Alexander Yur'evich Mayorov

Consensus statement by a panel of experts of the Russian Association of Endocrinologists (RAE) on initiation and intensificationof hypoglycemic therapy for type 2 diabetes mellitus

С учетом масштаба развивающейся эпидемии СД существует острейшая необходимость разработки эффективного терапевтического алгоритма сахароснижающего лечения, позволяющего достичь компенсации углеводного обмена и предупредить развитие тяжелых сосудистых осложнений этого заболевания. При этом приоритетом в выборе терапевтических средств должна стать эффективность сахароснижающего действия препаратов при их безопасности для пациентов (как крат- косрочной, так и отдаленной).

Optimizatsiya i intensifikatsiya insulinoterapii pri sakharnom diabete 2 tipa (klinicheskie rekomendatsii)

По данным Государственного регистра больных сахарным диабетом, на 1 января 2009 года в России сахарный диабет (СД) выявлен более чем у 3 миллионов человек, из них 2,7 миллиона приходится на 2 тип. Последние 15-20 лет интерес к выбору оптимальной терапии на всех этапах развития СД 2 типа возрастает. Это связано с одной стороны с появлением новых научных данных, а с другой стороны со всё увеличивающимися возможностями фармакологического воздействия у этой категории больных. В настоящее время специалисты выделяют 9 групп таблетированных и инъекционных препаратов. Эти данные представлены в одном из самых важных опубликованных за последнее время международных документов ? совместном консенсусе Американской Диабетической Ассоциации (ADA) и Европейской Ассоциации по исследованию диабета (EASD), а также в недавно опубликованном Консенсусе Американской Ассоциации Клинических Эндокринологов (AACE)/ Американской Коллегии Эндокринологов (ACE). В этом обзорном документе специально оговаривается сравнение различных препаратов в виде следующего заявления: в настоящее время недостаточно данных, чтобы поддержать рекомендацию по какому-то конкретному классу сахароснижающих препаратов или их комбинации в отношении влияния на предупреждение осложнений. Поэтому, справедливо судить и сравнивать сахароснижающие агенты, так же, как и их сочетание, в первую очередь по их способности снижать и поддерживать уровень HbA1c, а также по их безопасности, специфическим побочным эффектам, переносимости, удобстве в применении?. Далее в документе подчеркивается особая роль инсулина в лечении СД, обосновывая это следующим: ? инсулин является самым мощным сахароснижающим препаратом; ? своевременное начало инсулинотерапии обеспечивает оптимальный контроль гликемии и, соответственно, улучшает прогноз СД 2 типа, замедляя развитие в организме необратимых изменений; ? доказано влияние интенсивной инсулинотерапии на предупреждение развития сосудистых осложнений при диабете; ? по мере прогрессирования диабета заболеванием труднее управлять; в этом плане инсулин даёт дополнительные преимущества, поскольку его действие не зависит от остаточной секреторной активности бета-клеток. В настоящих рекомендациях будут затронуты все этапы инсулинотерапии СД 2 типа: начало, оптимизация и интенсификация.

Initiation and intensification of antihyperglycemic therapy in type 2 diabetes mellitus: Update of Russian Association of Endocrinologists expert consensus document (2015)

The current update of the consensus algorithm of initiation and intensification of the antihyperglicemic therapy in treatment of the patients with type 2 diabetes mellitus (2015) is based on the preliminary document issued by the Russian Association of the Endocrinologists in 2011. The update was needed due to new data on the safety of the traditional therapeutic options, availability of the new class of the antidiabetic medications, and necessity to add chapter about initiation and intensification of the insulin therapy. The patient-centered approach remains the absolute priority at any stage of diabetes care as it ensures the efficacy and safety of antihyperglycaemic treatment.

