Vol 23, No 3 (2020)

Original Studies
15-year risk of developing type 2 diabetes mellitus and its relationship with personal anxiety, sleep disturbance among men 45-69 years old in Russia /Siberia (international epidemiological study “HAPIEE”)
Gafarov V.V., Gromova E.A., Panov D.O., Mustafina S.V., Shcherbakova L.V., Malyutina S.K., Rymar O.D., Gagulin I.V., Gafarova A.V., Sazonova O.V.

BACKGROUND: Determine the effect of personal anxiety, sleep disorders on the 15-year risk of developing (RR) diabetes mellitus (DM) type 2 among men (M) 45-69 years in Russia / Siberia (Novosibirsk).

METHODS: In 2003–2005 As part of the IV screening of the international epidemiological study “HAPIEE”, a representative sample of m 45–69 years was examined (n=781 M, mean age-56.48±0.20 years, response – 61.00%). The level of personal anxiety (PA) was assessed using the Spielberger scale (HPA – high, MPA – medium, LPA – low). With the help of the scale “Knowledge and attitude to one’s health”, the level of sleep disorders (SD) was assessed. The period of observation of the cohort was 15 years. To check the statistical significance of the differences between the groups, the Pearson χ2 test was used. For risk assessment, Cox-regression single-factor and multivariate regression proportional hazards model was used (Cox-­regression).

RESULTS: Among persons with the first occurrence of DM type 2, HPA at the screening was 59.50%, and 63.30% had SD. The combination of HPA and SD was significant among M with the first-onset diabetes mellitus. During the 15-year period, among M with HLA, the risk of developing type 2 diabetes was 1.60 times higher than without. Among people with SD, the risk of developing type 2 diabetes was 2.40 times higher than without. In Cox – the proportional multifactor model, each variable had its own independent influence. HPA increased the RR DM of the 2nd type by 1.90 times, and SD – by 2.80 times.

CONCLUSION: It was established that a high level of PA and SD are independent predictors of type 2 diabetes, moreover, with SD, the risk of developing type 2 diabetes is higher than with a high level of PA.

Diabetes mellitus. 2020;23(3):204-209
Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome
Shikh E.V., Petunina N.A., Nedosugova L.V., Galstyan K.O., Kolmychkova K.I., Makhova A.A., Gorodetskaya G.I.

AIMSInvestigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities

MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment.

RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p<0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNFα and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher.

CONCLUSION: Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.

Diabetes mellitus. 2020;23(3):210-222
Serum electrolytes levels in patients with type 2 diabetes mellitus: a cross-sectional study
Reshma S., Sushith S., Prathima M.B., Janice D., Madan G.R., Gowda P., Kumar K.P., Rai M., Kalal B.S.

BACKGROUND: Diabetes Mellitus (DM) is a common metabolic disease worldwide. Electrolyte played significant roles in the normal functioning of the body, and deregulation is indicative of different types of disease and electrolyte disturbances are often reported in type 2 DM (T2DM).

AIM: The aim of the study was to estimate the levels of serum electrolytes in outpatients with T2DM and correlate serum electrolytes with random blood sugar (RBS).

MATERIALS AND METHODS: Patients with T2DM visiting the outpatient Departments of Medicine, between April 2016 and March 2017 were included. Of 148 diagnosed T2DM cases, 74 were had RBS level >300mg/dL (group-1) and 74 had RBS level ≤300mg/dL (group-2). Serum sodium (Na+), potassium (K+), chloride (Cl-) levels were measured by using the Roche 9180 electrolyte analyzer.

RESULTS: In this study, there was a significant decrease in serum Na+ levels in group 1 (131.83±4.36 mmol/L) compared to group 2 (134.15±4.90 mmol/L).The serum levels of K+ was found to be increased in group 1 (4.51±0.61 mmol/L) in comparison with group 2 (4.26±0.52 mmol/L). In group-1, an inverse relationship was present between serum Na+ (r=-0.342) and Cl- (r=-0.538) with RBS which was statistically significant. In group-2, a significant correlation was present between serum K+ and RBS (r=0.356, p<0.05).

