[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 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 сardiometabolic assessment of the glycemic variability in patients with diabetes mellitus: the role of the glucocardiomonitoring].

Aim To study quantitatively the two-way relationship between parameters of glycemic variability and development of cardiovascular events in patients with type 2 diabetes mellitus (DM) on chronic sulfonylurea (SM) therapy by synchronous, professional glucose and cardiac monitoring.Material and methods The study included 421 patients with type 2 DM on SM therapy. A 5-day synchronous glucose and cardiac monitoring was performed for these patients in a retrospective mode using an iPro2 (Medtronic, USA) continuous glycemia monitoring (CGM) system and Holter monitoring. Glycemic endpoints (CGM-parameters of glycemia variability and integral indexes) and cardiological endpoints (ventricular rhythm disorders (VRD), ST segment depression (dST), and corrected QT interval (QTc)) were evaluated.Results Clear correlations were found between the ST segment depression and the increase in TIR-HYPO index and the length of QTc. The strongest correlation was observed for VRD and the increase in TIR-HYPO. Moderate correlations were observed between VRD and the decrease in TIR-NORMO and between increased variabilities of glycemia (increases in SD and number of glycemia excursions >4 mmol/l/h) and integral indexes (mean CGM-level of glycemia and HbA1c). Elongation of the QTc interval was associated with increased TIR-HYPO, decrease in maximum glycemia, and development of dST.Conclusion The glucose and cardiac monitoring confirmed the close interrelation between the quality of glycemic control and cardiovascular disorders and should be recommended for a wider use in real-life clinical practice for determining the cardiometabolic status of patients and personalization of hypoglycemic therapy.

[Type 2 diabetes mellitus: Clinical aspects of genetics, nutrigenetics, and pharmacogenetics]. / Klinicheskie aspekty genetiki, nutriogenetiki i farmakogenetiki sakharnogo diabeta 2-go tipa.

The review gives modern knowledge of the genetics, pharmacogenetics and nutrigenetics of type 2 diabetes mellitus. The knowledge of genetic determinants can refine our understanding of the pathogenesis of this disease and introduce pharmacogenetic and nutrigenetic approaches to its effective therapy and prevention.

[Cardioprotective effects of glucagon-like peptide 1 receptor agonists].

In this paper we discuss pathogenetic mechanisms of cardiovascular risk reduction in patients with type 2 diabetes mellitus by glucagon-like peptide 1 (GLP-1) receptor agonists. Results of experimental studies and randomized clinical studies are presented, and perspectives for using GLP-1 agonists in patients with diabetic cardiovascular complications are described.

[Nonglycemic effects of dipeptidyl peptidase-4 inhibitors].

The review considers the major nonglycemic effects of dipeptidyl peptidase-4 inhibitors commonly used in diabetological practice, by using as an example sitagliptin, the first and most investigated representative of this class.

[Efficacy of pharmacological inhibition of intestinal saccharases in patients with diabetes mellitus type 2 and/or visceral obesity].

Inhibitors of intestinal enzymes regulate carbohydrate metabolism reducing glycemic index, glycemic load of food and postprandial glycemia which is a prognostic factor of DM2-related cardiovascular complications and death. This class of drugs was proposed for DM2 treatment in 1970s but still holds perspectives. The article gives a detailed description of the mechanism of action, efficacy and safety of inhibitors of alpha-glucosidase and alpha-amilase in experimental and clinical controlled trials.