The incidence of diabetes mellitus (DM) is steadily increasing. InRussia, as in many countries, diabetes is a socially significant disease, while patients with type 2 diabetes account for 85–90% of the total number of people with diabetes. The development of optimal treatment tactics for diabetes mellitus is now one of the most urgent tasks of modern medicine.

Combination of lifestyle changes and drug therapy is necessary to achieve and maintain optimal glycemic control in type 2 diabetes. Currently, various hypoglycemic drugs of both tableted and injectable forms with different mechanisms of action are used. The article presents data on modern approaches to the selection of glucose reducing drugs for type 2 diabetes mellitus.

Many anti-diabetic drugs are now available to treat type 2 diabetes mellitus, including sulfonylureas, glinides, α-glucosidase inhibitors, thiazolidinediones, incretin-related drugs, glucagon-like peptide-1 (GLP-1) analogues, sodium-glucose co-transporter 2 (SGLT2) inhibitors and, certainly, metformin. It holds a central position, given its role in reducing hyperglycemia and the risk of life-threatening complications. The International Diabetes Federation annually confirms the appropriateness of the appointment of metformin as a first step in the treatment of type 2 diabetes mellitus along with lifestyle modification [1].

An accurate differential diagnosis of the type of diabetes mellitus (DM) is one of the important conditions for a personalized choice of adequate therapy in modern diabetology. In this regard, particular attention is paid to the secondary diabetes due to a whole group of heterogeneous exocrine pancreatic diseases resulting from different pathogenesis, which are combined for classification purposes with chronic pancreatitis (CP) taking the leading role. The literature review presents an integral view of the problem based on an analysis of modern diabetological and gastroenterological guidelines. It discloses terminological transformation of this diabetes into type 3c diabetes and discusses the problem of assessing prevalence of type 3c diabetes. Clinical features are considered in close connection with pathogenetic, which makes it possible to represent type 3c DM as a special morphofunctional disorder with an emphasis on high risk of ductal adenocarcinoma of the pancreatic gland. The complexity of its verification is discussed in close connection with the diagnosis of СP. The article describes the approaches to the therapy of type 3c diabetes depending on its specific cause and emphasises the special significance of correction of exocrine pancreatic deficiency. It substantiates the variety of clinical subtypes of type 3c diabetes with different degrees of carbohydrate metabolism disorders, which suggests the use of various hypoglycemic therapy regimens. In the absence of specific algorithms, it discusses the principles of monitoring hyperglycaemia compared with those for type 1 and 2 diabetes: possibilities and limitations of non-insulin hypoglycemic drugs and the principles of insulin therapy.

GLP-1 receptor agonists are a class of drugs with high efficacy, a good safety profile recommended as second-line drugs after metformin for the treatment of type 2 diabetes mellitus. Dulaglutide is a GLP-1 analogue designed for once weekly subcutaneous injection using recombinant technology and approved for use as monotherapy or in combination with other hypoglycemic agents in many countries. The randomized multicenter clinical trials have shown the advantage of dulaglutide monotherapy it had with respect to glycemic control over metformin in patients previously on diet therapy and no less efficacy compared with liraglutide monotherapy in daily injections. When used in combination with other hypoglycemic agents (including metformin, sulfonylurea preparations, metformin and pioglitazone, metformin and prandial insulin, insulin glargine), dulaglutide was no less effective than liraglutide at a dose of 1.8 mg per day and lowered the glycated hemoglobin level more significantly than sitagliptin, exenatide for injections twice a day and insulin glargine in the studies lasting 26–104 weeks. In this case, dulaglutide at a dose of 1.5 mg/week resulted in a weight loss lasting for two years of therapy. Dulaglutide was generally well tolerated, and a convenient disposable once-weekly self-injecting syringe-pen of the drug significantly improved the patient’s quality of life and encouraged adherence to therapy.

