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Hyperprolactinemia has multiple etiologies and is the most common endocrine manifestation of pathology of the hypo­thalamic-pituitary axis. Hyperprolactinemic hypogonadism is of great scientific interest due to the prevalence of endocrine pathology in the reproductive period and its effect on metabolic processes. Hyperprolactinemia is one of the serious obstacles to the implementation of reproductive function in both women and men. The article discusses current issues of diagnosis and management tactics for patients with hyperprolactinemia of various etiologies within the framework of preconception preparation.

Rapid changes in the morphological characteristics of the population, which began in the middle of the last century, are due to changes in the habitat. The “obesogenic” environment that is formed in urbanized spaces contributes to physical inactivity and a hypercaloric diet, and the processes of globalization contribute to obesity in the population in all countries of the world. From the obesity epidemic declared by WHO in 1988, humanity has moved to an obesity pandemic. The presented review analyzes global and Russian trends in the development of obesity. Data on the prevalence of latent obesity and diagnostic criteria for this condition are presented. An analysis of data on the dynamics of BMI in the world and in the Russian Federation was carried out. Various options for the topography of fat deposition and their relationship with comorbid diseases are considered. The structure of the subcutaneous fat depot in the abdominal area and the influence of the outer (superficial subcutaneous abdominal adipose tissue, SSAT) and deep (deep subcutaneous abdominal adipose tissue, DSAT) layers of subcutaneous fatty tissue in the abdominal area on the risks of developing diseases are discussed. The results of assessing the diagnostic value of the T/A substitution in the FTO gene (rs9939609) for predicting the proportion of fat mass and abdominal fat deposition in adults are presented.

It has now been shown that overweight and obesity are associated with the development of at least 13 types of cancer, including cancer of the breast, colon and rectum, endometrium, esophagus (adenocarcinoma), gallbladder, stomach, kidney (renal cell), liver, ovaries, pancreas and thyroid glands, as well as multiple myeloma. Obesity-related cancers account for about 40% of all cancers. Thus, obesity is ahead of smoking as the most common modifiable risk factor for carcinogenesis. This review collects the latest data on the impact of obesity phenotypes on the risk of developing cancer, including a discussion of the contribution of the metabolically healthy obesity phenotype (MHO) to tumorigenesis. Possible mechanisms contributing to the emergence and progression of cancer are analyzed, for example: stimulation of cell proliferation, evasion of growth suppressors, inhibition of apoptosis and provision of replicative immortality, induction of angiogenesis, activation of invasion and metastasis, influence on genome instability, as well as chronic low-grade inflammation that contributes to the development of cancer. Understanding how obesity influences the above mechanisms may facilitate the development of new cancer prevention and treatment strategies for obese populations.

We recommend acromegaly to be ruled in all patients with characteristic changes in appearance (A3). In all patients without characteristic changes in appearance, we recommend to rule out acromegaly, if several clinical signs suspicious for acromegaly are present (B3). We recommend acromegaly to be ruled out in all patients with pituitary adenoma (B3). We recommend to rule out acromegaly in all patients with prolactin-secreting adenomas (C4). For laboratory confirmation of acromegaly, we recommend to measure serum insulin-like growth factor-1 (IGF-1, somatomedin C) level (A3). In patients without obvious clinical signs of acromegaly and/or with a moderate increase in IGF-1 levels (IGF-1 index less than 1.3), we recommend to assess the response of somatotropic hormone (GH) to hyperglycemia (GH during an oral glucose tolerance test) (B3). In all patients with biochemically confirmed acromegaly, magnetic resonance imaging of the pituitary gland with intravenous contrast is recommended to assess pituitary adenoma size, location and growth pattern (A3). We recommend to measure blood glucose and glycated hemoglobin in all patients with confirmed acromegaly (B3). We recommend to measure serum prolactin levels in all patients with acromegaly (B3).In all patients with acromegaly and pituitary adenoma, transnasal transsphenoidal adenomectomy is recommended as first-line treatment if the patient’s consent is given and there are no contraindications (A1). For all patients with acromegaly for whom neurosurgical treatment is indicated, surgical intervention is recommended in medical centers, specializing in pituitary diseases, by neurosurgeons who perform at least 50 such operations per year (A3). We recommend that morphological and immunohistochemical examination of the removed pituitary adenoma is performed in all patients with acromegaly (A3). We do not recommend routine medical therapy for acromegaly before surgery as a mean to reduce tumor size (B2).For patients with acromegaly in whom neurosurgical treatment is not indicated or ineffective or while patient awaiting for the effect of radiation therapy, we recommend medical therapy (A1). Long-acting first-generation somatostatin analogues are recommended as first-line drug therapy for acromegaly. In case of partial/complete resistance to or intolerance to somatostatin analogs, pegvisomant is recommended as a second-line medical therapy for acromegaly (A1). We recommend starting pegvisomant from a single dose of 40–80 mg per day subcutaneously, then continue injections at a starting dose of 10 or 15 mg per day with IGF-1 monitoring after 4–6 weeks and dose adjustment if necessary (B2). In patients with acromegaly and a moderate increase in IGF-1 levels, we recommend to initiate cabergoline as medical monotherapy or, if somatostatin analogs are ineffective, in combination with them (B2).In patients with acromegaly, if the disease remains active after surgical treatment, if drug treatment is unavailable, intolerable or ineffective, and repeated neurosurgical intervention is inappropriate, it is we recommend radiation therapy (A1). A multidisciplinary approach is recommended in the management of acromegaly complications (C3).

