title: Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin.
abstract: BACKGROUND
  Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood.
  
  
  OBJECTIVE
  The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients.
  
  
  METHODS
  This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2).
  
  
  METHODS
  Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment.
  
  
  METHODS
  Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry.
  
  
  RESULTS
  Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = -0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition.
  
  
  CONCLUSIONS
  Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D.
authors.affiliation: Joslin Diabetes Center (M.W., M.-E.P., C.B., A.B.G.), Boston, Massachusetts 02215; Harvard Medical School (M.W., M.-E.P., A.B.G.), Harvard University, Boston, Massachusetts 02115; and Laboratory Genetic Metabolic Diseases (S.M.H.), Departments of Clinical Chemistry and Pediatrics, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Marlene
authors.initials: M
authors.lastname: Wewalka
authors.forename: Mary-Elizabeth
authors.initials: ME
authors.lastname: Patti
authors.forename: Corinne
authors.initials: C
authors.lastname: Barbato
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood* / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013654:Taurine / Q000097:blood* / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D007328:Insulin; D013654:Taurine