## Diabetes mellitus

Since 1998 the “Diabetes Mellitus” (or “Sakharni Diabet”) Journal publishes timely articles, balancing both clinical and experimental research, case reports, reviews and lectures on pressing problems of diabetology. The Journal is aimed to provide a forum to discuss etiology and pathogenesis, clinical features, modern diagnostic and treatment approaches to diabetes mellitus and its complications, as well as associated conditions.

The Journal:

• features original research articles, reflecting world diabetology development;
• issues thematic editions on specific areas (diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, etc.);
• publishes chronicle of major international congress sessions and workshops on diabetes mellitus, as well as state-of-the-art guidelines;
• is intended for scientists, diabetologists, endocrinologists and specialists of allied trade, general practitioners, family physicians and pediatricians.

Editor-in-Chief

Ivan I. Dedov, PhD, Professor (ORCID: 0000-0002-8175-7886)

Indexation

The Diabetes Mellitus journal is currently indexed in Scopus (Elsevier), Emerging Sources Citation Index (Web of Science, Clarivate Analytics), Google Scholar, DOAJ and Russian Science Citation Index (eLibrary.ru).

All accepted articles in the Diabetes Mellitus journal are published in Gold Open Access (in accordance with Budapest Open Access Initiative) format with Free Full-text access to all articles via several websites (dia.endojournals.ruwww.elibrary.ruwww.cyberleninka.ru) and mobile applications for iOS® (available in AppStore). All accepted articles publish with the Creative Commons International license (CC BY-NC-ND 4.0) for more freely distribution and usage worlwide.

The journal is open for English and Russian language manuscripts. All English language manuscripts are published in bilingual format (with help of Russian association of endocrinologists the editorial team makes translations for all accepted english-language articles). So, the journal provide an additional readers auditory for published articles.

### Announcements

#### New version of Editorial Policies

The journal has updated its editorial policies regarding publication standards and ethical compliance.
01.06.2019
Posted: 01.06.2019

## Vol 23, No 2 (2020)

Original Studies
Dynamic monitoring of HbA1c in Russian regions: data comparison of mobile medical center (Diamodul) and national diabetes register of Russian Federation
Vikulova O.K., Zheleznyakova A.V., Isakov M.А., Serkov A.A., Shestakova M.V., Dedov I.I.
###### Abstract

BACKGROUND: Glikogemoglobin (HbA1c) is a key clinical marker for evaluating the effectiveness of glucose-lowering therapy for patients with diabetes mellitus (DM) and the quality of diabetic care.

AIMS: to conduct dynamic monitoring of the quality of glycemic control in DM patients based on a comprehensive examination in mobile medical center (Diamodul) during repeated visits to the regions in 2019 compared with visits of Based Federal program “Diabetes Mellitus” (2005–2010) and data of the National diabetes register (NDR).

MATERIALS AND METHODS: The object of the study: patients with T1DM and T2DM examined in Diamodul in 2019 in Voronezh region (Vr), Krasnodar region (Kr) (n = 600), there were “dynamic” group of re-examined (Vr n = 224; Kr n = 113), “random” group of new patients (Vr n = 72; Kr n = 191); group of adult patients from NDR with indicated HbA1c in 2019 (n = 2410067).

RESULTS: According to Diamodul, the HbA1c levels are significantly worse than they were reported to NDR: the proportion of patients achieved HbA1c <7% for T1DM is 13.3% and 11.7%; T2DM – 25.1% and 28.6%, in Kr and Vr, respectively; in NDR: T1DM – 37.4%, T2DM – 52.2%. The average HbA1c values in the Diamodul are higher than in NDR by 0.95% for T1DM, 1.41% for T2DM patients. The proportion of patients with HbA1c≥9% decrease in dynamic of examinations through years in T1: in Vr from 53.1% in 2005 and 55.8% in 2010 to 42.9% in 2019, in Kr from 53.2% in 2006 to 43.8% in 2019; also there were decreases in the average HbA1c values in Vr from 9.3% in 2005 and 9.4% in 2010 to 8.8% in 2019; in Kr from 9.1% in 2006 to 8.7% in 2019. In T2DM patients with the best parameters of DM control in a whole, the positive trends were less pronounced and are assessed as non-deterioration: the proportion of HbA1c≥9 % in Vr: 34.7%–34.7%–36.4%, in Kr 40.1%–28.4%; average values of HbA1c: 8.2%–8.4%–8.5% and 8.6%–8.4%, respectively.

CONCLUSIONS: The data of the research clearly indicates the need for 100% inclusion of HbA1c in the examination standards in all DM patients at the primary level at least 1 time per year, in order to monitor the real clinical situation, the effectiveness of glucose-lowering therapy and its timely intensification to prevent development of complications.

