The PPAR gamma 2 polymorphism Pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients

Recently, a highly prevalent polymorphism of the PPAR gamma2-receptor (Pro1 2Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism m ay be associated with increased insulin sensitivity. However, an effect ind ependent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hype rinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPAR gamma2-Pro12Ala mutation and 37 control subjects negative for the PPA R gamma2-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 c lamp was significantly lower (63.3 muU/ml +/- 2.8) than in the control grou p (74.9 muU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPAR gamma2-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 ind ex was significantly higher in the PPAR gamma2-Pro12Ala group (12.5 mg/kg x min x muU/ml +/- 0.9 vs. 9.7 mg/kg x min x muU/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 PPAR gamma2-Pro1 2Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0. 097). In conclusion, these data suggest that the PPAR gamma2-Pro12Ala mutat ion is associated with better insulin sensitivity of glucose disposal and p ossibly, also of antilipolysis.