Vol 22, No 1 (2019)

Original Studies
Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study
Mokrysheva N.G., Dobreva E.A., Mirnaya S.S., Dedov I.I.
Abstract

Background: Patients with primary hyperparathyroidism (PHPT) have increased mortality risk predominantly attributed to cardiovascular disease. Taking the risk factors for cardiovascular disease into account, such as overweight, atherogenic dyslipidaemia, carbohydrate metabolism disorders and insulin resistance (IR), investigation on the the study of the state of carbohydrate and lipid metabolism in patients with PHPT will help to shed light on the pathogenic mechanisms of the disease and, perhaps, to complement the algorithm for selecting treatment strategies for patients with PHPT.

Aims: To study the prevalence of carbohydrate and lipid metabolism disorders among patients with PHPT and to identify the relationship between these two disorders with the indicators of mineral metabolism.

Materials and methods: A case-control study of a total of age-matched 256 female patients, 220 patients with PHPT and 36 healthy individuals. The group patients with PHPT were sub-divided into two groups, symptomatic and mild form of PHPT. To verify the form of PHPT, ultrasound examinations of the parathyroid glands and kidneys, two-energy x-ray absorptiometry, biochemical studies (concentration of total and ionised calcium, serum phosphorus and the activity of alkaline phosphatase) and assessment of parathyroid hormone concentration were performed. The relationship between form of PHPT and body weight were evaluated retrospectively according to the survey. Among the 109 participants with PHPT (symptomatic PHPT: 82 patients; mild PHPT: 27 patients) and healthy individuals, the biochemical and hormonal parameters of fat (lipid spectrum of blood) and carbohydrate metabolism (content of immunoreactive insulin, HOMA index, presence of fasting glycemia disorder, glucose tolerance disorders and type 2 diabetes mellitus) were evaluated.

Results: The symptomatic PHPT was associated with low body mass index (BMI) while the mild PHPT with high BMI. During an oral glucose tolerance test, the postprandial glycemia in symptomatic PHPT was significantly higher than that in mild PHPT (p = 0.036). The content of immunoreactive insulin in the symptomatic PHPT was not correlated with the concentration of parathyroid hormone, but positively correlated with the concentration of ionised calcium in the blood (r = 0.31; p = 0.006). Patients with PHPT showed a direct positive correlation between BMI and IR index (r = 0.67; p < 0.001). It is shown that patients with PHPT have increased LDL content in the blood, and the actual blood lipid concentration is associated with the state of kidney function.

Conclusions: The obtained data confirm the relationship between phosphorus–calcium metabolism disorders in PHPT and carbohydrate and lipid metabolism disorders. Prospective, controlled studies are warranted to better elucidate the causal relationships of mineral, carbohydrate and fat metabolism disorders in PHPT.

Diabetes mellitus. 2019;22(1):8-13
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Symptomatic and silent cerebral ischemia (detected on MRI) in patients with type 2 diabetes mellitus after carotid revascularization procedures
Tanashyan M.M., Antonova K.V., Medvedev R.B., Skrylev S.I., Krotenkova M.V., Romantsova T.I.
Abstract

Background: Type 2 diabetes mellitus (T2DM) is a significant independent risk factor for ischaemic stroke. Carotid revascularisation procedures are an effective method of primary and secondary stroke prevention. However, patients developed postoperative acute ischaemic lesions (AILs), which were identified via magnetic resonance imaging (MRI) of the brains. Most of the patients with these AILs lack clinically overt symptoms.

Aims: To assess the risk of ischaemic brain damage in patients with T2DM in the setting of carotid angioplasty with stenting (CAS) or carotid endarterectomy (CAE).

Materials and methods: This open prospective study comprised of 164 patients with carotid atherosclerosis, who have undergone either CAS or CAE. Patients with T2DM were included in Group 1: 38 patients and 28 patients with CAE. Group 2 included patients without T2DM: 62 patients with CAS and 36 patients with CAE. All patients underwent a thorough neurological examination and diffusion-weighted brain MRI. In patients with T2DM, plasma glucose levels and glycated haemoglobin (HbA1c) were determined and their relationships to brain damage were evaluated.

