Metabolic syndrome is associated with a significantly increased risk for gout in young men, but the risk can be mitigated by improvement in individual components of the syndrome, based on data from a pair of population-based studies totaling more than 4 million individuals.
Gout remains the most common type of inflammatory arthritis in men, and the rate has been rising among younger adults, Yeonghee Eun, MD, PhD, of Sungkyunkwan University, Seoul, South Korea, and colleagues wrote. An increasing body of evidence suggests a link between gout and metabolic syndrome (MetS), but large studies have been lacking, especially in younger adults.
In a study published in Frontiers in Medicine, the researchers reviewed data from 3,569,104 men aged 20-39 years who underwent a health checkup between 2009 and 2012 in South Korea, based on the Korean National Health Insurance Service. The primary outcome of incident gout was identified using claims data. The mean age of the participants was 31.5 years.
Over a mean follow-up of 7.4 years, the incidence of gout was 3.36 per 1,000 person-years. The risk of developing gout was more than twice as high among individuals who met MetS criteria than in those who did not (adjusted hazard ratio, 2.44).
MetS was defined as the presence of at least two of the following components: hypertriglyceridemia, abdominal obesity, reduced HDL cholesterol, elevated blood pressure, and elevated fasting glucose.
Overall, individuals with all five MetS components had a fivefold increase in gout risk, compared with people who did not have MetS (aHR, 5.24). In an analysis of each component of MetS, hypertriglyceridemia and abdominal obesity showed the strongest association with gout (aHRs of 2.08 and 2.33, respectively).
The impact of MetS on risk of incident gout was greater in younger participants, which suggests that the management of MetS in young people should be emphasized, the researchers said.
In a further analysis of body mass index subgroups, MetS had the greatest impact on gout risk for individuals who were underweight (aHR, 3.82). “In particular, in the underweight group, the risk of gout increased 10-fold when abdominal obesity was present,” the researchers said.
The study was limited by several factors including potential selection bias and potential overestimation of gout incidence because of the use of diagnostic codes, the researchers noted. Other limitations included lack of control for nutritional or dietary risk factors and the inability to include cases that occurred after the study period.
However, findings were strengthened by the large number of participants with MetS who were underweight or normal weight, the researchers wrote. More research on the mechanism of action is needed, but the data suggest that MetS is a key risk factor in the development of gout in young men.
In a second study, published in Arthritis & Rheumatology, Dr. Eun and colleagues examined associations between MetS changes and incident gout in young men. Although previous studies have shown that changes in MetS status can alter the risk of cardiovascular events, atrial fibrillation, end-stage renal disease, and all-cause mortality, the impact of these changes on gout has not been well studied, they said. The researchers used the same study cohort, the National Health Insurance Service database in South Korea. They reviewed data from 1,293,166 individuals aged 20-39 years. Of these, 18,473 were diagnosed with gout for an incidence rate 3.36/1,000 person-years. The researchers compared gout incidence for men who met criteria for MetS at three health checkups and those without MetS.
Overall, patients with MetS at all three checkups had a nearly fourfold higher risk of gout than those who never had MetS, with an adjusted hazard ratio of 3.82, the researchers wrote. The development of MetS over the study period more than doubled the risk of gout, but recovery from MetS reduced incident gout risk by approximately 50% (aHR, 0.52).
In findings similar to the Frontiers in Medicine study, the greatest associations with gout were noted for changes in elevated triglycerides and changes in abdominal obesity; aHRs for development and recovery for elevated triglycerides were 1.74 and 0.56, respectively, and for abdominal obesity, 1.94 and 0.69, respectively.
More research is needed to explore the mechanism by which both abdominal obesity and elevated triglycerides drive the development of gout, the researchers wrote in their discussion.
Also similar to the Frontiers study, the associations among changes in MetS and incident gout were greater for the youngest participants (in their 20s) and in the underweight or normal weight BMI groups.
Limitations of the second study included possible selection bias because of the study population of workplace employees who participated in regular health checks and the lack of data on women or on men aged 40 years and older, the researchers noted. Other limitations included possible misclassification of MetS because of varying health checkup results and drug claims, and lack of data on serum urate, which prevented assessment of hyperuricemia as a cause of gout.
However, the results were strengthened by the large sample size and suggest that MetS is a modifiable risk factor for gout, the researchers concluded.
Neither of the studies received outside funding. The researchers had no financial conflicts to disclose.