Vol 89, No 10 (2017)

A practitioner has a wide range of the hypoglycemic drugs for type 2 diabetes mellitus (T2DM) treatment, which can be used within a normal or near-normal range for long-term glycemic control. However, the question remains whether there are ways to achieve not only satisfactory glycemic control, but also T2DM remission (or even complete cure). The review presents an update on the concept of T2DM remission and describes the ways of its possible achievement with non-drug and drug treatments and surgery. The mechanisms of T2DM remission are given.

Aim. To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). Subjects and methods. A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. Results. During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. Conclusion. The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

Aim. To reveal the features of microcirculatory parameters in compensated and decompensated type 2 diabetes mellitus (T2DM). Subjects and methods. A total of 196 patients with T2DM were examined and divided into 2 groups: 1) 52 patients (40.4% of men) aged 52.8±8.7 years with compensated T2DM (glycated hemoglobin (HbA1с), 6.3±0.5%); 2) 68 patients (38.2% of men) aged 52.8±8.1 years with decompensated T2DM (HbA1с, 9.4±1.7%). Both patient groups had concomitant hypertension (its prevalence, degree, stage of hypertension were comparable). A control group consisted of 76 volunteers (40.8% of men) aged 52.2±8.7 years with normal carbohydrate metabolism and without signs of cardiovascular disease (HbA1с, 5.3±0.49%). Capillary blood flow in the finger nail-fold area was investigated in all the participants. A digital optical capillaroscope with image-processing software was used to obtain quantitative blood microcirculatory parameters. The diameters of arterial and venous capillary segments were measured, by calculating the remodeling rate. The degree of capillary tortuosity, network density, and polymorphism and the size of the perivascular zone (PZ) were estimated. Blood rheological properties and capillary blood flow velocity were also investigated. Results. The decompensated T2DM group compared to the compensated T2DM group was found to have a narrowing of the arterial capillary segment diameter (8.4±2.0 µm; p=0.009) and an increase in remodeling rates (1.47±0.22; p=0.000). The tendency of the PZ size to be larger in patients with decompensated T2DM compared to those with compensated T2DM (p=0.080) and the increase in this indicator compared to the control group (p=0.001) reflect the presence of edema syndrome in Group 2, as laboratory confirmed by a statistically significantly elevated sodium level (p=0.000; p=0.006). The enlarged venous capillary segment demonstrates involvement of the venous component in microcirculatory disorders in T2DM. The reduction in the density of the capillary network and the increase in capillary tortuosity and polymorphism, which were also observed in the patients of both groups versus the control group, are referred to as disorders that are characteristic of T2DM. Conclusion. In decompensated T2DM, capillary bed structural and functional changes are found as a narrowing of the arterial capillary segment, an increase in the rate of remodeling, and enlargement of the PZ. Digital capillaroscopy opens up new possibilities for assessing the magnitude of changes in the microcirculatory system in DM and can simultaneously evaluate the efficiency of treatment, by monitoring the status of the microvasculature.

Aim. To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. Subjects and methods. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. Results. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). Conclusion. The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically significantly associated with the development of T2DM; however, its predisposing effect has been identified in its combination with the variant genotypes of the polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

