Insulin Resistance as a Mediator of the Association Between Obesity, High-Intensity Binge Drinking, and Liver Enzyme Abnormalities in Young and Middle-Aged Adults: a Cross-sectional Study

Jiayi Zhu^1,2Yinglong Duan³Ying Li¹Yi Zhou³Zitong Lu²Nandan Chen²Juan Luo²Xingxing Wang²Xiaoqian Dong²Shu Kei Cheng⁴Yuan Liu^5*

• ¹Department of Health Management Center, Third Xiangya Hospital, Central South University, Changsha, Anhui Province, China
• ²Xiangya School of Nursing, Central South University, Changsha, Hunan Province, China
• ³Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
• ⁴School of Health Science, Western Sydney University, Penrith, New South Wales, Australia
• ⁵Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Binge drinking (BD) and obesity are well-established risk factors for liver enzyme abnormalities, but how varying intensities of BD interact with obesity to affect liver function remains unclear. This study aims to examine whether insulin resistance (IR) mediates the associations between different levels of BD, obesity, their interaction, and liver enzyme abnormalities.This cross-sectional study included 137878 young and middle-aged adults who underwent physical examinations in southern China between August 2017 and March 2024. BD was self-reported, and IR was assessed using the triglyceride-glucose (TyG) index. Causal mediation analysis within the counterfactual framework was used to quantified the mediating role of the TyG index in the associations involving BD intensity, obesity, their interaction, and liver enzyme abnormalities.The interaction between obesity and high-intensity binge drinking(HIBD) was significantly associated with liver enzyme abnormalities(OR, 1.591; 95% CI, 1.401-1.806). IR, measured by the TyG index, statistically accounted for 36.6% (OR, 1.034; 95% CI, 1.029-1.039) of this association, exceeding the proportion explained in the HIBD alone (25.9%) or obesity alone (16.7%) pathways. No significant mediating effect of IR was observed for non-BD or low-intensity BD, regardless of obesity status.The TyG index is a critical mediator in the synergistic effects of HIBD and obesity on liver enzyme abnormalities. Targeting IR and reducing the intensity of alcohol consumption may help mitigate liver injury in young and middle-aged adults with obesity.