BACKGROUND: Obesity is a pathology that highly contributes to the development of type 2 diabetes mellitus and cardiovascular diseases. Meanwhile, different obesity phenotypes have varying levels of risk, and the indication of early predictors that can help determine the likelihood of developing cardiometabolic disorders is an important task. Since obesity is characterized by excessive energy intake, hormones involved in energy homeostasis (leptin and other adipokines, ghrelin, incretins) can be considered as serious candidates for the role of such predictors. The profile of changes in their level in the post-­nutrition status testifies in favor of the development of resistance not only to insulin, but also to leptin, and to ghrelin, and, possibly, to incretins.AIM: This study aims to investigate the relationship between the dynamics of the level of hormones involved in energy homeostasis in a sample with a standard carbohydrate breakfast and metabolic health.MATERIALS AND METHODS: Metabolic parameters (including НОМА-IR and НОМА-B, lipid profile, glucose level, blood pressure) were assessed in 90 obese patients (BMI 37.31±4.83 kg/m2). Additionally, biomarkers such as adiponectin, CRP were measured. Levels of leptin, ghrelin, GLP1 and GIP were assessed before and 60 minutes after a standard carbohydrate breakfast. These hormone levels were classified depending on the nature of the changes, considering the physiological dynamics described in the literature in healthy people or not. Patients were divided into groups of metabolically healthy and ­metabolically unhealthy obesity, first using the most commonly known criteria (Meigs et al.), then based on the criteria discussed in the literature for perfectly healthy obesity, in which there are no metabolic disorders.RESULTS: The analysis revealed that patients without metabolic disorders had a ghrelin level profile similar to that in healthy people without obesity, while patients with at least one of the manifestations of the metabolic syndrome showed evidence of ghrelin resistance (the level of ghrelin on an empty stomach was reduced, and after food it was not adequately reduced). Adiponectin levels were normal in metabolically healthy patients. Incretin levels showed unidirectional changes in obesity, regardless of metabolic status. The level of CRP did not differ between the groups. The glycemic level was significantly lower in metabolically healthy patients (the group was characterized by normal insulin levels and had a lower degree of insulin resistance).CONCLUSION: The data obtained allow us to consider ghrelin resistance as an early and rather sensitive indicator of the development of metabolic disorders in obesity.

BACKGROUND: Recent clinical descriptions have shown that in adult patients, the cause of nondiabetic hypoglycemia (NDH) may be various genetically determined disorders of glucose metabolism or insulin synthesis/bioavailability. In this connection, in adult patients with NDH of unclear genesis, it is important to conduct a genetic study in order to search for mutations in genes associated with congenital disorders of glucose metabolism (CDGM).AIM: To evaluate the effectiveness of genetic testing to exclude CDGM in adult patients with idiopathic NDH.MATERIALS AND METHODS: Based on the analysis of the literature, a targeted panel has been developed, including 30 genes, mutations in which are associated with the following groups of diseases: 1) congenital hyperinsulinism (KCNJ11, ABCC8, GLUD1, HADH, UCP2, HNF4A, HNF1A, GCK, INSR, SLC16A1); 2) glycogen storage diseases (AGL); 3) other carbohydrate metabolism disorders (ALDOB, FBP1); 4) glycosylation defects (PMM2, ALG3, PGM1, MPI); 4) defects in fatty acid oxidation (ACADM, ETFA, ETFB, ETFDH, FLAD1, SLC25A32, SLC52A1, SLC52A2, SLC52A3); 5) disorders of ketone body metabolism (CPT1A, CPT2, HMGCL); 6) mitochondrial disorders (DLD). Twenty nine patients (n=29: with idiopathic NDH n=17 and with insulinoma n=12) aged 19 to 66 years underwent a genetic study using this custom panel.RESULTS: As a result of the examination 12 genetic variants (all heterozygous) were identified in 8 patients with idiopathic NDH (47%, 95% CI (23%; 72%)), at that two mutations were detected in three patients: in the genes AGL and HMGCL; ACADM and FLAD1, respectively; and one patient had three mutations: one mutation in the ETFA gene and two mutations in the ABCC8 gene. Frequencies of genetic variants: AGL — 18%, 95% CI (4%; 43%), ETFA — 12% (1%; 36%), HMGCL — 6% (0%; 29%), ALDOB — 6% (0%; 29%), CPT1A — 6% (0%; 29%), ABCC8 — 6% (0%; 29%), ACADM — 6% (0%; 29%), FLAD1 — 6% (0%; 29%). 5 genetic variants (all heterozygous) were identified in 5 patients with insulinoma (42%, 95% ДИ (15%; 72%)). Frequencies of genetic variants: ABCC8 — 17%, 95% CI (2%; 48%), HNF1A — 8% (0%; 38%), ETFDH — 8% (0%; 38%), MPI — 8% (0%; 38%). We did not include benign variants in this analysis. At the same time, clinically significant variants were identified only in one patient from the group with idiopathic NDH (6%, 95% CI (0%; 29%)) in the ABCC8 gene and in one patient from the group with insulinoma (8%, 95% CI (0%; 38%)) in the same gene congenital hyperinsulinism (CHI).CONCLUSION: A panel of 30 genes has been developed, variants of which are associated with a CDGM. The results of our study confirm the possibility of detecting CDGM in adulthood, in particular CHI, and indicate the need for genetic testing, primarily in patients with idiopathic NDH.

