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• There were differential effects in different testosterone active states in gout. • Higher total testosterone in males linked to lower gout risk, not in females. • Higher free testosterone and bioavailable testosterone, higher risks of gout in males. • Higher SHBG were associated with lower risks of gout both in males and females. • Females have the lowest risk of gout at around 70 nmol/L SHBG levels. To investigate the associations between sex hormones and gout. A total of 448,836 individuals free of gout at baseline were included from the UK Biobank. Cox regression models were used to estimate hazard ratios (HRs) for gout. Besides, we investigated the causal relationship between bioavailable testosterone (BAT) and gout using mendelian randomization (MR). There were differential effects in different testosterone active states in gout. One-unit higher log-transformed total testosterone (TT) was associated with a 52 % [95 % CI, 0.39–0.58] lower risk of gout in males. In contrast, free testosterone (FT) and BAT were associated with a 74 % [95 % CI, 1.38–2.20] and a 78 % [95 % CI, 1.41–2.25] higher risk of gout in males respectively. For MR, the weighted median [OR, 1.70; 95 % CI, 1.14–2.56;] and inverse variance-weighted [OR, 1.25; 95 % CI, 0.96–1.62; P = 0.09] method revealed significant and approximately significant positive effect of genetic liability to BAT levels on the risk of gout respectively. Sex hormones were potentially associated with gout. Notably, we were the first to explore different testosterone states on gout and found that FT and BAT may increase the risk of gout in males, which is opposite to TT. And the former are active states of androgens, may be more accurately reflect the association between androgens and gout. [ABSTRACT FROM AUTHOR]

• The combined effects of multiple air pollutants may differ from those of single air pollutants. • The combined exposure to air pollutants was positively associated with the incidence of ischemic heart disease. • The association was more pronounced among individuals with diabetes compared to those without. Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. This study included 388 780 individuals (20 036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 μm (PM 2.5), PM with diameters between 2.5 and 10 µm (PM coarse), PM with diameters ≤ 10 μm (PM 10), nitrogen dioxide (NO 2), and nitrogen dioxides (NO x), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. During a median of 12.9 years of follow-up, 27 333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03–1.23) among individuals with T2D, while the HR was 1.06 (1.03–1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (P interaction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D. [ABSTRACT FROM AUTHOR]