enzyme-linked immunosorbent assay., Results: Serum Reg3β and OSM levels were significantly higher in cases as compared to controls. Serum Reg3β and OSM levels were positively correlated with random blood glucose, serum CK-total, CK-MB levels, and negatively correlated with serum high-density lipoprotein cholesterol (HDL-C) levels. Receiver operating characteristics curve analysis showed that serum OSM and Reg3β levels can be used for the diagnosis of ACS in patients with T2DM as compared to CK-MB levels. On regression analysis, serum Reg3β level was positively associated with body mass index and negatively with serum HDL-C levels and serum OSM level was positively associated with waist circumference and random blood glucose and negatively with serum HDL-C levels., Conclusion: Serum Reg3β and OSM levels may be used as complementary markers besides traditional cardiac markers for the diagnosis of ACS in patients with T2DM. However, further studies are still needed to verify our claim., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest related to this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)