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Vol 64, No 5 (2018)

Original Studies

The variability of glycemia in patients with type 1 diabetes mellitus: a relationship with cognitive dysfunction and the results of magnetic resonance methods

Samoilova I.G., Rotkank M.A., Zhukova N.G., Matveeva M.V., Tolmachev I.V., Kudlai D.A.

Abstract

BACKGROUND: today the variability of glycemia is an important problem in achieving control over diabetes mellitus. Cognitive dysfunction is one of the complications of this disease. It can be assumed that the basis of cognitive impairment, as manifestations of diabetic encephalopathy, is the influence of the variability of glycemia not only on the anatomical structure, but also on the metabolic composition of the brain tissue.

AIM: to study the measures of glycemic variability, as well as their relationship with the results of neuropsychological testing and magnetic resonance methods in patients with type 1 diabetes mellitus.

MATERIALS AND METHODS: a one-stage (cross-sectional), one-center comparative study of patients with type 1 diabetes mellitus and persons without diabetes, comparable in sex and age, was conducted. All participants underwent neuropsychological testing, magnetic resonance imaging and proton magnetic resonance spectroscopy of the brain, were determined fasting plasma glucose and glycated hemoglobin. Patients with type 1 diabetes mellitus had continuous monitoring of glycemia, according to which the measures of glycemic variability were calculated. The statistical processing of the results is performed in the IBM SPSS Statistics 20.0 program.

RESULTS: 58 patients with type 1 diabetes mellitus and 20 persons without diabetes comparable in sex and age were examined, there was a decrease in scores in the performance of neuropsychological testing (p <0.05), according to the results of magnetic resonance imaging –  a decrease in the gray matter volume (p = 0.004) and an increase in white matter volume (p = 0.001), according to the proton magnetic resonance spectroscopy – a number of clinically significant changes in the metabolic composition of brain cells (p <0, 05).For patients with type 1 diabetes mellitus, the measures of glycemic variability were studied. Correlation links were found between the total result of the MoCa test and the LI (r = -0.34, p = 0.008), MODD (r = -0.36, p = 0.005) and ADRR (r = -0.28, p = 0.032).A negative relationship was found between the CONGA and hippocampal volume on the left (r = -0.27, p = 0.044). A number of correlations between the measures of glycemic variability and the content of major metabolites in different regions of the brain were also revealed (p <0.05).

CONCLUSIONS: in patients with type 1 diabetes mellitus and the presence of cognitive dysfunction, anatomical and metabolic disorders of the brain statistically associated with the variability of glycemia were revealed.

Problems of Endocrinology. 2021;64(5):
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Mechanisms of wound healing in rats with streptozotocin-induced diabetes mellitus

Ivanov E.V., Gavrilova S.A., Morozova M.P., Klochikhina E.M., Erdiakov A.K., Gorbacheva A.M., Dzhemilova Z.N., Artemova E.V., Galstyan G.R., Koshelev V.B.

Abstract

BACKGROUND: The lack of fundamental knowledge about the role of nervous system on the physiological tissue repair  determine the applicability of pathogenetic aspects studying of wound healing formation. It was noted that the disturbance of wound healing and the formation of a diabetic foot, a severe disabling complication of diabetes mellitus, is accompanied by disorders of the nervous system and / or ischemia.

AIM: to study the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin model of diabetes mellitus in rats.

MATERIALS AND METHODS: The study was performed on male white mongrel rats (n = 70). Animals were wounded 42 days after modeling diabetes by injection of streptozotocin (DM group , in order to reduce mortality, this group received insulin detemir, Levemir®, at a dose of 2 units / kg in saline solution subcutaneously) or after injection of citrate buffer (CB group). Sampling of the skin was carried out on the 8th, 16th and 24th days after modeling the wound. All animals were assessed pain sensitivity. The obtained skin fragments were fixed, dehydrated and paraffin filled in a standard procedure. Sections were stained with hematoxylin and eosin, antibodies specific for Ki67, α1, β1 and β2-adrenoceptors were used for immunohistochemical staining. An intact animal was used as a control group.

RESULTS: In the DM group, the tail withdrawal time on the 56th day significantly increased in comparison with the control group (p = 0.017). In the CB group, a persistent tendency to faster wound healing is observed than in animals with diabetes, the differences are statistically insignificant p = 0.64 because of the wide spread of data in diabetic. The intensity of staining on Ki67 was significantly lower in the group of diabetes mellitus (p = 0.045). In the remote areas of the skin, a progressive decrease in the density of β2-adrenergic receptors was observed in the control group.

