TY - JOUR
T1 - Metabolomic phenotyping of obesity for profiling cardiovascular and ocular diseases
AU - Zhong, Pingting
AU - Tan, Shaoying
AU - Zhu, Zhuoting
AU - Bulloch, Gabriella
AU - Long, Erping
AU - Huang, Wenyong
AU - He, Mingguang
AU - Wang, Wei
N1 - Funding Information:
This study was funded by the Fundamental Research Funds for the Central Universities, Sun Yat-sen University (23qnpy164) and the National Natural Science Foundation of China (82000901).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6/12
Y1 - 2023/6/12
N2 - 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/m2), overweight (OW, metBMI of 25–29.9 kg/m2), obesity (OB, metBMI ≥ 30 kg/m2), overestimated (OE, metBMI-actBMI > 5 kg/m2), and underestimated (UE, metBMI-actBMI < − 5 kg/m2). 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.
AB - 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/m2), overweight (OW, metBMI of 25–29.9 kg/m2), obesity (OB, metBMI ≥ 30 kg/m2), overestimated (OE, metBMI-actBMI > 5 kg/m2), and underestimated (UE, metBMI-actBMI < − 5 kg/m2). 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.
KW - Age-related eye disease
KW - Comorbidity
KW - Metabolome
KW - Mortality
KW - NMR
KW - Obesity
KW - Systemic diseases
UR - http://www.scopus.com/inward/record.url?scp=85161941289&partnerID=8YFLogxK
U2 - 10.1186/s12967-023-04244-x
DO - 10.1186/s12967-023-04244-x
M3 - Journal article
C2 - 37308902
AN - SCOPUS:85161941289
SN - 1479-5876
VL - 21
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
IS - 1
M1 - 384
ER -