In recent decades, the biorhythms of the endocrine system sparked a new generation of research and debates among researchers on the changes of biorhythms in the development of carbohydrate metabolism disorder (CMD). The hormone melatonin produced by the pineal gland is of particular interest from the perspective of chronobiology. Melatonin circulating in blood can act as a typical hormone, reaching far-located target cells, and play a key role as a paracrine signal molecule for regional coordination of cellular functions [1]. This hormone synchronizes hormonal stimuli and metabolic processes subject to the changing time of day [2]. Melatonin is involved in the regulation of insulin secretion and contributes to the pathophysiology of carbohydrate metabolism disorders. Therefore, there is an active discussion among researchers about the prospects of using melatonin for the treatment of diabetes mellitus (DM). Such conditions as impaired fasting glycemia (IFG), impaired glucose tolerance (IGT), obesity, dyslipidemia have been recognized as independent pathological processes that require attention of doctors. Our work was aimed at studying circadian rhythms of physiological functions (body temperature, fasting glycaemia, heart rate) and the role of leptin in the development of carbohydrate metabolism disorders (IFG, IGT, type 2 DM). The study showed that the predominance of adipose tissue over the muscular plays an important role in the development of CMD, which forms abdominal obesity against the background of environmental external factors and human behavioural features, as well as the development of leptin and insulin resistance, which, as glucose metabolism disorder progresses, leads to insulin and leptin deficiency. This work reflects the changes in biological rhythms that occur prior to the manifestation of type 2 DM. Changes in diurnal fluctuations of basal temperature (BT), fasting glycemia, and heart rate occur against the background of obesity and during the development of early carbohydrate metabolism disorder (ECMD) and type 2 DM, the aggravation of metabolic disturbances leads to a change in the circadian rhythms pattern, which in turn can be both a consequence and a cause of CMD. The thermoregulation disorder is closely related to the leptin level and indicates an involvement of melatonin hormone in the process, which, after additional studies, may be used as a drug of therapy and prevention of carbohydrate metabolism disorders.

The article deals with one of the frequent complications in diabetes mellitus diabetic neuropathy, which is associated with early disability of patients and an impaired quality of life. Distal neuropathy is the most common clinical form of diabetes. In this review, the clinical presentation, pathogenesis, and current treatment options with vitamin B complex are discussed in detail.

The review is devoted to the features of statin therapy in patients with type 2 diabetes to prevent serious cardiovascular complications.

Secondary hyperparathyroidism (SHPT) is a disabling complication of chronic kidney disease (CKD), which is characterized by a significant increase in the rate of metabolic processes in bone tissue, leading to a disruption in its structure and an increased risk of fractures, as well as cardiovascular pathology. Vitamin D deficiency, which is the main pathogenetic link in the development of mineral-bone disorders (MBD), contributes to a decrease in insulin secretion, insulin resistance, and pancreatic β-cell defect. Due to the effects on carbohydrate and lipid metabolism, renin-angiotensin-aldosterone system (RAAS), and also participation in oxidative stress, vitamin D is considered today as an integral part of the treatment of cardiorenal syndrome, the concept of which is based on the existence of mutually affecting various pathogenetic factors that adversely affect in relation to the heart and kidneys. A meta-analysis of observational studies has shown that a high concentration of vitamin D in the blood serum is associated with a 43% reduction in cardiometabolic disorders in patients with diabetes mellitus (DM), CKD and SHPT, compared to low concentrations. Perspective drugs for correction of phosphoric-calcium metabolism, improvement of renal function and reduction of cardiovascular risks in this cohort of patients include paricalcitol.

Hypoglycemic syndrome is a symptom complex that results from low blood sugar levels. In the endocrinologist practice, an insulinoma that is a small tumor in the pancreas that produces an excess amount of insulin is regarded as the main cause of hypoglycemia in patients without diabetes mellitus. Various molecular and genetic disorders develop in the insulinoma tissue, that lead to a change in the secretion of insulin and its precursors.

There is often a situation when it is not possible to establish the cause of lowering blood glucose levels. In such cases, the development of hypoglycemia can result from various genetically determined enzyme, autoimmune and receptor disorders that cause a change in glucose metabolism or the synthesis/bioactivity of insulin. In the mild course of such congenital diseases, hypoglycemic conditions may first manifest in adulthood.

The review describes various genetic predictors (mutations) that play a decisive role in the development of enzyme, autoimmune, receptor and proliferative disorders and, as a consequence, hypoglycemia.

Diabetes insipidus (DI) is a syndrome characterized by the excretion of abnormally large volumes of diluted urine. It can be caused by two fundamentally different defects that must be distinguished for safe and effective management. First: central DI, due to inadequate production/secretion of vasopressin (AVP) and nephrogenic DI, due to renal insensitivity to AVP. Second: primary polydipsia, due to suppression of AVP secretion by excessive fluid intake. This review provides methods of differential diagnosis of DI. The article highlights the availability of functional tests and pituitary MRI in correct diagnosis of central DI. Common treatment algorithms of DI and management of DI in the neurosurgical patients are also discussed. The article provides comparative data of the efficacy and safety of various pharmacological forms of desmopressin in the treatment of central DI.

According to the World Health Organization (WHO), the number of overweight people around the world has more than tripled since1975. In2016, 39% of adults aged 18 and over were overweight, and 13% were obese. Most of the world’s population live in countries where overweight and obesity kills more people than underweight. However, WHO experts believe that obesity can be prevented. How relevant is the problem of overweight and obesity forRussia? What is its medical significance? Are there pharmacotherapeutic products that can efficiently and safely help an overweight person get rid of such problem? These and other questions are answered by Ashot Musaelovich Mkrtumyan, Honored Doctor of Russia, Professor, Doctor of Medical Sciences, Head of the Department of Endocrinology and Diabetology of the Medical Faculty and Faculty of Postgraduate Education of theEvdokimovMoscowStateMedicalStomatologicalUniversity.

