Insulin Resistance and Rheumatoid Arthritis

Insulin resistance and Rheumatoid arthritis


Rheumatoid arthritis (RA) is a chronic condition where the bodies immune system damages the tissue, joints and internal organs. Causing pain and swelling and over long periods can erode bones, joints and internal organs.

Insulin is a hormone secreted from the pancreas (the beta cells of the Langerhans islets). Its main functions are the metabolism of nutrients, mainly carbohydrates and glucose homeostasis in circulating blood.

RA has an underlying driving factor of hyperinsulinemia (insulin resistance). Insulin increases inflammatory markers within the body, increasing inflammation and pain, especially in the synovial membrane (this membrane lines all body joints) [i]

The increase in insulin concentrations over an extended period is associated with a disruption of the GLUT4 transporter. It then decreases glucose uptake into muscles and inhibits gluconeogenic enzyme expression in the liver, increasing insulin resistance. [ii]


How does insulin resistance increase inflammation

Elevated levels of tumour necrosis factor, interleukin-6 (IL-6) and interleukin-8 (IL-8) [interleukins regulate cell growth and stimulate inflammation] have been found in people with insulin resistance. With the increase of these interleukins, C-reactive protein [binds to foreign and damaged cells] increases inflammation.[iii]

Tumour necrosis factor is linked to insulin resistance through the disturbance in lipid metabolism, coagulation, endothelial function and affecting the insulin receptor inhibiting GLUT4.



Increase inflammation and Rheumatoid Arthritis


Where does the inflammation begin?

Studies have shown that RA's inflammation can start in the oral mucosa, specifically the gingivitis and periodontal regions, with an increase in severity and prevalence of periodontitis associated with the onset of RA. The studies are suggesting that the initial inflammation and autoimmunity begins outside the joints.

After the onset of RA plasma cells within the synovial joints can produce auto-antibodies increasing inflammation and reducing movement.

The gut microbiome influences the development of the adaptive and innate immune response. Studies have shown that the microbiota has specific alterations that can enhance susceptibility to arthritis. [iv]

The gut microbiota also regulates energy metabolism through short-chain fatty acid and lipopolysaccharide metabolism, affecting insulin and leptin secretion and modulating inflammation, improving or worsening insulin resistance. [v]



How to treat insulin resistance


Dietary factors definitely play a role in improving RA and hyperinsulinemia, increasing low glycemic load and anti-inflammatory foods (salmon, sardines) and reducing foods known to cause inflammation (sugar, processed) is a great way to start. Increase water consumption to improve liver clearance and reduce portion size at meals.

Increasing exercise, especially weight-bearing exercise, stimulates slow-twitch muscles. Uses[vi] glucose as its energy source to reduce stored glucose in adipose (fat) tissue, resulting in reduced inflammation. Increase outside activity to improve vitamin D uptake; this can improve bone density. [vii]





References

[i]Insulin Resistance Linked to Rheumatoid Arthritis Flares. (n.d.). Retrieved February 4, 2021, from https://www.rheumatologynetwork.com/view/insulin-resistance-linked-rheumatoid-arthritis-flares [ii] Ferraz Amaro, I., Díaz González, F., González Juanatey, C., & González Gay, M. Á. (2011). Insulin resistance and rheumatoid arthritis. Reumatología Clínica (English Edition), 7(2), 124–129. https://doi.org/10.1016/s2173-5743(11)70023-5 [iii] Gallagher, L., Cregan, S., Biniecka, M., Cunningham, C., Veale, D. J., Kane, D. J., Fearon, U., & Mullan, R. H. (2020). Insulin-Resistant Pathways Are Associated With Disease Activity in Rheumatoid Arthritis and Are Subject to Disease Modification Through Metabolic Reprogramming: A Potential Novel Therapeutic Approach. Arthritis and Rheumatology, 72(6), 896–902. https://doi.org/10.1002/art.41190 [iv] Demoruelle, M. K., Deane, K. D., & Holers, V. M. (2014). When and where does inflammation begin in rheumatoid arthritis? In Current Opinion in Rheumatology (Vol. 26, Issue 1, pp. 64–71). NIH Public Access. https://doi.org/10.1097/BOR.0000000000000017 [v] Lu, J., Ma, K. L., & Ruan, X. Z. (2019). Dysbiosis of Gut Microbiota Contributes to the Development of Diabetes Mellitus. Infectious Microbes and Diseases, 1(2), 43–48. https://doi.org/10.1097/IM9.0000000000000011 [vi] Philippou, E., & Nikiphorou, E. (2018). Are we really what we eat? Nutrition and its role in the onset of rheumatoid arthritis. In Autoimmunity Reviews (Vol. 17, Issue 11, pp. 1074–1077). Elsevier B.V. https://doi.org/10.1016/j.autrev.2018.05.009