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05-03-2016, 10:02 PM
Psoriasis, Obesity, and Diabetes May Share Genetic Link

A new study among twins in Denmark has found a strong association between psoriasis, type 2 diabetes, and obesity, with modest evidence suggesting a genetic link between the three conditions. Results were published online on April 27 in JAMA Dermatology.

"The reason for the association between psoriasis, type 2 diabetes, and obesity is not only common lifestyle, but we also found a genetic association between psoriasis and obesity that was independent of other important factors," lead author Ann Sophie Lonnberg, MD, from the University of Copenhagen, Denmark, told Medscape Medical News by email.

The work is also the first to evaluate how the contribution of genes and environment may play a role in the links between psoriasis, type 2 diabetes, and obesity.

In addition to genetics, lifestyle factors — lack of exercise, an unhealthy diet, smoking, alcohol consumption, and stress — could explain the associations between psoriasis, type 2 diabetes, and obesity, Dr Lonnberg explained.

Shared inflammatory pathways may also be involved, because chronic inflammation has been implicated in all three disorders. Finally, medication play a role. Overtreatment of psoriasis with corticosteroids has been linked to type 2 diabetes and obesity, although these cases are rare.

Twin Study Provides New Insights

In an accompanying editorial, Joel M Gelfand, MD, medical director in the Dermatology Clinical Studies Unit and director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania Perelman School of Medicine, Philadelphia, says the association of psoriasis with type 2 diabetes mellitus and obesity has been extensively studied and has been the subject of numerous meta-analyses that clearly establish an association of psoriasis with both obesity and diabetes.

However, the current study — in both monozygotic and dizygotic twins, with and without psoriasis — is "unique" and provides "new insights into these associations," he notes.

The study included Danish twins between the ages of 20 to 71 years. Participants self-reported psoriasis using questionnaires, and researchers checked the accuracy of the responses against hospital discharge diagnoses of psoriasis. Data on type 2 diabetes came from discharge diagnoses in the Danish National Register. Participants also self-reported body mass index (BMI).

The analysis included data from 33,588 twins (54% women and 46% men; average age, 44.5 years), with a psoriasis prevalence of 4.2%, diabetes prevalence of 1.4%, and average BMI of 24.5. There were 449 psoriasis-discordant twins.

Only 6.3% of participants had a BMI between 30 and 34.

Results adjusted for sex, age, smoking, and BMI showed that participants with psoriasis had a 53% increased risk of type 2 diabetes (odds ratio [OR], 1.53; P = .04) and an 81% risk of having a high BMI, defined as >35.0 (OR, 1.81; P = .001). Participants with a BMI of at least 35 had almost twice the risk for psoriasis as those of normal weight.

The analysis suggested a genetic link between psoriasis and type 2 diabetes (genetic correlation 0.13, P = .17), although the results were not statistically significant. Results also showed a genetic link between psoriasis and BMI, which was statistically significant (genetic correlation, 0.12; P < .001).
The results "indicate a common genetic etiology for psoriasis and obesity," say the researchers.

In his editorial, Dr Gelfand says the strength of the genetic associations between psoriasis, BMI, and diabetes is "modest" but "consistent with emerging genetic evidence linking psoriasis to diabetes."

The environmental contributions to psoriasis and type 2 diabetes (genetic correlation 0.10, P = .63), and psoriasis and BMI (−0.05; P = .44) were not significant.

The cross-sectional nature of the study makes it impossible to determine whether psoriasis may predispose to type 2 diabetes or vice versa. Also, results may underestimate the link between psoriasis and type 2 diabetes, because of the low prevalence of diabetes in this study, say the researchers.

Dermatologists on Front Line: Assess Psoriasis Patients for Diabetes

The new study has several implications for clinical practice, Dr Gelfand notes in his editorial.

Psoriasis is a complex disease, associated with several risk factors and comorbidities that make it important to treat — including cardiovascular, metabolic, and renal disease, which can all, in turn, have a large, negative impact on overall health, including premature death.

"The dermatologist is on the front line in educating patients with psoriasis about their disease, treatment options, and risks of comorbidities."

Given the association of psoriasis — particularly more severe disease — and increases in BMI, "patients with psoriasis, particularly those ages 40 to 70 with more extensive skin disease, should receive medical screenings for diabetes," and dermatologists have an important role to play in this respect, he told Medscape Medical News in an email.

However, "the ultimate goal is to determine which patients with psoriasis — be it based on their genetic profile, severity of psoriasis, or other risk factors — have the highest risk of developing diabetes so that prevention efforts can be targeted [most] successfully," he stressed.

In turn, patients with diabetes who also have psoriasis may have higher risk of diabetic complications and worse glycemic control. Also, the risk for diabetic complications increases with the severity of psoriasis.

Conversely, obesity and diabetes can affect treatment for psoriasis. Obese patients with diabetes are at increased risk for liver fibrosis when they take methotrexate, for example. Also, the effectiveness of psoriasis treatments decreases with increasing BMI.

And "patients with psoriasis who are overweight or obese may lower their risk of diabetes while making the skin disease less active if they are able to achieve and maintain a healthier body weight," he concludes.

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The authors report no relevant financial relationships. Dr Gelfand reports consulting for and receiving honoraria and/or grant support from one or more of the following: Abbvie, AstraZeneca, Celgene, Coherus, Eli Lilly, Janssen Biologics (formerly Centocor), Sanofi, Merck, Novartis, Endo, Valeant, Pfizer, Amgen, Janssen, Novartis, Regeneron, and Pfizer (to the trustees of the University of Pennsylvania); and having received payment for continuing medical education work related to psoriasis. Dr Gelfand is a co–patent holder of resiquimod for treating cutaneous T-cell lymphoma.

JAMA Dermatol. Published online April 27, 2016. Abstract, Editorial