CONCLUSIONS: The study showed lower levels of Na+ and higher K+ levels in group-1 compared to group-2 subjects. This study showed that the distribution of serum Na+ and K+ levels is dependent on plasma glucose levels in patients with DM and also suggests that monitoring the electrolyte levels in hyperglycemia is pertinent in the management of diabetes.

Diabetes mellitus. 2020;23(3):223-228
The role of lipid droplets in the emergence of diabetes mellitus type 2
Astakhova L.V., Katserov D.S., Matskova L.V.

The increased incidence of diabetes mellitus type 2 (DM2T) all over the world and in Russia in particular, indicates a lack of effectiveness of antidiabetic therapy and suggests the existence of gaps in the understanding of the mechanisms of onset and clinical course of this disease as well as a concomitant lack of effectiveness of antidiabetic therapy. It is known that metabolic disorders that cause DM2T are caused by disturbances in mitochondrial activity resulting in increased cellular fatty acid inclusions and insulin resistance. The present review presents the current state of knowledge about new cellular structures, fat inclusions or, using a more conventional term, lipid droplets (LDs), as a pathological feature accompanying the occurrence of DM2T. The review describes the biochemical and functional characteristics of LDs and their possible role in the onset and development of diabetes. The interrelationship of LDs and mitochondria and the effect of LDs on the nervous system are considered. Particular attention is paid to highlighting the effect of the microbiota of the gastrointestinal tract on the dynamics of the emergence of LDs. The GIT microbiota plays an important role in the development and course of many human diseases associated with metabolic disorders. Further knowledge of the relationship between the gastrointestinal microbiota and the dynamics of LD emergence will uncover new aspects of the molecular mechanism of mitochondrial function, which gives the prospect of preventive approaches in the treatment of obesity, metabolic disorders and diabetes.

Diabetes mellitus. 2020;23(3):267-274
Hyperglycemia and possible mechanisms of β-cell damage in patients with COVID-19
Kalmykova Z.A., Kononenko I.V., Sklyanik I.A., Shestakova M.V., Mokrysheva N.G.

Progressive decrease in the weight and functional reserve of β-cells is one of the main pathogenetic mechanisms of development of type 2 diabetes mellitus (DM2). The rate of progression of these processes is strictly individual, which largely determines the course of DM2 and the effectiveness of the therapy. As a rule, apoptosis and necrosis are the main mechanisms of β-cell damage and death in CD2. At the same time, recent studies allow us to consider the destruction and death of β-cells as the outcome of other types of programmed cell death (PCG), the role of innate immunity in the Genesis of CD2 IS actively discussed. This article provides an overview of the data of domestic and foreign literature of recent years regarding the molecular, intracellular characteristics of different types of β-cell PCG in CD2. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Diabetes mellitus. 2020;23(3):229-234
COVID-19 and kidneys
Shamkhalova M.S., Mokrysheva N.G., Shestakova M.V.

COVID-19 poses a real threat to patients with comorbid conditions such as diabetes mellitus (DM), hypertension, cardiovascular, renal or hepatic disorders. Kidney damage is very likely in people with diabetes who have undergone a new infection, and the risk of developing acute renal injury is associated with mortality. Potential mechanisms of kidney involvement in the clinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are important for individuals on extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelium cells and podocytes, and red blood cell aggregation in severely COVID-19 patients. By including individuals with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated.

Diabetes mellitus. 2020;23(3):235-241
The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus
Vikulova O.K., Zuraeva Z., Nikankina L.V., Shestakova M.V.

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the  pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. This review presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE ­inhibitors and ARBs therapy on the disease outcome, and presents the perspectives of the treatment with recombinant ACE 2.

Diabetes mellitus. 2020;23(3):242-249
1,5-anhydroglucitol in diabetes: its role in diagnostics, screening, glycemic status assessment, and the prediction of complications
Klimontov V.V., Dashkin M.V.

