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Unexpected Link Between Psoriatic Arthritis (PsA) and Diabetes

Jan 9, 2021
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy

Patients with psoriatic arthritis may be more prone to develop type 2 diabetes than the general population.  

Psoriatic arthritis (PsA) is often strongly connected to metabolic disorders, including obesity and diabetes, with the highest prevalence in North America. Patients with PsA consistently reveal the highest risk of developing type 2 diabetes compared to the general population, and even patients with sole psoriasis. Research takes a closer look into the risk of type 2 diabetes with PsA, the mechanism driving the link, and the effects of PsA systemic therapies on insulin sensitivity. 

 

Researchers have discovered distinct underlying pathways that link PsA to type 2 diabetes. Cytokines, mainly including TNF- α, were suggested to be one of the main drives behind the relationship. Cytokines induce insulin resistance and suppress the expression of glucose transporter type 4 (GLUT-4), which is a protein that allows glucose to enter adipose tissue and muscle cells. TNF- α specifically is found in large quantities within the muscle of patients with insulin resistance and non-insulin-dependent diabetes. This presence suggests that TNF- α is involved in the pathogenesis of insulin resistance. Adipokines, another group of cytokines, may contribute to the correlation between PsA and type 2 diabetes. Adiponectin, which is a type of adipokine, has both anti-inflammatory and insulin-sensitizing properties. However, TNF- α and other cytokines decrease their secretion. Regarding the effects of systemic therapies, certain drug classes used in the treatment of PsA were seen to have worsening effects on either blood glucose levels or insulin sensitivity.  

Glucocorticoids, which involve sensitivity to glucose and the ability to release insulin, cause steroid-induced diabetes. Researchers found that older patients with increased HbA1c levels and low estimated glomerular filtration rates (eGFR) are at the highest risk of steroid-induced diabetes when taking glucocorticoids. Furthermore, NSAIDs commonly accepted in patients with PsA are associated with increased coronary artery disease and renal disease risk. Patients with type 2 diabetes have higher chances of developing coronary artery disease. Therefore, NSAIDs have a negative impact and are expected to be limited in use with these patients. Safer options in patients with type 2 diabetes and PsA include methotrexate, leflunomide, sulfasalazine, apremilast, anti-IL 17, and anti-IL 12/23. TNF- α blocking agents show positive results for up to six months and are associated with glucose control and reduced insulin resistance.  

Examining the relationship parameters, a previous study analyzed the difference between male and female patients with PsA and the risk of diabetes progressing. Women showed 18.7% (95% CI, 1.02 to 2.52) prevalence of diabetes compared to men with an 11.2% prevalence (95% CI, 0.42 to 1.22). This study proved women as having more significant rates of risk, and suggests that they are better candidates for diabetes screening. Women were also found to have higher erythrocyte sedimentation rates (ESR), body mass index (BMI), and tender joint count than men, explaining this observation. Another study evaluated patients with raised disease activity. It was revealed that patients with tender joint count (95% CI, 1.08 to 2.18) and ESR (95% CI, 1.03 to 1.41) had more leading risks of developing type 2 diabetes. A cross-sectional study researched the timing of onset and its relationship to diabetes. Results showed that in patients with late psoriasis onset (after 40 years), developing type 2 diabetes was significantly more frequent (95% CI, 1.9 to 12.4).  

The prevalence of type 2 diabetes has been found significantly more abundant in patients with PsA. Patients with higher levels of disease activity are particularly at a higher risk. It would be beneficial to screen patients with PsA sooner for type 2 diabetes. Inflammation, metabolic disturbances, systemic therapies, and even risk factors like obesity and inactivity had evidence as being the culprits in the relationship between PsA and type 2 diabetes. Patients with PsA and type 2 diabetes are encouraged to focus on three key pieces: weight control, diet, and exercise. These components can contribute to less insulin resistance and significantly lower blood glucose levels, making management for PsA and type 2 diabetes better. 

Practice Pearls: 

  • Patients with PsA have increased risks of developing type 2 diabetes due to specific pathogenic mechanisms of cytokines like TNF- α and adipokines. 
  • Glucocorticoids and NSAIDs worsen conditions for patients with type 2 diabetes and PsA. 
  • Women with PsA, patients with increased PsA disease activity, and late psoriasis onset have a higher risk of developing type 2 diabetes. 
  • Weight control, diet, and exercise are encouraged for PsA and type 2 diabetes management. 

 

Bello, Giacomo Dal, et al. “Psoriatic Arthritis and Diabetes Mellitus: A Narrative Review.” Rheumatology and Therapy, vol. 7, no. 2, 2020, pp. 271–285., doi:10.1007/s40744-020-00206-7. 

Eder, Lihi, et al. “The Risk of Developing Diabetes Mellitus in Patients with Psoriatic Arthritis: A Cohort Study.” The Journal of Rheumatology, vol. 44, no. 3, Jan. 2017, pp. 286–291., doi:10.3899/jrheum.160861. 

Maya Palmer, PharmD. Candidate, Florida A&M University College of Pharmacy

 

Related: see articles on psoriatic arthritis, rheumatoid arthritis, psoriasis, and diabetes.