International Research Journal of Pharmacy and Medical Sciences ISSN (Online): 2581-3277 59 Priyanka Tanwar, Mamta Naagar, and Manish Kumar Maity, “Relationship between Type 2 Diabetes Mellitus and Osteoarthritis,” International Research Journal of Pharmacy and Medical Sciences (IRJPMS), Volume 6, Issue 2, pp. 59-70, 2023. Relationship between Type 2 Diabetes Mellitus and Osteoarthritis Priyanka Tanwar 1* , Mamta Naagar 2 , Manish Kumar Maity 2 1 Department of Pharmacology, Bhagvan Mahavir Institute of Medical Sciences, Sonipat-131030, Haryana, India 2 Department of Pharmacy Practice, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be university), Mullana-133207, Ambala, Haryana, India *Address for correspondence - Priyanka Tanwar Department of Pharmacology, Bhagvan Mahavir Institute of Medical Sciences, Sonipat-131030, Haryana, India Email id – rphpriyanka1995@gmail.com Abstract— Type 2 diabetes mellitus (T2DM), Overweight (obesity), and osteoarthritis (OA) are chronic disorders that commonly coexist. While the mechanical effects of increased body weight on joints may explain lower limb OA; in this review we wanted to see the relation between T2DM and OA and how T2DM plays a role in OA pathogenesis. The impact of T2DM on the progression of OA is a topic of investigation. T2DM causes OA through two key pathways: oxidative stress and low-grade chronic inflammation, both of which are caused by persistent hyperglycemia and insulin resistance. T2DM is a risk factor for the advancement of OA and has a detrimental influence on the results of arthroplasty. Some of the most commonly prescribed anti-OA medications, such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroid injections have been linked to safety concerns, while other anti-OA medications, such as glucosamine and intra-articular hyaluronic acid, may be safe in OA patients with T2DM. In this review we conducted a thorough assessment to see the relationship between T2DM and OA. Keywords—Type 2 Diabetes Mellitus, Osteoarthritis (OA), Bone Remodeling, Fracture Healing, Bone Marrow Dysfunction. I. INTRODUCTION ype 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are two frequent illnesses whose incidence is expected to rise [1, 2]. Because of their high incidence and common risk factors, OA and T2DM usually coexist. The link between OA and obesity is well-established [3], and obesity is common in patients with T2DM [4, 5]. Aging has long been recognized as a risk factor for T2DM and OA. T2DM is expected to affect 4.6 million persons in the United States aged between 18 – 44 years, 14.3 million people aged between 45–64 years, and 12.0 million people aged ≥ 65 years [6]. Similarly, radiographically characterised knee OA affects 14 percent of those over 25 years and 37 percent of those over 60 years [7]. T2DM is a common, complicated illness with a hereditary component and environmental risk factors, including bad lifestyle behaviors that contribute to overweight and obesity. The disease's prevalence rises sharply with age, with T2DM afflicting more than 10 % of the population over the age of 65 years. The condition is caused by a deficiency in insulin production by pancreatic beta-cells, as well as cellular insulin resistance, which is seen mostly in skeletal muscles and the liver, but sometimes in other tissues [8, 9]. Prolonged hyperglycemia, both fasting and postprandial, causes AGEs, oxidative stress, and low-grade inflammation, as well as damage to the arteries, mostly in the heart, kidneys, eyes, and nerves, but also in other tissues [10]. Nearly half of T2DM patients (47.3 %) had some kind of arthritis [11]. OA is a condition that affects the joints of the hand, hip, and knee. Aside from the numerous localizations, OA has been classified into phenotypes such as age-related, metabolic syndrome (MetS)-related (closely associated to abdominal obesity), genetic-related, and post-traumatic OA [12, 13]. The mechanical impact of overweight/obesity on joints may readily explain lower limb OA in MetS-associated OA [14]. Other MetS components, such as dysglycemia (which is similar to prediabetes), elevated blood pressure, and atherogenic dyslipidemia, may all have a role in OA pathogenesis, either together or separately [15–17]. It is important to note that, according to the unified criteria, more than three-quarters of T2DM patients have MetS [18]. Hypertension, dyslipidemia, and the number of MetS factors present have been found to be substantially linked with the severity of symptomatic knee OA; however, no connection between the severity of radiographic knee OA and MetS factors has been reported in the same research [19]. We want to examine if T2DM is associated to OA outside of weight gain and if T2DM has a role in OA pathogenesis in this review. The impact of T2DM on the progression of OA is also a topic of investigation. There are a variety of pharmacologic therapy options available that can help control the symptoms of OA. However, evidence is emerging that some of the most often given anti-OA medicines, including as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), are dangerous [20–23]. In addition, we looked at the T