Endocrine Abstracts

Background and aims: The rs5219 variant in the KCNJ11 have been consistently associated with type 2 diabetes (T2D) and therapeutic response to sulfonylureas in type 2 diabetic patients. However, the impact of KCNJ11 genetic polymorphism on the antidiabetic efficacy of vildagliptin has not yet been evaluated. This study was aimed to investigate the association of KCNJ11 rs5219 with vildagliptin glucose lowering ability by monitoring continuous blood glucose profile.

Materials and methods: We included 48 (18 men) drag-naïve patients (mean age 58.5±5.6 years; mean body mass index 31.1±4.5 kg/m²) with newly diagnosed T2D, who had clinical indications to start vildagliptin therapy. The patients in this data set had mean HbA1c of 7.73%±1.1%. All participants received vildagliptin at an initial dose of 50 mg once a day. KCNJ11 rs5219 (C>T) genetic polymorphism genotyping was performed by real-time polymerase chain reaction. Several parameters, including mean 24-hour blood glucose level, minimum 24-hour blood glucose level, time of relatively low blood glucose, and indices of glucose variability (24-hour standard deviation), were extracted from continuous glucose monitoring (CGM) data obtained using a CGM system iPro2 for a 72-hour period.

Results: The frequencies of the CC, CT and TT genotypes were 41.7%, 37.5% and 20.8% respectively. Minor allele T frequency was 0.39. Genotype distribution followed Hardy-Weinberg equilibrium. All patients receiving 50 mg of vildagliptin per day, were divided into two groups based on rs5219 genotype: CC-genotype carriers (n=20) and CT/TT-genotype carriers (n=28). The minimum 24-hour blood glucose level was significantly lower in CT/TT- genotype carriers than in CC-genotype carriers: 4.0 [3.5; 5.4] vs 6.0 [5.9; 6.3] mmol/l (P=0.042) respectively. Additionally, the mean 24-hour blood glucose level tended to be lower in CT/TT-genotype carriers than in CC-genotype carriers: 6.3 [5.4; 6.8] vs 7.6 [5.9; 6.4] mmol/l and time of relatively low blood glucose tended to be prolonged in patients with rs5219 polymorphism compared to those with wild genotype: 20.0 [0.0; 75.0] vs 0.0 [0.0; 0.0] min; P=0.075 and 0.20 respectively. No differences in measures of glycemic variability between the genotype groups were observed: 24-hour standard deviation of CC-genotype carriers was 1.2 [0.9;1.3] mmol/l vs 0.9 [0.8;1.1] mmol/l of CT/TT-genotype carriers (P>0,05).

Conclusions: Despite limited sample size, we can conclude that the KCNJ11 rs5219 polymorphism is associated with better response to vildagliptin treatment in medication-naïve patients with newly diagnosed T2D, although patients with the CT/TT- genotypes are more likely to develop mild hypoglycemia than patients with CC-genotype.