Vol 22, No 4 (2019)

Cover Page
Evidence Based Diabetology
Diagnosis and rational treatment of painful diabetic peripheral neuropathy: an interdisciplinary expert consensus
Galstyan G.R., Starostina E.G., Yakhno N.N., Gurieva I.V., Churyukanov M.V., Strokov I.A., Tokmakova A.Y., Kukushkin M.L., Martynov A.I., Shestakova M.V.

Abstract

Diabetic peripheral neuropathy is a common chronic complication of diabetes mellitus, significantly impairing well-being, quality of life and functioning of patients. The prevalence of diabetic peripheral neuropathy in the Russian Federation ranges from 0.1% to 67.2% in type 1 and from 0.1 to 42.4% in type 2 diabetes mellitus. However, based on the large-scale epidemiological studies, the true prevalence of diabetic peripheral neuropathy is much higher (50 to 70%), with its painful variant occurring in 16% to 30% of patients. Despite the fact that diabetic peripheral neuropathy remains the most common chronic complication of diabetes mellitus, its diagnosis and therapy leave much to be desired. To optimize diagnostic and treatment approaches to painful diabetic peripheral neuropathy, a group of experts representing the leading Russian professional medical associations has developed clinical guidelines for the diagnosis and rational therapy of patients with painful diabetic peripheral neuropathy.

This document presents practical aspects of the clinical diagnosis of painful diabetic peripheral neuropathy and an algorithm for differential diagnosis of pain in the lower extremities in patients with diabetes mellitus. The use of symptomatic analgesics with central action, such as anticonvulsants, antidepressants and opioids, is based on the main aspects of neuropathic pain pathophysiology. The characteristics of each drug class are given, with consideration of evidence on their efficacy, tolerability, and the possibility of combination therapy. The data on the first, second, and third lines of agents is presented in accordance with several international clinical guidelines. The need for a tailored drug choice, taking into account the evidence-based data on their efficacy and safety, concomitant drug therapy, tolerability, cost and preferences of the patient, age of the patient and concomitant disorders, is emphasized.


Diabetes mellitus. 2019;22(4):305-327
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Original Studies
A systematic review of the clinical effectiveness of monitoring patients with diabetes mellitus using individual blood glucose meters with function of transmitting measurements via gsm channel or via the internet
Fedyaeva V.K., Zhuravlev N.I., Galeeva Z.A.

Abstract

BACKGROUND: In recent years, there has been an active introduction of telecommunication technologies in various spheres of scientific and practical knowledge, including medicine. Diabetes mellitus (DM) is one of the most common chronic non-communicable diseases requiring constant monitoring of the patient’s condition. For telemedicine monitoring of patients with DM, glucose self-monitoring devices with the option of transmitting patient’s measurements via GSM channel or via the Internet have been developed.

AIM: To evaluate the clinical effectiveness of telemedicine observation of patients with DM using individual glucose self-monitoring devices with option of transmitting patient’s measurements via a GSM channel or via the Internet.

MATERIALS AND METHODS: Publications about clinical trials were searched in PubMed. The search, selection and evaluation of the methodological quality of clinical trials were carried out by two independent researchers. Clinical trials were included in the review if the clinical efficacy of remote monitoring of patients with DM using individual glucose self-monitoring devices with the option of transmitting the results of measurements taken by the patient via a GSM channel or via the Internet was evaluated in comparison with traditional observation methods.

RESULTS: As a result of the systematic search, 10 original randomized controlled trials (RCTs) with different methodological quality were selected. It was found that the use of remote technologies for 12 months does not affect the level of glycated hemoglobin, however, it allows to increase the frequency of achieving individual therapeutic goals in patients with type 2 DM. In addition, it was found that the use of remote technologies allows to reduce the frequency of outpatient visits of patients with type 2 DM, but does not reduce the length of hospitalization and the frequency of an emergency calls of these patients.

