Year: 2026
Type: article
Abstract: BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: =0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.
Source: Circulation Research
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: American Diabetes Association, American Heart Association, Brigham and Women's Hospital, National Institutes of Health, University of California, San Diego, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Atherogenic Lipoproteins and Cardiovascular risk: Exploring the Roles of Metabolomic and Lipidomic Markers, Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota, Obesity Genes, Energy Regulation in Response to Weight-Loss Diets, G151562090, G1707825329, G1766783752, G1832025683, G1861573265, Genetic Markers of CHD in Type 2 Diabetes, G2111759553, G2214254730, G2359455135, Biochemical Markers in the nurses' Health Study Cohort, G2795818635, G294025628, G3602225402, G361298724, G3896680578, G401738796, G4102267556, G4284213306, G4302869984, G4376790518, G4553208282, G4799943342, G5511382046, Genome-wide interactions with diet patterns on long-term weight change, G5773412657, G5795941451, G588599347, G5893983254, G6080346254, G6200764915, G6279045020, G654976064, G6812933845, G6822753503, G7063308019, G7129568825, G7236893434, G7286868595, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study, G7552017953, G8015828976, G8046189488, Premenopausal Hormone Levels and Risk of Breast Cancer, G846304955, G8787159316, G9000003116, G9000007198, G9000019617, G9000028482, G9000028950, G9000043058, G9000045028, G9000058679, G9000099730, G9000113857, G9000157792, G9000166677, G9000185549, Life Course Cancer Epidemiology Cohort in Women, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Nutrigenetics and Nutrigenomics for Precision Weight-Loss Diet Interventions, RISK FACTORS FOR CVD IN WOMEN, Risk Factors for Ischemic Stroke in Women, Circulating plasma metabolites, diet, and risk of type 2 diabetes, G958196485
OpenAlex ID: W7204932885