BACKGROUND. Due to its role as a risk factor for the emergence of metabolic illnesses including type 2 diabetes, cardio-vascular disease, and certain cancers with pandemic evolution, obesity is a serious public health concern. Diabetes mellitus type 2 (T2DM) poses a major risk to human health. The byproducts of the breakdown of cholesterol are bile acids, which are crucial for preserving cholesterol homeostasis. Research indicates that bile acids might control insulin sensitivity, energy metabolism, and glucose tolerance. Farnesoid X receptors (FXRs) are crucial for controlling bile acid production and hepatic glucose metabolism. The ligand for FXR The semisynthetic derivative of chenodeoxycholic acid, a bile acid, is obeticholic acid (OCA). Research indicates that bile acids may be a viable therapeutic target for type 2 diabetes (T2DM) given that therapy with oleic acid (OCA) enhanced insulin sensitivity and decreased indicators of liver inflammation and fibrosis in individuals with T2DM and nonalcoholic steatohepatitis (NASH).AIM. To assess Obeticholic acid’s effectiveness in obese individuals with prediabetes.MATERIALS AND METHODS. Over the course of three months, we performed a randomized single blind placebo controlled trial on eighty-two overweight and obese patients with prediabetes in the outpatient clinic at Ain Shams University Hospital. Through block randomization, patients were split into two groups (Group A received daily oral tablets containing 5 mg of obeticholic acid, while Group B received non-sweet capsules as a placebo). Three follow-up visits were conducted to ensure adherence and monitor for any emergence of side effects.RESULTS. 82 patients of matched age and sex criteria who underwent block randomization into 2 equal groups, group (A) representing cases and group (B) the placebo controlled group, with 3 months’ regular follow up showed at end of treatment statistically significant difference in weight being lower in group (A) with p-value 0.004 with decreased parameters of glycemic profile (Fasting insulin, FPG, HOMA_IR, 2h PP, HbA1c) in group (A) with p-value <0.001 except 2hpp which p-value is 0.006. Also ALT was much decreased in group(A) with p-value <0.001. Lipid profile didn’t show significant difference between 2 groups except for TGs which deceased in follow up in group (A) with p-value <0. 001. Additionally, it should be highlighted that there was no statistically significant difference between the control group’s baseline and post-treatment data.CONCLUSION. In individuals who are overweight or obese and have insulin resistance and prediabetes, activation of FXR by OCA results in enhanced insulin sensitivity. Patients who received OCA also lost weight.
{"title":"Obeticholic Acid and Insulin Sensitivity in Overweight Patients with Prediabetes","authors":"H. Amer, M. Nesim, H. Mansour, E. Nasr, N. Ahmed","doi":"10.14341/omet13088","DOIUrl":"https://doi.org/10.14341/omet13088","url":null,"abstract":"BACKGROUND. Due to its role as a risk factor for the emergence of metabolic illnesses including type 2 diabetes, cardio-vascular disease, and certain cancers with pandemic evolution, obesity is a serious public health concern. Diabetes mellitus type 2 (T2DM) poses a major risk to human health. The byproducts of the breakdown of cholesterol are bile acids, which are crucial for preserving cholesterol homeostasis. Research indicates that bile acids might control insulin sensitivity, energy metabolism, and glucose tolerance. Farnesoid X receptors (FXRs) are crucial for controlling bile acid production and hepatic glucose metabolism. The ligand for FXR The semisynthetic derivative of chenodeoxycholic acid, a bile acid, is obeticholic acid (OCA). Research indicates that bile acids may be a viable therapeutic target for type 2 diabetes (T2DM) given that therapy with oleic acid (OCA) enhanced insulin sensitivity and decreased indicators of liver inflammation and fibrosis in individuals with T2DM and nonalcoholic steatohepatitis (NASH).AIM. To assess Obeticholic acid’s effectiveness in obese individuals with prediabetes.MATERIALS AND METHODS. Over the course of three months, we performed a randomized single blind placebo controlled trial on eighty-two overweight and obese patients with prediabetes in the outpatient clinic at Ain Shams University Hospital. Through block randomization, patients were split into two groups (Group A received daily oral tablets containing 5 mg of obeticholic acid, while Group B received non-sweet capsules as a placebo). Three follow-up visits were conducted to ensure adherence and monitor for any emergence of side effects.RESULTS. 82 patients of matched age and sex criteria who underwent block randomization into 2 equal groups, group (A) representing cases and group (B) the placebo controlled group, with 3 months’ regular follow up showed at end of treatment statistically significant difference in weight being lower in group (A) with p-value 0.004 with decreased parameters of glycemic profile (Fasting insulin, FPG, HOMA_IR, 2h PP, HbA1c) in group (A) with p-value <0.001 except 2hpp which p-value is 0.006. Also ALT was much decreased in group(A) with p-value <0.001. Lipid profile didn’t show significant difference between 2 groups except for TGs which deceased in follow up in group (A) with p-value <0. 001. Additionally, it should be highlighted that there was no statistically significant difference between the control group’s baseline and post-treatment data.CONCLUSION. In individuals who are overweight or obese and have insulin resistance and prediabetes, activation of FXR by OCA results in enhanced insulin sensitivity. Patients who received OCA also lost weight.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140699816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Kashtanova, Y. Polonskaya, L. V. Shcherbakova, E. Stakhneva, V. S. Shramko, S. Mustafina, A. D. Khudyakova, Yulia I. Ragino