CONCLUSION: Thus, evidence was obtained of the potential therapeutic benefits of remote observation of patients with diabetes based on data from foreign clinical studies. Based on the results obtained, a Russian clinical trial of this medical technology can be recommended.

Diabetes mellitus. 2019;22(4):328-335
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Serum adipokine concentrations in patients with type 2 diabetes: the relationships with distribution, hypertrophy and vascularization of subcutaneous adipose tissue
Klimontov V.V., Bulumbaeva D.M., Bgatova N.P., Taskaeva I.S., Orlov N.B., Fazullina O.N., Soluyanov M.Y., Savchenko S.V., Konenkov V.I.

Abstract

Academy of Sciences, Novosibirsk, Russia 2Novosibirsk State Medical University, Novosibirsk, Russia

BACKGROUND: Adipose tissue (AT) dysfunction plays an important role in metabolic disorders in obesity and type 2 diabetes. The role of distribution, hypertrophy and vascularization of AT in adipokine secretion disturbances remain to be clarified.

AIMS: To determine the relationships between serum concentrations of adipokines and the mass and distribution of AT, diameter of adipocytes and vascularization of subcutaneous AT in patients with type 2 diabetes.

MATERIALS AND METHODS: A total of 125 patients were examined, including 82 subjects with obesity. Thirty persons without diabetes and obesity, matched by sex and age, were acted as control. Concentrations of leptin, resistin, visfatin, adipsin and adiponectin in fasting serum were determined using multiplex analysis. Mass and distribution of AT was assessed by dual-energy X-ray absorptiometry. Samples of SAT were obtained from umbilical region using a knife biopsy in 25 patients and in 15 individuals who died in accidents. Blood and lymphatic vessels in SAT were revealed with immunohistochemistry, using antibody to CD-34 and podoplanin respectively. The volume and numerical density, ultrastructure of blood and lymphatic vessels, and mean diameter of subcutaneous adipocytes were evaluated.

RESULTS: Patients with diabetes, as compared to control, had significantly higher levels of leptin, resistin, adipsin and visfatin (all p<0.001). Adiponectin showed no differences. Concentrations of leptin, resistin, visfatin, adipsin and adiponectin correlated positively with gynoid fat mass. Additionally, leptin and adipsinshowed positive correlations with truncal and central abdominal fat mass. Concentration of leptin, but not other adipokines, was associated with hypertrophy of subcutaneous adipocytes. A decrease in volumetric density of microvessels(р=0.01) and increase in volume and numerical density of lymphatic vessels (both р=0.02) was observed in subcutaneous AT from diabetic subjects. The swelling of cytoplasm, mitochondria, cisterns of granular endoplasmic reticulum and reduced content of micropinocytotic vesicles was revealed in lymphatic capillaries. Resistin and visfatin showed inverse associations with density of microvessels.

CONCLUSION: Endocrine dysfunction of AT in patients with type 2 diabetes, manifested by elevation of serum concentrations of leptin, resistin, visfatin and adipsin, is associated with mass and distribution of AT, hypertrophy of subcutaneous adipocytes and vascularization abnormalities of subcutaneous AT.

Diabetes mellitus. 2019;22(4):336-347
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The effect of empagliflozin on the development of chronic heart failure after myocardial infarction according to a 12-month prospective study
Nekrasov A.A., Timoschenko E.S., Strongin L.G., Nekrasova T.A., Baranova A.A., Botova S.N., Timoschenko M.V., Yaroslavtseva M.A.

Abstract

BACKGROUND: Although the positive cardiovascular effect of empagliflozin has been established, its influence on the formation of heart failure (HF) in patients with type 2 diabetes mellitus (T2D) after myocardial infarction (MI) remains unknown.

AIM: To study the effect of empagliflozin on the formation of chronic HF after MI in patients having diabetes mellitus of type 2 (DM 2), according to 12-month follow-up data.