Metabolic characteristics and therapeutic potential of brown and ?beige? adipose tissues

According to the International Diabetes Federation, 10.9 million people have diabetes mellitus (DM) in Russia; however, only up to 4 million are registered. In addition, 11.9 million people have impaired glucose tolerance and impaired fasting glucose levels [1]. One of the significant risk factors for type 2 DM (T2DM) is obesity, which increases insulin resistance (IR). IR is the major pathogenetic link to T2DM. According to current concepts, there are three types of adipose tissue: white adipose tissue (WAT), brown adipose tissue (BAT) and ?beige?, of which the last two types have a thermogenic function. Some research results have revealed the main stages in the development of adipocytes; however, there is no general consensus regarding the development of ?beige? adipocytes. Furthermore, the biology of BAT and ?beige? adipose tissue is currently being intensively investigated, and some key transcription factors, signalling pathways and hormones that promote the development and activation of these tissues have been identified. The most discussed hormones are irisin and fibroblast growth factor 21, which have established positive effects on BAT and ?beige? adipose tissue with regard to carbohydrate, lipid and energy metabolism. The primary imaging techniques used to investigate BAT are PET-CT with 18F-fluorodeoxyglucose and magnetic resonance spectroscopy. With respect to the current obesity epidemic and associated diseases, including T2DM, there is a growing interest in investigating adipogenesis and the possibility of altering this process. BAT and ?beige? adipose tissue may be targets for developing drugs directed against obesity and T2DM.

Attitudes in patients with diabetes mellitus type 1 and type 2

Aims. To compare disease attitudes in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM) and to evaluate relationship between attitudes and psychological welfare of these groups. Materials and Methods. We examined 140 patients with T1DM and 70 patients with T2DM on insulin therapy (mean age 22.6?3.2 and 60.1?7.8 years; male/female ratio 47/93 and 15/55; duration of diabetes 12.1?5.7 and 11.4?6.5 years, HbA 1c 9.3?2.2 и 9.0?1.4%, respectively). Psychological parameters were assessed by following methods: Bekhterev Disease Attitude Typing (DAT), Colour Attitude Test (CAT), SF-36 (36-Item Short Form Health Survey), Spielberger Anxiety Inventory (SAI), CES-D Depression Scale, Dembo-Rubinstein (DR) technique for self-esteem assessment. Results. DAT showed increased sensitive attitude to their disease in patients with T1 and T2DM, being significantly higher in T2DM. According to CAT, T2DM patients perceive DM as a disease, associated with severe manifestations and complications, while T1DM patients tend to incorporate the notion of diabetes with lifestyle. Cluster analysis showed negative disease attitude to be associated independently of diabetes type with decrease in quality of life and emotional deterioration (higher anxiety and depression score, as measured by SF-36, SAI and CES-D). Conclusion. Disease attitude typing and correction is important in management of DM. Emotional acceptance allows improvement in quality of life and promotes psychological welfare. Also, despite the absence of direct relationship between HbA 1c and disease attitudes (which, is plausibly non-linear), emotional acceptance may favour glycemic compensation due to increase in compliance.

Insulin resistance in pathogenesis of type 2 diabetes mellitus

This review focuses on the mechanisms of impaired sensitivity to insulin associated withevolution of carbohydrate metabolism disorders from enhanced fasting glycemia (EFG) to impaired glucose tolerance (IGT) and type 2 diabetes.Disturbances of glucose utilization at the receptor and post-receptor levels are considered along with the role of glucose and lipotoxicity. Original dataon insulin resistance (IR) in patients with disorders of carbohydrate metabolism are presented. Insulin sensitivity in DM2, EFG and IGT is shownto be 50, 25 and 15% lower respectively than in normal subjects. M-index positively correlates with BMI and quality of metabolic control (HbA 1c and triglyceride levels). The differences in clinical and biochemical characteristics of DM2 patients are analysed depending on the degree of IR.Adiponectin and resistin levels in DM2 are shown to be lower than in healthy subjects while TNF-a and proinsulin levels increase. Therapy withmetformin, pyoglitazone, and insulin improves insulin sensitivity even in patients with early disturbances of carbohydrate metabolism. It is concludedthat intensive hypoglycemic therapy should be initiated before marked deterioration of insulin sensitivity developed.

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

Background The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

A glucokinase gene mutation in a young boy with diabetes mellitus, hyperinsulinemia, and insulin resistance

We report the case of a 12-year-old boy with a glucokinase (GCK) mutation, and diabetes with hyperinsulinemia and insulin resistance. For 4 years, the patient intermittently received insulin medications Actrapid HM and Protaphane HM (total dose 5 U/day), with glycated hemoglobin (HbA1c) levels of 6.6%–7.0%. After extensive screening the patient was found to carry a heterozygous mutation (p.E256K) in GCK (MIM #138079, reference sequence NM_000162.3). Insulin therapy was replaced by metformin at 1,700 mg/day. One year later, his HbA1c level was 6.9%, postprandial glycemia at 120 min of oral glucose tolerance test was 15.4 mmol/L, hyperinsulinemia had increased to 508.9 mU/L, homeostasis model assessment index was 114.2 and the Matsuda index was 0.15. Insulin resistance was confirmed by a hyperinsulinemic euglycemic clamp test – M-index was 2.85 mg/kg/min. This observation is a rare case of one of the clinical variants of diabetes, which should be taken into account by a vigilant endocrinologist due to the need for nonstandard diagnostic and therapeutic approaches.

Nonalcoholic fatty liver disease: cause or consequence of insulin resistance?

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are pathological conditions that are co-occurring, and have been reaching epidemic proportions. One of the most significant risk factors for the development of both T2DM and NAFLD is obesity, which increases existing insulin resistance (IR). IR thought to be one of the main pathogenic causes linking T2DM and NAFLD. In recent years, there has been increased interest in obtaining non-invasive methods for assessing fibrosis and determining indications for liver biopsy, such as the NAFLD fibrosis score, extended liver fibrosis panel, and transient elastography. However, liver biopsy remains the gold standard for diagnosing NAFLD. Given that patients with T2DM are at higher risk of NAFLD than the general population, and that the presence of diabetes is a risk factor for the progression of NAFLD, patients with T2DM should be more closely monitored by clinicians. The present review paper is devoted to the search for cause–effect relationships of concurrent diseases such as NAFLD and disorders of carbohydrate metabolism, and priority areas of diagnosis of NAFLD.

Insulin resistance and its possible personal stress moderators

Background . Recently, insulin resistance (IR) has been actively investigated by experts in various fields. Here we aim to study the effect of stress on the development of IR. Objective. To study the associations between IR and personal stress moderators (self-attitude, locus of control and coping strategies) as well as the related performance lifestyles. Methods . The study included 63 patients (16 men; mean age, 48.2 ± 11.7 years). Of these participants, 26 were diagnosed with type 2 diabetes mellitus, 10 with impaired glucose tolerance, 6 with impaired fasting glucose and 21 with normal glucose tolerance. The levels of HbA1c and IR ratio were determined using HOMA. Well-known psychological assessment questionnaires were used to assess the effect of personal stress moderators. Results . There was a significant relationship between IR and personal stress moderators. A positive self-attitude was associated with a lower risk of IR (p < 0.05), which can be explained by a decrease in the risk of developing stress. Assertive coping strategies were most pronounced in subjects with a low level of IR (p < 0.05). Personal characteristics also determined an individual’s lifestyle, which may have an impact on the increase in IR. There was an association between high levels of IR and unhealthy alimentary preferences (p < 0.05). Such preferences were also associated with personal characteristics, such as external locus of control, less positive self-attitude and passive coping strategies (p < 0.05). People with high IR rarely engage in a regular physical activity; there was a direct correlation between the frequency of physical activity and assertive coping strategies (p < 0.01). Married participants had high levels of IR (p < 0.05). Conclusion . There were significant relationships between IR and personal stress moderators, such as self-attitude and coping strategies. Besides the direct effects on stress levels, personality traits may also indirectly increase the risk of IR by influencing the individual’s lifestyle. There is a need to investigate the fact that married people have higher levels of IR.