BACKGROUND: Diabetes mellitus and obesity are two closely related diseases that are a global public health problem. Obesity is characterized by an increase in the volume of adipose tissue and a change in the production and function of adipocytokines, which leads to a violation of the regulation of insulin sensitivity and glucose metabolism, contributing to the development of insulin resistance and diabetic pathology.AIM: The aim of this study was to evaluate the concentrations of individual adipocytokines and metabolic hormones in patients with DM2 and without diabetes, depending on the presence/absence of abdominal obesity (AO).MATERIALS AND METHODS: A single-center observational cross-sectional study was conducted. A population subsample of men and women aged 25–44 years was examined. Socio-demographic data were collected, anthropometric measurements were performed. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, were determined in blood serum by multiplex analysis using a set of reagents Human Metabolic Hormone V3 (USA) and Human Adipokine Panel 1 (USA) on a Luminex MAGPIX flow fluorimeter (USA). interleukin 6, insulin, leptin, monocytic chemotactic factor 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor-1 (PAI-1) and resistin.RESULTS: The study included 105 people. The main group consisted of 35 people with diabetes mellitus, 11 of them without AO and 24 with AO, the control group consisted of 70 people without diabetes mellitus (35 people with AO and 35 without AO), comparable in gender and age with the main group. In individuals with abdominal obesity, regardless of the presence of type 2 diabetes mellitus, the levels of C-peptide, GLP-1, insulin, leptin and TNF-alpha are higher than in individuals without abdominal obesity. The chance of having diabetes mellitus and AO is associated with an increase in leptin levels (OR=1.367, 95% CI: 1.050–1.779, p=0.020).CONCLUSION: The results of our study show that the indicators of the adipocytokine profile differ significantly in individuals with the presence/absence of abdominal obesity. According to our data, leptin makes the greatest contribution to the development of SD2 against the background of AO. Further research is needed to identify causal relationships and determine whether treatment that regulates adipocytokine levels can help in personalized approaches to the prevention and treatment of type 2 diabetes mellitus.
{"title":"Associations of adupocutokine and metaboliv hormone level in young people aged 25-44 years with type 2 diabetes mellitus and abdominal obesity","authors":"E. Kashtanova, Y. Polonskaya, L. V. Shcherbakova, E. Stakhneva, V. S. Shramko, S. Mustafina, A. D. Khudyakova, Yulia I. Ragino","doi":"10.14341/omet12974","DOIUrl":"https://doi.org/10.14341/omet12974","url":null,"abstract":"BACKGROUND: Diabetes mellitus and obesity are two closely related diseases that are a global public health problem. Obesity is characterized by an increase in the volume of adipose tissue and a change in the production and function of adipocytokines, which leads to a violation of the regulation of insulin sensitivity and glucose metabolism, contributing to the development of insulin resistance and diabetic pathology.AIM: The aim of this study was to evaluate the concentrations of individual adipocytokines and metabolic hormones in patients with DM2 and without diabetes, depending on the presence/absence of abdominal obesity (AO).MATERIALS AND METHODS: A single-center observational cross-sectional study was conducted. A population subsample of men and women aged 25–44 years was examined. Socio-demographic data were collected, anthropometric measurements were performed. The levels of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, were determined in blood serum by multiplex analysis using a set of reagents Human Metabolic Hormone V3 (USA) and Human Adipokine Panel 1 (USA) on a Luminex MAGPIX flow fluorimeter (USA). interleukin 6, insulin, leptin, monocytic chemotactic factor 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor-1 (PAI-1) and resistin.RESULTS: The study included 105 people. The main group consisted of 35 people with diabetes mellitus, 11 of them without AO and 24 with AO, the control group consisted of 70 people without diabetes mellitus (35 people with AO and 35 without AO), comparable in gender and age with the main group. In individuals with abdominal obesity, regardless of the presence of type 2 diabetes mellitus, the levels of C-peptide, GLP-1, insulin, leptin and TNF-alpha are higher than in individuals without abdominal obesity. The chance of having diabetes mellitus and AO is associated with an increase in leptin levels (OR=1.367, 95% CI: 1.050–1.779, p=0.020).CONCLUSION: The results of our study show that the indicators of the adipocytokine profile differ significantly in individuals with the presence/absence of abdominal obesity. According to our data, leptin makes the greatest contribution to the development of SD2 against the background of AO. Further research is needed to identify causal relationships and determine whether treatment that regulates adipocytokine levels can help in personalized approaches to the prevention and treatment of type 2 diabetes mellitus.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140704265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
В преддверии 100-летнего юбилея Эндокринологического Национального Центра исполняется 20 лет с момента выхода в свет первого выпуска журнала «Ожирение и метаболизм».