Results: In CAS, there were no statistically significant differences in the AIL frequency in patients with and without T2DM. AILs were found in 15 patients with T2DM (39.8%) and 29 patients without T2DM (46.8%, р = 0.24); three patients without T2DM were diagnosed with stroke. Of the 28 patients with T2DM who underwent CAE, 13 had AIL (46.4%); three had stroke (10.7%). In patients without T2DM, AILs were less prevalent in seven cases (19.4%, р = 0.012) and appeared asymptomatic. Following CAS, the baseline HbA1c levels were higher in patients with T2DM who developed AILs compared to those who did not develop AIL, 7.8% ± 1.4% vs 7.1 ± 1.1% (р = 0.0469). Negative impact of hyperglycaemia on the risk of cerebral ischaemia was observed in patients who underwent CAE, the baseline fasting plasma glucose level was 8.5 ± 1.9 mmol/l vs 7.0 ± 1.5 mmol/l in patients without AIL (р = 0.014). The baseline HbA1c levels in patients with and without AILs were 8.0% ± 1.7% and 6.9% ± 0.9% respectively (р = 0.023).

Conclusions: Carotid revascularisation procedure for patients with carotid atherosclerosis may be associated with risk of stroke and asymptomatic acute cerebral ischaemic lesions, which are more prevalent in patients with T2DM. Also, increased HbA1c levels is a risk factor for AIL.

Diabetes mellitus. 2019;22(1):14-24
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Features the interaction of functional and metabolic remodeling of myocardium in comorbid course of ischemic heart disease and 2 type diabetes mellitus
Afanasiev S.A., Kondratieva D.S., Egorova M.V., Akhmedov S.D., Budnikova O.V., Popov S.V.
Abstract

Background: Metabolic and structural changes in cardiomyocytes in diabetes mellitus lead to aggravation of contractile myocardial dysfunction in coronary heart disease (CHD). The contractility dysfunction of cardiomyocytes is determined by a change in the levels of sarcoplasmic reticulum (SR) Ca2+-ATPase and energetic supply of the cardiomyocytes.

Aims: To study the features of functional remodeling of the heart muscle in coronary heart disease with and without type 2 diabetes mellitus (DM2) depend on the level of Ca2+-ATPase and the activity of enzymes involved in energy metabolism.

Materials and methods: The work was performed on the heart biopsy of patients with CHD and patients with CHD combined with DM2. The inotropic reaction of myocardial strips on rest periods was assessed. The expression level of Ca2+-ATPase, the activity of enzymes succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) and the intensity of oxidative phosphorylation processes were determined.

Results: The interval-force relationship in patients with CHD with and without DM2 had both negative and positive dynamics. The positive dynamics corresponds to the "high content" of the Ca2+-ATPase and the negative dynamics corresponds to the "low content" were found. At the combined pathology the positive inotropic dynamics is more pronounced and corresponds to a higher protein level. In the patients myocardium with CHD the activity of SDH and LDH was higher, while the oxygen uptake rate by mitochondria was higher in the myocardium with combined pathology.

Conclusions: The potentiation of inotropic response of patient myocardium with CHD with and without DM2 corresponds to the "high level" of Ca2+-ATPase. In the combined pathology the inotropic capabilities of the myocardium are more expressed. In CHD the synthesis of ATP in cardiomyocytes is realized mainly due to glycolytic processes and Krebs cycle. In combined pathology the ATP synthesis is realized to a greater extent due to the oxidative phosphorylation.

Diabetes mellitus. 2019;22(1):25-34
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Interdisciplinary cooperation between dentists and endocrinologists for identification and management of diabetes mellitus
Maslak E.E., Naumova V.N.
Abstract

Background: DM mellitus (DM) leads to worsening periodontal diseases, and in turn the inflammatory diseases of maxillofacial region adversely affect the glycemic control and exacerbate the severity of DM, thereby engendering a vicious cycle that compromises the DM management in patients. Taking account of the bidirectional relationship between DM and periodontal disease, interdisciplinary examination of patients with both DM and periodontal diseases is warranted to improve the health outcomes in patients.

