Aim.
To evaluate the association of rs2476601 and rs2488457 polymorphisms with type 1 diabetes mellitus (T1DM) in several ethnic populations of Russian Federation and to estimate the cross-populational differences of these polymorphisms.
Materials and Methods.
A case-control design was applied to study the aforementioned polymorphisms in five ethnic populations of Russian Federation: Bashkir, Yakut, Buryat, Udmurt, Russian. We analyzed DNA samples from 491 patients with T1DM and 408 control subjects. Polymorphisms were identified with RFLP-PCR and RT-PCR. Strength of association was evaluated as odds ratio (OR). All calculations were performed with StatSoft STATISTICA (version 6) and Microsoft Excel 2003 software applications.
Results.
PTPN22 1858Т+ genotypes were associated with T1DM in Udmurt, Russian and Bashkir populations and PTPN22 1123C+ genotype in Buryat population. We did not find any associations of PTPN22 gene polymorphisms with T1DM in Yakut population. Cross-ethnic comparison of polymorphism frequencies showed statistically significant differences. Allele frequency distribution in Buryat population significantly differs from that of other studied ethnic groups with G-1123C (rs2488457; 71.3%) being a significantly more common finding than C type allele. Russian population of Moscow and Moscow Region is also characterized by higher prevalence of Ttype allele (13%) in C1858Т (rs2476601) polymorphism.
Conclusion.
Ethnic populations of Asian regions of Russian Federation, characterized by lower rates of T1DM (Yakut and Buryat) demonstrated highest prevalence of G-allele in G-1123C (rs2488457) polymorphism. On the contrary, analyses from Russian population of Moscow and Moscow Region, known to have higher rates of T1DM, suggest higher prevalence of T-allele in C1858Т (rs2476601) polymorphism.

Pineal hormone melatonin synchronizes insulin secretion and glucose homeostasis with solar periods. Misalliance between melatonin-mediated circadian rhythms and insulin secretion characterizes diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Insulin deficiency in T1DM is accompanied by increased melatonin production. Conversely, T2DM is characterized by diminished melatonin secretion. In genome-wide association studies the variants of melatonin receptor MT2 gene (rs1387153 and rs10830963) were associated with fasting glucose, beta-cell function and T2DM. In experimental models of diabetes melatonin enhanced beta-cell proliferation and neogenesis, improved insulin resistance and alleviated oxidative stress in retina and kidneys. However, further investigation is required to assess the therapeutic value of melatonin in diabetic patients.

AIM: To evaluate the plasma level of circulating heptocyte growth factor (HGF) in patients with comorbidity of post-infarction chronic heart failure (CHF), type 2 diabetes mellitus (T2DM) and obesity. We also aimed to assess possible correlations between HGF levels and parameters of carbohydrate and lipid metabolism, as well as myocardial functional characteristics and classic biochemical severity markers for CHF.17Сахар ный диабет КардиологияСахарный диабет. 2013;(2):17-25

MATERIALS AND METHODS: We enrolled 100 patients for participation in this study, including the following subgroups: 20 individuals with- out cardiovascular and glycemic disorders, 30 patients with CHF, 25 patients with CHF/T2DM comorbidity and 25 diabetic patients with no signs of heart failure. Quantitative plasma HGF analysis was performed with enzyme-linked immunosorbent assay (ELISA).

RESULTS: Plasma HGF was elevated both in patients with CHF and T2DM as measured against healthy control group. The elevation was most prominent in patients with CHF/T2DM comorbidity and was found to correlate with HbA_1c level (r=0.52, p=0.03). Plasma HGF also correlated with BMI (r=0.42, p=0007) in a unified study group, though we observed no statistically significant difference between subgroups with a trend toward higher HGF in obese patients with CHF/T2DM comorbidity (626.1?254.1 pg/ml vs 742.0?210.7 pg/ml respectively; p >0.05). Interestingly, plasma HGF was also significantly higher in controls with BMI >30 km/m2 (324.1?107.7 pg/ml vs 436.9?112.3 pg/ml, p=0.03).Circulating HGF correlated with plasma levels of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and such structural and functional myocardial characteristics as left atrial size and maximum volume along with left ventricular ejection fraction (EF), end-diastolic volume (EDV) and end-diastolic dimension (EDD).

CONCLUSION: These findings suggest that HGF may potentially serve as a prediction marker for unfavorable myocardial remodeling and poor prognosis in CHF patients with T2DM and obesity, though this possibility should be further investigated in follow-up studies.