Diabetes mellitus. 2020;23(2):104-112
The dynamics of the main epidemiological indicators among living in Moscow patients with diabetes mellitus (2013–2018)
Antsiferov M.B., Demidov N.A., Kalashnikova M.F., Duhareva O.V., Vikulova O.K., Shestakova M.V.
###### Abstract

BACKGROUND: State Register of Diabetes Mellitus (SRDM) plays an important role in the dynamic analysis of the epidemiological parameters that evaluate the disease itself and its complications, and also helps to analyze the quality of specialized medical care for patients. To solve modern scientific and practical problems, it is important to analyze data not only among the entire population of Russia, but also in large administrative-territorial subjects of the country.

AIMS: To Study the dynamics of the main epidemiological indicators (values) among patients with type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) living in Moscow for the period from 2013 to 2018 according to the State Register of Diabetes Mellitus (SRDM).

MATERIALS AND METHODS: The analysis of Moscow region of the SRDM database was conducted. According to it there were registered 345.1 thousand patients with diabetes by 01.01.2019.

RESULTS: During the period from 2013 to 2018 the total number of patients with DM increased up 9.8% (from 314.4 thousand to 345.1 thousand people). DM2 accounts for 94% of the total number of patients.

According to SRDM the prevalence of DM1 on 100 thousand population has grown up 6.9% (from 152.2 in 2013 to 162.7 in 2018); DM2 – by 9.6% (from 2864.7 in 2013 to 3139.4 in 2018). The incidence of DM1 per 100 thousand people decreased down to 6.4% (from 4.7 in 2013 to 4.4% in 2018); DM2 – grew up 4.3% (from 198.1 in 2002, to 206.6 in 2018).

Throughout the study period the incidence of DM2 was higher among women, while the opposite trend was observed among women with DM1. The mortality among people with DM1 in 2018 was 1.6 per 100 thousand among adult population (in 2017 it was 1.7); among patients with DM2 the mortality was 56.6 people per 100 thousand among adult population (in 2017 it was 65.6).

The first place among the direct causes of death among patients with DM1 and DM2 in 2018 was occupied by cardiovascular diseases (57.5% and 67.9%, respectively), the second place – oncological diseases (9.9% and 12.2%).

CONCLUSIONS: The results of the epidemiological analysis showed that since 2013 in Moscow there has been an increase in the prevalence of diabetes, against the background of stable indicators of incidence (except for the organizational period of adapting to the new online data entry system of SRDM). The leading causes of death of patients with diabetes are cardiovascular and oncological diseases.

Diabetes mellitus. 2020;23(2):113-124
Factors of vascular calcification in patients with type 2 diabetes mellitus on long-term dialysis
Archakova T.V., Nedosugova L.V.
###### Abstract

PURPOSE: Defining vascular calcification markers in patients on long-term hemodialysis (LTH) with type 2 diabetes mellitus (type 2 diabetes) and without type 2 diabetes.

MATERIALS AND METHODS: The study was conducted in 82 patients with chronic kidney disease (CKD) (51 men, 31 women) on LTH, of which 25 patients (10 men, 15 women) had type 2 diabetes and 57 people (33 men, 24 women) had no diabetes. All patients underwent evaluation of calcium-phosphate metabolism, control of intact PTH (iPTH), inorganic phosphorus, and total calcium. All patients were tested for the level of fibroblast growth factor-23 (FGF23) in blood serum using a multi-enzyme immunoassay kit, and the correlation between these parameters and the presence of vascular calcification was evaluated.

RESULTS: A correlation was found between the severity of vascular calcification and the calcium-phosphate metabolism. In the group with type 2 diabetes, there is a correlation between the level of FGF23, iPTH, inorganic phosphorus and vascular calcification. There is also a correlation between the time on LTH and the increase in the level of FGF23 in patients with type 2 diabetes.

CONCLUSION: We obtained data that can indicate a more pronounced change in the vascular wall in patients with type 2 diabetes on LTH in comparison with patients without diabetes mellitus on LTH, which allows to associate high cardiovascular mortality in patients with type 2 diabetes on LTH with accelerated development of vascular calcification.