1,5-anhydroglucitol (1,5-AG) is a short-term indicator of glycemic status, reflecting hyperglycemic glucose excursions over the prior 1–2 weeks. As glucose level remains in the normal range, plasma concentration of 1,5-AG is maintained stable due to the balance between intake with the food and renal excretion. Under hyperglycemic conditions, when the renal threshold for glucose is exceeded, concentration of 1,5-AG decreases due to competitive inhibition of 1,5-AG reabsorption by glucose. In clinical practice, plasma 1,5-AG is used for retrospective assessment of postprandial glucose fluctuations in diabetic subjects with mild or moderate elevation of HbA1c. The marker is also applied in clinical trials of new agents affecting postprandial glycemia. The advantages of 1,5-AG as a marker of glycemic status are stability, independence on the physiological state when sampling, applicability for patients with abnormalities of hemoglobin and lifespan of erythrocytes. Meantime, the value of this marker is limited in subjects with renal tubular acidosis, 4-5 stages of chronic kidney disease, renal glucosuria, in those receiving acarbose and SGLT2 inhibitors. Application of 1,5-AG for the diagnosis and screening of type 2 diabetes, gestational diabetes and prediabetes has been tested. It was revealed that sensitivity of 1,5-AG as screening tool may be insufficient in individuals with mild hyperglycemia, especially if fasting hyperglycemia prevails. Therefore, it has been proposed to combine 1,5-AG with assessment of fasting glucose for the screening purposes. In type 2 diabetic subjects low plasma 1,5-AG is a predictor of renal failure, cardiovascular events, including ischemic heart disease, heart failure and stroke. Decreased 1,5-AG concentration in pregnant women is a risk factor for gestational diabetes and macrosomia. Chromatography and enzymatic methods are used to determine 1,5-AG in blood, urine and other biological fluids. Currently, the relatively high cost and lack of standardization restrain the use of 1,5-AG in clinical practice. Further studies are needed for estimation of 1,5-AG value as a marker of glycemic status in type 1 diabetes, in patients with different levels of HbA1c and different magnitude of glucose variability, as well as in situations where the clinical value of HbA1c is limited.

Diabetes mellitus. 2020;23(3):250-259
Modern aproaches to diabetic macular edema diagnosticks
Doga A.V., Volodin P.L., Ivanova E.V., Buryakov D.A., Nikitin O.I., Avakyan F.A.

Diabetic macular edema (DME) continues to be an important problem of modern ophthalmology and endocrinology. The risk of edema is higher in patients with type 2 diabetes. Thus, this is the main cause of irreversible vision loss in these patients. DME is one of the prognostically unfavorable and difficult to treat manifestations of diabetic retinopathy. As the main cause of vision loss in diabetic patients, diabetic macular edema is often not diagnosed immediately, which causes difficulties in the treatment of pathology. Thus, early diagnosis and timely treatment of this disease is the key to successfully counteract the uncontrolled decline in the patient’s visual functions.

In this article, the team of authors highlighted the possibilities of informative instrumental research methods available in the Arsenal of modern ophthalmological services. Based on the analysis of modern literature, the main principles of these diagnostic methods were indicated, their key capabilities and limitations compared to each other were highlighted. Knowledge of these characteristics is, in our opinion, an integral and most important tool in the Arsenal of a practicing ophthalmologist who supervises patients with this pathology.

Diabetes mellitus. 2020;23(3):260-266
Case report
Simultaneous pancreas‐kidney transplantation in type 1 diabetes mellitus. Clinical options
Severina A.S., Larina I.I., Shutovа A.S., Shamkhalova M.S., Dmitriev I.V., Pinchuk A.V., Arzumanov S.V., Shestakova M.V.

Simultaneous pancreas-kidney transplantation (SPKT) is the most promising treatment option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) due to diabetic nephropathy (DN). Successful SPKT eliminates uremic intoxication and hyperglycemia – the leading trigger of vascular diabetic complications. Therefore, euglycemia is an important metabolic change in patients after surgery and remains only one of the factors for the saved renal allograft functioning. In the case of resuming renal replacement therapy by dialysis after SPKT, the management and monitoring of the pancreatic graft remains open. Special attention to the pancreatic graft’s function is due to both the potential risk of surgical complications, and some probability of T1DM relapse with the need to resume insulin therapy. In patients with saved function of both transplants, the assessment of the dynamics of diabetic complications in general becomes more important. The results of few studies in this regard remain contradictory. Thus, clinical options can be unpredictably diverse and require not only search for the root cause, but also optimization of rehabilitation tactics, even if the expected results are achieved.

Diabetes mellitus. 2020;23(3):275-282

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