Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

Abstract

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.

Transcription factor EB enhances autophagy and ameliorates palmitate‐induced insulin resistance at least partly via upregulating AMPK activity in skeletal muscle cells

“…1,2 One of the most prominent metabolic changes observed in IR is glucose metabolism disorder. 3 Skeletal muscle is responsible for consuming nearly 80% of the glucose uptake in the body and plays a major role in insulin-stimulated glucose disposal. 4,5 Studies have shown a significant decrease in insulin-stimulated glucose uptake and insulin sensitivity in skeletal muscle in IR.…”

Characteristics of Patients with Type 2 Diabetes Mellitus in Al-Ihsan Regional General Hospital

“…T2DM has a pathogenic effect on OA through several pathways: a) chronic hyperglycemia, which induces oxidative stress, overproduction of proinflammatory cytokines and AGEs in joint tissue; b) insulin resistance, which can both act locally and causes a systemic low-grade inflammatory state; c) leptin, which causes chondrocyte apoptosis while increasing MMP and cytokine production from chondrocytes; d) increased FFA associated obesity and insulin resistance may also modulate the development of OA; e) GLUT-1, the amount is increased in the plasma membrane of joint cells and chondrocytes, thereby increasing glucose uptake in hyperglycemic conditions, causing the production of IL-1β, TGF-β1, and MMPoxidative stress, and AGEs which ultimately leads to OA. [41][42][43][44] The close relationship between TB and DM has long been known. Evidence that DM is often comorbid for TB and vice versa has also been confirmed.…”

Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis

“…Insulin resistance in patients with type 2 diabetes has been suggested to promote the progression of OA regardless of body mass ( 37 , 38 ). Recent studies attribute the association between insulin resistance and OA to increased expression of proinflammatory cytokines, as well as the production of tissue-degrading enzymes and downregulation of the synthesis of structural proteins of the articular cartilage ( 39 ). We expand on these observations, showing that in our study population the severity of OA symptoms is associated with insulin resistance irrespective of the glucose tolerance.…”