The PPAR gamma 2 amino acid polymorphism Pro 12 Ala is prevalent in offspring of Type II diabetic patients and is associated to increased insulin sensitivity in a subgroup of obese subjects

Aims/hypothesis. Recently a mutation in the coding sequence of the adipocyt e specific isoform peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) was described, leading to the substitution of Proline to Alanine at codon 12. Mutations in PPAR gamma 2 could have a role in people who are at increased risk for the development of obesity and Type II (non-insulin-d ependent) diabetes mellitus. Methods. Non-diabetic first-degree relatives (n = 108) Of subjects with Typ e II diabetes were characterized by oral glucose tolerance tests and euglyc aemic hyperinsulinaemic glucose clamp to determine insulin sensitivity. Results. We found 75 (69%) probands without the PPAR gamma ProAla12 substit ution, 28 heterozygotes (26%) and 5 (4%) homozygotes. When the whole group was analysed for an association between the mutation and insulin sensitivit y, no statistical significance could be shown. Only in the group with sever e obesity more than 30 kg/m(2), an association (p = 0.016) of the polymorph ism with an increase in insulin sensitivity was found. Conclusion/interpretation. These observations suggest that the mutation ill the PPAR gamma 2 molecule may have a role in subgroups prone to the develo pment of obesity and Type II diabetes.