CONCLUSION: Morphological data indicate a worsening of regeneration processes, which was not accompanied by a statistically significant reduction in healing. There was no decrease in the density of β2-adrenergic receptors at the edges of the wound in the development of diabetes mellitus. The data obtained gives no evidence that the change in innervation precedes the disturbances in the process of tissue repair in the streptozotocin model of diabetes mellitus in rats.

Problems of Endocrinology. 2021;64(5):
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Kisspeptins Regulation of male sex development: focus on diagnostic and therapeutic opportunities of delay of puberty and hypogonadotropic hypogonadism

Nikitina I., Yuchlina Y., Nagornaya I., Vasileva E.

Abstract

Background. Kisspeptins, ligands of G protein–coupled receptor 54 ( KISS1R) encoded by the KiSS-1 gene, have recently emerged as key players of the gonadotropic axis.

It was found that KiSS-1/ KISS1R system plays an important role in the neuroendocrine control of gonadotropin secretion, brain sex differentiation, puberty onset and fertility.

Objective To investigate   the possible  relation between the serum level of kisspeptin and different stages of puberty in healthy boys and boys with delay of puberty onset  and hypogonadotropic hypogonadism. 

Methods. 43 boys in total were examined. They were divided into  three groups. Group 1 (boys aged 14-17 years with delay of puberty and hypogonadotropic hypogonadism, n=12). Group 2 (control, boys aged 14-18 years with normal puberty, Tanner stages IV-V, n=16). Group 3 (control, prepubertal boys aged 6-10 years, Tanner stage I).

Results. The level of kisspeptin in blood in group 2 and 3 did not have any differences (14,12 + 1,5 pg/ml and 16,27 + 1,44  pg/ml respectively, p>0,05). Unlike the above, the level of kisspeptin in group 1 was significantly higher than in both groups 2 and 3 (43,65 + 9,8 pg/ml  as opposed to 16,27+1,44 pg/ml,   p<0,01; 43,65 + 9,8   pg/ml  as opposed to 14,12+1,5 pg/ml, p<0,01 respectively).

Conclusions. The serum level of kisspeptins was found to be equal in boys, sexually developed regardless of their age and stage of puberty.  In contrast, the level of kisspeptins was significantly higher in boys affected with gonadotropic hypogonadism.  It can be caused by  KISS1R insensitivity or loss of biological activity of kisspeptin. The latter condition can be corrected by novel therapeutic technologies such as treatment with exogenous kisspeptin

Problems of Endocrinology. 2021;64(5):
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FEATURES OF BONE METABOLISM (SCLEROSTIN, KATESININE K) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND POSTMENOPAUSAL OSTEOPOROSIS.

Nurullina G., Akhmadullina G.

Abstract

Backgraund:deterioration of bone quality in type 2diabetes mellitus leads to a decreased strength and an increased risk of low-energy fractures.

Aims:to study the features of bone metabolism in patients with type 2 diabetes mellitus and postmenopausal osteoporosis.

Materials and methods:102 women in the postmenopausal period at the age of 46 to 67 years were examined. All patients were divided into 4 groups: 39 patients with type 2 diabetes (T2DM) and postmenopausal osteoporosis (PO) in the first group, 25 patients with PO in the second group, 21 patients in the third group with T2DM, in the fourth group (control) - 17 people. The study of ionized calcium, phosphorus, total alkaline phosphatase (ALP), parathyroid hormone, 25 (OH) vitamin D, bone mineral density was performed in the first three groups, sclerostin and cathepsin K was performed in the first, second and control groups.

Results: there was no significant difference in sclerostin levels between groups, apositive association was found between sclerostin and НВА1с (r = 0.43, p = 0.009) in the group of patients with T2DM and PO, a negative association was found between sclerostin and ionized calcium (r = -0.45, p = 0.037)in the group of patients with PO. The level of cathepsin K in the group of T2DM and PO was significantly lower than in the level in the PO group (p = 0.046). In the groups with diabetes there was a lower level of 25 (OH) vitamin D. The ALP in the group of T2DM was significantly lower than in the PO group (p = 0.022). The total alkaline phosphatase in the groups with CD2 was significantly lower than in the PO group, and negatively correlated with the duration of the menopause..

Conclusions: lower bone metabolism in type 2 diabetes mellitus  is one of the pathogenetic mechanisms of bone strength reduction.