AIM: The purpose of this study was to analyze the characteristics of management, diagnosis and treatment of patients with vitamin D deficiency/ by endocrinologists in the regions of Russian Federation using a sociological survey.MATERIALS AND METHODS: A cross-sectional sociological uncontrolled study was carried out. To implement this work, we used an online questionnaire “Questioning doctors on vitamin D” specially developed on the basis of the Google forms platform. The study was conducted in January 2021.All the data obtained were entered into an electronic database in MS Excel. Statistical processing was performed using the IBM SPSS Statistics 25 software.RESULTS: The survey involved 707 physicians from 86 regions of the Russian Federation. Our study revealed that not all doctors strictly adhere to clinical recommendations in patient management. Issues identified include unjustifiably widespread ordering of 25(OH)D blood tests (58.5%), lack of consideration for individual patient characteristics and clinical situations in dose selection (99.2%) and prescription of active metabolite or analogs of vitamin D to correct low 25(OH)D levels in blood (14.7%). Furthermore, recommendations for improving clinical guidelines focused on the lack of illustrative material (21.1%), expanding patient information sections (20.7%), and insufficient coverage of issues arising in clinical practice (14.6%). Our study also highlighted limited capabilities of laboratory diagnostics for assessing vitamin D status in patients in Russia. The survey revealed that only 9.2% of respondents have the ability to measure 1,25(OH)2D concentrations, and only 1.4% can order tests for 24,25(OH)2D. About 8.3% of participants did not specify which tests for assessing vitamin D status are available for prescription. Technical enhancement of laboratories and the inclusion of all recommended laboratory study requirements in the compulsory health insurance system could address this.Regarding vitamin D toxicity, 25% of surveyed doctors encountered it. Main causes included self-administration of elevated doses of cholecalciferol by patients (62%) or prescribed by physicians (40%), the use of active metabolites or analogs of vitamin D (21%), incorrect dosing of cholecalciferol preparations as indicated by the manufacturer (18%), and defects in CYP24A1 (13%). Rare causes included granulomatous and lymphoproliferative diseases (11.5%).CONCLUSION: The current clinical guidelines of the Russian Association of Endocrinologists for «Vitamin D Deficiency in Adults» are generally effective and widely used by clinicians. However, they do not entirely meet the needs of specialists and require refinement in terms of improving structure and clarity of presentation, expanding illustrative material, and justifying the frequency of laboratory diagnostics. Cases of vitamin D toxicity observed in clinical practice were predominantly associated with incorrect administration of vitamin D supplements. The identified high frequency of vitamin D toxicity in real clinical practice necessitates additional attention to this issue during the update of clinical recommendations.

Acromegaly is a rare neuroendocrine disease caused by excessive production of growth hormone (GH), which acts as a trigger for cartilage tissue destruction leading to joint damage.Patients with acromegaly, especially in the active stage, often complain of joint pain in various locations. Joint pain can be one of the first symptoms of the disease, the intensity of which worsens without proper treatment. Increased production of GH leads to configuration changes in the joints, which in turn trigger destructive processes typical of degenerative diseases such as osteoarthritis. Despite successful treatment of acromegaly, joint-related issues can persist and significantly worsen the quality of life for patients. In this regard, the search for potential markers of early joint involvement in acromegaly is relevant for use in predicting the severity of arthropathy progression and monitoring this cohort of patients.This review provides a general overview of the effects of growth hormone on cartilage tissue, the characteristics of musculoskeletal pathology in patients with acromegaly and possible markers associated with early joint damage.

