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Gout and Metabolic Syndrome: a Tangled Web

  • Gabrielle E. Thottam
  • Svetlana Krasnokutsky
  • Michael H. Pillinger
Crystal Arthritis (M Pillinger and S Krasnokutsky, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Crystal Arthritis

Abstract

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.

Keywords

Gout Metabolic syndrome Uric acid Diabetes Fructose Hypertension 

Notes

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.

Compliance with Ethical Standards

Conflict of Interest

None of the authors have any direct conflict of interest regarding this manuscript. However, for the purpose of full disclosure, we note the following: Dr. Pillinger serves and/or has served as a consultant for Horizon, Ironwood and SOBI, and has been an investigative site for a sponsored, FDA-mandated trial by Takeda. Dr. Krasnokutsky has served as a consultant for Horizon and Ironwood. Dr. Thottam has no disclosures to report.

Human and Animal Rights Informed Consent

This review article did not directly involve any clinical research or human subjects. We do reference currently unpublished data from an ongoing study, and note that the study in question has been approved by the Institutional Review Board of New York University School of Medicine.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Gabrielle E. Thottam
    • 1
    • 2
  • Svetlana Krasnokutsky
    • 2
    • 3
  • Michael H. Pillinger
    • 2
    • 3
  1. 1.Department of MedicineRoger Williams Medical CenterProvidenceUSA
  2. 2.Crystal Diseases Study Group, Division of Rheumatology, Department of MedicineNew York University School of MedicineNew YorkUSA
  3. 3.Rheumatology Section, Department of MedicineVA New Harbor Health Care SystemNew YorkUSA

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