Problems of Endocrinology. 2021;64(5):
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Reviews

On the connection of diabetes mellitus type 2 with air pollution by particulate matter

Kolpakova A.F., Sharipov R.N., Volkova O.A.

Abstract

We review the contemporary literature data about the connection of air pollution by particulate matter (PM) with diabetes mellitus (DM) type 2 depending on their size, origins, chemical composition, and concentration in air by using the PubMed and RSCI databases. Traffic-related PMs, which contains transition metals, are recognized as most dangerous. Long-term exposure to high concentrations of fine and ultrafine PM is associated with increased risk of morbidity and mortality from DM type 2. Short-term exposure to PM causes the oxidative stress in lungs that leads to vascular insulin resistance and inflammation. PM-induced oxidative stress is the central trigger of inflammatory reactions leading to development of systemic inflammation. Exposure to fine PMs considerably increases expression of proinflammatory genes and corresponding signaling pathways. Numerous experimental studies and mathematical models confirmed capability of PM to unbalance glucose homeostasis, increase inflammation in adipose tissue, liver, and central nervous system. Up to date, the role of PM in the pathogenesis of DM type 2 is not clear, and the entire scheme of underlying molecular and cellular interactions has not been completed so far. Application of the formalized description approach to reconstruction of the PM-related network will help to reach better understanding of the air pollution role in the pathogenesis of human diseases, particularly, DM type 2. This understanding can facilitate to improve the existing therapies and preventive medicine.

Problems of Endocrinology. 2021;64(5):
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Klinefelter syndrome in children and adolescents (review)

Bespalyuk D.

Abstract

Klinefelter syndrome is the most common sex chromosomal abnormality and the most frequent form of primary male hypogonadism. The presence of additional X-chromosome in karyotype leads to such most frequent manifestations as infertility, azoospermia, small testicular volume, high levels of gonadotropins and low testosterone level, tall stature with disproportional body shape, learning difficulties and speech-language disorders. Despite the high incidence of the syndrome, only 25% of patients learn about their disease during life. Late diagnosis and untimely treatment are often caused by severe clinical disease polymorphism, different symptom onset times in patients, and a high incidence of associated conditions, in connection with which patients can be observed by different specialists without knowing the underlying diagnosis.

This review presents data on the history of the study, the etiology of the syndrome, clinical and laboratory parameters characteristic of childhood, adolescence and adulthood. The most common concomitant diseases are highlighted and current data on their prevalence, as well as the effect of testosterone replacement therapy on them, are presented.

Problems of Endocrinology. 2021;64(5):
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Androgen sensitivity - beyond the well-known: literature review.

Khripun I., Vorobyev S.

Abstract

The attention of researches in recent years has been attracted to the study of gonadal and extragonadal effects of testosterone in men. One of the mechanisms via the effects of T may be implemented is the CAG repeat polymorphism within the androgen receptor gene, conditioning androgen sensitivity. In this review, we extensively discuss the literature data on the effect of polymorphism of the androgen receptor gene on embryogenesis and sex differentiation, regulation of spermatogenesis, progression of prostatic cancer and benign prostatic hyperplasia, hypogonadism, control of carbohydrate and lipid metabolism, bone mineral density, endothelial function, response on testosterone replacement therapy, as well as psycho-social aspects of a man's personality.

Problems of Endocrinology. 2021;64(5):
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Perspectives of application of intranasally administered insulin for correction of metabolic and hormonal disorders in diabetes mellitus and metabolic syndrome

Shpakov A.O., Derkach K.V., Surkova E.V., Bespalov A.I.

Abstract

In recent years, the possibility of using intranasally administered insulin to treat Alzheimer's disease and other cognitive disorders has been widely studied. At the same time, the possibility of its use in the treatment of diabetes mellitus is practically not investigated, which is due to the insufficient study of the molecular mechanisms of its action on the hormonal and metabolic status of the organism. The review discusses literature data and the results of our own research on the role of insulin in the central regulation of energy homeostasis, as well as on the experience of using intranasally administered insulin to correct eating disorders and metabolic and hormonal dysfunctions developing under conditions of experimental diabetes mellitus and metabolic syndrome. In studies involving healthy volunteers, various effects of intranasally administered insulin were shown, including effects on cognitive function, eating behavior and weight loss, and the gender specificity of its action was found. In the course of numerous studies of intranasally administered insulin in animal models of diabetes mellitus, not only stabilization of carbohydrate homeostasis was shown, but also a positive effect in the form of restoration of the functional activity of insulin signaling pathways in the hypothalamus and other parts of the brain. We have presented and analyzed data on the systemic effects of intranasally administered insulin in rodents with experimental models of diabetes mellitus, as well as in healthy individuals.

