Clinical effect of thiazolidinediones in subjects with disorders of carbohydrate metabolism in case of polymorphism rs1801282

Abstract

BACKGROUND: The polymorphism rs1801282 (Pro12Ala) may be one of the reasons for the heterogeneous response of patients with carbohydrate metabolism disorders to thiazolidinedione therapy. Studies of this polymorphism in patients with metabolic syndrome (MS) will help identify a group of patients in whom the use of thiazolidinedione is advisable.
 AIMS: To assess the clinical effect of thiazolidinediones in patients with metabolic syndrome, depending on the presence of polymorphism rs1801282.
 MATERIALS AND METHODS: All patients with newly diagnosed MS with impaired carbohydrate metabolism were included in the open cohort study. All patients were recommended a diet, expansion of physical activity and pioglitazone at a dose of 30 mg per day. After the appointment of the therapy, the patients come to the center back at 12 weeks.
 The main outcome in the study assessed in patients with impaired glucose tolerance (IGT) was fasting glycemia and 2 hours after glucose tolerance test, in patients with type 2 diabetes HbA1c.
 RESULTS: 109 patients were included in the study. Of these, 14 were carriers of rs1801282, the other 95 had a typical PPAR genotype. After the appointment of therapy in the groups of IGT and type 2 diabetes, improvement of glycemic control was observed. The degree of decrease in fasting plasma glucose and after glucose tolerance test was more pronounced with IGT in patients with polymorphism rs1801282 compared with the rest (plasma fasting plasma glucose level was -0.7 [-0.9, -0.7] vs. -0, 4 [-0.5, -0.3] mmol/L, p=0.001; plasma glucose level 2 hours after glucose tolerance test was -1.1 [-1.8, -0.3] vs. -0.5 [-0.7, -0.1] mmol/L, p=0.031). In patients with type 2 diabetes, no data were obtained for the statistically significant effect of rs1801282 polymorphism on the results of pioglitazone, but there was a tendency for a greater decrease in fasting plasma glucose in the case of carrying the polymorphic gene (-1.9 [-2.2, -1.8] against -1,5 [-1,7, -1,2] mmol/l, p=0,073).
 CONCLUSIONS: The study shows the effect of polymorphism rs1801282 on the results of pioglitazone in patients with MS, both in IGT and in type 2 diabetes. Carrying polymorphism leads to a significant decrease in fasting glycemia and after glucose tolerance test in patients with IGT. The tendency to improve the parameters of carbohydrate metabolism (fasting glycemia, HbA1c) was noted in a subgroup of patients with type 2 diabetes.