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

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1133515
• Main Authors: Basnet, Til Bahadur, Du, Shanshan, Feng, Ruimei, Gao, Jie, Gong, Jiamin, Ye, Weimin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2023
• Subjects: China; diabetes; Diabetes Mellitus; Dyslipidemias - complications; Dyslipidemias - epidemiology; Endocrinology; Fatty Liver; Humans; hyperuricemia (HUA); Hyperuricemia - complications; Hyperuricemia - epidemiology; Mediation Analysis; Medicin och hälsovetenskap; multiple mediators; prediabetes; Prediabetic State - complications; Prediabetic State - epidemiology; Risk Factors; hyperuricemia (HUA); diabetes; multiple mediators; China; prediabetes
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1133515

Fatty 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. Baseline 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 fatty liver, BMI, and dyslipidemia. In 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; < 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. Hyperuricemia 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.