title: Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.
abstract: OBJECTIVE
  Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS).
  
  
  METHODS
  DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method.
  
  
  RESULTS
  There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016).
  
  
  CONCLUSIONS
  Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.
authors.affiliation: Department of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland. ursula.mager@uku.fi
authors.forename: U
authors.initials: U
authors.lastname: Mager
authors.forename: V
authors.initials: V
authors.lastname: Lindi
authors.forename: J
authors.initials: J
authors.lastname: Lindström
authors.forename: J G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: T T
authors.initials: TT
authors.lastname: Valle
authors.forename: H
authors.initials: H
authors.lastname: Hämäläinen
authors.forename: P
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.forename: S
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: M
authors.initials: M
authors.lastname: Laakso
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: M
authors.initials: M
authors.lastname: Uusitupa
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D005387:Finland; D054439:Ghrelin; D018149:Glucose Intolerance / Q000235:genetics*; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D036361:Peptide Hormones / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D012306:Risk
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones