Diabetes mellitus

Diabetes mellitus is a most serious socio-medical and economic problems facing health authorities throughout the world. A major threat is vascularcomplications of the disease. The currently available diagnostic tools, up-to-date means for monitoring glycemia, introduction of innovative insulinpreparations and hypoglycemic agents, development of high-technology therapeutic modalities may greatly improve disease prognosis, reduce the frequencyof chronic complications, related disablement and mortality rates. The targeted control of major risk factors, viz. hyperglycemia, hypertension,and dyslipidemia, during the patients lifetime starting from the onset of diabetes remains the most promising strategy for the prevention of diabeticcomplications. An indispensable condition for efficacious management of diabetes is the elaboration of active screening programs for the early diagnosisof complications and optimal organization of the clinico-diagnostic process in the framework of multidisciplinary approach.

Aim.
Comparative assessment of the prevalence of diabetic complications (DC) and the main metabolic indices in adult patients with DM1 and DM2 in the periodfrom 2003 to 2009.
Materials and methods.
The study based on the Diabet Tsentr mobile module was designed to perform screening (2003) and rescreening (2009) for DC in severalregions of the Russian Federation. Laboratory analyses included measurement of blood HbA_1c, creatinine, urea, total cholesterol levels, and albumin in singlevoidurine samples. The patients underwent fundoscopy, evaluation of all forms of sensory responsiveness, measurement of arterial pressure, and ECG. The resultswere treated with the use of Statistica 6 software. They are presented as median, 25th and 75th percentiles (Me[25%;75%]). The difference between the groups wasregarded as statistically significant at p<0.05.
Results.
The prospective study reveled a significant decrease in the prevalence of diabetic cataract from 36.8 to 33.7%, diabetic retinopathy from 41.4 to 31.8%,nephropathy from 39.6 to 30.6%, arterial hypertension from 68.9 to 65.3, angina from 28.8 to 20.5%, myocardial infarction from 7.5 to 5.2% (=<0.05) amongadult patients. Mean HbA_1c level dropped by 0.8 and 0.5% in DM1 and DM2 patients respectively. Mean systolic pressure decreased by 10 and 2 mmHg in thetwo groups. The number of DM1 and DM2 patients with decompensate carbohydrate metabolism decreased by 12.5 and 7.3% respectively. The number of DM2patients in need of insulin and combined therapy increased up to 18.2 and 7.7%.
Conclusion.
Controlled epidemiologic studies are indispensable for obtaining reliable information about the prevalence of DM and its complications and for updatingregister data. Comparative assessment of the efficiency of diagnostic and therapeutic aid to the patients revealed positive dynamics of morbidity characteristics.

Diabetes mellitus (DM) is frequently associated with disturbances of the sexual function underlain by hypogonadism and neuropathy. These pathologicalconditions are successfully managed by androgens, alpha-lipoic acid, and phosphodiesterase type 5 inhibitors, besides compensation of carbohydratemetabolism. This paper reports results of evaluation of different methods for the treatment of erectile dysfunction in DM patients basedat Endocrinological Research Centre. Their combination ensured higher than 90% efficiency of therapy.

Aim.
To consider technical aspects of antihyperglycemic injection therapy in patients with type 1 and type 2 diabetes mellitus.Methods.
The analysis included 200 adult patients (60 men and 140 women) receiving injection therapy for at least 6 months. They filled a 40-iremquestionnaire designed to estimate socio-demographic parameters, the use of different devices for insulin injection, and the most frequent mistakesmade by the patients. Their mean age was 51.7?15.1 years, duration of DM 11.9?9.1 years, mean HbA_1c level 8.4?1.5%.
Results.
130 (65%) patients used semiautomated injection pens, 39 (19.5%) disposable syringes, 31 (15.5%) both devices. Most patients (122, 61%)used 8 mm needles, 32 (16%) used 12.7 mm needles, 31 (15.5%) 10 mm, 28 (14%) 12 mm, 19 (9.5%) 6 mm, 18 (9.0%) 5 mm. 64 (32%) patientsused needles of different length, 25 (12.5%) could not give a definitive information about the needle length they used. Location of injection sites variedconsiderably in individual patients. 87 (43.5%) made injections within a single anatomic regions (62 into the anterior abdominal wall, 19 into theanterolateral surface of the thigh, 5 into shoulders, and 1 into buttocks. 113 (56.5%) patients made injections into two or more regions. 83 (41.5%)developed lipodystrophy at injection sites, 42 (50.6%) continued to use them for injections (12 did it on a regular basis and 30 occasionally). HbA_1clevels were 9.5 and 8.2% in patients who made injections into affected sites and who had no lipodystrophic changes respectively (p=0.02). Over halfof the interviewed patients (106 or 53%) were informed about correct subcutaneous injection technique by the attending endocrinologist, 60 (30%)were taught by the nursing staff while staying in a hospital or visiting an endocrinological dispensary, 28 (14.%) were educated at Diabetes schools,9 (4.5%) when seeing the local therapist, and 19 (9.5%) by non-professionals.
Conclusion.
Many patients make serious mistakes when self-administering insulin. Incompliance with the guidelines on insulin injections leading tothe impairment of carbohydrate metabolism, the technical aspects of injections must be in the focus of attention of any practitioner. New (2010) internationalguidelines on the injection technique are overviewed.

Aim.
To study efficiency and safety of hydroxizine (H) and tofisopam (T) therapy in DM patients with generalized organic anxiety disorders and subsyndromicanxiety the overall prevalence of which among diabetic patients amounts to 45-50%.
Materials and methods.
This open prospective randomized comparative study included 60 DM patients with anxiety disorders (AD) of whom 95%presented with arterial hypertension. The medicines were prescribed at mean therapeutic doses for 3 months followed by 1 month withdrawal period.The efficiency of anxiolytics was estimated from dynamic patterns of reactive anxiety (RA), personal anxiety (PA, Spielberger scale), somatic anxietysymptoms (Giessen questionnaire), HbA_1c level, systolic and diastolic AP (SAP, DAP), heart rate.
Results.
Therapy with anxiolytics for 3 months resulted in the decrease of the HbA_1c level from 7.9?1.4 to 7.4?1.4%, total somatic anxiety scorefrom 38.0?13.2 to 31.5?12.2, PA from 52.5?9.7 to 47.1?8.8, RA from 32.3?9.0 to 25.5?9.3, SAP from 141.4?12.4 to 129.8?13.5 mmHg,DAP from 82.3?7.4 to 77.8?8.6 mm Hg, HR from 76.3?9.5 to 72.7-5.6 (in all cases p<0.05). Subgroups treated with H and T had similarclinical, laboratory, and psychological characteristics before and after therapy. However, H caused a more pronounced fall in PA scores than Twhereas T reduced DAP and HR to a greater degree than H. Termination of therapy was not accompanied by clinical symptoms of withdrawal syndrome.All the above parameters remained stable within 1 month after treatment excepting DAP in the subgroup given T (a rise from 76.5?5.6 mmHg 3 months after the onset of therapy to 81.0?8.3 mm Hg 1 month after its withdrawal (p<0.05). By the end of the treatment period, 7 patientsfrom the H subgroup and 6 from the T subgroup dropped out of the study including 1 and 0 ones respectively who discontinued presumably due to thedrug-related adverse events.
Conclusion.
1. Anxiolytic therapy of AD in patients with DM significantly reduces intensity of chronic anxiety; this effect persists within 1 month afterthe termination of therapy. 2. Simultaneously, manifestations of major risk factors of vascular disorders (glycated hemoglobin, AP) decrease. 3. Meantherapeutic doses of atarax and grandaxin are well tolerated and safe for DM patients who do not develop withdrawal syndrome after the terminationof therapy. 4. Despite comparable, on the whole, results of therapy with atarax and grandaxin, the former agent appears to have greater effect on thepsychological component and the latter on the somatic (vegetative) component of AD.

Aim.
To elucidate therapeutic effect of metformin-sitaglitin combination on the dynamics of indices of insulin resistance and functional activity of pancreaticbeta-cells, lipid metabolism and body weight in patients with type 2 diabetes mellitus (DM2) and obesity.
Materials and methods.
The study included 32 patients treated by a combination of metformin (500-2550 mg/day) and sitagliptin (100 mg) for18 weeks. Standard parameters of carbohydrate and lipid metabolism, body mass index (BMI), blood adiponectin and leptin levels were measured, indices of insulin resistance and functional activity of pancreatic beta-cells were calculated.
Results.
Therapy with metformin-sitagliptin combination ensured compensation of fasting and postprandial hyperglycemia, reduced HbA_1c level, increasedfunctional activity of beta-cells, decreased peripheral insulin resistance and BMI, had beneficial effect on lipid metabolism and hormonalactivity of adipose tissue.
Conclusion.
Metformin-sitagliptin combination can be recommended as a clinically efficacious modality for the treatment of patients with diabetesmellitus and obesity.

Diabetes mellitus (DM) is a stably growing pathology leading to micro- and macrovascular complications. Despite high potential of medicamentaltherapy for DM its efficacy needs to be further improved. Uncompensated postprandial hyperglycemia is known to be responsible for many diabeticcomplications. Moreover, it by itself aggravates disturbances of insulin secretion through the toxic effect of glucose. Insulin therapy remains a principaltool for the treatment of DM. Its efficiency was greatly improved with the advent of fast-acting insulin analogs obtained by reducing stability of hexamers.Insulin glulysine (Apidra) is the fastest-acting analog licensed for the treatment of DM1 and DM2 in adult patients in 2004 (FDA, EMEA) andin children above 6 years in 2008 (EMEA). A characteristic feature of this analog is the absence of Zn2+ in its molecule that substitutes polysorbate-20 acting as a surfactant and providing additional protection of monomers from denaturation.

