State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China.
School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China.
J Transl Med. 2023 Jun 12;21(1):384. doi: 10.1186/s12967-023-04244-x.
BACKGROUND: We aimed to evaluate the impacts of metabolomic body mass index (metBMI) phenotypes on the risks of cardiovascular and ocular diseases outcomes. METHODS: This study included cohorts in UK and Guangzhou, China. By leveraging the serum metabolome and BMI data from UK Biobank, this study developed and validated a metBMI prediction model using a ridge regression model among 89,830 participants based on 249 metabolites. Five obesity phenotypes were obtained by metBMI and actual BMI (actBMI): normal weight (NW, metBMI of 18.5-24.9 kg/m), overweight (OW, metBMI of 25-29.9 kg/m), obesity (OB, metBMI ≥ 30 kg/m), overestimated (OE, metBMI-actBMI > 5 kg/m), and underestimated (UE, metBMI-actBMI < - 5 kg/m). Additional participants from the Guangzhou Diabetes Eye Study (GDES) were included for validating the hypothesis. Outcomes included all-cause and cardiovascular (CVD)-cause mortality, as well as incident CVD (coronary heart disease, heart failure, myocardial infarction [MI], and stroke) and age-related eye diseases (age-related macular degeneration [AMD], cataracts, glaucoma, and diabetic retinopathy [DR]). RESULTS: In the UKB, although OE group had lower actBMI than NW group, the OE group had a significantly higher risk of all-cause mortality than those in NW prediction group (HR, 1.68; 95% CI 1.16-2.43). Similarly, the OE group had a 1.7-3.6-fold higher risk than their NW counterparts for cardiovascular mortality, heart failure, myocardial infarction, and coronary heart disease (all P < 0.05). In addition, risk of age-related macular denegation (HR, 1.96; 95% CI 1.02-3.77) was significantly higher in OE group. In the contrast, UE and OB groups showed similar risks of mortality and of cardiovascular and age-related eye diseases (all P > 0.05), though the UE group had significantly higher actBMI than OB group. In the GDES cohort, we further confirmed the potential of metabolic BMI (metBMI) fingerprints for risk stratification of cardiovascular diseases using a different metabolomic approach. CONCLUSIONS: Gaps of metBMI and actBMI identified novel metabolic subtypes, which exhibit distinctive cardiovascular and ocular risk profiles. The groups carrying obesity-related metabolites were at higher risk of mortality and morbidity than those with normal health metabolites. Metabolomics allowed for leveraging the future of diagnosis and management of 'healthily obese' and 'unhealthily lean' individuals.
背景：本研究旨在评估代谢体重指数（metBMI）表型对心血管疾病和眼部疾病结局风险的影响。
方法：本研究纳入了英国和中国广州的队列。利用英国生物库的血清代谢组学和 BMI 数据，本研究基于 249 种代谢物，通过岭回归模型在 89830 名参与者中开发和验证了 metBMI 预测模型。通过 metBMI 和实际 BMI（actBMI）得到了 5 种肥胖表型：正常体重（NW，metBMI 为 18.5-24.9kg/m²）、超重（OW，metBMI 为 25-29.9kg/m²）、肥胖（OB，metBMI≥30kg/m²）、高估（OE，metBMI-actBMI>5kg/m²）和低估（UE，metBMI-actBMI<-5kg/m²）。来自广州糖尿病眼病研究（GDES）的额外参与者被纳入验证假设。结局包括全因和心血管（CVD）死亡率，以及 CVD 事件（冠心病、心力衰竭、心肌梗死[MI]和中风）和年龄相关性眼病（年龄相关性黄斑变性[AMD]、白内障、青光眼和糖尿病性视网膜病变[DR]）。
结果：在 UKB 中，尽管 OE 组的 actBMI 低于 NW 组，但 OE 组的全因死亡率风险明显高于 NW 预测组（HR，1.68；95%CI 1.16-2.43）。同样，OE 组的心血管死亡率、心力衰竭、心肌梗死和冠心病的风险比 NW 组高 1.7-3.6 倍（均 P<0.05）。此外，OE 组发生年龄相关性黄斑变性的风险明显更高（HR，1.96；95%CI 1.02-3.77）。相比之下，UE 和 OB 组的死亡率以及 CVD 和年龄相关性眼病的风险相似（均 P>0.05），尽管 UE 组的 actBMI 明显高于 OB 组。在 GDES 队列中，我们使用不同的代谢组学方法进一步证实了代谢 BMI（metBMI）指纹在心血管疾病风险分层中的潜力。
结论：metBMI 和 actBMI 的差异确定了新的代谢亚型，这些亚型表现出不同的心血管和眼部风险特征。携带肥胖相关代谢物的组比具有正常健康代谢物的组具有更高的死亡率和发病率风险。代谢组学为“健康肥胖”和“不健康消瘦”个体的诊断和管理提供了新的可能。
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