Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Center of Evidence-Based Medicine, Institute of Medical Sciences, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Public Health. 2022 Jan 28;9:823739. doi: 10.3389/fpubh.2021.823739. eCollection 2021.
This study assessed temporal relationships of serum uric acid (SUA) with blood glucose and determine the mediating effects of body mass index (BMI) and dyslipidemia on the relation of SUA and risk of type 2 diabetes.
Participants aged ≥ 45 years were participated in 2011 and followed up until 2015. Cox proportional hazards regression with a robust variance estimator was performed to explore the association of SUA with the risk of diabetes, and crosslagged path analysis was introduced to examine the temporal relationships between SUA and blood glucose. A mediation analysis was finally used to identify the mediating effect of BMI and dyslipidemia on the relation of SUA and the future risk of diabetes.
A total of 9,020 participants were included with an average age of 58.59 years at baseline in 2011, and 53.6% of them were women. Linear dose-response relationship was identified by restricted spline cubic analysis between baseline SUA and follow-up blood glucose (the non-linear trend for fasting plasma glucose (FPG): β = -0.71, = 0.52; for HbA1c: β = 0.05, = 0.07; for risk of diabetes: β = 0.12, = 0.39). Additionally, compared with the lowest quartiles of SUA, the adjusted risk ratios of diabetes were 1.00 (95% : 0.82-1.23), 1.08 (95% : 0.89-1.31), and 1.37 (95% : 1.11-1.96) for quartile 2-4 (-trend < 0.01), respectively. Further additional adjustments for BMI or dyslipidemia, these ratios were not statistically significant. In addition, a unidirectional relationship from baseline SUA to follow-up FPG (ρ = 0.24, = 0.03) was further confirmed using crosslagged path analysis. After stratifying by genders, the above results were only significant in the women subgroup, and we thus conducted a mediation analysis in women and found that the BMI and dyslipidemia partially mediated the effect of SUA on diabetes with a 23.05 and 18.82% mediating effect, respectively.
These findings provide strong evidence that hyperuricemia preceded diabetes, and the effect of baseline SUA on follow-up type 2 diabetes was more pronounced among middle-aged and elderly Chinese women, especially in postmenopausal women, and this effect is partly mediated by BMI and dyslipidemia at baseline.
本研究评估了血清尿酸（SUA）与血糖之间的时间关系，并确定了体重指数（BMI）和血脂异常对 SUA 与 2 型糖尿病风险关系的中介作用。
年龄≥45 岁的参与者于 2011 年参加，并随访至 2015 年。采用稳健方差估计的 Cox 比例风险回归来探讨 SUA 与糖尿病风险的关系，引入交叉滞后路径分析来检验 SUA 与血糖之间的时间关系。最后进行中介分析，以确定 BMI 和血脂异常对 SUA 与未来糖尿病风险关系的中介作用。
共纳入 9020 名参与者，平均年龄为 2011 年基线时的 58.59 岁，其中 53.6%为女性。通过受限样条三次分析，在基线 SUA 与随访血糖之间发现了线性剂量反应关系（空腹血浆葡萄糖的非线性趋势：β=-0.71，=0.52；糖化血红蛋白：β=0.05，=0.07；糖尿病风险：β=0.12，=0.39）。此外，与 SUA 的最低四分位相比，四分位 2-4 的糖尿病调整风险比分别为 1.00（95%：0.82-1.23）、1.08（95%：0.89-1.31）和 1.37（95%：1.11-1.96）（-趋势<0.01）。进一步额外调整 BMI 或血脂异常后，这些比值无统计学意义。此外，使用交叉滞后路径分析进一步证实了从基线 SUA 到随访 FPG 的单向关系（ρ=0.24，=0.03）。按性别分层后，上述结果仅在女性亚组中具有统计学意义，因此我们在女性中进行了中介分析，发现 BMI 和血脂异常分别部分介导了 SUA 对糖尿病的影响，其介导效应分别为 23.05%和 18.82%。
这些发现提供了强有力的证据表明高尿酸血症先于糖尿病发生，并且基线 SUA 对中老年中国女性随访 2 型糖尿病的影响更为明显，尤其是绝经后女性，这种影响部分由基线时的 BMI 和血脂异常介导。
