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Rising body mass index (BMI) increased the risk of several rheumatic diseases, particularly for women, and for both gout and psoriatic arthropathies.

That's according to findings that appear in .

Scientists applied data from the large and well-established cohort. One standard deviation increase in BMI increased the incidence rate for all individuals in several rheumatic diseases, including rheumatoid arthritis (IRR 1.52 [95% CI 1.36-1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43-1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31-2.48]), gout (IRR 1.73 [95% CI 1.56-1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14-1.57]).

BMI was found to be a stronger risk factor for women for psoriatic arthropathy (P for sex interaction = 3.3 × 10^-4) and gout (P=4.3 × 10^-3). Investigators also observed an enhanced risk of osteoarthritis in premenopausal women compared with postmenopausal women (P=1.8 × 10^-3).

First author Torgny Karlsson, PhD, is a statistician with the Department of Immunology, Genetics and Pathology at Uppsala Universitet in Sweden. His exchange with the Reading Room has been edited for length and clarity.

What was the purpose of this study?

Karlsson: The majority of previous studies were designed to identify an association between obesity and rheumatic disease, but not necessarily a causation. It means that these studies showed that obesity is correlated with an increased risk of rheumatic diseases but they were not able to determine whether obesity causes rheumatic disease or whether rheumatic disease results in obesity through mechanisms such as hypoactivity, or both. In this study we implemented a method called mendelian randomization which makes use of genetic variants to study the effect of an exposure, like obesity, on an outcome, like psoriatic arthropathy. This method is considered an analog to randomized controlled trials and is a powerful tool for investigating particular causal relations.

In addition, it is not well known whether BMI has a different causal effect on the development of rheumatic disease in men compared to women, or whether the effect is equal in underweight, normal-weight, and overweight individuals. These questions were all addressed in this study.

What were your key findings?

Karlsson: We showed that high BMI increases the risk of developing five different rheumatic diseases: rheumatoid arthritis, osteoarthritis, psoriatic arthropathy, gout, and inflammatory spondylitis. We also found that BMI is a stronger risk factor in women than men for psoriatic arthropathy and gout. Furthermore, the effect of an increased BMI on gout was found to be different in individuals with different baseline BMI.

Did any of the findings surprise you?

Karlsson: Through performing an advanced type of analysis, we detected that the causal effect on gout of increasing BMI one unit differs between lean, normal-weight, and obese individuals. Generally, when people gain weight, their risk of developing gout increases. However, interestingly, this increase in risk is bigger in normal weight people (those with a BMI of 25 kg/m²) both compared to those who are underweight, and those who are already overweight.

The strong effect of BMI on psoriatic arthropathy in women compared to an apparent null effect in men is also interesting and somewhat surprising, especially since the overall number of cases in UK Biobank are nearly exactly the same in both sexes.

What are your take-home messages for clinicians?

Karlsson: Interventions that decrease BMI are likely to have beneficial effects on disease rates for different rheumatic diseases. For some diseases, such as gout, weight gain prevention and keeping the people at risk in the normal range of BMI could possibly be of more importance.

Key points:

• Increases in BMI led to increased risk of several rheumatic diseases.
• Risks are higher for women in certain cases than men, and in premenopausal women compared with postmenopausal.
• Interventions that decrease BMI, particularly for those at risk of rheumatic diseases, could be more important than ever.

Read the study here and expert commentary on the clinical implications here.