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 1 (2020)

Original Studies
Type 2 diabetes and prediabetes prevalence in patients with different risk factor combinations in the NATION study
Shestakova E.A., Lunina E.Y., Galstyan G.R., Shestakova M.V., Dedov I.I.

Abstract

BACKGROUND: Type 2 diabetes (T2D) is multifactorial disease. NATION epidemiological study may provide the information about the prevalence of T2D and prediabetic state in patients with different risk factor combinations in Russian population.

AIMS: To evaluate the prevalence of T2D and prediabetic state in NATION cohort depending on the amount of diabetes risk factors.

MATERIALS AND METHODS: NATION is an epidemiological, cross-sectional study, designed to assess the prevalence of T2D in Russian adult population, where HbA1c was used to establish T2D (HbAc≥6,5%) and prediabetes (5,7%≤HbA1c<6,5%). Patients with T2D were either previously diagnosed or newly diagnosed. Current study presents an additional analysis of NATION cohort focused on the prevalence of T2D and prediabetic state among patients with different risk factor combinations.

RESULTS: T2D and prediabetic state prevalence gradually increased among patients with following risk factors (prevalence of T2D and prediabetes respectively): low physical activity (4,3%, 18,3%), rare fruit and vegetable consumption (4,8%, 18,7%), T2D family history (7,7%, 20,3%), age ≥45 years (9,5%, 31,3%), obesity grade 1 (9,6%, 30,3%), obesity grade 2 (14,6%, 37,8%), obesity grade 3 (20,1%, 39,7%), hypertension (14,7%, 38,2%), history of diabetes during pregnancy (14,1%, 24,7%). Prevalence of T2D with single and multiple risk factors was compared to the prevalence of T2D in young patients (<45 years) without additional diabetes risk factors. Age ≥45 years was associated with 7-fold increase in T2D prevalence; obesity – 8,8-fold; family history – 5,7-fold; hypertension – 10,8-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors). When one patient had several risk factors combined, the prevalence of T2D increased progressively: combination of age ≥45 years and family history led to 10,7-fold rise; combination of age ≥45 years and BMI≥30kg/m2 – 11,2-fold; combination of age ≥45 years, family history and BMI≥30kg/m2 – 15,3-fold; combination of age ≥45 years, family history, BMI≥30kg/m2 and hypertension – 19,1-fold (p<0,001 for comparisons of every group with patients <45 years of age without other risk factors).

CONCLUSIONS: Presence of multiple risk factors, such as age ≥45 years, obesity and hypertension led to progressive increase in the prevalence of T2D and prediabetic state. These data are important to identify patients at the highest risk of T2D among Russian population.

Diabetes mellitus. 2020;23(1):4-11
A prospective randomized controlled trial of bone metabolism in patients with charcot foot
Zaitseva E.L., Tokmakova A.Y., Zhilyaev V.M., Malysheva N.M., Sazonova N.I., Galstyan G.R., Vorontsov A.V.

Abstract

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot’s foot) - is a progressive destructive inflammatory disease of the osteoarticular apparatus of the foot, untimely and inadequate treatment of which can lead to the formation of gross deformities. More often, DNOAP is unilateral, bilateral lesion is relatively rare. It is not always possible to trace the relationship between the debut of DNOAP with trauma and chronic hyperglycemia. There is data demonstrating the role of individual pro-inflammatory factors in the pathogenesis of DNOAP, however, studies combining the evaluation of various metabolic markers of Charcot’s foot formation are currently extremely poor.

AIM: To evaluate the hormonal and metabolic markers of bone formation and resorption in patients with DNOAP and without this diabetic complication.

METHODS: A prospective, controlled trial included 70 patients with type 2 diabetes mellitus (37 men and 43 women) who formed 2 groups: group 1 included patients with DNOAP, group 2 was formed by patients with diabetes without foot skeleton damage. All patients underwent a study of 1,25-OH-vitamin D, sclerostin, pro-MMP-1, C-terminal propeptide type 1 collagen (PICP), type 1 collagen, osteocalcin, PTH, 25-OH-vitamin D, beta-cross-slaps.

