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  1. N. McCormick1,2,3,4,
  2. C. Yokose1,3,4,
  3. L. Lu2,5,
  4. A. Joshi3,4,6,
  5. H. Choi1,2,3,4
  1. 1Massachusetts General Hospital, Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Boston, United States of America
  2. 2Arthritis Research Canada, -, Richmond, Canada
  3. 3Massachusetts General Hospital, The Mongan Institute, Boston, United States of America
  4. 4Harvard Medical School, Medicine, Boston, United States of America
  5. 5Brigham and Women’s Hospital, Channing Division of Network Medicine, Boston, United States of America
  6. 6Massachusetts General Hospital, Clinical & Translational Epidemiology Unit, Boston, United States of America


Background: Gout and the metabolic (insulin resistance) syndrome frequently coexist. Intravenous insulin has been shown to raise serum urate (SU) levels in physiologic studies and a Mendelian Randomization study also showed a causal role of insulin on the risk of gout. However, it is unknown whether habitual hyperinsulinemic dietary intake confers gout risk.

Objectives: Prospectively examine the relation between two distinct insulin-related dietary indices and risk of incident gout in three large cohorts of US women and men over 30 years.

Methods: We studied 164,090 women from Nurses Health Study I (1986-2016) and II (1989-2017) and 40,598 men from Health Professionals Follow-up Study (1986-2016), who were free of gout at baseline. Dietary intake and covariates were assessed by validated questionnaires every 4 years. Insulinemic potential of diet was evaluated using 1) food-based empirical dietary index for hyperinsulinemia (EDIH) score that was pre-defined based on circulating C-peptide levels1 and reflects insulin resistance;2 and 2) dietary insulin index (DII), which reflects transient, postprandial insulin secretion.2 We assigned EDIH and DII scores for each participant, adjusted for total energy intake, and prospectively examined the association between scores and incident gout (using ACR survey criteria for gout3), adjusting for potential confounders.

Results: We ascertained 2,874 incident gout cases over 5,124,490 person-years of follow-up. In pooled multivariable-adjusted analyses, those in the highest EDIH quintile had 1.76-times (95% CI: 1.56 to 1.99) higher gout risk, compared with the lowest (Table 1). This attenuated with further adjustment for BMI (a likely causal intermediate) but remained positive (RR 1.30, 1.15 to 1.48). DII scores were inversely associated with gout risk (RR 0.66, 0.58 to 0.74) (Table 1).

Table 1.

Risk Ratio (95% CI) of Gout According to Quintiles of Insulin-Related Dietary Index

Conclusion: EDIH scores, reflecting chronic hyperinsulinemia (i.e., greater insulin resistance with reduced clearance), were positively associated with the risk of incident gout, even beyond the pathway through adiposity. Conversely, higher DII scores, which reflect short-term, postprandial elevations in insulin levels (and also greater insulin clearance and sensitivity) conferred a lower risk. This corroborates human physiologic experiments and Mendelian Randomization studies showing insulin resistance can increase SU levels by decreasing renal excretion of urate, and supports lowering insulinemic potential of diet as a strategy to reduce gout risk.

References: [1]Tabung et al. PMID 27821188

[2]Lee et al. PMID 32618519

[3]Wallace et al. PMID 856219

Disclosure of Interests: Natalie McCormick: None declared, Chio Yokose: None declared, Leo Lu: None declared, Amit Joshi: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, Vaxart, Grant/research support from: Ironwood, Horizon

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