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Background: Metabolic risk factors are a significant cause of global burden among adolescents and young adults, but there is a lack of attention to the burden attributable to these metabolic risk factors globally., Aims: This study aims to provide comprehensive estimates of five important metabolic risk factors and the attributable disease burden in people aged 15-39 years from 1990 to 2021, based on the Global Burden of Disease Study (GBD) database., Methods: Global total deaths and disability-adjusted life years (DALYs) were used to describe the burden attributable to five common metabolic risk factors, including high fasting plasma glucose (FPG), high low-density lipoprotein cholesterol (LDL-C), high systolic blood pressure (SBP), high body mass index (BMI), and kidney dysfunction, in adolescents and young adults. The estimated annual percentage changes (EAPC) of DALYs were utilized to depict the trends from 1990 to 2021., Results: From 1990 to 2021, the DALY rates attributable to all metabolic risk factors showed a globally significant upward trend, with EAPC reaching 33.0 % (27.4-38.7). Compared to females, males had a heavier burden and a more significant increase in deaths and DALYs attributable to metabolic risk factors. High BMI and high FPG have become the top two metabolic risk factors in 2021, with summary exposure variables (SEV) rising by 84.2 % and 53.6 %, respectively. Low-middle socio-demographic index (SDI), middle SDI, and high SDI regions experienced upward regional trends in DALY rates, while low SDI regions remained stable. Among 204 countries and territories, 101 (49.5 %) showed a significant increase in DALY rates, as indicated by the EAPC., Conclusions: There is a substantial global burden attributable to metabolic risk factors in adolescents and young adults in 2021, especially high BMI and high FPG. This calls for further investigation and intervention to address this emerging trend., Competing Interests: Conflict of interest Christopher D. Byrne has received grant support from Echosens. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. Anoop Misra has received honoraria from Novo Nordisk, Astra Zeneca, Janssen, Lupin, Eli Lilly, US Vitamins, and Boehringer Ingelheim. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Alice P.S. Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Sander Lefere has received research grant from Inventiva. Mohit Kehar is a consultant for Mirum. Nicholas Beng Hui Ng has received honoraria from Novo Nordisk and Abbott. No other disclosures were reported., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex., Methods: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI)., Results: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17])., Conclusion: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide., Competing Interests: Declaration of competing interest John D. Ryan received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. Luca Valenti reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie, Resalis, grants from Gilead. Alice Pik-Shan Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Gregory Y. H. Lip serves as consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation programme. Anoop Misra has received honorarium from Abbott, Roche, Jannsen, Boehringer Ingelheim, Lupin, Cipla, US Vitamins, and Novo Nordisk. Christopher D. Byrne has received grant support from Echosens. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Christos S. Mantzoros reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. No other disclosures were reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood., Methods: We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m 2 for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI., Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest., Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI., Funding: National Natural Science Foundation of China and National Key R&D Program of China., Competing Interests: Christopher D. Byrne has received grant support from Echosens. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. Anoop Misra has received honoraria from Novo Nordisk, AstraZendeca, Janssen, and Boehringer Ingelheim. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. No other disclosures were reported; John D. Ryan received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. Christos S. Mantzoros reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. The other authors report no disclosure., (© 2024 The Author(s).)