RESULTS: The results of the studies confirmed the presence of vitamin D deficiency in all patients with diabetes mellitus included in the study, revealed the absence of statistically significant differences between the groups in the values of sclerostin, pro-MMP-1; 25-OH-vitamin D, type I collagen, and osteocalcin (p > 0.05). However, significant differences were found in the 1.25-OH vitamin D levels: patients with DNOAP presented the lower rates of 1,25-OH-vitamin D in comparison to control group (p <0.05). Beta-cross and PICP levels were significantly higher in DNOAP patients as well (p <0.05). Those findings show the more severe collagen degradation in patients with DNOAP and can be the genetically predisposed cause of DNOAP development. Though further studies are needed.

CONCLUSION: In patients with DNOAP a decrease in 1,25-OH-vitamin D levels was found, as well as the alteration of the synthesis and destruction of collagen (beta-cross-slaps and PICP) compared to patients with diabetes mellitus without osteoarticular disorders.

Diabetes mellitus. 2020;23(1):12-18
Keratinocytes differentiation and wound healing in rats with streptozotocin – induced diabetes and severe hyperglycemia
Ivanov E.V., Morozova M.P., Rzhavina E.M., Gorbacheva A.M., Gavrilova S.A., Erdiakov A.K., Galstyan G.R., Koshelev V.B.

Abstract

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing.

AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model.

MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17.

RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds.

CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation.

Diabetes mellitus. 2020;23(1):19-28
MRI of the arterial wall in resistant hypertension associated with type 2 diabetes mellitus
Ryumshina N.I., Falkovskaya A.Y., Gusakova A.M., Mordovin V.F., Usov V.Y.

Abstract

BACKGROUND: Damage of arterial walls in diabetes mellitus associated with arterial hypertension is major factor delivering lesion of target organs. Currently, enough data is not available about imaging and quantitative evaluations of arterial wall. There is no enough data available about the relations between MRI and inflammatory and metabolic markers in patients with resistant arterial hypertension concomitant with diabetes mellitus.

AIMS: Quantitative assessment of the intensity of paramagnetic contrast enhancement of the arterial wall, in particular renal arteries walls, in relation with inflammatory and metabolic markers in patients with resistant arterial hypertension concomitant with diabetes mellitus.

MATERIALS AND METHODS: The study groups were comprised of 28 patients (ageing 60,7±6,5 years) with resistant hypertension accompanied with diabetes mellitus and 17 patients (aging 57,7±5,0 years) with resistant hypertension without diabetes mellitus. The average systolic/diastolic pressure obtained from a 24-h monitor study was as high as 156,8±16,9/81,9,0±13,5 mm Hg in the group with diabetes and 154,8±11,9/88,5±10,4 mm Hg in the group without diabetes. The values of glycaemia, the level of glycated haemoglobin, and C-reactive protein were determined. The MRI studies were carried out using 1,5 Т MRI Toshiba Vantage Titan scanner. After that, the intravenous contrast enhancement has been carried out (with 0,5 М paramagnetic, as 0,2 ml/Kg). The index of enhancement (IE) was then calculated from these data, as a ratio of intensities of contrast-enhanced image to the initial nonenhanced MRI scan.

RESULTS: The correlation was obtained for IE of arterial wall and data of blood pressure. Increased IE was correlated with ageing and hemodynamic factors. Also the correlation was observed for IE proximal, medium and distal parts of renal arteries and values of glycaemia and NOMA-index were obtained. Negatively correlated values for IE and adiponectin in the group with diabetes mellitus were obtained. The association between IE and C-reactive protein remained significant in the group without diabetes mellitus.