在我们即将迎来国家内分泌中心成立 100 周年之际，《肥胖与代谢》创刊也已 20 周年。
{"title":"Obesity and Metabolism Journal: 20th anniversary","authors":"I. I. Dedov","doi":"10.14341/omet13116","DOIUrl":"https://doi.org/10.14341/omet13116","url":null,"abstract":"В преддверии 100-летнего юбилея Эндокринологического Национального Центра исполняется 20 лет с момента выхода в свет первого выпуска журнала «Ожирение и метаболизм».","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140704863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. F. Nikolaeva, K. Petrova, O. Vasyukova, R. M. Guseinova, I. Minniakhmetov, R. Khusainova, N. Mokrysheva, V. Sigin
Obesity is a complex, heterogeneous, actively progressive disease manifested by excessive formation of adipose tissue in the body and usually has a high cardiometabolic risk and specific complications. Currently, new data are emerging that explain the pathogenesis of obesity not only by genetic variations and imbalance between energy intake and expenditure, but also by the influence of epigenetic mechanisms, such as DNA methylation. DNA methylation is the most studied epigenetic modification, whose status in the cell can be altered by various external and internal environmental factors, including diet, lifestyle, and hormones. These changes may lead to dysregulation of genes responsible for metabolic processes associated with the development of obesity. However, studies investigating epigenetic marks as potential mediators of obesity are heterogeneous in design, methodology, and results. This review discusses a conceptual framework analyzing the relationship between DNA methylation, obesity, inflammation, and response to weight loss, including after bariatric surgery, as well as material selection and methodology issues to consider when designing studies in this area.
肥胖症是一种复杂的、异质性的、主动进展性疾病，表现为体内脂肪组织的过度形成，通常具有较高的心脏代谢风险和特定的并发症。目前，新的数据表明，肥胖症的发病机理不仅与遗传变异和能量摄入与消耗失衡有关，还与 DNA 甲基化等表观遗传机制的影响有关。DNA 甲基化是研究最多的表观遗传修饰，其在细胞中的状态可因饮食、生活方式和激素等各种内外环境因素而改变。这些变化可能会导致负责与肥胖发展相关的代谢过程的基因失调。然而，将表观遗传标记作为肥胖症潜在介导因素进行调查的研究在设计、方法和结果上都不尽相同。本综述讨论了分析 DNA 甲基化、肥胖、炎症和减肥反应（包括减肥手术后）之间关系的概念框架，以及设计该领域研究时应考虑的材料选择和方法问题。
{"title":"The potential of DNA methylation markers in the study of obesity","authors":"A. F. Nikolaeva, K. Petrova, O. Vasyukova, R. M. Guseinova, I. Minniakhmetov, R. Khusainova, N. Mokrysheva, V. Sigin","doi":"10.14341/omet13058","DOIUrl":"https://doi.org/10.14341/omet13058","url":null,"abstract":"Obesity is a complex, heterogeneous, actively progressive disease manifested by excessive formation of adipose tissue in the body and usually has a high cardiometabolic risk and specific complications. Currently, new data are emerging that explain the pathogenesis of obesity not only by genetic variations and imbalance between energy intake and expenditure, but also by the influence of epigenetic mechanisms, such as DNA methylation. DNA methylation is the most studied epigenetic modification, whose status in the cell can be altered by various external and internal environmental factors, including diet, lifestyle, and hormones. These changes may lead to dysregulation of genes responsible for metabolic processes associated with the development of obesity. However, studies investigating epigenetic marks as potential mediators of obesity are heterogeneous in design, methodology, and results. This review discusses a conceptual framework analyzing the relationship between DNA methylation, obesity, inflammation, and response to weight loss, including after bariatric surgery, as well as material selection and methodology issues to consider when designing studies in this area.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139605433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. V. Ivashchenko, K. Komshilova, N. V. Molashenko, A. A. Lavreniuk, A. M. Lapshina, I. V. Kim, V. A. Ioutsi, M. A. Antsupova, M. V. Utkina, N. M. Platonova, E. A. Troshina, N. Mokrysheva
Hyperandrogenism is the most prevalent cause of menstrual cycle abnormalities and infertility in women. Here, we present a case of a 32-year-old woman with a 7-year history of menstrual irregularity and infertility. Laboratory test results revealed elevated 17-hydroxyprogesterone, progesterone 21-deoxycortisol. Abdominal computed tomography found a 3,9х2,9х2,6 cm left adrenal tumor. Non-classic congenital adrenal hyperplasia was diagnosed initially, however, treatment with supraphysiological doses of dexamethasone proved ineffective and progesterone and 17-hydroxyprogesterone levels remained high. Genetic testing revealed no 21-hydroxylase deficiency. Laparoscopic adrenalectomy was performed with subsequent pathological report being compatible with an adrenal cortical adenoma. 17-hydroxyprogesterone, progesterone 21-deoxycortisol levels returned to the normal range postoperatively and the patient’s menstrual cycle normalized without additional medication. Steroid metabolites producing adenomas are also extremely rare with only a few cases found in patients without previous CAH diagnosis. When a patient with clinically and biochemically diagnosed NCCAH demonstrate no typical features and shows poor response to steroid therapy, the patient should receive multisteroid LC–MS/MS assay for glucocorticoids and androgens, adrenal and ovarian imaging and undergo CYP21A2 gene mutation analysis.
