title: Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study.
abstract: OBJECTIVE
  To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function.
  
  
  METHODS
  An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity.
  
  
  RESULTS
  After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = -0.357; waist circumference: β = -0.380; body fat mass: β = -0.375) and disposition index (BMI: β = -0.215; waist circumference: β = -0.248; body fat mass: β = -0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = -0.133), acute insulin response to glucose (β = -0.148) and disposition index [β = -0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively.
  
  
  CONCLUSIONS
  Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction.
authors.affiliation: Nutrition and Dietetic Research Group, Imperial College London, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Johns
authors.forename: L
authors.initials: L
authors.lastname: Goff
authors.forename: L J
authors.initials: LJ
authors.lastname: Bluck
authors.forename: B A
authors.initials: BA
authors.lastname: Griffin
authors.forename: S A
authors.initials: SA
authors.lastname: Jebb
authors.forename: J A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: T A B
authors.initials: TA
authors.lastname: Sanders
authors.forename: G
authors.initials: G
authors.lastname: Frost
authors.forename: A
authors.initials: A
authors.lastname: Dornhorst
mesh_terms: D050154:Adiposity; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology*; D004739:England / Q000453:epidemiology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin