ArticleDiabetologia2018
Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- The ratio of circulatory levels of sphingolipids to steroids predicts asthma exacerbations.Nature communications · 2026Article
- NMR-based clinical metabolomics for predictive screening of gestational diabetes mellitus (GDM) during the first trimester: a pilot study on North Indian population.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Targeted LC-MS profiling reveals dysregulated glycolytic flux and TCA cycle stalling in POAG plasma.Scientific reports · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Alterations in ether lipid metabolism in obesity revealed by systems genomics of multi-omics datasets.PLoS biology · 2025Article
- Human Physiologic Responses to Insulin in Indigenous Americans Identify a Metabolic Susceptibility Profile Linked to Diabetes.Diabetes care · 2025Article
- Omentin associates with serum metabolite profiles indicating lower diabetes risk: KORA F4 Study.BMJ open diabetes research & care · 2024Article
- Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.Metabolites · 2023Article
- Review
- Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip.Metabolites · 2022Article
- Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development.Metabolites · 2022Article
- Fetal Exposure to Maternal Smoking and Neonatal Metabolite Profiles.Metabolites · 2022Article
- Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults.Life (Basel, Switzerland) · 2022Article
- Maternal Body Mass Index, Early-Pregnancy Metabolite Profile, and Birthweight.The Journal of clinical endocrinology and metabolism · 2022Observational
- Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males.Science advances · 2021Article
- Prospective analysis of circulating metabolites and endometrial cancer risk.Gynecologic oncology · 2021Observational
- Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study.Genome medicine · 2020Article
- Pre-diagnostic biomarkers of type 2 diabetes identified in the UAE's obese national population using targeted metabolomics.Scientific reports · 2020Article
- Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population.BMJ open diabetes research & care · 2020Article
- Quantile contours and allometric modelling for risk classification of abnormal ratios with an application to asymmetric growth-restriction in preterm infants.Statistical methods in medical research · 2020Article
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Authors and funding
44 authors at 12 institutions in 5 countries.
Funding
Abstract
aims/hypothesisCirculating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.
methodsWe measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case-control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.
resultsThere were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 × 10 CONCLUSIONS/
interpretationIn this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.
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