title: Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study.
abstract: BACKGROUND
  Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency.
  
  
  METHODS
  Patients with type 2 diabetes (n  =  34) and control subjects (n  =  17) were recruited. We measured baseline fasting plasma and 4-hour post-methionine load (L-methionine, 0.1 mg/kg body weight) concentrations of homocysteine, betaine, and the betaine metabolite N,N-dimethylglycine. Baseline urine excretions of betaine, dimethylglycine and glucose were measured on morning urine samples as the ratio to urine creatinine. Statistical determinants of the post-methionine load increase in homocysteine were identified in multiple linear regression models.
  
  
  RESULTS
  Plasma betaine concentrations and urinary betaine excretions were significantly (p  <  0.001) more variable in the subjects with diabetes compared with the controls. Dimethylglycine excretion (p  = 0.00014) and plasma dimethylglycine concentrations (p  =  0.039) were also more variable. In diabetes, plasma betaine was a significant negative determinant (p  <  0.001) of the post-methionine load increase in homocysteine. However, it was not conclusive that this was different from the relationship in the controls. In the patients with diabetes, a strong relationship was found between urinary betaine excretion and urinary glucose excretion (but not with plasma glucose).
  
  
  CONCLUSIONS
  Both high and low plasma betaine concentrations, and high and low urinary betaine excretions, are more prevalent in diabetes. The availability of betaine affects the response in the methionine load test. The benefits of increasing betaine intake should be investigated.
authors.affiliation: Biochemistry Unit, Canterbury Health Laboratories, PO Box 151, Christchurch, 8140, New Zealand. michael.lever@otago.ac.nz
authors.forename: Michael
authors.initials: M
authors.lastname: Lever
authors.forename: Sandy
authors.initials: S
authors.lastname: Slow
authors.forename: David O
authors.initials: DO
authors.lastname: McGregor
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Dellow
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Chambers
mesh_terms: D000368:Aged; D001622:Betaine / Q000097:blood* / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D005260:Female; D006029:Glycosuria / Q000097:blood / Q000175:diagnosis / Q000652:urine; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009520:New Zealand; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006710:Homocysteine; D001622:Betaine; C025138:dimethylglycine; D008715:Methionine; D012521:Sarcosine