{"title":"Steroid metabolites producing adenoma: a case report","authors":"K. V. Ivashchenko, K. Komshilova, N. V. Molashenko, A. A. Lavreniuk, A. M. Lapshina, I. V. Kim, V. A. Ioutsi, M. A. Antsupova, M. V. Utkina, N. M. Platonova, E. A. Troshina, N. Mokrysheva","doi":"10.14341/omet13050","DOIUrl":"https://doi.org/10.14341/omet13050","url":null,"abstract":"Hyperandrogenism is the most prevalent cause of menstrual cycle abnormalities and infertility in women. Here, we present a case of a 32-year-old woman with a 7-year history of menstrual irregularity and infertility. Laboratory test results revealed elevated 17-hydroxyprogesterone, progesterone 21-deoxycortisol. Abdominal computed tomography found a 3,9х2,9х2,6 cm left adrenal tumor. Non-classic congenital adrenal hyperplasia was diagnosed initially, however, treatment with supraphysiological doses of dexamethasone proved ineffective and progesterone and 17-hydroxyprogesterone levels remained high. Genetic testing revealed no 21-hydroxylase deficiency. Laparoscopic adrenalectomy was performed with subsequent pathological report being compatible with an adrenal cortical adenoma. 17-hydroxyprogesterone, progesterone 21-deoxycortisol levels returned to the normal range postoperatively and the patient’s menstrual cycle normalized without additional medication. Steroid metabolites producing adenomas are also extremely rare with only a few cases found in patients without previous CAH diagnosis. When a patient with clinically and biochemically diagnosed NCCAH demonstrate no typical features and shows poor response to steroid therapy, the patient should receive multisteroid LC–MS/MS assay for glucocorticoids and androgens, adrenal and ovarian imaging and undergo CYP21A2 gene mutation analysis.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139602946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The relevance of developing an individual model of psychological support for patients with bariatric surgery «12 targets» in the framework of a multidisciplinary approach to the treatment of obesity is due to the fact that the effectiveness of surgical treatment is significantly influenced by the individual psychological characteristics of the patient. A comprehensive assessment of the psychological state of patients and the implementation of psychocorrective measures before and after bariatric surgery can improve the effectiveness of surgical treatment and prevent the risk of relapse. The individual model of the psychological support of the bariatric patient is built on the principle of a psycho-correction program, which is an integrative approach using psychotherapeutic tools from various areas of clinical psychology and psychotherapy. 12 universal targets of psycho-corrective influence in work with bariatric patients have been identified. The program is implemented in two stages: psychological preparation for bariatric surgery, psychological adaptation to physiological and psychological changes in the postoperative period. 20 bariatric patients took part in the program of individual psychological support, 11 of them (group 1) participated in all stages of psycho-corrective measures; 9 people (group 2) did not undergo psychological preparation for surgery, they were already included in the second stage of work on psychological adaptation to physiological and psychological changes in the postoperative period. Intermediate results of evaluating the effectiveness of psychological support for patients, which are based on the percentage of BMI reduction, show the achievement of stability in reducing overweight in the process of psychological interventions in both groups. The described model of psychological work will allow clinical psychologists working in a multidisciplinary team in bariatrics to focus on the universal targets of the problem field of a bariatric patient.
{"title":"Individual model of psychological support bariatric surgery patients «12 targets»","authors":"A. Neimark, Shushanna A. Eganian","doi":"10.14341/omet12936","DOIUrl":"https://doi.org/10.14341/omet12936","url":null,"abstract":"The relevance of developing an individual model of psychological support for patients with bariatric surgery «12 targets» in the framework of a multidisciplinary approach to the treatment of obesity is due to the fact that the effectiveness of surgical treatment is significantly influenced by the individual psychological characteristics of the patient. A comprehensive assessment of the psychological state of patients and the implementation of psychocorrective measures before and after bariatric surgery can improve the effectiveness of surgical treatment and prevent the risk of relapse. The individual model of the psychological support of the bariatric patient is built on the principle of a psycho-correction program, which is an integrative approach using psychotherapeutic tools from various areas of clinical psychology and psychotherapy. 12 universal targets of psycho-corrective influence in work with bariatric patients have been identified. The program is implemented in two stages: psychological preparation for bariatric surgery, psychological adaptation to physiological and psychological changes in the postoperative period. 20 bariatric patients took part in the program of individual psychological support, 11 of them (group 1) participated in all stages of psycho-corrective measures; 9 people (group 2) did not undergo psychological preparation for surgery, they were already included in the second stage of work on psychological adaptation to physiological and psychological changes in the postoperative period. Intermediate results of evaluating the effectiveness of psychological support for patients, which are based on the percentage of BMI reduction, show the achievement of stability in reducing overweight in the process of psychological interventions in both groups. The described model of psychological work will allow clinical psychologists working in a multidisciplinary team in bariatrics to focus on the universal targets of the problem field of a bariatric patient.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139605261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Yukina, E. A. Troshina, N. Nuralieva, S. V. Popov, O. Rebrova, N. Mokrysheva