Diabetes mellitus. 2020;23(2):125-131
Review
Course and treatment of diabetes mellitus in the context of COVID-19
Shestakova M.V., Mokrysheva N.G., Dedov I.I.
###### Abstract

In 2020, the world is facing a historically unparalleled public health challenge associated with the invasion of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is also a challenge for the healthcare systems worldwide. Patients with diabetes mellitus (DM) are most vulnerable to COVID-19 because of the peculiarities of their immune response to a virus attack and due to their high susceptibility to viral activity because of hyperglycemia and other comorbid conditions and obesity that often accompany DM. The severity of the COVID-19 disease requires a mandatory review of the usual anti-hyperglycemic therapy. Maintaining optimal glycemic control and preventing the development of ketoacidosis remain extremely important; therefore, insulin becomes the priority drug for glycemic control in most cases. The search for new drugs to fight against the coronavirus infection continues with new randomised clinical drug trials being launched. Innovative anti-diabetic agents are also being tested as candidates for potentially effective anti-coronavirus agents.

Diabetes mellitus. 2020;23(2):132-139
Fast-acting insulin aspart: a review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences
Haahr H., Heise T.
###### Abstract

Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) with two added excipients, L-arginine and niacinamide, to ensure formulation stability with accelerated initial absorption after subcutaneous administration compared with previously developed rapid-acting insulins. The pharmacokinetic/pharmacodynamic properties of faster aspart have been characterised in clinical pharmacology trials with comparable overall methodology. In subjects with type 1 (T1D) or type 2 (T2D) diabetes, the serum IAsp concentration-time and glucose-lowering effect profiles are left-shifted for faster aspart compared with IAsp. In addition, faster aspart provides earlier onset, doubling of initial exposure, and an up to 2.5-fold increase in initial glucose-lowering effect within 30 min of subcutaneous injection, as well as earlier offset of exposure and effect. Similar results have been shown using continuous subcutaneous insulin infusion (CSII). The improved pharmacological properties of faster aspart versus IAsp are consistent across populations, i.e. in the elderly, children, adolescents and the Japanese. Thus, the faster aspart pharmacological characteristics more closely resemble the mealtime insulin secretion in healthy individuals, giving faster aspart the potential to further improve postprandial glucose control in subjects with diabetes. Indeed, change from baseline in 1-h postprandial glucose increment is in favour of faster aspart versus IAsp when used as basal-bolus or CSII treatment in phase III trials in subjects with T1D or T2D. This review summarises the currently published results from clinical pharmacology trials with faster aspart and discusses the potential clinical benefits of faster aspart compared with previous rapid-acting insulin products.

Diabetes mellitus. 2020;23(2):140-160
Lipodystrophy at the insulin injection sites: current trends in epidemiology, diagnostics and prevention
Klimontov V.V., Lazarev M.M., Letyagin A.J., Bulumbaeva D.M., Bgatova N.P.
###### Abstract

Lipodystrophy at the injection sites is most common local complication of insulin therapy. The history of its study started in 1926, when first cases of lipoatrophy at the sites of insulin injections were described. As we moved to human insulin and insulin analogues, immune mediated atrophic form of lipodystrophy has been replaced by hypertrophic one, which reflects anabolic and mitogenic effect of insulin.

Lipohypertrophy at the injection sites is detected by physical examination in 40-70% of insulin-treated subjects. The detection efficiency depends on health care provider`s skills. Therefore, training of medical doctors and nurses in physical examination of injection sites seems to be reasonable.

In recent years, ultrasound was introduced for diagnostics of insulin-induced lipohypertrophy. The method is more sensitive compared to palpation; ultrasound-verified lipohypertropthy was detected in more than 80% of cases. In patients with wide-spread lipohypertrophy ultrasound can be used to find suitable sites for injections (“ultrasound injection map”). Strain sonoelastography and 3D-power Doppler ultrasound can be used for quantitative estimation of rigidity and vascularization of lipohypertrophy. Both MRI and infrared images are considered as promising diagnostic tools.

In a number of studies, it has been shown that the presence of lipohypertrophy is associated with high HbA1c levels, enhanced glycemic variability, «unexplained» hypoglycemia, and increased insulin doses. Thereby, lipohypertrophy aggravates the diabetes-related costs.

The main risk factor for lipohypertrophy is inappropriate injection technique, including the lack of the site rotation, injections into lipodystrophic lesions, small injection area, reuse or excessive length of the needles. Accordingly, training patients in the injection technique is the basis for prevention of complication. The cessation of injections in lipohypertrophy areas and regular site rotation is essential for adequate titration of insulin dose and achievement of glycemic targets.

