Aims/hypothesis: Recently a mutation in the coding sequence of the adipocyte specific isoform peroxisome proliferator-activated receptor gamma2 (PPARgamma2) was described, leading to the substitution of Proline to Alanine at codon 12. Mutations in PPARgamma2 could have a role in people who are at increased risk for the development of obesity and Type II (non-insulin-dependent) diabetes mellitus.
Methods: Non-diabetic first-degree relatives (n = 108) of subjects with Type II diabetes were characterized by oral glucose tolerance tests and euglycaemic hyperinsulinaemic glucose clamp to determine insulin sensitivity.
Results: We found 75 (69%) probands without the PPARgamma ProAla12 substitution, 28 heterozygotes (26%) and 5 (4%) homozygotes. When the whole group was analysed for an association between the mutation and insulin sensitivity, no statistical significance could be shown. Only in the group with severe obesity more than 30 kg/m2, an association (p = 0.016) of the polymorphism with an increase in insulin sensitivity was found.
Conclusion/interpretation: These observations suggest that the mutation in the PPARgamma2 molecule may have a role in subgroups prone to the development of obesity and Type II diabetes.