Gout and Metabolic Syndrome: a Tangled Web

Gabrielle E. Thottam, Svetlana Krasnokutsky, Michael H. Pillinger

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations


Purpose of review: The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout’s physiologic and epidemiologic relationships with its major co-morbidities. Recent findings: Increasing evidence supports gout’s association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Summary: Gout is both an inflammatory and a metabolic disease. With further investigation of urate’s role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

Original languageEnglish (US)
Article number60
JournalCurrent rheumatology reports
Issue number10
StatePublished - Oct 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements Dr. Pillinger is supported in part by NYU CTSA grant 1UL1TR001445 from the National Center for the Advancement of Translational Science (NCATS), NIH. Dr. Krasnokutsky is supported in part by an Investigator Award from the Rheumatology Research Foundation.

Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.


  • Diabetes
  • Fructose
  • Gout
  • Hypertension
  • Metabolic syndrome
  • Uric acid


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