AIM: to identify the features of immune reactions in practically healthy individuals in response to short-term cold exposure, depending on the level of total cholesterol in the blood.MATERIALS AND METHODS: On the basis of the Laboratory of Ecological Immunology of the Institute of Physiology of Natural Adaptations of the Federal Research Center for Integrated Arctic Studies named after Academician N.P. Laverov of the Ural Branch of the Russian Academy of Sciences, 108 practically healthy women living in Arkhangelsk aged 21 to 50 years were examined. Blood was taken from the ulnar vein on an empty stomach in the morning before and immediately after general cooling for 5 minutes at a temperature of -25 °C. The complex of immunological studies included the study of venous blood hemograms: the number of platelets, erythrocytes, leukocytes, total hemoglobin in the blood, leukograms, phagocytic activity of neutrophils and blood monocytes, determination of cytokines IL-1β, IL-6, TNF-α. The study of the lipid profile included the determination of total cholesterol, glucose, triglycerides, phospholipids.RESULTS: In the Q1 group, no cases of hemoglobin deficiency were recorded, while in the Q4 group, hemoglobin deficiency was recorded in 14.29% of the surveyed, and after a short–term general cooling — in 21.43%. The total number of platelets, as well as the thrombocrit index in the Q4 group was significantly higher (259.07×10^3 cells/µl and 0.27%, respectively). The Q4 group had higher average monocyte levels in the leukocytogram (0.40±0.10×10^9 cl/l and 6.26±1.43% compared with 0.24±0.06×10^9 cl/l and 4.46±1.40%, p

BACKGROUND: Obesity is a progressive health and economic problem of modern society. Endocrine-metabolic changes in childhood and adolescence have an impact on cognitive status, which is accompanied by changes in the perfusion of gray and white matter of the brain, as well as its architectonics.AIM: Verification of fatty acid (FA) levels in relation to cognitive function and brain neuroimaging data in adolescents with obesity.MATERIALS AND METHODS: The study is a single-center observational one-stage comparative. 60 teenagers aged 10–16 years were selected to participate. The main study group was formed of 34 adolescents with obesity (SDS BMI ≥+2.0), 26 subjects with normal weight made up the control group. The calculation of SDS BMI was performed on the WHO «Anthroplus» calculator. To obtain anthropometric data, a vertical height meter MSK — 233, scales and a soft centimeter tape were used. The levels of free fatty acids in the blood serum were determined by chromatomass spectrometry on the Agilent 7000B detector. For neurocognitive testing, the Montreal Cognitive Function Assessment Scale and the Ray test were used. Contrast-free perfusion magnetic resonance imaging of the brain was performed on a Signa Creator “E” MR tomograph by GE Healthcare, 1.5 Tl, China, by Arterial Spin Labeling. For MR tractography, the GE Sygna Creaton 1.5 Tesla apparatus was used using the method of diffusion imaging with high angular resolution HARDI (High Angular Resolution Diffusion Imaging). Statistical processing of the obtained results was carried out using IBM SPSS Statistics software.RESULTS: According to the results of a comparative analysis, adolescents with obesity were distinguished by an increased content of free LC and a decrease in cognitive functions (p

BACKGROUND: Cytokines secrete all cells when there is a threat of damage to it. Leptin, having all the properties of a cytokine, produces fat cells. It was of interest to identify the ratio of leptin concentrations and cytokines activating preventive inflammatory reactions in the blood of practically healthy Northerners with hyperlipoproteidemia.AIM: To identify the ratio of concentrations of leptin and IL-1ß, TNF-α, IL-6 and IL-10 in the blood of practically healthy Northerners with hyperlipoproteidemia.MATERIAL AND METHODS: A survey of 286 practically healthy people aged 35-55 years living in the Arkhangelsk region was conducted. The body mass index in persons of the first group (n=211) was in the range of 19.5-26.8 kg/m2 and corresponded to the norm; and 75 people of the second group (body mass index 31-40 kg/m2). Concentrations of leptin, interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined in the blood by ­enzyme immunoassay on an automatic Evolis enzyme immunoassay analyzer from Bio-Rad (Germanytotal ­cholesterol (OH), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoV), high-density lipoproteins (HDL), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), oxidized low-density lipoproteins (LDL), triglycerides (TG), phospholipids (FL) on the biochemical analyzer «Stat fax 1904 Plus» of the company «Awareness Technology, Inc.» USA.RESULTS: Fasting hyperlipoproteidemia in practically healthy people is associated with an increase in the concentration of leptin in the blood within the physiological content. The closest relationship between an increase in leptin levels and concentrations of proinflammatory cytokines IL-1ß, TNF-α and IL-6 was established (r=0.68, 0.74 and 0.83, respectively; p

BACKGROUND. Due to its role as a risk factor for the emergence of metabolic illnesses including type 2 diabetes, cardiovascular 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