Metformin is a major antihyperglycemic agent used for the treatment of DM2. Analysis of the mechanism of its action is presented. Cardioprotectiveand anticancer activities of metformin are discussed. Results of multicentre studied of metformin are described.

Obesity associated with the enhanced risk of cardiovascular disorders plays a key role in the evolvement and progression of type 2 diabetes mellitus(DM2). Incretin mimetics are the sole class of hypoglycemic agents that not only effectively correct hyperglycemia but also reduce body weight. Exenatide(Byetta) is the first drug of this class approved for the use as monotherapy. This paper presents a detailed review of the available data on thescope of exenatide effects and the results of its clinical studies that confirm high efficiency of Byetta used for both monotherapy and combined therapyof DM2.

Current therapeutic strategies of type 2 diabetes mellitus are aimed at reducing the risk of acute and late vascular complications by means of normalizationof glycemia, improvement of life quality and expectancy, minimization of socio-economic losses. The adequate glycemic control should besupplemented by screening for and correction of risk factors of cardiovascular disorders; it may help to prevent or delay the development of macrovascularcomplications.

The management of chronic lesions in DM patients implies a multifactor approach, its important component being the adequate treatment of thewound bed. The new hydrosurgical technology for the purpose based on the VersaJet system poses a number of technical problems and requires assessmentof its applicability and efficiency in patients with different forms of diabetic foot syndrome. Results of the work with this system (62 patients)revealed its advantages, such as reduction of treatment duration and the number of repeat treatments, higher probability of wound healing at sitesdifficult to access (heel, tendon projection regions, etc.). It is concluded that the VersaJet system may be recommended for the use in surgical departmentsproviding specialized medical aid to patients with DM and pyonecrotic foot lesions.

Aim.
To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM) and chronickidney disease (CKD).
Materials and methods.
The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR) > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33), 2 - DM2 patients with diabetic nephropathy (n=24), 3 - DM2 patients with ischemic nephropathy (IN) (n=33) verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta), 4 - DM1 patients with DN (n=30). Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU) by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy). Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b), angiotensin II (AT II), monocyte chemoattractant protein (MCP-1),regulated on activation normal T cell expressed and secreted (RANTES), adhesion factors (intracellular adhesion molecule (ICAM-1), vascular celladhesion molecule (VCAM-1) vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), asymmetric dimethylargnine (ADMA), homocysteine(HCYST), metalloproteinases (MMP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-I).
Results.
DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6) and extracellular matrix degradation factor(MMP-9) levels compared with patients without CKD and healthy subjects. These changes were unrelated to the type of diabetes or the cause ofnephropathy, which suggests their contribution to renal pathology through the universal mechanism of tubulointerstitial fibrosis. Activation of profibrogeniccytokines in DM patients with CKD was closely associated with endothelial dysfunction manifest as enhanced production of blood adhesive angiogenic, thrombogenic factors (FW, PAI, VICAM, sICAM, VEGF), and endothelium-affecting factors (ADMA, homocysteine). Mediators of inflammationand fibrogenesis in these patients negatively correlated with GFR and positively with AU, the main markers of renal dysfunction. Hyperuricemia,TGF-1b, ADMA, and MCP-1 are considered to be the risk factors of impaired renal filtration function.
Conclusion.
The level of profibrogenic cytokines and ndothelial dysfunction factors in DM patients with different renal lesions reflects severity of tubulointerstitialfibrosis. It may be used for the purpose of prognostication and substantiation of intensification of secondary prophylaxis of renal insufficiency.

Despite substantial progress in the treatment of type 1 diabetes mellitus achieved by the end of the last century due to the advent of human insulins,intensive insulinotherapy, means of glycemia self-control, and active patient self-management education, compensation of the diseases in childrenand adolescents remains a challenging problem. This paper is focused on the use of insulin analogs in these patients and main difficulties encounteredby pediatricians in the correction of therapy.

В настоящее время академик РАМН И.Г. Акмаев является главным научным сотрудником ? консультантом лаборатории молекулярной эндокринологии ФГУ ЭНЦ. Он также принимает активное участие в работе редакционных коллегий ряда научных журналов, среди которых ?Сахарный диабет?, ?Ожирение и метаболизм?, ?Проблемы эндокринологии? и пр.

В Стокгольме 20-24 сентября состоялся 46 конгресс Европейской ассоциации по изучению диабета (EASD). С момента своего основания в 1965 г. EASD ежегодно организует крупнейшие конгрессы, посвященные исследованиям в области диабетологии по всему миру. Было организовано около 100 секций в виде пленарных лекций, симпозиумов, устных и постерных презентаций. Открывал конгресс Ulf Smith, президент EASD и EFSD.