Obesity is a chronic disease associated with cardiometabolic risk factors, primarily cardiovascular diseases and type 2 diabetes mellitus. In 2016,Russiaregistered a new drug for treating obese patients liraglutide 3.0 mg, which is an analogue of human glucagon-like peptide-1. Given the urgency of the problem, we present a clinical case that shows the efficacy of therapy with liraglutide 3.0 mg daily in a patient with obesity, and its effect on metabolic risk factors.

A well-known crucial role of Vitamin D is in the maintenance of musculoskeletal system. In terms of high prevalence of violations of calcium-phosphorus metabolism, in the following article we will touch upon some aspects bone metabolic dysfunction, caused by Vitamin D deficiency. Moreover, recent researches reveal that the great amount of Vitamin D and their importance lead us to calling it a global regulator of homeostasis of human body, so below we are to analyze and generalize the pleiotropic effects of Vitamin D, concerning its influence on organs and systems of organs. Also in this article we bring up the results of some researches, which have persuasively demonstrated that the optimal level of Vitamin D in blood has a positive effects on a humans health and protects it from many more diseases of civilization. Futhermore, there are going to be regarded various methods for medication correction of vitamin D deficiency, and one clinical case of an inadequate diagnosis and treatment of hypovitaminosis D.

The associations or relationship of MetS and its components with thyroid gland (TG) dysfunction are well known, and the study was aimed at establishing the clinical and functional features of the thyroid gland dysfunction combined with the metabolic syndrome. The study included 90 patients aged 18 years and older with the presence of comorbidities which included metabolic syndrome and thyroid diseases (MetS and TG); with MetS without TG dysfunction and with TG dysfunction without MetS. A comparative assessment of BMI, insulin, HOMA-IR index, lipid profile values was carried out in the studied subgroups of patients depending on the functional state of the thyroid gland. The study showed that the comorbid course of subcompensated hypothyroidism and MetS is associated with aggravation of hyperinsulinemia and insulin resistance, with a tendency towards an increase in BMI, an unfavourable shift in lipid metabolism.

It has been established that during pregnancy women may develop physiological resistance to the action of insulin, which in itself is a risk factor for carbohydrate metabolism disorders. Early diagnosis of hyperglycemia in women at risk for diabetes at the beginning of pregnancy and in women with diagnosed diabetes before pregnancy at the planning stage may prevent pregnancy and childbirth complications. Self-monitoring of blood glucose for such patients is an integral part of the guidelines on follow-up of such women. The achievement of normoglycemia throughout the gestation period makes it possible to forecast perinatal outcomes such as reduced rates of development of macrosomia, severe degrees of diabetic fetopathy, and an increased rates of natural births. The use of modern technologies for the management of glycemia during pregnancy, namely portable glucometers for daily monitoring of blood glucose, determines the choice of therapy for women with various carbohydrate metabolism disorders during pregnancy.

Chronic hyperglycemia imposes damage on a number of cell types and is strongly correlated with the variety of related complications such as eyes, kidneys, cardiovascular system etc. This fact implies pharmacological treatment. Some are metabolic neutral, some are apt to provoke hypoglycemia and/or hyperglycemia, invert pharmacological response. To take into account a potential role of treatment on glucose level is crucial for pharmacotherapy in patient with T2DM. Besides, some drugs may distort the meaning of lab tests.

A comparative analysis of the changes in the immune and genetic status in patients with metabolic syndrome (MetS) combined with thyroid pathology has been performed in comparison with patients only with MetS or thyroid gland (TG) dysfunction.

Materials and methods: 90 patients were recruited and assigned to one of three groups: A group of patients with MetS and TG dysfunction; a group of patients only with MetS; group of patients only with TG dysfunction. All patients underwent immune status assessment – CD3, CD4, CD8, CD16, CD4 +/CD8 +, and tumour necrosis factor (TNF) and C-reactive protein (CRP) levels were studied in a biochemical blood test. Genetic analysis consisted in determining the frequencies of alleles and genotypes of four polymorphic markers: rs10865710 of the PPARG3 gene, rs1042713 and rs1042711 of the ADRB2 gene and rs5443 of the GNB3 gene. Results: The combination of MetS with TG dysfunction regardless of the presence or absence of autoimmune thyroid diseases was characterized by aggravation of disorders in the Tand B-cell components of immune system, an increase in IgG, CRP, and TNF levels. Genetic analysis showed frequent detection of the A allele, the AA genotype of the polymorphic marker rs1042713 of the ADRB2 gene, coding β2-adrenoreceptor in the Kazakh population.