Background/Aims: The objectives of our study were to determine salivary α-amylase activity (stress biomarker) and its association with psychological status and quality of life (QoL), disease duration and intensity of symptoms (pain/burning) in patients with OLP. Methods: A total of 50 subjects participated in this case-control study: 30 patients with oral lichen planus (OLP); 20 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am to avoid diurnal fluctuations. Psychological status was assessed using the Croatian validated version of the original Depression, Anxiety and Stress Scale (DASS-21). The impact of oral health on QoL was assessed using the Croatian version of the Oral Health Impact Profile Questionnaire (OHIP-CRO14). Results: There was no statistically significant difference in salivary α-amylase activity between patients with OLP (N=30) and control subjects (N=20) (133813.3 vs. 166815.5 U/L, p=0.314; t-test). Depression, anxiety and stress showed no statistically significant difference between patients with OLP and control subjects (p=0.076, p=0.111, p=0.209; t-test). The patients with OLP had statistically significantly poorer QoL (total) compared to control subjects (p=0.004, t-test). There was a moderate positive correlation between symptom intensity (pain/burning) and poor QoL (total) (r=0.584, p

Background/Aims: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. Methods: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. Results: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. Conclusion: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.

Background/Aims: Inhaled particulate air pollution is associated with cardiotoxicity with underlying mechanisms including oxidative stress and inflammation. Carnosol, commonly found in rosemary and sage, is known to possess a broad range of therapeutic properties such as antioxidant, anti-inflammatory and antiapoptotic. However, its cardioprotective effects on diesel exhaust particles (DEPs)-induced toxicity have not been studied yet. Hence, we evaluated the potential ameliorative effects of carnosol on DEPs-induced heart toxicity in mice, and the underlying mechanisms involved. Methods: Mice were intratracheally instilled with DEPs (1 mg/kg) or saline, and 1 hour prior to instillation they were given intraperitoneally either carnosol (20 mg/kg) or saline. Twenty-four hours after the DEPs instillation, multiple parameters were evaluated in the heart by enzyme-linked immunosorbent assay, colorimetric assay, Comet assay and Western blot technique. Results: Carnosol has significantly reduced the elevation in the plasma levels of lactate hydrogenase and brain natriuretic peptide induced by DEPs. Likewise, the augmented cardiac levels of proinflammatory cytokines, lipid peroxidation, and total nitric oxide in DEPs-treated groups were significantly normalized with the treatment of carnosol. Moreover, carnosol has markedly reduced the heart mitochondrial dysfunction, as well as DNA damage and apoptosis of mice treated with DEPs. Similarly, carnosol significantly reduced the elevated expressions of phosphorylated nuclear factor-кB (NF-кB) and mitogen-activated protein kinases (MAPKs) in the hearts. Furthermore, the treatment with carnosol has restored the decrease in the expression of sirtuin-1 in the hearts of mice exposed to DEPs. Conclusion: Carnosol significantly attenuated DEP-induced cardiotoxicity in mice by suppressing inflammation, oxidative stress, DNA damage, and apoptosis, at least partly via mechanisms involving sirtuin-1 activation and the inhibition of NF-кB and MAPKs activation.

Three recently-completed, large clinical trials in the U.S, New Zealand, and Australia, referred to herein as the ‘mega-trials’, were conducted to determine the impact of supplemental vitamin D on a variety of outcomes including falls and fractures. The trials were similar in design and collectively included over 50,000 generally vitamin D replete, older men and women. The mega-trials established that vitamin D supplementation with the equivalent of 2000 to 3300 IU/d of vitamin D3 had no favorable effect on risk of falls or fractures. This review focuses on specific design elements of the trials and how they likely influenced these trial findings. While these trials were in progress, evidence emerged that circulating 25-hydroxyvitamin D levels have a U-shaped association with risk of falling, raising concern about a potential untoward effect of high dose supplementation. There is compelling evidence that in older, vitamin D- and calcium-insufficient nursing home residents, the combination of vitamin D and calcium in modest replacement doses dramatically reduces the risk of hip and other fractures. Community-dwelling older adults in many populous countries around the globe have widespread vitamin D and calcium insufficiency. It is time to follow the evidence trail and determine the effect of vitamin D and calcium replacement on their risk of falls and fractures.

During liver regeneration, especially after a hepatectomy, hepatocytes experience significant lipid accumulation. These transiently accumulated lipids are generally believed to provide substrates for energy supply or membrane biomaterials for newly generated hepatocytes. Remarkably, a recent study found that acute lipid accumulation during regeneration can act as a signal for chromatin remodeling to regulate regeneration. Chen, Y.H., et al. identified MIER1 (mesoderm induction early response protein 1) as a crucial inhibitor of liver regeneration through in vivo CRISPR screening. MIER1 binds to and restrains cell cycle genes’ expression. During liver regeneration, acute lipid accumulation suppresses MIER1 translation via the EIF2S pathway, resulting in transient down-regulation of MIER1 protein, which promotes cell cycle gene expression and liver regeneration. Interestingly, the researchers also found that the dynamic regulation of MIER1 was impaired in fatty and aging livers with chronic steatosis, while of knockout of MIER1 in these animals improved their regenerative capacity. In conclusion, this study provides valuable insights into the complex mechanisms underlying liver regeneration and highlights the potential therapeutic applications of targeting MIER1 for improving liver regeneration in disease states associated with impaired lipid homeostasis.