CONCLUSIONS: MRI with contrast enhancement of arterial walls allows evaluating the anatomy of renal arteries and allows quantifying the pathophysiologic factors of their walls in patients with resistant hypertension accompanied with diabetes mellitus. MRI characteristics of the arterial wall were associated not only with hemodynamic and metabolic data, but also with markers of inflammation.

Diabetes mellitus. 2020;23(1):29-36
Perioperative glycemic control in patients with coronary artery disease and diabetes mellitus type 2 undergoing coronary artery bypass grafting: results of pilot study
Golukhova E.Z., Bulaeva N.I., Lifanova L.S., Pugovkina Y.V.

Abstract

BACKGROUND: According to different studies, diabetes mellitus type 2 (DM2) is associated with higher mortality after undergoing coronary artery bypass grafting (CABG). Perioperative hyperglycaemia, even in non-DM2 patients, is associated with adverse outcomes after CABG. Thus, successful perioperative blood glucose control (BGC) is mandatory to reduce the risk of death and postoperative complications. Nowadays, the most effective method for BGC in the operating room is still unknown.

AIMS: To assess the continuous glucose monitoring (CGM) efficacy in association with insulin pump therapy in patients with coronary artery disease (CAD) and DM2 undergoing CABG in intra- and early postoperative periods.

METHODS: The study involved 97 patients undergoing isolated CABG. Patients were divided into two groups: 48 patients with DM2 and 49 patients without DM2. In both groups of patients, we used CGM in intra- and early postoperative periods (72 hours). In some patients with DM2, CGM was associated with insulin pump therapy (MiniMed Paradigm Veo 554/754) to successfully control postoperative glucose level. Besides commonly used tests (such as HbA1C and lipid profile), we analysed high sensitive C-reactive protein (hs-CRP) levels before surgery, and then at 1 hour, 12 hours and 7 days after CABG in order to estimate their prognostic value.

RESULTS: During the 48 hours after CABG, there was a trend towards having higher glucose levels in both groups of patients with and without DM2 according to CGM. In patients with DM2, the glucose level was significantly increased (р<0,05). Insulin pump therapy resulted in glycemic control improvement in early follow-up (72 hours). Moreover, there were no hypoglycaemic episodes in patients on insulin pump therapy and also in patients prescribed bolus insulin therapy. We revealed the trend towards lower rate of postpericardiotomy syndrome (PCTS) in patients on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (p=0,1). Hs-CRP level was lower in patients with DM2 who were on insulin pump therapy compared to patients prescribed bolus insulin therapy in the early postoperative period (р<0,05). This most likely confirms that insulin pump therapy decreases systemic inflammatory response.

CONCLUSIONS: Thus, we demonstrated the CGM feasibility, safety and efficacy in association with insulin pump therapy in patients with DM2 undergoing CABG.

Diabetes mellitus. 2020;23(1):37-45
Life satisfaction, disease management attitudes and nutritional status of diabetes mellitus patients in Azad Kashmir, Pakistan: a hospital based cross-sectional study
Jalil A., Usman A., Akram S., Zulfiqar N., Arshad W.

Abstract

BACKGROUND: The life satisfaction of diabetes mellitus patients in association with the disease management attitudes and nutritional status have never been investigated yet in Pakistani administered Azad Jammu & Kashmir.

AIM: The purpose of this study is to analyze the patient satisfaction about life with diabetes mellitus in association with disease management and nutritional status.

METHODS: A cross sectional survey was conducted among 496 patients in DHQ hospital, Mirpur Azad Jammu & Kashmir. The questionnaire comprised of two sections: 1) Diabetes Attitude Scale (DAS-3); 2) Patient profile, DM history, nutritional status and dietary habits. The findings are generated by binary logistic regression and multivariate regression analyses.

