The Psoriasis and Comorbidity Series: Understanding the Link between Psoriasis, Diabetes, and Obesity

Take a moment and think back to the times you have ordered blood work on a patient with psoriasis prior to initiation of a systemic medication. Did you notice if their glucose was elevated? Did you even look at their glucose?

As someone who treats a large population of patients with psoriasis, I found myself disappointed when I realized that I have been guilty of quickly mentioning these comorbidities to my patients but not spending as much time discussing it as I do with cardiovascular disease (CVD).  This made me aware of the fact that I likely am not the only one breezing over these important comorbidities, so I thought it would be a good opportunity to shed some light on these conditions and give them the attention they deserve.

To begin, let’s quickly review the shared underlying mechanisms associated with psoriasis, type 2 diabetes mellitus (DM), and obesity. These three entities share interrelated inflammatory cytokines that give positive feedback that further promote each of these comorbidities.¹ Due to western dietary habits and lack of exercise, we are seeing an increase in body mass index (BMI) and autoimmune diseases.¹  Studies have demonstrated that psoriasis is associated with DM independent of sex, age, smoking and BMI, which suggest that these conditions share common underlying genetic variations and mechanisms.¹

Furthermore, we know that adipose tissue, which was once considered an inactive energy storage, is actually a very active endocrine organ that secretes many pro-inflammatory mediators.² It is no surprise that as BMI increases, so do circulating cytokines, such as tumor necrosis factor-alpha (TNF-α).  As TNF-α, a known insulin antagonizer, increases, so does insulin resistance and hyperinsulinemia. This further perpetuates obesity, and the positive feedback cycle continues. In addition to TNF-α, serum levels of both IL-17 and IL-23 are significantly higher in patients with psoriasis and patients with obesity with and without psoriasis. Data is conflicting regarding the role IL-17 and IL-23 plays in DM, but evidence is growing to suggest that they could be involved in the pathogenesis as well.³

Data is also emerging to suggest that the association of psoriasis with obesity and DM occur early in the course of the disease, as evidenced by the increase in incidence of obesity and insulin resistance in children with psoriasis.⁴ This suggests that we, as dermatologists, should be routinely screening our patients from initial diagnosis for BMI and signs and symptoms of DM. The American Diabetes Association recommends checking a fasting plasma glucose every 2 years for high-risk patients,⁵ which includes this patient population. A multidisciplinary approach to treating these patients is often warranted as comorbidities emerge, and lifestyle modification should always be encouraged. 

There are several factors to consider when choosing the right treatment for your patient with psoriasis and obesity who has, or likely will develop, DM.  It is well known that patients with obesity and psoriasis have an increased risk of nonalcoholic fatty liver disease.⁶ Additionally, psoriasis is considered an independent predictor of advanced liver fibrosis, regardless of other factors such as age, BMI, hypertension, and DM.⁷  This makes methotrexate a poor choice for this population. Furthermore, patients with obesity tend to achieve lower efficacy from biologic agents than their leaner counterparts, and this is especially true for TNF agents with fixed dosing.^8-9  In addition, it has been suggested that TNF inhibitors may cause weight gain.^10-11

Overall, the IL-17 inhibitors tend to fare better across all body weights and have not been associated with weight gain. In a post hoc analysis of 3 studies, secukinumab and etanercept were found to lower fasting plasma glucose levels over 12 weeks.¹³ In a pooled analysis of its phase 3 trials, apremilast demonstrated weight loss and lowering of hemoglobin A_1C.¹³  Currently, there is not much data on the effects of IL-23 inhibitors on these comorbidities, although trials are underway, including a Phase 2/3 trial of ustekinumab for the treatment of type 1 diabetes.¹⁴

Given that DM development is independent of psoriasis severity, and that obesity is a risk factor in itself for developing psoriasis, it is more important than ever that we adapt our clinical practice to incorporate early screening and prevention for this population. While it seems like a daunting task, it may be beneficial to start with incorporating a relevant review of systems and adding a fasting glucose test to blood work every 2 years. Referral to our endocrine and primary care colleagues for co-management is always beneficial.

Dr Hawley is an associate clinical professor at Michigan State University College of Osteopathic Medicine and medical director of The Derm Institute of West Michigan in Grand Rapids, MI.

References

1. Brauchli YB, Jick SS, Meier CR. Psoriasis and the risk of incident diabetes mellitus: a population-based study. Br J Dermatol. 2008;159(6):1331-1337. doi:10.1111/j.1365-2133.2008.08814.x

2. Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig. 2016;26(1):25-42. doi:10.1515/hmbci-2015-0073

3. Granata M, Skarmoutsou E, Trovato C, Rossi GA, Mazzarino MC, D'Amico F. Obesity, Type 1 Diabetes, and Psoriasis: An Autoimmune Triple Flip. Pathobiology. 2017;84(2):71-79. doi:10.1159/000447777

4. Gutmark-Little I, Shah KN. Obesity and the metabolic syndrome in pediatric psoriasis. Clin Dermatol. 2015;33(3):305-315. doi:10.1016/j.clindermatol.2014.12.006

5. American Diabetes Association. Screening for diabetes. Diabetes Care. 2002;25(suppl 1): s21-s24.doi: 10.2337/diacare.25.2007.S21

6. Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):758-764. doi:10.1016/j.jhep.2009.04.020

7. Gisondi P, Barba E, Girolomoni G. Non-alcoholic fatty liver disease fibrosis score in patients with psoriasis. J Eur Acad Dermatol Venereol. 2016;30(2):282-287. doi:10.1111/jdv.13456

8. Gordon K, Korman N, Frankel E, et al. Efficacy of etanercept in an integrated multistudy database of patients with psoriasis. J Am Acad Dermatol. 2006;54(3 Suppl 2):S101-S111. doi:10.1016/j.jaad.2005.11.1088

9. Menter A, Gordon KB, Leonardi CL, Gu Y, Goldblum OM. Efficacy and safety of adalimumab across subgroups of patients with moderate to severe psoriasis. J Am Acad Dermatol. 2010;63(3):448-456. doi:10.1016/j.jaad.2009.09.040

10. Renzo LD, Saraceno R, Schipani C, et al. Prospective assessment of body weight and body composition changes in patients with psoriasis receiving anti-TNF-α treatment. Dermatol Ther. 2011;24(4):446-451. doi:10.1111/j.1529-8019.2011.01439.x

11. Tan E, Baker C, Foley P. Weight gain and tumour necrosis factor-alpha inhibitors in patients with psoriasis. Australas J Dermatol. 2013;54(4):259-263. doi:10.1111/ajd.12044

12. Gerdes S, Pinter A, Papavassilis C, Reinhardt M. Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients. J Eur Acad Dermatol Venereol. 2020;34(3):533-541. doi:10.1111/jdv.16004

13. Puig L, Korman N, Greggio C. Long-term hemoglobin A_1c changes with apremilast in patients with psoriasis and psoriatic arthritis: pooled analysis of phase 3 ESTEEM and PALACE trials and phase 3b LIBERATE trial. Presented at: 2019 American Academy of Dermatology Annual Meeting; Washington, DC; March 1-5, 2019. Abstract 9706.

14. Davidovici BB, Sattar N, Prinz J, et al. Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol. 2010;130(7):1785-1796. doi:10.1038/jid.2010.103