Bisalbuminemia is a rare, typically benign condition marked by the presence of a bifid albumin band on serum protein electrophoresis. It can either be inherited due to a point mutation or acquired in association with various medical conditions, most commonly diabetes mellitus. Bisalbuminuria, the presence of bifid albumin in urine, may or may not accompany bisalbuminemia. Both conditions are often discovered incidentally during screening for monoclonal gammopathy. Bisalbuminemia and related variants provide insights into albumin's genetic diversity and functional roles, influencing clinical diagnostics and research in human genetics. Understanding these variants aids in distinguishing benign conditions from potential disease states, guiding appropriate clinical management. In this case-based review, we present a case of hereditary bisalbuminemia identified unexpectedly during an investigation of a positive Direct Antiglobulin Test Coombs in an adult female patient. This review aims to highlight the key features of bisalbuminemia, a rare condition that should be recognized by clinicians.

Paraneoplastic hypoglycemia, also known as non-islet cell tumor hypoglycemia (NICTH), is a rare but critical condition occurring in patients with different types of malignancy. This condition is commonly linked to tumors producing insulin-like growth (IGF) factors, particularly IGF-2 and its precursors, which disrupt glucose homeostasis and lead to excessive glucose consumption. The diagnosis typically involves documenting symptomatic hypoglycemia and ruling out other potential causes. Essential diagnostic tools include imaging studies and laboratory tests, specifically measuring IGF-2 levels and the IGF-2:IGF-1 ratio. Treatment strategies for NICTH are multifaceted and may include surgical resection of the tumor if feasible, pharmacological interventions such as corticosteroids to suppress IGF-2 production, or supportive measures to manage acute hypoglycemic episodes. Novel therapeutic approaches targeting IGF-2, such as monoclonal antibodies or siRNA, are also being explored and hold promise for future treatment options. This review aims to enhance understanding of paraneoplastic hypoglycemia, focusing on its pathogenesis and diagnosis, to guide optimal medical treatment.

The worldwide surge in obesity and associated metabolic disorders is emerging as a significant public health issue for societies and healthcare systems. Available evidence has shown that alterations in the gut microbiota could be implicated in the pathogenesis of obesity and associated disorders. A healthy gut microbiome is characterized by richness and high microbial diversity. Gut microbiota affect how the host responds to diet, and conversely, the host may modify the gut microbiota through changes in dietary habits. Diet can impact and alter the composition, diversity, and species richness of the gut microbiota over time. An unhealthy diet, high in fat and sugar, may lead to decreased microbial diversity, reduced synthesis of metabolites that maintain gut permeability, damage to the mucus layer, increased bacterial translocation and lipopolyssacharide which can trigger endotoxemia, chronic subclinical inflammation and metabolic disorders. Currently, the impact of diet on gut microbial composition and its involvement in the pathogenic mechanisms underlying metabolic disorders is one of the most promising areas of research in nutrition. This special issue has gathered original research articles in topics related to diet patterns, gut microbiota, obesity and associated metabolic disorders as well as brief reports, reviews and perspectives in the wider field of translational and clinical metabolic research. In particular, the aim of this Special Issue was to present evidence connecting gut microbiota with metabolic disorders, explore the underlying mechanisms of this association, and examine how diet patterns may influence this relationship.

Background: Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. Methods: Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). Results: Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p

Background: Hypertension is a major public health problem in developing countries. Globally, nearly 1.13 billion adults had hypertension in 2015 and this is estimated to increase to 1.56 billion by 2025. Hyperuricemia is an important predictor of the progression of hypertension and is common in hypertensive patients. Hypertensive patients with hyperuricemia are at higher risk of cardiovascular disease. Objective: To assess the prevalence of hyperuricemia and its associated factors among hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital (UGCSH). Method: An institutional-based cross-sectional study was conducted on 248 hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital from January 2020 to February 2021. A convenient sampling technique was employed to select study participants. Socio-demographic and clinical characteristics were collected using a structured questionnaire via face-to-face interviews and reviewing medical records respectively. The biochemical parameters were measured by using a Mindray BS-200E chemistry analyzer. Data was entered using EpiData version 4.6.0.0 and analyzed using STATA vs. 14.0. Bivariable and multivariable binary logistic regression were fitted to identify factors associated with hyperuricemia. The odds ratio and 95 % CI were calculated to assess the strength of the association and a P-value