RESULTS: Overall, 64% of the patients interviewed reported dissatisfaction with their life with DM. Majority of the patients were females (66%), BMI value above 25.0 (56%). Gender male (AOR=1.82; 95%CI=1.15-2.88) and low income (AOR=3.16; 95%CI= 1.13-8.80) and middle income (AOR=4.70; 95%CI=1.52-15.5) were significantly associated with life dissatisfaction. There was higher likelihood of life dissatisfaction among patients with low food intake (AOR=1.82; 95%CI= 1.20-2.76); patients’ belief on: no need of taking insulin to treat their diabetes have a mild disease (AOR=1.56; 95%CI= 1.01-2.41); not much use in trying to have good blood sugar control because complications of diabetes happen anyway (AOR= 1.63; 95%CI= 1.18-2.23); emotional effects of diabetes are small (AOR=1.47; 95%CI= 1.02-2.14); decisions regarding daily diabetes care should be made by the patient (AOR= 2.15; 95%CI= 1.19-3.88).

CONCLUSION: Findings implied the need of organizing counselling sessions for DM patients that promote regular physical activity to improve health and disease management. The consultation and regular visits of a nutritionist may help the patients in achieving better health outcomes.

Diabetes mellitus. 2020;23(1):46-55
Review
Nephroprotective potential of glucagon-like peptide-1 receptor agonists
Shamkhalova M.S., Sklyanik I.A., Shestakova M.V.

Abstract

Patients with diabetes mellitus (DM), which is a key factor in the development of kidney diseases, are increasingly competing for limited healthcare resources. Diabetic kidney disease (DKD) remains a significant cause of end-stage renal failure in the patients of many countries and is also associated with a high risk of cardiovascular pathology and mortality. The variety of clinical phenotypes of DKD in patients with type 2 diabetes mellitus (DM2) occurring due to a variety of pathogenetic factors and the characteristics of the evolution of complications under the influence of contemporary therapeutic methods, has been a special subject of discussion in recent years. Optimal control of the level of glycaemia and hypertension and timely blockade of the renin–angiotensin–aldosterone system do not provide sufficient protection for the kidneys. Over the recent decade, the nephroprotective potential of a group of modern anti-hyperglycaemic agents, i.e., glucagon-like peptide 1 receptor agonists (GLP1 RA) has been actively discussed. GLP1 RA have proven to be quite effective in controlling glycaemia and metabolic syndrome components (weight, systolic blood pressure and lipid profile) and in significantly reducing the risk of the primary, three-component endpoint (major adverse cardiac events: cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) according to large studies on cardiovascular safety. The renal effects of GLP1 RA are attributed to a wide range of direct and indirect effects of glucagon-like peptide-1 on renal structures and functions owing to their anti-inflammatory, anti-oxidant and anti-apoptotic properties.

Diabetes mellitus. 2020;23(1):56-64
Non- high-density lipoprotein cholesterol and cardiovascular disease in patients with diabetic dyslipidaemia
Zambon A.

Abstract

Elevated levels of blood lipids are one of the major risk factors for cardiovascular (CV) disease in patients with type 2 diabetes mellitus. Diabetic dyslipidaemia is characterised by the presence of potentially atherogenic lipids, including high levels of plasma triglycerides (TGs), mild-to-moderately elevated levels of low-density lipoprotein cholesterol (LDL-C), and low levels of high-density lipoprotein cholesterol (HDL-C). Statin therapy to reduce LDL-C levels is the mainstay of treatment practice to reduce CV risk. However, despite achieving targets for LDL-C, patients with diabetic dyslipidaemia remain at a high risk of residual CV events. Hence there is a need to target other components (i.e. elevated TGs) of the atherogenic dyslipidaemia that are not affected by treatment with statins. This review highlights the clinical benefits of using non-HDL-C, a single marker that includes all atherogenic lipoproteins, as a leading treatment target to reduce the residual CV risk.

Diabetes mellitus. 2020;23(1):65-71
Hypoglycemia and the risk of cognitive impairment and dementia in elderly and senile patients with type 2 diabetes
Ostroumova O.D., Surkova E.V., Goloborodova I.V., Starodubova A.V., Kochetkov A.I., Kiknadze T.D., Galstyan G.R.

