The pharmacogenetics of hypoglycemia and the glycemic variability at the patients ith type 2 diabetes mellitus

Aim. To investigate the link between the hypoglycemia (registrated accurately by the professional Continuous Glucose Monitoring – CGM; severe hypoglycemia at home) and the hetero-/homozygote carriage of single nucleotide polymorphisms (SNP) of cytochrome system’s gene CYP2C9 (rs1799853 CYP2C9*2 и rs1057910 CYP2C9*3) at the patients with Type 2 Diabetes Mellitus (T2DM) used sulphonylurea (SU).

Materials and methods. In Study “Case-Control” 120 T2DM-SU-patients genotyped by SNPs of gene CYP2C9 (using PCR-RT) had been done the professional CGM (System iPro2, Medtronic) recorded Time in Range of Hypoglycemia (TIR-HYPO), level of Minimal CGM-hypoglycemia (MinGl) and standard CGM-parameters of Glycemic Variability. Severe hypoglycemia at home was recorded from visit to visit. The odds ratio (OR) of metabolic disturbances had been assessed for carriage SNPs in comparison with wide alleles.

Results. The Study established that carriage of SNPs rs1799853 and rs1057910 gene CYP2C9 at T2DM-SU-patients associated with rising of Glycemic Variability and frequency of CGM-hypoglycemia (MinGl decreasing, increasing of TIR-HYPO and number of Glycemia Excursion >4 mmol/L/h), as well as increasing severe hypoglycemia at home (p<0.05). Thus, OR at the carriage of rs1799853 and rs1057910 respectively equaled: for CGM-hypoglycemia – 7.78 (3.02–20.01) and 5.80 (0.23–145.87); number of Glycemia Excursion >4 mmol/L/h – 5.76 (2.29–14.43) and 4.44 (1.43–13.76); MinGl<3.9 mmol/L – 4.39 (1.79–10.75) and 6.26 (1.84–21.30); CV>40% (vs<30%) – 3.63 (1.04–12.62) and 15.22 (0.59–393.94); p<0.05.

Conclusion. At the real clinical practice the assessment of carriage of SNPs of gene CYP2C9 before inclusion of SU to glucose-lowering scheme of T2DM-therapy it necessary to carry out for the detecting patients with a higher risk of hypoglycemia and rising of Glycemic Variability.