Problems of Endocrinology. 2021;64(5):
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Case Reports

Differential diagnosis of congenital hyperinsulinism histological form using [18F]-DOPA PET/CT

Gubaeva D., Melikian M., Ryjkova D., Mitrofanova L., Nikitina I.

Abstract

Backgraund: Congenital hyperinsulinism (CHI) is a complex condition, which is caused by hyperproduction of insulin by pancreatic β-cells. The care management is strongly depends on the histological form of the disease.
Aims: Differential diagnosis of congenital hyperinsulinism histological form using [18F]-DOPA positron emission tomography (PET) with computed tomography (CT) in patients with pharmacoresistant CHI.
Materials and methods: [18F]-DOPA PET/CT was performed in 17 patients with pharmacoresistant CHI. Subsequently, [18F]-DOPA PET/CT results were compared with the morphological study of postoperative pancreatic tissue which is known as the "gold standard" for differential diagnosis of histological forms of CHI.
Results: Diffuse form of CHI was diagnosed in 7 of 17 patients based on the results of [18F]-DOPA PET/CT, the focal form was found in the remaining 10 patients. In patients with focal disease, the median pancreatic ratio 50-60 minutes after [18F]-DOPA injection was 1.64 (from 1.14 to 3.51). Moreover in this group of patients local accumulation of radioactive tracer on PET images was visually observed. In patients with diffuse form of CHI, the median pancreatic ratio 50-60 minutes after [18F]-DOPA injection was 1.15 (from 1.02 to 1.42). The expected morphological form of CHI was confirmed by histological study in 16 children after the surgical treatment. In one patient the surgery and histological study was not performed due to relatively stable euglycemia.
Conclusions: Results of PET/CT with [18F]-DOPA in patients with CHI should be analyzed using both visual and design parameters.
Problems of Endocrinology. 2021;64(5):
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Positron emission tomography, combined with computed tomography with 18F-fluorocholine in topical diagnosis of parathyroid glands tumors and secondary changes in bone tissue in hyperparathyroid osteodystrophy. Two clinical observations.

Mokrysheva N., Krupinova J., Dolgushin M., Odzharova A., Voronkova I., Voskoboynikov V., Kuznecov N.

Abstract

Primary hyperparathyroidism (PHPT) in 1% of cases is caused by parathyroid carcinoma (PC). The outcomes of the PC depend on quantitative processing and adequacy of the initial surgery.

A major difficulty is to differentiate PC metastasis in bones from hyperparathyroid osteodystrophy.

This article describes clinical cases of patients with severe form of PHPT accompanied by hyperparathyroid osteodystrophy, that was suspected to be cancer metastasis. The positron emission tomography combined with computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDH) and/or 18F-fluorocholine was included in the algorithm of the examination. The histological examination of postoperative material confirmed benign tumors of the PG in both patients, and bone lesions detected during PET/CT were assessed as hyperparathyroid osteodystrophy. 

Accumulation of 18F-fluorocholine in bone destruction areas does not allow to differentiate hyperparathyroid osteodystrophy from metastases. In both cases, the accumulation of 18F-fluorocholine was detected only in the tumor.

Problems of Endocrinology. 2021;64(5):
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Description of the first case of a rare form of isolated deficiency of glucocorticoids due to mutations in the gene NNT

Chernyak I., Kalinchenko N., Tlif A., Kleshenko E., Petrov V., Vasiliev E., Tyulpakov A.

Abstract

Familial glucocorticoid insufficiency of FGD, MIM * 202200 – a rare  form of the primary chronic adrenal glands deficiency (PCED), characterized by resistance of adrenal cortex to AKTG, reduction in secretion of glucocorticoids and adrenal androgens. Currently at least7 genes are described in which mutations lead to development of SGN : MC2R, MRAP, STAR, CYP11A1 [2,3] NNT, TXNRD2, AAAS. For the first time a mutation in NNT gene described by Meimaridou , E., Kowalczyk, J in 2012,  one  patient at molecular and genetic inspection without clinics,  9  patients has clinical picture SGN. Determine the exact cause of the occurrence of PHNN allows to modify the carried-out treatment, to forecast development of possible complications and the associated  violations  of the functions other  bodies, and also carrying out medical genetic counseling for the family.

Problems of Endocrinology. 2021;64(5):
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