title: The PPARgamma2 polymorphism pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients.
abstract: Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.
authors.affiliation: Dept. of Endocrinology, University of Tübingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jacob
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
authors.forename: R
authors.initials: R
authors.lastname: Becker
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: M
authors.initials: M
authors.lastname: Nielsen
authors.forename: K
authors.initials: K
authors.lastname: Löblein
authors.forename: E
authors.initials: E
authors.lastname: Maerker
authors.forename: A
authors.initials: A
authors.lastname: Volk
authors.forename: W
authors.initials: W
authors.lastname: Renn
authors.forename: B
authors.initials: B
authors.lastname: Balletshofer
authors.forename: F
authors.initials: F
authors.lastname: Machicao
authors.forename: K
authors.initials: K
authors.lastname: Rett
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008657:Metabolic Clearance Rate; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005947:Glucose