OP0005 DIETARY HYPERINSULINEMIC POTENTIAL AND RISK OF INCIDENT GOUT: 3 PROSPECTIVE COHORT STUDIES OF US MEN AND WOMEN
Authors: N. McCormick, C. Yokose, L. Lu, A. Joshi, H. Choi
Journal: Annals of the Rheumatic Diseases (2021)

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 levels 1 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 gout 3 ), 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 EDIH (measure of insulin resistance ) Q1: lowest circulating insulin levels Q2 Q3 Q4 Q5: highest circulating insulin levels P for trend N cases 430 482 598 631 733 Person-years 1,025,129 1,025,285 1,025,574 1,025,301 1,023,651 Age-adjusted RR 1.00 (Ref) 1.13 (1.00-1.29) 1.43 (1.26-1.61) 1.53 (1.36-1.73) 1.85 (1.64-2.09) &lt;.0001 MV-Adjusted * RR 1.00 (Ref) 1.11 (0.98-1.27) 1.39 (1.22-1.57) 1.47 (1.30-1.67) 1.76 (1.56-1.99) &lt;.0001 MV-Adjusted ** RR (+ BMI ) 1.00 (Ref) 1.03 (0.90-1.17) 1.21 (1.06-1.37) 1.21 (1.07-1.37) 1.30 (1.15-1.48) &lt;.0001 Dietary Insulin Index (measure of transient, post-prandial secretion and sensitivity ) Q1: lowest insulin sensitivity Q2 Q3 Q4 Q5: greatest insulin sensitivity P for trend N cases 783 611 527 498 455 Person-years 1,024,763 1,025,730 1,025,075 1,025,538 1,023,834 Age-adjusted RR 1.00 (Ref) 0.79 (0.71-0.88) 0.69 (0.62-0.77) 0.65 (0.58-0.73) 0.59 (0.53-0.66) &lt;.0001 MV-Adjusted * RR 1.00 (Ref) 0.79 (0.71-0.88) 0.69 (0.62-0.77) 0.66 (0.59-0.74) 0.60 (0.53-0.67) &lt;.0001 MV-Adjusted ** RR (+ BMI ) 1.00 (Ref) 0.78 (0.70-0.87) 0.69 (0.62-0.77) 0.67 (0.60-0.75) 0.66 (0.58-0.74) &lt;.0001 *Multivariable (MV) models adjusted for age (month), White race, smoking, menopause (women only), hormone use (women only), physical activity, history of hypertension, and diuretic use **MV + BMI models further adjusted for BMI (a likely causal intermediate) 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