Gout & Cardiometabolic Co-Morbidities

Chicago—Gout is a global scourge, affecting about 55 million people worldwide.¹ As many rheumatologists have observed clinically, gout and cardiometabolic diseases tend to swim in the same waters. With this in mind, the ACR Convergence 2025 session, Gazing into the Crystal Ball: Gout and Cardiometabolic Comorbidity Management, provided tremendous insights into this important topic.

Metabolic Syndrome & Gout

Dr. McCormick

The first speaker was Natalie McCormick, PhD, an instructor in medicine at Massachusetts General Hospital, Boston, and her talk focused on the metabolic syndrome (MetS) and its relationship to gout. MetS is a cluster of interrelated metabolic abnormalities—including central obesity, insulin resistance, dyslipidemia and hypertension—that together increase the risk of cardiovascular disease and type 2 diabetes. Several large cohort studies have demonstrated that individuals with MetS have a markedly higher risk of incident gout, with chronic MetS conferring up to a four-fold increased risk compared with those without MetS.^2,3 The risk of gout further rises with the number of MetS components present; among these components, hypertriglyceridemia and abdominal obesity show the strongest associations with gout.² Clinically, the coexistence of gout and MetS increases cardiovascular risk, a fact that highlights the need for systemic screening for MetS-related conditions in patients with gout.

Dr. McCormick went on to discuss her research on the interesting topic of how to assess the causal relationship between insulin resistance, hyperuricemia and gout using bidirectional Mendelian randomization, a research method that uses genetic variants as natural experiments to assess whether an observed association between a risk factor and a disease is likely to be causal. In other words, genetic data was used to figure out whether insulin resistance causes hyperuricemia and gout, or if high uric acid causes insulin resistance.

Dr. McCormick and her colleagues used genome-wide association data from the UK Biobank, which is a prospective cohort of approximately 500,000 individuals aged 40–69 years recruited across the United Kingdom. They also used individual-level, electronic medical record-linked data from the UK Biobank. The authors found that genetic risk for insulin resistance leads to higher uric acid levels and a greater risk of gout, but having genes for high uric acid does not cause insulin resistance. Put another way, insulin resistance can cause gout, but gout does not cause insulin resistance. This implies that treating insulin resistance (such as through diet, exercise or medications) could help lower uric acid and reduce the risk of gout.³