title: Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity.
abstract: OBJECTIVE
  Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insulin resistance in obese men, we used this fatty acid to investigate the effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations, including their associations with change in insulin sensitivity.
  
  
  METHODS
  We randomised (double-blind) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), intact proinsulin, insulin, the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed before and after supplementation.
  
  
  RESULTS
  Supplementation with t10c12CLA increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C-peptide concentrations (p<0.001) in comparison with control subjects. Adiponectin, however, did not change significantly. The change in proinsulin, but not the proinsulin : insulin ratio, was related to impaired insulin sensitivity (r= -0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose, adiponectin and BMI. Conversely, the correlation between insulin sensitivity and specific insulin (r=-0.46, p<0.001) did not remain significant after adjustment for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin concentrations ( r= -0.34, p<0.01).
  
  
  CONCLUSIONS
  In obese men, t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity, independently of changes in insulin concentrations. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular disease. The use of weight-loss supplements containing this fatty acid is worrying.
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden. ulf.riserus@oxlip.ox.ac.uk
authors.forename: U
authors.initials: U
authors.lastname: Risérus
authors.forename: B
authors.initials: B
authors.lastname: Vessby
authors.forename: P
authors.initials: P
authors.lastname: Arner
authors.forename: B
authors.initials: B
authors.lastname: Zethelius
mesh_terms: D000005:Abdomen / Q000033:anatomy & histology / Q000503:physiopathology; D052242:Adiponectin; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000503:physiopathology; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000139:chemically induced* / Q000150:complications*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D036341:Intercellular Signaling Peptides and Proteins; D044243:Linoleic Acids, Conjugated; C496197:trans-10,cis-12-conjugated linoleic acid