Lack of association between KCNJ11 (rs5219) and ABCC8 (rs757110) polymorphisms and sulphonylurea treatment response in type 2 diabetes patients in Novosibirsk region

Aim. Sulfonylureas (SU) are widely used in everyday clinical practice in treatment of patients with type 2 diabetes mellitus (T2DM). There is a considerable variability in SU effects, which may be caused by psychological, social, biological and genetic factors. The aim of the study was to investigate the association between rs5219 KCNJ11 gene and rs757110 ABCC8 gene polymorphism and long-term response to SU-drugs of second and third generation in the Novosibirsk region. Materials and Methods. 326 patients with type 2 diabetes in the Novosibirsk region were examined. Patients were divided into 2 groups, depending on HbA1c level. The first group included patients with target HbA1c levels on SU monotherapy. The second group included patients who did not reach target HbA1c levels on the highest dose of SU. Genotyping of KCNJ11 (rs5219) and ABCC8 (rs757110) was performed by TaqMan real-time PCR (ICBFM SB RAS, Novosibirsk, Russia). Results. Patients with type 2 diabetes with a good response to SU-therapy compared to the group of patients with a poor response to SU-therapy were older (65.8?9.1 years vs. 61.6?7.9 years, p

Neonatal Diabetes – From Gene Discovery yo Clinical Practice Changes

Diabetes mellitus is one of the most common chronic diseases but also one of the most heterogeneous. Apart the common phenotypes of type 1 and type 2 diabetes, around 1-2% of all cases arise from a single gene mutation and are known as monogenic diabetes. Diabetes diagnosed within the first 6 months of life is known as neonatal diabetes and has been extensively studied during the last two decades. Unraveling the genetic cause and molecular mechanism of this rare diabetes phenotype led to a dramatic change in the treatment of these children who often can be switched from insulin to sulphonylurea treatment. The aim of this paper is to review the known genetic causes of neonatal diabetes and to highlight the most recent aspects of the disease caused by mutations in the KATP and insulin genes, with a special focus on the individualized treatment of these cases

Variation in CDKAL1 Gene Is Associated With Therapeutic Response to Sulphonylureas

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.