Abstract

Research results show that poor glycemic control and recurrent episodes of severe hypoglycaemia are associated with a decrease in cognitive function in elderly people with type 2 diabetes mellitus (T2DM). On the other hand, patients with diabetes mellitus associated with cognitive impairment/dementia are most at risk of developing hypoglycaemic conditions. It is obvious that the relationship between hypoglycaemia and dementia is very complex and has a mutually aggravating nature.

Studies also show that individuals of older age groups with diabetes and cognitive impairment have a high risk of developing hypoglycaemic conditions, such as unwanted side effects from glucose-lowering therapy. In this case, of particular interest is the question that is being actively studied at the present time, which is concerning the effect of different groups of glucose-lowering antidiabetic drugs on the cognitive status and the rate of cognitive decline in diabetic patients with cognitive impairment.

In this review, we attempted to summarise, systematise, and present data available in the literature concerning the effect of hypoglycaemia on the risk of cognitive impairment and dementia in elderly and senile patients with type-2 diabetes, as well as the degree of participation in this process of of various groups of sugar-lowering antidiabetic drugs.

Diabetes mellitus. 2020;23(1):72-87
Biomarkers for diabetic retinopathy
Budzinskaya M.V., Lipatov D.V., Pavlov V.G., Petrachkov D.V.

Abstract

A data analysis on the actual direction of biomedicine, the study of biomarkers in diabetic retinopathy (DR), was done. Biomarkers identification is important for screening, diagnosis, monitoring, prevention and prediction of the clinical response of the patient to the treatment. In addition, studying the biomarkers allows increase of the effectiveness and safety of using various treatment options. The review examines two main groups of biomarkers, molecular and visualised, which shows the current state of the problem and the prospects for studying biomarkers in the context of the DR treatment. Nowadays, searching for and finding new biomarkers is important and will allow us to develop individual treatment regimens for DR and personalised medicine in an interdisciplinary aspect: ophthalmology and endocrinology.

Diabetes mellitus. 2020;23(1):88-94
Diabetic retinopathy: history, modern approaches to management, prospective views of prevention and treatment
Demidova T.Y., Kozhevnikov A.A.

Abstract

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus (DM). As DR progresses, it could be complicated with a significant decrease or complete loss of vision. It is the leading cause of blindness in the working-age population and, according to global estimates, occurs in one in every three patients with diabetes. DR has been studied for more than 160 years, and the implementation of retinal laser coagulation into clinical practice in the 20th century, and then vascular endothelial growth factor (VEGF) inhibitors in the 21th century, allowed us to influence vascular proliferation in DR and reduce the risk of vision loss from diabetic macular oedema (DME). However, these tools can only stop the progression of DR at the stages with risk of complications with vision loss, and prevention – screenings and the impact on risk factors (hyperglycaemia, arterial hypertension, and dyslipidemia) – remains as the main method of management of DR. Possible new risk factors (hypodynamy, obesity, body weight deficiency, and obstructive sleep apnoea syndrome) attract a lot of attention, and there is ongoing research for early markers of DR in the fundus, which could allow more active influence on the pathological process in its early stages. This review focuses on epidemiology, history of research, proven and possible risk factors, and current and promising approaches to the prevention and treatment of DR, including accurate, less traumatic laser techniques (PASCAL, NAVILAS, and D-MPL), and intravitreal antiangiogenic drugs in studies.

Diabetes mellitus. 2020;23(1):95-105
News
What are new opportunities for clinical practice the VERIFY study opens and which values for native diabetes patients? Joint conclusion on the advisory board results. November 6, 2019
Shestakova M.V., Antsiferov M.B., Ametov A.S., Galstyan G.R., Demidova T.Y., Zilov A.V., Markova T.N., Petunina N.A., Chernikova N.A., Shamkhalova M.S.

Abstract

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications.

However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target.

A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients.

Diabetes mellitus. 2020;23(1):106-110