Aims: This study aims to evaluate the perceptions of dentists and endocrinologists on the interdisciplinary cooperation for identification and management of patients with DM.

Materials and methods: Studying patients’ knowledge about DM and their compliance in providing endocrinological recommendations, dental screening survey to identify DM’ risk and signs The research was done in 2015-2016 years using clinical survey (dental status survey), statistical analysis. 432 patients from different dental organizations and 433 doctors (371 – dentists and 62 – endocrinologists) took part in the research. The research was approved by Regional research ethics committee. The written informed consent was taken from each participant.

Results: There was insufficient interdisciplinary collaboration for identification and management of patients with diabetes, and lack of motivation among dental patients to endocrinological survey. Hence, it is important to incorporate definitive screening for risk of DM for patients with inflammatory periodontal disease and include dentists in consultation for patients with DM. The feasibility of statutory determination of collaboration between specialists in identification and management of patients with DM was found, dental lectures are necessary in DM school.

Conclusions: Our findings suggest the necessity of including dentists in the standard of medical management of patients with DM and incorporating DM screening by a questionnaire upon dental examination.

Diabetes mellitus. 2019;22(1):35-43
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Dynamics of heart rate variability in rats with streptozotocin-induced diabetes
Morozova M.P., Gavrilova S.A., Ivanov E.V., Gorbacheva A.M., Rzhavina E.M., Erdyakov A.K., Dzhemilova Z.N., Artemova E.V., Tokmakova A.Y., Koshelev V.B., Galstyan G.R.
Abstract

Background: Diabetes mellitus (DM) has a negative impact on all organs. This is due to insufficiency of blood supply and the disruption of the trophic function of the nervous system. One of the most serious complication of DM is diabetic foot caused be vascular and neurological reasons. Correction of vascular disorders is effectively treated by modern therapeutic approaches, but the damage of nervous system has been studied insufficiently.

Aims: To investigate the dynamics of damage to the vegetative nervous system on the laboratory model of DM.

Materials and methods: DM in rats was induced by injection of streptozotocin at a dose of 65 mg/kg in citrate buffer (DM group). The control group of rats received a citrate buffer equivalent (CB group). Rats with DM were given a maintenance therapy with insulin in a dose of 2 units/kg/day. On 42 days of experience, a round wound with a diameter of 2 cm on the back of the animals was observed. Before the DM simulation, then on the 42, 50, 58 and 66 days of its development, an electrocardiogram (ECG) was recorded in the rats at a frequency of 2 kHz digitising in a state of calm wakefulness and after cold exposure. For 5 minutes ECG fragments, heart rate and heart rate variability (HRV) in the temporal domain were calculated, characterising: 1) the total heart rate variability (tHRV) according to SDRR, SDHR, KVRR and KVHR; 2) the effect of the parasympathetic department of the autonomic nervous system (aANS) for RMSSD and pNN3; 3) the contribution of the sympathetic department of the ANS (sANS) by SDAvgRR, SDAvgHR. The spectral parameters were estimated in the frequency domain: the total power of the spectrum is TR (range: 0–2.5 Hz), the powers in the low and high frequency ranges are LF (range: 0.2–0.8 Hz) and HF (range: 0.8–2.5 Hz) LF/HF. Weekly, the tail withdrawal time was measured in a temperature pain test (55°C).

Results: During the development of diabetes, the level of glucose in the blood increased 4–7 times compared with the normal level. The reaction time of the pain test in rats with DM increased by 20%–30% at the end of the experiment. At 42 days, the development of bradycardia (267 beats/min) was observed in rats with DM. The indicators of tHRV decreased by a factor of 2 due to a decrease in the contribution of sANS. The reaction to CP in the SD group differs from the norm by the severity of the individual components of the HRV structure, which indicates functional denervation of the heart and the development of diabetic neuropathy.