Aim. To reveal possible associations between metabolic syndrome (MS) and reduced lung function. Subjects and methods. In 2013—016, a cross-sectional survey was conducted in 908 Novosibirsk dwellers, which included spirometry to evaluate external respiratory function (ERF). For the detection of MS, the investigators used the 2009 All-Russian Research Society of Cardiologists criteria: waist circumference (WC) > 80 cm for women and >94 cm for men in combination with two of the following criteria: blood pressure (BP) ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoproteins (HDL) cholesterol <1.0 mmol/l for men and <1.2 mmol/l for women, low-density lipoprotein (LDL) cholesterol >3.0 mmol/l, and glucose ≥6.1 mmol/l. Results. The mean values of WC were significantly greater with a forced expiratory volume in one second (FEV1) <80% than those with a FEV1 of ≥80% in both men (p=0.002) and women (p=0.050); in women, the mean values of WS were higher than those with a FEV1/forced vital capacity (FVC) <70% than those with a FEV1/FVC of ≥70% (p=0.047); the mean systolic and diastolic BP levels were significantly more with reductions in FEV1 and FVC, and the level of HDL cholesterol was significantly lower than that with a FEV1 of < 80% in men only. Significant correlations were found between FEV1 and all components of MS in men, between the majority of components of MS and FVC in men, between WC, BP, and FEV1/FVC in men and women, between plasma glucose levels and FEV1/FVC in women. Linear regression analysis revealed significant inverse correlations of FEV1 with TG, glucose, BP; those of FVC with TG, glucose; at the same time a positive association with HDL cholesterol in men, and only a negative correlation of FEV1/FVC with WC. Conclusion. The revealed associations between MS and reduced lung function can most likely be explained by the greater prevalence of both MS and its components (hypertension, hypertriglyceridemia, hyperglycemia, LDL hypercholesterolemia) among Novosibirsk men. This is consistent with the assertion that the decline in ERF, particularly FEV1, may be a marker of future cardiovascular disease morbidity and mortality.

Aim. To assess correlation of cytokines levels and therapy regimes a relationship of the time course of changes in the cytokines IFN-γ, IFN-α, IL-18, and TNF-α to the treatment option for influenza A (H1N1) pdm09 with umifenovir (Arbidol) 800 mg/day for 5 days (n=50); oseltamivir (Tamiflu) 150 mg/day for 5 days (n=50); umifenovir (Arbidol) 800 mg/day for 5 days in combination with Kagocel 72 mg/day for 2 days.; 36 mg/day for 2 days (n=50); oseltamivir ((Tamiflu) (150 mg/day for 5 days) in combination with Kagocel 72 mg/day for 2 days; 36 mg/day for 2 days (n=50). A comparison group consisted of 30 healthy volunteers. Material and methods. The state of immunologic reactivity was assessed twice: at admission of the patients to an infectious disease clinic (at 1—3 disease days) and in the early convalescent period (at 7—8 disease days): venous blood samples were collected to determine the concentrations of IFN-γ, IFN-α, IL-18, and TNF-α by a solid-phase enzyme immunoassay. Results. All the patients in the acute phase of influenza A showed a statistically significant increase in the levels of IFN-γ, IFN-α, and IL-18 as compared with the control group. The groups receiving monotherapy in the early convalescent period had a decrease in the IFN-γ, IFN-α, and IL-18 concentrations that could be compensated by the combined use of the immunomodulator Kagocel. No statistically significant changes in the levels of TNF-α were found in the patients of all the groups, but the groups receiving monotherapy exhibited its lower concentrations in the convalescence period. Conclusion. The combination of etiotropic antiviral drugs with Kagocel enhances the efficiency of antiviral therapy. Monitoring of antiviral cytokines during the treatment of influenza A is a convenient tool to verify the efficiency of antiviral therapy and needs to be more widely introduced into medical practice.

Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disease in women. The prevailing complaints at a young age are menstrual irregularities, infertility, and hyperandrogenism-related problems. However, metabolic disorder-induced complications have been in the foreground over years. The review gives the current ideas on a change of clinical manifestations in the natural course of PCOS, as well as the pathogenetically grounded prevention of complications in patients.

In recent years, one of the promising areas in clinical medicine is the study of impaired ments in endothelial function and arterial wall stiffness, which can be referred to as one of the important predictors of cardiovascular events in patients with chronic kidney disease, including that of diabetic etiology. There is strong evidence that endothelial function and great artery stiffness may be used as reliable clinical and instrumental indicators to evaluate the efficiency of therapeutic measures and the rate of progression of cardiovascular disorders in type 2 diabetes mellitus. The article presents data on the role of endothelial dysfunction and arterial wall stiffness in the progression of chronic kidney disease in type 2 diabetes mellitus and discusses the possibility of their correction with pharmacological agents.

The review is devoted to the analysis of the literature on the possible association of Helicobacter pylori infection with type 2 diabetes mellitus, metabolic syndrome and its supposed mechanisms.