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The aim of the present study was to analyse effects of sulphonylurea treatment on parameters of glycaemic control in relation to transcription factor 7-like 2 (TCF7L2) genotypes. In 87 patients with type 2 diabetes who failed to achieve glycaemic control on metformin monotherapy, effects of 6-month sulphonylurea in addition to metformin on reductions in haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels were evaluated. Reduction in HbA1c and FPG in response to 6-month sulphonylurea treatment was significantly higher in patients with CC genotype compared to those with the CT+TT genotype (1.16 ± 0.07 vs. 0.86 ± 0.07%, p = 0.003; 1.57 ± 0.12 vs. 1.14 ± 0.14 mmol/l, p = 0.031, respectively). In the multivariate analysis, baseline HbA1c and the TCF7L2 genotype were the only significant predictors of HbA1c reduction. In conclusion, the magnitude of HbA1c and FPG reductions after 6-month sulphonylurea treatment in addition to metformin is related to the TCF7L2 gene polymorphism.

SummaryBackgroundWe aimed to analyse quantitative effects of treatment with sulphonylurea in addition to metformin on parameters of glycemic control in relation to KCNQ1 genotypes, and to identify factors predictive for the response to sulphonylurea treatment.Material/MethodsEffect of 6-month sulphonylurea therapy in addition to metformin on glycemic control according to KCNQ1 genotypes was evaluated in 87 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. KCNQ1 rs163184 (T>G) polymorphism was determined by real-time PCR with melting analysis of unlabeled probe.ResultsThe reduction in fasting plasma glucose (ΔFPG) after 6-month sulphonylurea therapy significantly differed among 3 KCNQ1 genotype groups (ANOVA, p=0.017). In a recessive genetic model, carriers of the T-allele (TT+TG) achieved significantly lower FPG levels in comparison with patients with the GG genotype (6.95±0.13 vs. 7.50±0.21 mmol/L, p=0.033). Consequently, ΔFPG was significantly higher in the TT+TG group compared to the GG group (1.58±0.13 vs. 1.04±0.18 mmol/L, p=0.016). In multiple linear regression analysis KCNQ1 genotype (p=0.016) and baseline FPG (p<0.001) were the only significant independent predictors of ΔFPG (R2=0.48).ConclusionsOur results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in addition to metformin in patients with type 2 diabetes is related to the variation in KCNQ1. The FPG response to sulphonylureas was significantly lower in carriers of the risk GG genotype.

The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90±1.08 vs. 7.48±1.12 mmol/l, p=0.013). Consequently, adjusted ΔFPG was significantly higher in the AG+GG compared to the AA group (1.48±1.51 vs. 1.02±1.33 mmol/l, p=0.022). Similar trend was observed for HbA1c levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1.