Background: Diabetes mellitus is becoming major health challenge with continually increasing burden. High costs of conventional medicines and numerous side effects associated with them, on the other hand, easy availability and accessibility of traditional herbal medicines calls upon experimental investigations to validate their effect on lowering blood glucose level. Methods: The dried fruit of Rosa abyssinica was macerated with 70 % ethanol and the extract's in vitro antidiabetic activity was investigated using dinitrosalisylic acid method for alpha amylase inhibitory activity. Furthermore, the in vivo hypoglycemic and Antihyperglycemic effects of various doses of the extract (100, 200 and 400 mg/kg) was determined on normoglycemic, glucose loaded (1500 mg/kg) and Streptozotocine (180 mg/kg)-induced diabetic mice models. Results: The acute oral toxicity study revealed the plant showed no toxic effect on swiss albino mice at 2000 mg/kg. The in vitro alpha amylase inhibitory activity study showed that the extract has comparable IC50 value of 21.37 ± 4.252 μg/ml with the standard drug acarbose (IC50 value of 26.72 ± 3.59 μg/ml). On the other hand, in normal mice, none of the dose levels except at 400 mg/kg significantly reduces blood glucose level. This is in contrast to the oral glucose tolerance test, which the extract produced significant reduction at 60, 90 and 120 min following glucose challenge. The 70 % ethanolic fruit extracts of Rosa abyssinica also experienced profound antidiabetic activity in streptozotocin-induced diabetic model. In the single-dose study, both RAFE200 and RAFE400 demonstrated a significant (P˂0.05) reduction in blood glucose levels at 1, 2, 3, and 4 h. Similarly, in the repeated-dose study, RAFE200 and RAFE400 not only significantly reduced blood glucose levels but also produced a notable improvement in animal body weight. Conclusion: The 70 % ethanolic fruit extracts of Rosa abyssinica have shown significant in vitro alpha amylase inhibition effect and an in vivo blood glucose level lowering effects in diabetic mice.Therefore, this study supports the traditional use of Rosa abyssinica in the management of diabetes mellitus.

Obesity management can effectively reduce the risks and complications associated with obesity and improve the quality of life of patients. After assessing the advantages and limitations of various obesity management approaches, self-management has been strongly recommended due to the advantages of minimal side effects and lower costs compared to treatment via drugs and surgery. However, successfully implementing lifestyle intervention strategies requires scientific guidance and strong determination. With the development of electronic and information technology, lifestyle intervention has transformed considerably. A new concept, called Gamified Digital Therapeutics (GDTx), represents a gaming format with Digital Therapeutics (DTx). It can effectively enhance patient compliance and accessibility to chronic disease management. Here, we review recent studies on the application of GDTx for the self-management of obesity and discuss three aspects surrounding its completion rates, satisfaction levels, and effectiveness. In contrast to traditional approaches to obesity self-management, implementing GDTx effectively corrects unhealthy dietary and lifestyle habits, markedly enhancing the dissemination of nutritional and exercise-related health knowledge. Of particular significance is the evident improvement in the adherence of obese patients to weight loss programs. Despite numerous studies indicating that GDTx may offer an effective solution for obesity self-management, there are still several limitations in the medicalization of GDTx for self-management of obesity. This review aimed to provide a reference for subsequent studies and promote the widespread application of GDTx in obesity self-management to help reduce the obesity rate and alleviate the burden on obese patients.

Diabetic Nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Studies have indicated that Transforming Growth Factor beta1 (TGFβ1) is the most potent factor contributing to renal fibrosis, and understanding the exact pathogenic mechanism of renal fibrosis is crucial for alleviating the condition. Previous research has identified Yin Yang 1 (YY1) as an effective inhibitor of TGF-β1. Our study, through dual-luciferase reporter gene assays and Western blot experiments, screened and obtained the small molecule compound PdⅡ. Subsequently, validation in a high-glucose-induced renal mesangial cell injury model showed that PdⅡ treatment significantly increased the expression of YY1 protein and mRNA, while correspondingly reducing the expression of TGFβ1 protein and mRNA. Dual-luciferase reporter gene assay results revealed that, compared to the control group, the luciferase transcription activity of YY1 molecules increased in the PdⅡ treatment group, and the luciferase transcription activity of TGFβ1 decreased. By further designing mutations in the binding sites between TGFβ1 and YY1 on the promoter, transfecting fluorescent enzyme reporter gene plasmids with TGFβ1 mutant promoter into mesangial cells damaged by high glucose, and then treating the cells with PdⅡ, it was observed that the luciferase transcription activity of TGFβ1 did not decrease. Therefore, these results suggest that PdⅡ may inhibit TGFβ1 transcriptional activity by activating YY1, thereby slowing down the progression of diabetic nephropathy.

