title: Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2 Diabetes.
abstract: BACKGROUND
  Several compounds in the choline oxidation pathway are associated with insulin resistance and prevalent diabetes; however, prospective data are scarce.We explored the relationships between systemic and urinary choline-related metabolites and incident type 2 diabetes in an observational prospective study among Norwegian patients.
  
  
  METHODS
  We explored risk associations by logistic regression among 3621 nondiabetic individuals with suspected stable angina pectoris, of whom 3242 provided urine samples. Reclassification of patients was investigated according to continuous net reclassification improvement (NRI >0).
  
  
  RESULTS
  After median (25th to 75th percentile) follow-up of 7.5 (6.4-8.7) years, 233 patients (6.4%) were registered with incident type 2 diabetes. In models adjusted for age, sex, and fasting status, plasma betaine was inversely related to new-onset disease [odds ratio (OR) per 1 SD, 0.72; 95% CI, 0.62-0.83; P < 0.00001], whereas positive associations were observed for urine betaine (1.25; 1.09-1.43; P = 0.001), dimethylglycine (1.22; 1.06-1.40; P = 0.007), and sarcosine (1.30; 1.13-1.49; P < 0.001). The associations were maintained in a multivariable model adjusting for body mass index, hemoglobin A1c, urine albumin-to-creatinine ratio, estimated glomerular filtration rate, C-reactive protein, HDL cholesterol, and medications. Plasma betaine and urine sarcosine, the indices most strongly related to incident type 2 diabetes, improved reclassification [NRI >0 (95% CI) 0.33 (0.19-0.47) and 0.16 (0.01-0.31), respectively] and showed good within-person reproducibility.
  
  
  CONCLUSIONS
  Systemic and urinary concentrations of several choline metabolites were associated with risk of incident type 2 diabetes, and relevant biomarkers may improve risk prediction.
authors.affiliation: Department of Clinical Science, gard.frodahl.svingen@helse-bergen.no.
authors.forename: Gard F T
authors.initials: GF
authors.lastname: Svingen
authors.affiliation: Department of Heart Disease.
authors.forename: Hall
authors.initials: H
authors.lastname: Schartum-Hansen
authors.affiliation: Department of Clinical Science.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Science, Laboratory for Clinical Biochemistry.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Global Public Health and Primary Care, and Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: Department of Clinical Science, Hormone Laboratory, and KG Jebsen Center for Diabetes Research, Department of Pediatrics, University of Bergen, Bergen, Norway;
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.affiliation: KG Jebsen Center for Diabetes Research, Department of Pediatrics, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Pål R
authors.initials: PR
authors.lastname: Njølstad
authors.affiliation: Department of Heart Disease.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seifert
authors.affiliation: Department of Clinical Science.
authors.forename: Elin
authors.initials: E
authors.lastname: Strand
authors.affiliation: Department of Clinical Science.
authors.forename: Therese
authors.initials: T
authors.lastname: Karlsson
authors.affiliation: Department of Clinical Science, Department of Heart Disease, KG Jebsen Center for Diabetes Research, Department of Pediatrics, University of Bergen, Bergen, Norway;
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
mesh_terms: D000368:Aged; D002794:Choline / Q000378:metabolism* / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D002794:Choline