MATERIALS AND METHODS: 47 patients with MI and DM 2 were included; 21 received standard therapy for MI and diabetes (group 1); 26 patients, in addition, received empagliflozin (group 2). The patients were investigated in 3 and 12 months, to assess the dynamics of glycemic control, 6-minute walk test, echocardiography.

RESULTS: During postinfarction period, the 6-minute walk distance was increasing in group 1 in a lesser degree (p = 0.18) than in group 2 (49.5%, p = 0.0004). The ejection fraction got better particularly in group 2 (p = 0.002). At baseline, the proportions of patients having HF with reduced and mid-range ejection fraction were 85.7% and 82.4% in groups 1 and 2 (p = 0.56) but in 12 months decreased to 71.4% and 29.4% (p = 0.012). In empagliflozin group diastolic function was improved in a third of the patients (p = 0.041). The pulmonary artery systolic pressure was increasing in group 1 (by 10,4%, p = 0.041) but decreasing in group 2 (by 24,0%, p = 0.019). Glycemic control was better in group 2 than in group 1.

CONCLUSION: According to 12-month follow-up data, empagliflozin has a positive effect on HF formation and symptoms in patients having MI and DM 2. This effect may be based on the ability of empagliflozin to improve the state of the heart including the delay of postinfarction remodeling, the improvement of pulmonary artery hemodynamics, systolic and diastolic function, the reduction of risk of chronic HF with reduced and mid-range ejection fraction.

Diabetes mellitus. 2019;22(4):348-357
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Ultrasonic predictors of macrosomia in gestational diabetes mellitus
Lysenko S.N., Chechneva M.A., Burumkulova F.F., Petrukhin V.A., Panov A.E., Plechanova M.A., Ulyatovskaya V.I., Zubkova N.A., Tyulpakov A.N.

Abstract

BACKGROUND: The basis of early ultrasound (US) diagnosis of diabetic fetopathy (DF) in pregnant with gestational diabetes mellitus (GDM) is the forehanded detection of macrosomia, especially its asymmetric forms. In pregnant with GDM on a diet therapy, the detection of macrosomia may be an indication for starting the insulin therapy. In pregnant with hyperglycemia due to mutation in the glucokinase gene (GCK), US fetal growth dynamics helps to assume the fetal genotype, as well as to stratify the risks of insulin therapy.

AIM: To determine the prognostic significance of asymmetric form of macrosomia and the value of the coefficients of proportionality for the diagnosis of DF in pregnant with GDM, including hyperglycemia due to mutation in the GCK gene.

MATERIALS AND METHODS: US fetometry was performed in 95 pregnant with GDM (including 22 pregnant with hyperglycemia caused by mutation in the GCK gene) (main group) and 427 healthy pregnant women (control group). Estimated fetal weight, standard fetometric indicators and coefficients of proportionality were evaluated. Retrospective analysis of US predictors of macrosomia was carried out after evaluating the weight of the newborn and clarifying the signs of DF.

RESULTS: In the group with GDM, 51 (53.7%) pregnant had children with phenotypic symptoms of DF, including macrosomia – 66,7% (34 children). We found statistically significant differences in fetal weight between the control group and the main group who gave birth to children with DF starting from 32 weeks. The coefficients of proportionality (femur length/abdominal circumference and the head circumference/abdominal circumference), characterizing the formation of the asymmetric macrosomia were significantly from 34 weeks (Р<0,05).

CONCLUSION: The most effective predictive fetometric indicators for the diagnosis of fetal macrosomia are the dimensions of fetal abdomen and fetal weight > 90 percentile for gestational age. A specific sign of DF in pregnant with GDM is the asymmetric macrosomia. In pregnant with a mutation in the GCK gene, the tendency to macrosomia was revealed only in the absence of a mutation in the fetus, but insulin therapy in the presence of a similar mutation in fetus did not lead to a significant decrease in its percentile ranges.

Diabetes mellitus. 2019;22(4):358-366
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Predicting diabetic self-care management based on the theory of planned behavior among elderly with type 2 diabetes in Thailand
Wongrith P.

