Zsu-Zsu Chen, Chang Lu, Jonathan M. Dreyfuss, Gaurav Tiwari, Xu Shi, Shuning Zheng, Danielle Wolfs, Laura Pyle, Petter Bjornstad, Laure El Ghormli, Robert E. Gerszten, Elvira Isganaitis
{"title":"青年 2 型糖尿病患者血糖控制的循环代谢物生物标志物","authors":"Zsu-Zsu Chen, Chang Lu, Jonathan M. Dreyfuss, Gaurav Tiwari, Xu Shi, Shuning Zheng, Danielle Wolfs, Laura Pyle, Petter Bjornstad, Laure El Ghormli, Robert E. Gerszten, Elvira Isganaitis","doi":"10.2337/dc23-2441","DOIUrl":null,"url":null,"abstract":"OBJECTIVE We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes\",\"authors\":\"Zsu-Zsu Chen, Chang Lu, Jonathan M. Dreyfuss, Gaurav Tiwari, Xu Shi, Shuning Zheng, Danielle Wolfs, Laura Pyle, Petter Bjornstad, Laure El Ghormli, Robert E. Gerszten, Elvira Isganaitis\",\"doi\":\"10.2337/dc23-2441\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.\",\"PeriodicalId\":11140,\"journal\":{\"name\":\"Diabetes Care\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.8000,\"publicationDate\":\"2024-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2337/dc23-2441\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/dc23-2441","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes
OBJECTIVE We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.
期刊介绍:
The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes.
Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.