GENETIC PREDICTORS OF DIFFERENCES IN CONTINUOUS GLYCEMIC CURVE PARAMETERS IN PATIENTS WITH TYPE 2 DIABETES RECEIVING VILDAGLIPTIN THERAPY
Thursday, May 7, 2020
11:45 AM – 12:00 PM
Participants should be aware of the following financial/non-financial relationships: Polina Shorokhova, MD: Disclosure information not submitted.
Objective : The intensity of therapeutic response under application of DPP-4 inhibitors may depent on carriage of rs7903146 polymorphism in TCF7L2 gene due to its important role in Wnt-pathway and incretin axis. The aim of the present study was to investigate the associations of single nucleotide polymorphism (SNP) rs7903146 with vildagliptin glucose lowering ability by means of continuous glucose monitoring (CGM).
Methods: We recruited 48 patients (37,5% male) with newly diagnosed type 2 diabetes mellitus (T2D), who had clinical indications to start vildagliptin therapy. The study group was on average 58,5±5,6 years old, average body mass index was 31,1±4,5 kg/m2 and average HbA1c was 7,73±1,1%. All patients received vildagliptin at an initial dose of 50 mg once a day. Participants were genotyped for rs7903146 polymorphism by Real-time PCR. Glycemic parameters such as, mean 24-hour glucose level, minimum 24-hour glucose level and 24-hour standard deviation were derived from data collected with a CGM system iPro2 for a 72-hour period. Analyses were performed in Statistica for Windows version 10.0 (StatSoft Inc., USA). A p-value of less than 0,05 was considered significant.
Results: The frequencies of the CC, CT and TT genotypes were 58,4%, 33,3% and 8,3% respectively. Minor allele T frequency was 0,25. Genotype distribution followed Hardy-Weinberg equilibrium. All patients receiving 50 mg of vildagliptin per day, were divided into two groups: CC-genotype carriers (n=28) and CT/TT-genotype carriers (n=20). Compared with CC-genotype carriers, CT/TT-genotype carriers exhibited a significantly higher the daily average blood glucose level 5,8 [5,2;6,6] vs 7,1 [6,6;7,9] mmol/l (p< 0,05) and significantly higher minimum 24-hour blood glucose level 3,7 [3,4;4,3] vs 5,9 [5,8;6,1] mmol/l (p< 0,05). No differences in measures of glycemic variability between the genotype groups were observed: 24-hour standard deviation of CC-genotype carriers was 0,9 [0,8;1,1] mmol/l vs 1,2 [0,8;1,2] mmol/l of CT/TT-genotype carriers (p >0,05). In 6 (21.4%) patients with wild genotype, episodes of mild hypoglycemia were observed. No episodes of hypoglycemia have been identified in patients with CT/TT genotypes.
Discussion/Conclusion: Our findings demonstrate that rs7903146 polymorphism could affect vildagliptin efficacy. Despite limited sample size, we can conclude that the risk allele T in TCF7L2 gene is associated with worse response to vildagliptin treatment in patients with newly diagnosed T2D. Although patients with the СС genotype are more likely to develop mild hypoglycemia than patients with CT/TT genotypes. Thus, this SNP in TCF7L2 gene may be considered an additional prognostic marker of vildagliptin treatment outcomes.