BACKGROUND: It is known that insulinoma in approximately 5% of cases is associated with multiple endocrine neoplasia type 1 syndrome (MEN1), in which the prognosis and management tactics of patients have been developed in detail. The diagnosis of MEN1 often does not require genetic confirmation, since the syndrome has a typical clinical picture. At the same time, a combination of this tumor with other hereditary syndromes is found in the literature, which are characterized by the presence of malignant neoplasms of various localizations, primary multiple lesions, hormonal and other disorders. Thus, it is relevant to search for the genetic causes that cause the development of insulinoma, in addition to MEN1.AIM: to evaluate the frequency of detection of genetic causes of the development of insulin-producing tumors of the pancreas, in addition to MEN1; to analyze the phenotypic characteristics of patients with such tumors.MATERIALS AND METHODS: Based on the analysis of literature for the period up to 2020, a panel has been developed that includes coding regions of 10 genes (MEN1, VHL, TSC1, TSC2, KRAS, YY1, CDKN2A, MLH1, ADCY1, CACNA2D2) involved in the development of insulinoma. In 32 patients diagnosed with insulinoma, verified by pathomorphological examination, with the absence of clinical and/or genetic data indicating MEN1 syndrome, a panel of genes was sequenced with subsequent analysis of the identified genetic variants and phenotypic data obtained from the medical records of patients. In one patient, an additional molecular genetic study of the «Endom» panel was performed, revealing genetic variants of coding regions of 377 genes associated with endocrine diseases.RESULTS: In 8 patients (25%, 95% CI (11%; 43%)), 9 variants of mutations were identified that were not classified as benign, at that two mutations in the TSC2 gene were detected in one patient. Frequencies of genetic variants: TSC2 — 13%, 95% CI (4%; 29%), MEN1 — 6% (1%; 21%), MLH1 — 3% (0%;16%), CDKN2A/P16INK4A — 3% (0%;16%). When comparing patients with the identified mutation, with the exception of benign (n=8), and patients without mutation or with a benign mutation (n=24), there were no differences in the Grade (degree of differentiation), Ki67 proliferation index, frequency of concomitant tumors, burdened history, multiple pancreatic lesions or recurrence of insulinoma, however, patients with germinal mutation were found at the level of statistical trend to be younger at the manifestation of insulinoma and to have bigger tumors. In a patient who underwent an additional molecular genetic study using the new «Endome» panel, previously undescribed gene variants (APC and KIF1B) associated with various sporadic tumors, including endocrine ones, were identified.CONCLUSION: A panel of 10 genes has been developed, mutations of which are associated with insulinoma. A relatively high incidence of genetically determined insulinoma was determined (25% of cases), in half of cases — agains
{"title":"NG Search for germinal mutations in insulinproducing pancreatic tumors","authors":"M. Yukina, E. A. Troshina, N. Nuralieva, S. V. Popov, O. Rebrova, N. Mokrysheva","doi":"10.14341/omet13068","DOIUrl":"https://doi.org/10.14341/omet13068","url":null,"abstract":"BACKGROUND: It is known that insulinoma in approximately 5% of cases is associated with multiple endocrine neoplasia type 1 syndrome (MEN1), in which the prognosis and management tactics of patients have been developed in detail. The diagnosis of MEN1 often does not require genetic confirmation, since the syndrome has a typical clinical picture. At the same time, a combination of this tumor with other hereditary syndromes is found in the literature, which are characterized by the presence of malignant neoplasms of various localizations, primary multiple lesions, hormonal and other disorders. Thus, it is relevant to search for the genetic causes that cause the development of insulinoma, in addition to MEN1.AIM: to evaluate the frequency of detection of genetic causes of the development of insulin-producing tumors of the pancreas, in addition to MEN1; to analyze the phenotypic characteristics of patients with such tumors.MATERIALS AND METHODS: Based on the analysis of literature for the period up to 2020, a panel has been developed that includes coding regions of 10 genes (MEN1, VHL, TSC1, TSC2, KRAS, YY1, CDKN2A, MLH1, ADCY1, CACNA2D2) involved in the development of insulinoma. In 32 patients diagnosed with insulinoma, verified by pathomorphological examination, with the absence of clinical and/or genetic data indicating MEN1 syndrome, a panel of genes was sequenced with subsequent analysis of the identified genetic variants and phenotypic data obtained from the medical records of patients. In one patient, an additional molecular genetic study of the «Endom» panel was performed, revealing genetic variants of coding regions of 377 genes associated with endocrine diseases.RESULTS: In 8 patients (25%, 95% CI (11%; 43%)), 9 variants of mutations were identified that were not classified as benign, at that two mutations in the TSC2 gene were detected in one patient. Frequencies of genetic variants: TSC2 — 13%, 95% CI (4%; 29%), MEN1 — 6% (1%; 21%), MLH1 — 3% (0%;16%), CDKN2A/P16INK4A — 3% (0%;16%). When comparing patients with the identified mutation, with the exception of benign (n=8), and patients without mutation or with a benign mutation (n=24), there were no differences in the Grade (degree of differentiation), Ki67 proliferation index, frequency of concomitant tumors, burdened history, multiple pancreatic lesions or recurrence of insulinoma, however, patients with germinal mutation were found at the level of statistical trend to be younger at the manifestation of insulinoma and to have bigger tumors. In a patient who underwent an additional molecular genetic study using the new «Endome» panel, previously undescribed gene variants (APC and KIF1B) associated with various sporadic tumors, including endocrine ones, were identified.CONCLUSION: A panel of 10 genes has been developed, mutations of which are associated with insulinoma. A relatively high incidence of genetically determined insulinoma was determined (25% of cases), in half of cases — agains","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139603632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. V. Kovaleva, A. K. Eremkina, A. R. Elfimova, A. M. Gorbacheva, N. Mokrysheva
BACKGROUND: Chronic hypoparathyroidism is a relatively rare disease, which usually treated active forms of vitamin D and oral calcium supplements. Supplementation with native vitamin D can be useful both for achieving «non-skeletal» effects of vitamin D and for a more stable serum calcium profile.AIM: The aim of this study was to estimate the daily serum calcium and 24-hour urine calcium levels depending on different 25(OH) vitamin D values in patients with chronic hypoparathyroidism on treatment of active forms of vitamin D and calcium supplements.MATERIALS AND METHODS: Forty patients with chronic hypoparathyroidism were involved in the study. All patients were divided in two groups, matched on sex and age, according to the median level of 25(OH) vitamin D in the total group.RESULTS: There were no significant differences between groups by total, albumin-adjusted serum calcium levels and urine calcium excretion. Patients with serum 25(ОН) vitamin D level ≥ 35 ng/ml had significant tendency to achieve more often the target levels of total serum calcium during the day (128 vs. 149 measurements during the day, p=0.049, χ2). However, this tendency disappeared for albumin-adjusted serum calcium levels (p=0.517, χ2). There frequency of hypercalcemia by albumin-adjusted serum calcium in the group of patients with 25(ОН) vitamin D ≥ 35 ng/ml (p=0.006, χ2) was significantly lower, but not for total serum calcium (a trend, p=0.042, χ2). As regards hypocalcemia, there were no significant differences by albumin-adjusted serum calcium (p=0.581, χ2) and it tends to lower frequency by total serum calcium (p=0.023, χ2).CONCLUSION: The additional administration of native vitamin D in patients with chronic hypoparathyroidism may have some advantages, related to the general concept of worldwide vitamin D deficiency and better disease control.