Conclusions: As the diabetes progressed, signs of neuropathy were observed. The overall HRV parameters decreased, the ratio of the contributions of sANS and pANS to the regulation of heart rate changed, and the temperature sensitivity decreased.

Diabetes mellitus. 2019;22(1):44-52
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Structured exercise program on Foot Biomechanics & Insulin Resistance among people living with type 2 diabetes with and without peripheral neuropathy
Kumar A., Hazari A., Maiya A., Shastry B., Nagiri S., K V.
Abstract

Background: The biomechanical changes in foot among people with type 2 diabetes mellitus often leads to various foot complications which could further add to diabetes related morbidity & mortality. These changes could be seen due to musculoskeletal factor like reduction in intrinsic foot muscle strength, tightness of lower limb muscles, postural changes, etc.

Aim: To design and determine the efficacy of a structured exercise program on foot kinetics and kinematics among type 2 participants

Materials and methods: A total of 35 participants with type 2 diabetes (n=15, type 2 diabetes mellitus without neuropathy and n=20, type 2 diabetes with peripheral neuropathy) were recruited. All participants were screened clinically & biochemically and given a set of structured exercise program, three times a week for 12weeks along with standard medical care.

Results: The mean age of the participants was 56±10.5 (Non neuropathy) 62.3±7.35 (Neuropathy) years, mean duration of diabetes was 8.7±8.95 (Non neuropathy), 10.97±8 (Neuropathy) years, mean Body mass index was 26.54± 4.83(Non neuropathy), 24.39±3.58 (Neuropathy), Significant differences have been observed in kinetic and kinematic variables.

Conclusion: The present study shows that the structured exercise protocol is very effective in improving the biomechanics of foot in people with type 2 diabetes with and without neuropathy. It could help to correct the structure and function of the foot and eventually could reduce the risk of foot complications like diabetic foot ulcers.

Diabetes mellitus. 2019;22(1):53-61
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The effect of OMEGA-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in patients with type 2 diabetes mellitus and cardiovascular autonomic neuropathy
Serhiyenko V.A., Mankovsky B.N., Serhiyenko L.М., Serhiyenko A.A.
Abstract

Background: Cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus (T2DM), which is characterized by lesion of nerve fibers in parasympathetic and sympathetic nervous system is one of the leading causes of heart arrhythmias and an independent risk factor for cardiovascular mortality in patients with T2DM. Therefore, the problem of effective treatment of CAN is particularly relevant.

Aims: To analyze the effect of long-chain polyunsaturated fatty acids (ω-3 PUFAs) on ambulatory blood pressure monitoring parameters in patients with T2DM and CAN.

Materials and methods: 36 patients with T2DM and confirmed CAN were divided into two groups. First group received hypoglycemic therapy (n=15, control) for three months; patients in group 2 (n=21) in addition were administered 1 capsule/q.d. of ω-3 PUFAs for three month.

Results: Treatment with ω-3 PUFAs led to significant decrease of the diastolic blood pressure (DBP) (p<0,01), diastolic blood pressure load (p<0,05), time index of DBP (p<0,05) during the day; DBP (p<0,05), diastolic blood pressure load (p<0,05), time index of DBP (p<0,05), SD DBP (p<0,01) during the night (compared to the control group).

Conclusions: The study showed that prescription of ω-3 PUFAs for three month was effective in decreasing diastolic blood pressure and its parameters among patients with T2DM and CAN.

Diabetes mellitus. 2019;22(1):62-69
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Review
Incretins today: multiple effects and therapeutic potential
Tsygankova O.V., Veretyuk V.V., Ametov A.S.
Abstract

Glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones initially discovered in the 1960s. GIP and GLP-1 have gained great scientific interest due to their properties in increasing insulin secretion and lowering blood glucose levels. The study of these incretin hormones has progressed substantially in recent decades, in that their systemic effects has begun to be actively discussed. In particular, incretins are involved in the pathogenesis of obesity and non-alcoholic fatty liver disease. Moreover, incretins are able to improve cognitive function, suppress the formation of β-amyloid plaques and provide an oncoprotective effect. Recent data show promising oncoprotective effect of GLP-1 agonists on prostate and breast cancer.

