DataSheet_1_Fatty liver mediates the association of hyperuricemia with prediabetes and diabetes: a weighting-based mediation analysis.docx

BackgroundFatty liver, obesity, and dyslipidemia are associated with prediabetes or diabetes risk, and hyperuricemia co-exists. The present study evaluated the role of multiple mediators, namely, fatty liver, body mass index (BMI), and dyslipidemia, in the association between hyperuricemia and diabetes status.
MethodsBaseline data from the ongoing Fuqing cohort (5,336 participants) were analyzed to investigate the association of hyperuricemia with diabetes status using a multinomial logistic regression model. Furthermore, causal mediation analysis with the weighting-based approach was performed to estimate hyperuricemia’s total natural direct effect (tnde), total natural indirect effect (tnie), and total effect (te) on prediabetes and diabetes risk, mediating jointly via fatty liver, BMI, and dyslipidemia.
ResultsIn multinomial analysis without considering mediators’ effects, hyperuricemia was associated with a higher risk of prediabetes only (odds ratio: 1.25; 95% CI: 1.09–1.43; p < 0.001). When fatty liver, BMI, and dyslipidemia were considered as multiple mediators in the association, hyperuricemia was linked to both prediabetes [tnde: 1.11, 95% CI: 1.04–1.11; tnie: 1.07, 95% CI: 1.05–1.09; and overall proportion mediated (pm): 42%, 95% CI: 27%–73%] and diabetes risk (tnde: 0.96, 95% CI: 0.82–1.14; tnie: 1.25, 95% CI: 1.18–1.33; and pm: 100%, 95% CI: 57%–361%). Hyperuricemia showed significant tnde, te, and tnie, mediated by fatty liver jointly with dyslipidemia (pm = 17%) or BMI (pm = 35%), on prediabetes risk.
ConclusionHyperuricemia could increase prediabetes or diabetes risk, partially mediated by fatty liver, BMI, and dyslipidemia. Fatty liver is the crucial mediator in the association between hyperuricemia and prediabetes.

背景 脂肪肝、肥胖与血脂异常均与糖尿病前期或糖尿病患病风险相关，且常与高尿酸血症（hyperuricemia）共存。本研究旨在探讨脂肪肝、体重指数（Body Mass Index, BMI）及血脂异常（dyslipidemia）作为多重中介变量，在高尿酸血症与糖尿病患病状态关联中的作用。方法 本研究对正在进行的福清队列（Fuqing cohort）的基线数据（共5336名参与者）进行分析，采用多项logistic回归模型探究高尿酸血症与糖尿病患病状态的关联。此外，本研究采用基于加权的方法开展因果中介分析，以估算高尿酸血症通过脂肪肝、BMI及血脂异常共同介导时，对糖尿病前期和糖尿病患病风险的总自然直接效应（total natural direct effect, tnde）、总自然间接效应（total natural indirect effect, tnie）及总效应（total effect, te）。结果 未考虑中介效应的多项回归分析显示，高尿酸血症仅与糖尿病前期患病风险升高相关（比值比：1.25；95%置信区间：1.09~1.43；P < 0.001）。当将脂肪肝、BMI及血脂异常作为该关联中的多重中介变量时，高尿酸血症与糖尿病前期[总自然直接效应（tnde）：1.11，95%置信区间：1.04~1.11；总自然间接效应（tnie）：1.07，95%置信区间：1.05~1.09；总中介比例（overall proportion mediated, pm）：42%，95%置信区间：27%~73%]及糖尿病患病风险[总自然直接效应（tnde）：0.96，95%置信区间：0.82~1.14；总自然间接效应（tnie）：1.25，95%置信区间：1.18~1.33；总中介比例（pm）：100%，95%置信区间：57%~361%]均存在关联。针对糖尿病前期患病风险，高尿酸血症通过脂肪肝与血脂异常联合介导（总中介比例=17%）或通过BMI介导（总中介比例=35%）时，其总自然直接效应、总效应及总自然间接效应均具有统计学意义。结论 高尿酸血症可升高糖尿病前期或糖尿病患病风险，该关联部分由脂肪肝、BMI及血脂异常介导。脂肪肝是高尿酸血症与糖尿病前期关联中的关键中介变量。