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02-06-2021 | Gout | News

Genetic data clarify relationship between hyperuricemia and insulin resistance

Author: Laura Cowen


medwireNews: Insulin resistance has a causal effect on hyperuricemia and subsequently gout, but hyperuricemia does not impact insulin resistance, suggests an analysis of genome-wide association data.

This suggests that “[r]educing insulin resistance could lower [serum urate concentrations] and gout risk, whereas lowering [serum urate] (e.g., allopurinol) is unlikely to mitigate insulin resistance and its cardiovascular-metabolic sequalae,” write Natalie McCormick (Harvard Medical School, Boston, Massachusetts, USA) and co-authors in Arthritis & Rheumatology.

McCormick and team used genome-wide association data from the CKDGen and MAGIC consortia, which provided genetically determined concentrations of serum urate and fasting insulin, respectively, to perform a bidirectional Mendelian randomization (MR) analysis. In all, more than 1.2 million people of European ancestry contributed to the study.

The researchers found that genetically determined serum urate was not significantly associated with fasting insulin concentration, a surrogate measure of insulin resistance.

By contrast, genetically determined fasting insulin concentrations were significantly and positively associated with serum urate levels. Specifically, each 1-unit (1.0 log pmol/L) increase in fasting insulin was associated with a significant 0.37 mg/dL increase in serum urate, which is the same as a 0.63 mg/dL increase in serum urate per one standard deviation (1.7 log pmol/L) increase in fasting insulin.

And the relationship strengthened when the data were adjusted for outlier single nucleotide polymorphisms and genetically determined BMI. In these cases, each unit increase in fasting insulin concentration was associated with 0.56 mg/dL and 0.69 mg/dL increases in serum urate levels, respectively.

The researchers observed similar relationships when they looked at the risk for gout: the odds for gout increased a significant 1.49-fold with each unit increase in fasting insulin concentration, but gout was not significantly associated with fasting insulin levels.

Furthermore, the findings were replicated in individual-level data from 360,453 members of the UK Biobank.

McCormick et al conclude that their study “provides evidence that genetically elevated fasting insulin, a measure of insulin resistance and precursor to cardiometabolic diseases, is causally associated with hyperuricemia, as well as the clinical endpoint of gout.”

They add that their findings should now “be confirmed in other ancestral populations.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Arthritis Rheumatol 2021; doi:10.1002/art.41779