Abstract

BACKGROUND: Type 2 diabetes, especially in the elderly, continues to plague the world. Thailand – a developing country – is not immune to these ravage effects and their distressing upsurge in health and economic societal burdens. Self-care management is an essential strategy to prevent complications and reduce type 2 diabetes complications.

AIM: This study aimed to examine the treatment outcome and factors predicting diabetes self-care behaviors among elderly in Thailand.

METHODS: A cross-sectional correlative predictive design using multiple linear regression models to evaluate data in elderly type 2 diabetics in Thailand (August through December 2017) to assess perceived behavioral control on diabetic self-care management. One hundred thirty-four participant’s data were collected via questionnaire along with individual health records becoming the foundation of this study.

RESULTS: Most patients controlled glycemic outcome (77.9 %) through self-care behaviors at moderate rates (majority – 55.9%). Subjective norms and perceived control strongly correlated with behavioral intention and self-care behaviors. Perceived behavioral control was the most important factor predicting intentions (β 4.025, p < .01) and self-care management behavior (β15.258, p < .001). Patients responding to items regarding self-care behavior for diet, exercise and medication adherence showed favorable outcomes.

CONCLUSION: More than half of the patients had moderate levels in self-care management and the majority had good glycemic outcomes. From the analysis, we find that perceived behavioral control is critical to predicting behavioral intention and diabetic self-care behavior among the elderly.

Diabetes mellitus. 2019;22(4):367-376
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Review
Growth factors in the treatment of diabetic foot syndrome
Komelyagina E.Y., Antsiferov M.B.

Abstract

Growth factors play a key role in wound healing, deficiency of which leads to delayed healing. Various growth factors are used in the treatment of chronic wounds, including diabetic foot ulcers. The purpose of this review was to analyse the literature data on the effectiveness of epidermal growth factor, platelet-rich plasma and platelet growth factor in patients with diabetic foot syndrome. The effect of treatment with these growth factors on healing of diabetic foot ulcers and healing time were analysed. Published studies, mostly with low level of evidence, demonstrate a positive effect of various growth factors on the healing process of diabetic foot ulcers. Currently, there is no conclusion on the advantages of growth factor therapy. Further studies with a high level of evidence are needed to justify their use in routine clinical practice.

Diabetes mellitus. 2019;22(4):377-383
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Case report
MODY2 diagnostic issues in adults
Kononenko I.V., Glibka A.A., Zubkova N.A., Mayorov A.Y., Tyulpakov A.N., Schmidt O.M.

Abstract

Approximately 90% of all cases of diabetes mellitus in adults involve type 2 diabetes, while the prevalence of maturity-onset diabetes of the young (MODY) remains undetermined leading to inappropriate treatment regimens. One of the most common monogenic forms of diabetes is a disease caused by a mutation in the glucokinase gene, MODY2. Knowledge of the clinical features of the disease allows the selection of patients with a high risk of mutation in the glucokinase gene and verification of diagnosis for molecular genetic research. This paper reflects the clinical features of MODY2 and the difficulties of diagnosis in adults. Furthermore, it presents a clinical case of a patient with MODY2 demonstrating all the features of this type of diabetes. A family member with a mutation in the gene allows to predict the nature of carbohydrate metabolism disorders in first degree relatives. A targeted study of only one part of the glucokinase gene in molecular genetic research is sufficient to confirm the diagnosis in relatives.

Diabetes mellitus. 2019;22(4):384-391
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Diabetes mellitus, chronic pancreatitis and primary hyperparathyroidism: is there a connection?
Gorbacheva A.M., Zaytseva N.V.