This review provides systematisation of recent data on the role and mechanisms of action of incretin hormones on carbohydrate metabolism, as well as effects not related to glucose homeostasis, which contributes to a better understanding of potential vectors for the development of incretinotropic therapy. In addition, this review offers insight into pathogenic prerequisites and highlights the current issues in creating innovative polyagonists for treatment of type 2 diabetes mellitus.

Diabetes mellitus. 2019;22(1):70-78
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Heart failure and diabetes mellitus: insight into comorbidity
Petunina N.A., Trukhin I.V., Trukhina L.V., Sizova Z.M., Zakharova V.L.
Abstract

Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities with a bidirectional relationship. Patients with HF have increased risk of developing DM, and those with DM are at greater risk of developing HF. HF does not fit clearly into the microangiopathy and macroangiopathy groups. It is known that coronary artery disease and arterial hypertension are the major causes of HF; however, it has been shown that DM can trigger functional and structural abnormalities in the myocardium via diabetic cardiomyopathy, a condition with either restrictive or dilated phenotype. While HF treatment is equally effective and safe in patients with and without DM, this statement is not applicable for antidiabetic treatment. Several antidiabetic drugs, such as rosiglitazone, pioglitazone and saxagliptin increase the risk of hospitalisation for HF, therefore these antidiabetic drugs are contraindicated in patients with DM and HF or patients at risk of developing HF. Despite a large number of clinical evidence, uncertainty about the safety of antidiabetic drugs in patients with HF always exists. In this review, the issues of DM treatment in patients with HF are addressed in detail.

Diabetes mellitus. 2019;22(1):79-87
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Case report
Diabetes mellitus associated with the mutation of the ABCC8 gene (MODY 12): features of clinical course and therapy
Ovsyannikova A.K., Rymar O.D., Shakhtshneider E.V., Klimontov V.V., Koroleva E.A., Voevoda M.I.
Abstract

Maturity-Onset Diabetes of the Young (MODY) is a heterogeneous group of diseases associated with genes mutations leading to dysfunction of pancreatic β-cells. Among the 14 identified MODY variants, MODY 1–5 are the most studied. The article reports a MODY 12 clinical case, with mutation in ABCC8, encoding the sulphonylurea receptor. Diabetes mellitus manifested in a 27-year-old man with hyperglycaemia up to 24 mmol/L, without ketosis. Non-proliferative diabetic retinopathy, microalbuminuria, dyslipidaemia and carotid atherosclerosis were revealed upon initial examination. The levels of pancreatic islet cell antibodies and glutamate decarboxylase antibodies were negative, while the level of C-peptide was within the normal range. Insulin therapy in the basal-bolus regimen was provided with a gradual dose reduction due to frequent hypoglycaemia. The preproliferative retinopathy with macular oedema was revealed after 4 months of therapy, and panretinal photocoagulation of both eyes was performed. A molecular genetics study revealed a mutation in the gene ABCC8, the same mutation was found in patient’s mother and uncle. Insulin therapy was cancelled, and the treatment of gliclazide MR 60 mg/day was initiated, which resulted in extreme glycaemic excursions. Thereby, sodium–glucose cotranporter-2 (SGLT2) inhibitor dapagliflozin 10 mg/day was added. A reduction in glucose variability parameters were observed on combination therapy. After 6 months till 1.5 years of treatment, glycaemic control was optimal, no hypoglycaemic episodes were observed. This case study demonstrates clinical features of MODY 12, and the potential of combination of sulfonylurea and SGLT2 inhibitor in the treatment of this disease.

Diabetes mellitus. 2019;22(1):88-94
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