Diabetes mellitus. 2020;23(2):161-173
Signaling pathways of β-cell death in type 2 diabetes mellitus: the role of innate immunity
Kalmykovа Z.A., Kononenko I.V., Smirnova O.M., Shestakova M.V.
###### Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, the development of which is mediated by both genetic disorders and various intracellular and extracellular molecular processes. One of the main pathogenetic mechanisms for the development of T2DM is a progressive decrease in the mass and functional reserve of β-cells, which largely determines the course of T2DM. The mechanisms of action of most sugar-lowering drugs are associated with increased secretion of insulin, so it is obvious that the effectiveness of the therapy will also largely depend on the functional state of β-cells. All this explains the great interest in studying the mechanisms of damage of β-cells in T2DM and factors that can accelerate this process, leading to their death and the development of a relative and then absolute insulin deficiency. The mechanisms of dysfunction β-cells in T2DM have not been studied much. This article provides an overview of the data of domestic and foreign literature of recent years on the molecular, intracellular features of various mechanisms of damage and death of β-cells in type 2 diabetes. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Diabetes mellitus. 2020;23(2):174-184
Molecular and morphological peculiarities of chronic placental insufficiency formation caused by different types of diabetes mellitus
Tral T.G., Tolibova G.K., Musina E.V., Yarmolinskaya M.I.
###### Abstract

Рathogenesis of the chronic placental insufficiency is largely determined by the type of diabetes mellitus and the degree of its compensation. Trophic function failure of placenta changes its hormonal activity, formation of respiratory disorders and development of oxidative stress. The histological structure of placentas among patients with type 1 diabetes mellitus (T1D) is represented by reduced chorionic villi dimensions of all levels. Stromal edema and increased number of mesenchymal stromal cells are found in the stem and intermediate villi, and hypervascularisation and thickening of syncytiocapillary membranes are detected in terminal villi. In type 2 diabetes mellitus (T2D), the histological structure of the placenta may be represented as a premature maturation and abnormal immaturity of the villous tree with focal fibrosis of villi stroma, hypervascularisation of villi, abundance of syncytial nodules and infarction in the subchorial space. The peculiarity of the placenta structure in gestational diabetes mellitus is predominantly an intermediate immature type of development with angiogenesis abnormality. Angiogenesis processes failure and endothelial dysfunction in chorionic villi associated with hyperglycaemia change the permeability of cell membranes, transferring cells to anaerobic respiration. Metabolic imbalance in the placenta causes the development of diabetic micro-angiopathy in the fetal-placental complex, antenatal hypoxia and negative perinatal outcomes.

Diabetes mellitus. 2020;23(2):185-191
Metabolic changes in patients with prostate cancer with androgen deprivation therapy
Peshkov M.N., Peshkova G.P., Reshetov I.V.
###### Abstract

Prostate cancer is the most common type of cancer among men. Androgen deprivation therapy (ADT) is the most effective treatment for this disease. The cornerstone of prostate cancer treatment is the inhibition of testosterone production, which interrupts testosterone-induced growth of the prostate tumour. A sharp decrease in testosterone, however, has several undesirable effects on the metabolic profile and bone metabolism and can also lead to fatigue, loss of libido, gynecomastia and anaemia, provoke vasomotor hyperaemia and generally affect the quality of life. To increase the good (long-term) survival of patients with prostate cancer, studying the side effects associated with treatment is important, and therefore, in every clinical situation, the benefits of ADT must be compared with the side effects associated with the treatment. This article focuses on the described metabolic complications of ADT, including obesity, diabetes, lipid changes, metabolic syndrome and cardiovascular diseases. It also contains practical recommendations for managing the side effects and complications based on the available guidelines issued by the medical professional community.

Diabetes mellitus. 2020;23(2):192-200
Case report
The combination of common neuroosteoarthropathy and diabetic dermatopathy in type 2 diabetes mellitus
Tokmakova A.Y., Gracheva E.S., Zaitseva E.L., Vorontsov A.V.
###### Abstract

Diabetic neuroosteoarthropathy (Charcot’s osteoarthropathy, DNAP, Charcot’s foot) is a common complication of diabetic neuropathy, which can be easily diagnosed in clinical practice and usually is corrected without leading to severe deformation of the affected joint in case of timely and adequate treatment. We present the result of long-term clinical observation of a patient with early development of complications of type 2 diabetes mellitus, diabetic dermatopathy, common DNOAP with damage to the joints of the feet, ankles, knees and elbows. A feature of the described clinical case is the prevalence of osteoarticular disorders with seizure of atypical diabetes zones – knee and elbow joints, the defeat of which is more characteristic of other diseases (such as collagenoses and syphilis), as well as a combination of DNOAP with diabetic dermatopathy. It seems that the causes of such a common arthropathic process lie in the long course of diabetic neuropathy, which debuted long before the diagnosis of type 2 diabetes, as well as the development and progression of this patient in the last decade of observing diabetic nephropathy and associated secondary hyperparathyroidism. In the modern literature, descriptions of combinations of dermatopathies with other complications of diabetes mellitus are extremely rare, and references to a combination of common DNAP and diabetic bullosis have not been found.

Diabetes mellitus. 2020;23(2):201-208