Abstract

Hyperparathyroidism is a relatively frequent condition characterized by hypersecretion of parathyroid hormone. There are several forms of primary hyperparathyroidism. Each form affects its target region. In the visceral form, nephrocalcinosis, nephrolithiasis and peptic and duodenal ulcers are common. The pancreas is also a target organ. This article describes a clinical case of a patient with diabetes mellitus and previously treated primary hyperparathyroidism. The patient was admitted to the hospital due to poor glycaemic control. During the hospitalization, diabetes mellitus developed as a consequence of frequent relapses of chronic pancreatitis (outcome of the visceral form of primary hyperparathyroidism and severe hypertriglyceridemia). Glycaemic control was achieved after treatment of acute pancreatitis and insulin administration. This clinical case is an example of the impact of previous primary hyperparathyroidism (even after radical treatment and remission) on the development of a multi-faceted comorbidity.

Diabetes mellitus. 2019;22(4):392-398
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Discussion
Is cancer incidence modified by SGLT2 inhibitors?
Berstein L.M.

Abstract

One of the most important achievements of diabetology in the second decade of the 21st century is undoubtedly the introduction of sodium-glucose cotransporter (SGLT2) inhibitors into clinical practice as a new class of glucose-lowering agents for type 2 diabetes. In addition to the glucosuria induced by these agents, which is their main pathway for achieving ‘antidiabetic recovery’, other consequences accompany the intake of SGLT2 inhibitors. These pathways, particularly in oncology, have not been extensively studied. Considering the analysis of the previous studies, this report demonstrates, although not significantly, that cancer morbidity in patients with T2DM treated with SGLT2 inhibitors may be organ-specific. In addition, agents within the class of SGLT-2 inhibitors may be useful in several variants of antitumor therapy, but this theory requires further study.

Diabetes mellitus. 2019;22(4):399-402
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Erratum
Corrigendum: The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2 (Diabetes mellitus. 2019;22(3). doi: 10.14341/DM10194)
Pokrovskaya E.V., Shamkhalova M.S., Shestakova M.V.

Abstract

A corrigendum on «The new views on the state of the gut microbiota in obesity and diabetes mellitus type 2» by Elena V. Pokrovskaya, Minara S. Shamkhalova, Marina V. Shestakova (2019). Diabetes Mellitus. 22(3). doi: 10.14341/DM10194
There is an error on the page 255: "Moreover, in obese patients, the concentration of circulating LPS increases by 20%, and in patients with diabetes mellitus, it increases by 125%. LPS is transported from cells of the large intestine into the bloodstream through chylomicrons or through intercellular gaps in the intestinal wall; by forming a complex of CD14 with Toll-like receptor 4 of macrophages and endothelial cells, it causes the release of anti-inflammatory cytokines: namely, interleukin-1, interleukin-6 and tumour necrosis factor alpha ". Instead of " pro-inflammatory cytokines" was published " anti-inflammatory cytokines ".
Literary source «Dahiya DK, Renuka, Puniya M, et al. Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol. 2017;8:563. doi: https://doi.org/10.3389/fmicb.2017.00563» is listed twice (№№ 7 and 13) in the list of references.
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.
The original article has been updated.

Diabetes mellitus. 2019;22(4):403-404
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Erratum: a synonymous variant in GCK gene as a cause of gestational diabetes mellitus (diabetes mellitus. 2019;22(2). Doi: 10.14341/dm9938)
Zubkova N.A., Rubtsov P.M., Burumkulova F.F., Ibragimova L.I., Makretskaya N.A., Vasilyev E.V., Petrov V.M., Tiulpakov A.N.

Abstract

An erratum on «A synonymous variant in GCK gene as a cause of gestational diabetes mellitus» by Natalya A. Zubkova, Petr M. Rubtsov, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov (2019). Diabetes mellitus. 22(2). doi: 10.14341/DM9938
An error was made in the list of authors: Fatima F. Burumkulova was not indicated as author of this article. The correct list of authors: Natalya A. Zubkova, Petr M. Rubtsov, Fatima F. Burumkulova, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov.
The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.
The original article has been updated.

Diabetes mellitus. 2019;22(4):405-406
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