This article addresses possible mechanisms for development of cardiovascular events (CVE) in type 2 diabetes mellitus (T2DM) patients treated with sulfonylurea derivatives (SU). Several problems are highlighted in this review, including molecular aspects of pancreatic and extrapancreatic action of these drugs, their comparative potential to induce hypoglycemic events (as predictors of acute CVE) and impairment of ischemic preconditioning, as well as antiarrhythmic activity of certain SU agents. Finally, efficacy and cardiovascular safety of glimepiride in T2DM patients is substantiated based on a survey of current literature.

This review addresses clinical picture of acute coronary syndrome (ACS) in patients with type 2 diabetes mellitus (T2DM), the corre- sponding epidemiology data, morphological characteristics and prognosis. ACS in patients with T2DM features fulminant development, and its high lethality is due to chronic ischemic alterations in myocardium (the so-called ?metabolic ischemia?), as well as concomitant microangiopathy. It is more common for patients with T2DM to develop such complications of ACS as cardiogenic shock, acute left ventricular failure and arrhythmia that result in increased lethality during early hours of hospital admission when myocardial necrosis is yet to occur. Percutaneous translumenal intervention is by far the most effective method of ACS management in patients with T2DM. Whenever it is not available, a thrombolytic approach is indicated.

2 diabetes mellitus (T2DM). Dyspnea during physical exertion should be considered an anginal equivalent in patients with T2DM, and suffocation causing admission to ICU ? as a possible sign of myocardial infarction. Proximal and distal coronary lesions combined with diabetic microangiopathy compromising collateral circulation are a frequent finding in these patients. Therefore an infusion of nitroglycerine may yield a rapid improvement in their condition. Treatment with low-molecular-weight heparin (LMWH) should be administered for a longer period due to rheological disturbances in T2DM. Diabetic patients with a history of myocardial infarction (MI) should receive a life-long therapeutic combination of two different antiplatelet agents. Carvedilol, a non-selective beta blocker/ alpha-1 blocker, and selective beta-1 blockers (e.g. nebivolol, bisoprolol) have better safety profile than other beta blockers concerning neurological aspects of hypoglycemic events.

AIM: To determine whether duplex ultrasonography (DU) without verification with diagnostic angiography (DA) is a sufficient visual- ization technique for pre-operative examination of patients with CLI (critical limb ischemia) indication for percutaneous transluminal balloon angioplasty (PTBA).

MATERIALS AND METHODS: We examined 254 patients (290 limbs in total) with diabetes mellitus (DM) and CLI. All participants were subdivided into two groups: ?A? (PTBA with pre-operative DU+DA) and ?B? (PTBA with pre-operative DU). We evaluated data coherence between DU and DA (pre- or intraoperative) methods, as well as DU diagnostic specificity and sensitivity in determining degree and localization of vascular lesions. We also investigated specific clinical factors compromising DU diagnostic capabilities in patients with DM.

RESULTS: Our data suggests adequate coherence between DU and DA for pre-operative visualization. Group ?B? showed significantly higher diagnostic sensitivity and specificity for visualization of the lower third of superficial femoral artery and tibial arteries despite abdominal obesity, grossly evident calcification and peripheral edema.

CONCLUSION: Duplex ultrasound is efficient and precise enough to determine optimal management tactics in most patients with DMand CLI without resort to invasive methods.

AIMS: To determine the prevalence of painful diabetic neuropathy (PDN), to evaluate the composition and efficacy of pharmacotherapy and to develop a differential algorithm for symptomatic treatment of PDN.

MATERIALS AND METHODS: 4494 outpatient subjects participated in this study. Severity of pain syndrome was assessed with DN4 question- naire (supplemented with NTSS-9 scale) and visual analogue scale (VAS). After initial examination, a pharmacological evaluation of treatment was performed.

RESULTS: Based on our data, prevalence of diabetic neuropathy was estimated at 54%, with painful form reaching 6.4%. Median age was 57.2-12.1, duration of diabetes mellitus - 16.5-10.6 years. Type 1 / type 2 ratio equaled 32.4% : 67.6%, male/female - 29.7%: 70.3%. Median HbA_1c level was 8.4?1.6%. Ratio of chronic/acute forms of neuropathy was 267 : 20. Pain severity (as measured by VAS) distribution was as following: 15.6% ? severe, 40.6% ? moderate, 12.3% - mild, and 31.3% ? no pain symptoms. We did not find PDN to be associated with any parameters but sensory deficit (NTSS-9 and NDS: r=0.4; p <0.001). 21% of patients with chronic painful neuropathy (CPN) demonstrated allodynia and hyperalgesia besides typical symptoms. 97.9% of patients were previously treated with "pathogenetic" agents, 2.1% received anticonvulsants; overall efficiency was estimated at 22%. Patients with CPN and allodynia did not respond to treatment with alpha-lipoic acid (ALA), but pregabalin was efficient. After the examination treatment composition was adjusted as follows: treatment was ceased in 23% of patients, 11.9% received ALA, 53.6% - anticonvulsants, and 11.5% - antidepressants; overall efficiency was estimated at 75%.