背景：慢性甲状旁腺功能减退症是一种相对罕见的疾病，通常需要服用活性维生素D和口服钙补充剂。目的：本研究旨在估算慢性甲状旁腺功能减退症患者在服用活性维生素 D 和钙补充剂治疗期间，不同 25（OH）维生素 D 值对其每日血清钙和 24 小时尿钙水平的影响。结果：根据总血钙、白蛋白调整血清钙水平和尿钙排泄量，各组间无显著差异。血清 25（ОН）维生素 D 水平≥ 35 纳克/毫升的患者有明显的趋势，即一天中血清总钙达到目标水平的次数更多（一天中测量 128 次对 149 次，P=0.049，χ2）。然而，在白蛋白调整血清钙水平方面，这种趋势消失了（p=0.517，χ2）。在 25（ОН）维生素 D≥35 纳克/毫升（p=0.006，χ2）的患者组中，按白蛋白调整血清钙计算的高钙血症发生率明显降低，但总血清钙的发生率却没有明显降低（趋势，p=0.042，χ2）。至于低钙血症，白蛋白调整血清钙（p=0.581，χ2）无显著差异，而总血清钙（p=0.023，χ2）的发生频率则趋于降低。
{"title":"The daily calcium profile in patients with chronic hypoparathyroidism depending on different 25(OH) vitamin D level","authors":"E. V. Kovaleva, A. K. Eremkina, A. R. Elfimova, A. M. Gorbacheva, N. Mokrysheva","doi":"10.14341/omet13042","DOIUrl":"https://doi.org/10.14341/omet13042","url":null,"abstract":"BACKGROUND: Chronic hypoparathyroidism is a relatively rare disease, which usually treated active forms of vitamin D and oral calcium supplements. Supplementation with native vitamin D can be useful both for achieving «non-skeletal» effects of vitamin D and for a more stable serum calcium profile.AIM: The aim of this study was to estimate the daily serum calcium and 24-hour urine calcium levels depending on different 25(OH) vitamin D values in patients with chronic hypoparathyroidism on treatment of active forms of vitamin D and calcium supplements.MATERIALS AND METHODS: Forty patients with chronic hypoparathyroidism were involved in the study. All patients were divided in two groups, matched on sex and age, according to the median level of 25(OH) vitamin D in the total group.RESULTS: There were no significant differences between groups by total, albumin-adjusted serum calcium levels and urine calcium excretion. Patients with serum 25(ОН) vitamin D level ≥ 35 ng/ml had significant tendency to achieve more often the target levels of total serum calcium during the day (128 vs. 149 measurements during the day, p=0.049, χ2). However, this tendency disappeared for albumin-adjusted serum calcium levels (p=0.517, χ2). There frequency of hypercalcemia by albumin-adjusted serum calcium in the group of patients with 25(ОН) vitamin D ≥ 35 ng/ml (p=0.006, χ2) was significantly lower, but not for total serum calcium (a trend, p=0.042, χ2). As regards hypocalcemia, there were no significant differences by albumin-adjusted serum calcium (p=0.581, χ2) and it tends to lower frequency by total serum calcium (p=0.023, χ2).CONCLUSION: The additional administration of native vitamin D in patients with chronic hypoparathyroidism may have some advantages, related to the general concept of worldwide vitamin D deficiency and better disease control.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139604078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND: dyslipidemia is currently considered to be one of cardiovascular risk factors. Angiotensin II receptor type I (AGTR1) genetic polymorphisms are known as candidate genes for hypertension, diabetes, as well as for diabetes and obesity complications. Until now, there are not much data on how 1166A>C (rs5186) polymorphism of the AGTR1 gene correlates with Northerners’ carbohydrate and lipid metabolism disorders. In addition, the data are contradictory. Following on from this, we see it is relevant to study the subject.AIM: this research assessed variants of 1166A>C (rs5186) polymorphism of the AGTR1 gene as a predictor of dyslipidemia, carbohydrate metabolism disorders, overweight, and hypertension.MATERIALS AND METHODS: the North residents from Magadan Region, Caucasian by ethnicity, aged from 24 to 56 (average age 43.7± 1.4 yrs) participated in the survey. By real-time polymerase chain reaction we determined the single nucleotide polymorphism of the AGTR1 (rs5186) gene. We also analyzed physical development and cardiovascular variables as well as the concentrations of glucose, insulin, glycosylated hemoglobin, C-reactive protein, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The insulin resistance index and the atherogenicity coefficient were calculated using standard methods.RESULTS: the examined subjects were one hundred and one volunteers. According to the results of genetic analysis, 55 people were assigned to the group of homozygotes for the wild type (AA) and 46 people were assigned to the group of the AGTR1*C allele variant carriers (heterozygotes and homozygotes AC+CC). Our findings contributed to the evidence on more unfavorable lipid pictures showed by the AGTR1*C allele variant carriers: significantly high values of total cholesterol (5,77±0,11, р=0.045), low-density lipoproteins (3,87±0,09, р=0.009), triglycerides (1,43±0,06, р=0.035), and atherogenicity coefficient (3,61±0,10, р=0.001), along with significantly low values of high-density lipoproteins (1,30±0,03, р=0,008). The above indicators were observed as opposed to significantly high fasting glycemia (5,74±0,14, р=0.006) and glycosylated hemoglobin (5,74±0,09, р=0.001) exhibited by the AA homozygotes subjects whose indices could be defined as the state of prediabetes. No intergroup differences were found in anthropometric or cardiovascular variables.CONCLUSION: thus, we could see impairments in the lipid pictures of the AGTR1*С polymorphic variant carriers along with the optimization of carbohydrate metabolism and no effect on the blood pressure or anthropometric characteristics.
