代謝症候群 (metabolic syndrome， MetS) 是一組相互關聯的代謝異常危險因子群，包括腹部肥胖、血脂異常、高血壓及高血糖，顯著增加心血管疾病及第二型糖尿病的風險。然而，針對年輕且體能活躍之成年族群，其發展機制及預測因子仍缺乏充分研究。 本研究以心肺適能與東部軍人健康世代研究 (Cardiorespiratory Fitness and Health in Eastern Armed Forces， CHIEF) 為基礎，納入 2，890 名年齡 18 至 39 歲、基線無代謝症候群之軍人，追蹤至 2020 年底，探討綜合性物質使用（酒精、菸草、檳榔）及六種非胰島素測量胰島素抗性指數 (non-insulin-based insulin resistance indices， NI-IR indices) 與中年前新發代謝症候群之關聯性。 物質使用分析顯示，相較於未使用者，使用一、兩、三種物質者新發代謝症候群之風險比 (hazard ratio， HR) 分別為 1.27 (95%信賴區間：1.06-1.54)、1.38 (1.12-1.69) 及 1.78 (1.37-2.32)，呈劑量反應關係 (p 趨勢值<0.001)；單獨飲酒及吸菸分別增加 24%及 46%風險。胰島素抗性指數分析顯示，六種指數均與新發代謝症候群顯著正相關，其中胰島素抗性代謝評分 (METS-IR) 預測效能最佳，受試者工作特徵曲線下面積 (AUROC) 為 0.782 (0.762-0.801)，依序為三酸甘油酯/高密度脂蛋白膽固醇比值 (0.752)、浙江大學指數 (0.743)、三酸甘油酯葡萄糖指數 (0.734)、總膽固醇/高密度脂蛋白膽固醇比值 (0.731) 及丙氨酸轉氨酶/天門冬氨酸轉氨酶比值 (0.674)。性別分層分析顯示，女性以總膽固醇/高密度脂蛋白膽固醇比值預測效能最佳 (AUROC: 0.793)。 本研究證實綜合性物質使用與中年前新發代謝症候群呈劑量反應正相關，METS-IR 為預測年輕族群代謝症候群之最佳 NI-IR 指數。結果強調針對年輕軍人進行物質使用衛教及代謝風險早期篩檢之重要性，可作為制定預防策略之實證依據。;Metabolic syndrome (MetS) is a cluster of interrelated metabolic abnormalities， including abdominal obesity， dyslipidemia， hypertension， and hyperglycemia， which significantly increase the risk of cardiovascular disease and type 2 diabetes mellitus. The global prevalence of MetS has been rising steadily in recent years， making it a major public health concern. However， research on the developmental mechanisms and predictive factors of MetS in young， physically active adult populations remains insufficient. This study aimed to investigate the associations of combined substance use (alcohol， tobacco， and betel nut) and various non-insulin-based insulin resistance (NI-IR) indices with incident MetS before midlife among young military personnel. The study population was derived from the Cardiorespiratory Fitness and Health in Eastern Armed Forces (CHIEF) cohort study， which enrolled 2，890 military personnel aged 18-39 years without baseline MetS， with follow-up from 2014 to the end of 2020. The substance use analysis yielded significant findings. A clear dose-response relationship was demonstrated between combined substance use and incident MetS. Compared with non-users， the hazard ratios (HRs) for incident MetS were 1.27 (95% confidence interval [CI]: 1.06-1.54) for one substance use， 1.38 (95% CI: 1.12-1.69) for two substances use， and 1.78 (95% CI: 1.37-2.32) for three substances use (p for trend < 0.001). Individual substance analyses revealed that alcohol consumption increased the risk by 24%， while cigarette smoking increased the risk by 46%. Subgroup analysis showed that the association between substance use and MetS was more pronounced among participants without baseline low high-density lipoprotein cholesterol (HDL-C) (p for interaction < 0.05). Results from the insulin resistance indices analysis showed that all six NI-IR indices were significantly positively associated with incident MetS. In the predictive performance comparison， the Metabolic Score for Insulin Resistance (METS-IR) demonstrated the highest predictive capacity， with an area under the receiver operating characteristic curve (AUROC) of 0.782 (95% CI: 0.762-0.801)， significantly superior to other indices. The ranking order was: triglyceride to HDL-C ratio (0.752)， Zhejiang University index (0.743)， triglyceride-glucose index (0.734)， total cholesterol to HDL-C ratio (0.731)， and alanine transaminase to aspartate transaminase ratio (0.674). Sex-stratified analysis revealed that the total cholesterol to HDL-C ratio had the best predictive performance in women (AUROC: 0.793). In conclusion， this study confirms that combined substance use is significantly associated with incident MetS before midlife in a dose-response manner， and METS-IR is the optimal NI-IR index for predicting new-onset MetS in young populations. These findings emphasize the importance of substance use education and early metabolic risk screening among young military personnel， providing evidence-based references for the development of prevention strategies.