CONCLUSION: Prevalence of PDN is relatively low. 15.6% of patients suffer from severe pain. Neuropathic pain intensity correlates only with sensory deficit and is not dependent on any other parameters. CPN consists of two forms with higher and lower intensity of pain symptoms. Symptomatic therapy is indicated in acute variant of PDN, but also in chronic cases accompanied with allodynia and hyperalgesia. ALA appears to be effective as an initial stage of management of moderate or mild CPN.

Aim.
To characterize leptin secretion in fasting state and upon intravenous glucose administration in patients with type 2 diabetes mel- litus (T2DM), prediabetes and obesity.
Materials and methods.
59 female patients took part in this study: 12 had no signs of glycemic disorder, 18 were diagnosed with prediabetes and 30 ? with newly diagnosed T2DM. Median age was 54 [48.6?60] years, median BMI ? 33.2 [29.0?37.2] kg/m2. All participants were tested for fasting leptin, fasting insulin and blood glucose levels. Prediabetic and diabetic subjects also received a bolus intravenous injection of 40% glucose solution (0.75 g/kg of body mass) with subsequent additional measurement of insulin levels at 2, 70 and 120 min upon injection, and leptin levels ? at 120 min.
Results.
Median fasting leptin in obese and patients with weight excess was 42.0 [22?60] ng/mL, which is about 2 times higher than normal reference maximum (27.6 ng/mL). Subjects with prediabetes and T2DM showed significantly lower median fasting leptin levels of 29.1 ng/mL [13.5?45.7] and 21.3 [14.3?42.2], respectively (p <0.05). After 2 h upon glucose administration we observed a statistically significant reduction in leptin level in both groups as compared to fasting state (p <0.05). In patients with prediabetes the drop reached 23.3% against 15.3% in diabetic subjects (p <0.05). Both groups demonstrated positive correlation between plasma leptin reduction and insulin area under the curve (AUC) during intravenous glucose tolerance test (r=0.4, р <0.05).
Conclusion.
1) Plasma leptin levels are increased in obese women with normal glucose tolerance (42.0 [22.0?60.0] ng/mL) and sig- nificantly decrease upon development of prediabetes or overt T2DM, which is likely associated with progression of insulin defi- ciency. 2) Leptin drop during intravenous glucose tolerance test was found to be in direct dependence with insulinemia and appeared more prominent in patients with prediabetes than in diabetics (23.1% and 11%, respectively, р=0.02).

Aim.
To investigate clinical peculiarities of cystopathy in correlation with duration of type 2 diabetes mellitus (T2DM).
Materials and Methods.
70 patients with T2DM (26 male and 44 female; mean age 63.3?4.2) were monitored under this study. Pres- ence, form and severity of diabetic dysfunction of lower urinary tract were evaluated based on natural history, complains, physical examination, urination records and urodynamic testing.
Results.
Clinical and urodynamic evidence for cystopathy was obtained in 61 participant (87.1%). 32 patients (45.7%) demonstrated signs of overactive bladder, while 29 (41.4%) had underactive bladder syndrome (UBS). We observed three stages in the development of diabetic cytopathy: latent stage followed by overactive bladder (in 5 years from first signs of T2DM) and finally by UBS (in 10 years, respectively).
Conclusion.
Our data shows association between clinical picture of diabetic cystopathy and duration of T2DM.

In this review we present a comparative analysis of alterations in hemostasis and blood coagulation during normal pregnancy with those in pregnant women with glycemic disorders (diabetes mellitus type 1 and 2, gestational diabetes).

According to international consensus, metformin is acknowledged as a first-line therapeutic agent for type 2 diabetes mellitus (T2DM). However, in most cases this treatment eventually requires intensification by supplementation with other hypoglycemic medications. The aim of the EDGE study (Effective Diabetes control with vildaGliptin and vildagliptin/mEtformin) was to assess the efficacy and safety of vildagliptin in comparison with other oral agents in routine management of patients with T2DM that has been poorly controlled by metformin monotherapy.

MODY is a heterogeneous group of diseases that stem from certain genetic mutations and are characterized by beta-cell dysfunction, early clinical onset (before the age of 25) and autosomal dominant inheritance. Nowadays many studies address atypical variants of diabetes mellitus (DM) and consequential problems in differential diagnosis. Though generally patients with MODY have normal body weight, the ongoing spread of obesity will probably produce comorbid forms and thus alter clinical picture. We present a case of DM in a 13-year-old patient that characterizes development of MODY3 in type 2 DM-like phenotype.