{"title":"1166A>C polymorphism of the AGTR1 gene as a marker metabolic disorders in the North residents","authors":"I. Bezmenova, I. Averyanova","doi":"10.14341/omet12986","DOIUrl":"https://doi.org/10.14341/omet12986","url":null,"abstract":"BACKGROUND: dyslipidemia is currently considered to be one of cardiovascular risk factors. Angiotensin II receptor type I (AGTR1) genetic polymorphisms are known as candidate genes for hypertension, diabetes, as well as for diabetes and obesity complications. Until now, there are not much data on how 1166A>C (rs5186) polymorphism of the AGTR1 gene correlates with Northerners’ carbohydrate and lipid metabolism disorders. In addition, the data are contradictory. Following on from this, we see it is relevant to study the subject.AIM: this research assessed variants of 1166A>C (rs5186) polymorphism of the AGTR1 gene as a predictor of dyslipidemia, carbohydrate metabolism disorders, overweight, and hypertension.MATERIALS AND METHODS: the North residents from Magadan Region, Caucasian by ethnicity, aged from 24 to 56 (average age 43.7± 1.4 yrs) participated in the survey. By real-time polymerase chain reaction we determined the single nucleotide polymorphism of the AGTR1 (rs5186) gene. We also analyzed physical development and cardiovascular variables as well as the concentrations of glucose, insulin, glycosylated hemoglobin, C-reactive protein, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The insulin resistance index and the atherogenicity coefficient were calculated using standard methods.RESULTS: the examined subjects were one hundred and one volunteers. According to the results of genetic analysis, 55 people were assigned to the group of homozygotes for the wild type (AA) and 46 people were assigned to the group of the AGTR1*C allele variant carriers (heterozygotes and homozygotes AC+CC). Our findings contributed to the evidence on more unfavorable lipid pictures showed by the AGTR1*C allele variant carriers: significantly high values of total cholesterol (5,77±0,11, р=0.045), low-density lipoproteins (3,87±0,09, р=0.009), triglycerides (1,43±0,06, р=0.035), and atherogenicity coefficient (3,61±0,10, р=0.001), along with significantly low values of high-density lipoproteins (1,30±0,03, р=0,008). The above indicators were observed as opposed to significantly high fasting glycemia (5,74±0,14, р=0.006) and glycosylated hemoglobin (5,74±0,09, р=0.001) exhibited by the AA homozygotes subjects whose indices could be defined as the state of prediabetes. No intergroup differences were found in anthropometric or cardiovascular variables.CONCLUSION: thus, we could see impairments in the lipid pictures of the AGTR1*С polymorphic variant carriers along with the optimization of carbohydrate metabolism and no effect on the blood pressure or anthropometric characteristics.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139602716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Lutsenko, E. Przhiyalkovskaya, O. Vikulova, M. A. Isakov, Zhanna Evgen'evna Belaya, L. Rozhinskaya, E. Pigarova, L. K. Dzeranova, E. Marova, G. A. Melnichenko, N. M. Platonova, E. A. Troshina, N. Mokrysheva
BACKGROUND: Pituitary adenomas are the third most common intracranial neoplasm. Clinical significance is determined by the nature of growth and hormonal activity, leading to disruption of various parts of metabolism. Medical registries are a valuable tool for assessing clinical and epidemiological parameters and obtaining data on real-life clinical practice.AIM: To analyze the epidemiological and clinical characteristics of four pituitary disorders in Russian Hypothalamic and Pituitary Tumor Registry (OGGO): acromegaly, Cushing’s disease, prolactin-secreting and non-functioning pituitary adenomasMATERIALS AND METHODS: The object of the study is the database of the OGGO registry, which includes 84 regions of the Russian Federation, as of 01/01/2023.RESULTS: The maximum prevalence of acromegaly in the Russian Federation was noted in Karelia (9.48/100 thousand) and Chuvash Republic (10.8/100 thousand) and in Tyumen region (8.9/100 thousand). The incidence of acromegaly in 2021 was 0.6/1 million population. The maximum prevalence of Cushing’s disease is observed in Karelia Republic (2.33/100 thousand), Chukotka (2.01/100 thousand), Kirov (1.79/100 thousand) and Tver region ( 1.79/100 