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

Abstract

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 systems geneCYP2C9(rs1799853CYP2C9*2 иrs1057910CYP2C9*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 geneCYP2C9(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 SNPsrs1799853andrs1057910geneCYP2C9at 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 (p0.05). Thus, OR at the carriage ofrs1799853andrs1057910respectively equaled: for CGM-hypoglycemia 7.78 (3.0220.01) and 5.80 (0.23145.87); number of Glycemia Excursion 4 mmol/L/h 5.76 (2.2914.43) and 4.44 (1.4313.76); MinGl3.9 mmol/L 4.39 (1.7910.75) and 6.26 (1.8421.30); CV40% (vs30%) 3.63 (1.0412.62) and 15.22 (0.59393.94);p0.05.
 Conclusion.At the real clinical practice the assessment of carriage of SNPs of geneCYP2C9before 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.

The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression

“…We believe that polymorphisms of genes encoding glutathione-metabolizing enzymes represent attractive biomarkers for the predictive genetic testing of impaired glutathione metabolism and could be used for assessing the susceptibility of an individual to numerous pathological conditions associated with glutathione deficiency such as diabetes [ 27 , 30 ], cardiovascular diseases [ 162 , 163 ], cancer [ 164 ], liver diseases [ 165 ], neurodegenerative disorders [ 166 ] as well as COVID-19 [ 167 , 168 ]. Genetic polymorphisms of GSS and GGT7 and other glutathione-metabolizing enzymes may become attractive markers for pharmacogenetic studies of type 2 diabetes and its complications [ 169 , 170 ] and further studies are required to focus on a comprehensive evaluation of genes affecting glutathione metabolism for their joint effects on glutathione metabolism and their contribution to the development and progression of type 2 diabetes.…”