thousand). The incidence of Cushing’s disease in 2021 was 0.1/1 million population. The maximum prevalence of prolactinomas is observed Karelia (13.33/100 thousand) and Chuvash Republic (12.35/100 thousand) and in Voronezh region (8.66/100 thousand). The incidence of prolactin-secreting adenomas in 2021 was 0.6/1 million population. The maximum prevalence of non-functioning pituitary adenomas is observed in the Karelia (15.08/100 thousand), Voronezh region (8.82/100 thousand), Tyumen region (8.11/100 thousand) and Sakha/Yakutia Republic (7.56 /100 thousand). The incidence of non-functioning pituitary adenomas in 2021 was 0.3/1 million population. The median age for acromegaly was 63.6 [53.2;71.5], for Cushing’s disease 49.2 [38.8;60.8], for prolactin-secreting adenomas 47.5 [38.3;59.7], for patients with non-functioning pituitary adenomas — 58.4 [43.8;67.9] . At the time of the last visit, remission was observed in 42.7% of patients with acromegaly, 62.5% with Cushing’s disease, 39.7% with prolactinomas and 76.6% of patients with non-active adenomas.CONCLUSION: The OGGO registry is a valuable tool for assessing epidemiological, clinical data and treatments used. At the same time, the quality of the analysis directly depends on the quality and completeness of the entered data. Further research in the field of epidemiology of endocrinopathies should be aimed at improving the quality and ease of data entry, which will allow obtaining the most complete patient characterization.
{"title":"Russian registry of hypothalamic and pituitary tumors: clinical and statistical analysis for 01.01.2023","authors":"A. Lutsenko, E. Przhiyalkovskaya, O. Vikulova, M. A. Isakov, Zhanna Evgen'evna Belaya, L. Rozhinskaya, E. Pigarova, L. K. Dzeranova, E. Marova, G. A. Melnichenko, N. M. Platonova, E. A. Troshina, N. Mokrysheva","doi":"10.14341/omet13054","DOIUrl":"https://doi.org/10.14341/omet13054","url":null,"abstract":"BACKGROUND: Pituitary adenomas are the third most common intracranial neoplasm. Clinical significance is determined by the nature of growth and hormonal activity, leading to disruption of various parts of metabolism. Medical registries are a valuable tool for assessing clinical and epidemiological parameters and obtaining data on real-life clinical practice.AIM: To analyze the epidemiological and clinical characteristics of four pituitary disorders in Russian Hypothalamic and Pituitary Tumor Registry (OGGO): acromegaly, Cushing’s disease, prolactin-secreting and non-functioning pituitary adenomasMATERIALS AND METHODS: The object of the study is the database of the OGGO registry, which includes 84 regions of the Russian Federation, as of 01/01/2023.RESULTS: The maximum prevalence of acromegaly in the Russian Federation was noted in Karelia (9.48/100 thousand) and Chuvash Republic (10.8/100 thousand) and in Tyumen region (8.9/100 thousand). The incidence of acromegaly in 2021 was 0.6/1 million population. The maximum prevalence of Cushing’s disease is observed in Karelia Republic (2.33/100 thousand), Chukotka (2.01/100 thousand), Kirov (1.79/100 thousand) and Tver region ( 1.79/100 thousand). The incidence of Cushing’s disease in 2021 was 0.1/1 million population. The maximum prevalence of prolactinomas is observed Karelia (13.33/100 thousand) and Chuvash Republic (12.35/100 thousand) and in Voronezh region (8.66/100 thousand). The incidence of prolactin-secreting adenomas in 2021 was 0.6/1 million population. The maximum prevalence of non-functioning pituitary adenomas is observed in the Karelia (15.08/100 thousand), Voronezh region (8.82/100 thousand), Tyumen region (8.11/100 thousand) and Sakha/Yakutia Republic (7.56 /100 thousand). The incidence of non-functioning pituitary adenomas in 2021 was 0.3/1 million population. The median age for acromegaly was 63.6 [53.2;71.5], for Cushing’s disease 49.2 [38.8;60.8], for prolactin-secreting adenomas 47.5 [38.3;59.7], for patients with non-functioning pituitary adenomas — 58.4 [43.8;67.9] . At the time of the last visit, remission was observed in 42.7% of patients with acromegaly, 62.5% with Cushing’s disease, 39.7% with prolactinomas and 76.6% of patients with non-active adenomas.CONCLUSION: The OGGO registry is a valuable tool for assessing epidemiological, clinical data and treatments used. At the same time, the quality of the analysis directly depends on the quality and completeness of the entered data. Further research in the field of epidemiology of endocrinopathies should be aimed at improving the quality and ease of data entry, which will allow obtaining the most complete patient characterization.","PeriodicalId":37832,"journal":{"name":"Obesity and Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139603148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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