Introduction: Approximately 25 % of diabetic patients develop diabetic foot ulcers (DFUs), significantly increasing morbidity, mortality, and healthcare costs. Effective control and prevention are crucial. Objective: This study aims to identify easily measurable parameters for predicting DFU risk by assessing the correlation between Phase Angle (PA) and the Triglyceride-Glucose (TyG) index with DFU risk. Materials and methods: A comparative case-control study was conducted at the General Hospital of Elche from March to June 2023 with 70 participants (33 with diabetes, 37 without). Cases had diabetes for over five years and a diabetic foot risk grade of 0, 1, or 2 (IWGDF 2019). Exclusion criteria included inability to walk, prior use of orthoses, and severe complications like edema or wounds. Predictive variables were PA, TyG index, body composition, and biochemical markers. Statistical analyses included Pearson/Spearman tests for correlations, Student's t-test/Mann-Whitney test for group comparisons, and ANOVA/Kruskal-Wallis tests for normally and non-normally distributed variables. Results: PAand TyG index were strongly linked to diabetic foot risk, supporting their potential as biomarkers. Significant relationships with other relevant biomarkers were also confirmed. Conclusion: PA and TyG index are valuable, easily measurable biomarkers for assessing diabetic foot risk, and can be monitored in primary care settings. Implementing these biomarkers in routine practice could enhance the management of diabetic complications, particularly in resource-limited settings, by enabling early detection and intervention, thus improving patient outcomes and reducing the burden of advanced complications.

Background: Diabetes mellitus (DM) is a major health concern worldwide. Diabetes patients are increasingly using herbal medicine (HM) without seeking advice from their healthcare providers. However, its impact on glycemic control is not documented in Ethiopia. Thus, this study aimed to assess herbal medicine use and its effect on glycemic control among diabetes patients at governmental hospitals in Debre Berhan town, Ethiopia. Methods: A cross-sectional study involving 430 diabetic patients was conducted at two different hospitals in Debre Berhan town from January 1 to March 30, 2024. Data were gathered using a guided self-administered questionnaire to collect data including glycemic control assessed via hemoglobin A1c (HbA1c) levels. Data was analyzed using SPSS version 25. Logistic regression model was used to assess the predictors of herbal medicine usage, while an independent samples t-test was conducted to compare the mean HbA1c levels between herbal medicine users and non-users among diabetes patients. Results: Of the 430 participants, 72.6 % were diagnosed with type 2 diabetes. The study revealed 48.1 % (95 % CI: 43.3–53) participants used herbal medicine. Moringa stenopetala (33.5 %), Trigonella foenumgraecum (27.4 %), and Thymus schimperi (17.9 %) were the predominant herbs utilized by diabetic patients. The use of herbal medicine was associated with the patients’ diabetic knowledge (AOR: 1.59; 95 % CI: 1.01–2.49), occupation (AOR: 3.7; 95 % CI: 1.36–10.23), income (AOR: 3.58; 95 % CI: 1.22–10.55), and family history of diabetes (AOR: 1.9; 95 % CI: 1.19–3.18). Glycemic status was not controlled for 86 % of herbal users compared to 66.8 % of non-users. Participants who used herbal medicine had significantly higher mean HbA1c by a mean difference of 0.41 (95%CI: 0.04–0.78). Conclusions: Herbal medicine use was common among diabetes patients in this study. Poor knowledge about diabetes, a family history of diabetes, lower income, and a farming occupation were identified as strong predictors of HM use. Patients who used herbal medicine had significantly higher mean HbA1c levels compared to non-users. Healthcare providers should engage patients in discussions about herbal medicine use, emphasizing the potential risks to glycemic management. Future research should explore specific herbs used, their mechanisms of action, and strategies to integrate herbal medicine safely into diabetes management protocols.

Aim: We tested whether skeletal muscle mass is associated with insulin sensitivity, pancreatic β-cell function, and postglucose glycemia. Methods: Appendicular skeletal muscle mass (ASM) (relative to body size, %ASM) by DXA, surrogate measures of insulin sensitivity, insulin secretion and the disposition index (insulin sensitivity adjusted insulin secretion: a product of the insulinogenic index and Matsuda insulin sensitivity index) inferred from serum insulin kinetics during a 75 g oral glucose tolerance test (OGTT) were evaluated in 168 young and 65 middle-aged women, whose BMI averaged

Background: Coffee berry extracts are anti-lipogenic and lipolytic. This study aims to investigate the effect and mechanism of coffee pulp on high-fat diet (HFD)-induced glucose and lipid metabolism disorder in mice. Methods: The type 2 diabetes (T2D) mouse model was established by feeding the C57BL/6 J mice with HFD. Mice were administered with coffee pulp diluted in drinking water before or after the establishment of the T2D mouse model. After treatment, the body weight and fasting blood glucose (FBG) of mice were monitored; the intraperitoneal glucose tolerance test (IPGTT) of mice was performed; plasma insulin was determined by ELISA; serum total cholesterol (TC), triglyceride (TG) and liver TG were determined by biochemical analysis; hematoxylin-eosin (H&E) staining was used to evaluate organ histomorphology. Gene expression of key genes in de novo lipogenesis (DNL) in the liver was examined by quantitative reverse transcription PCR (RT-qPCR). Results: Mice that consumed coffee pulp after modeling showed reduced FBG and liver TG, improved IPGTT, and alleviated fatty liver. Consuming coffee pulp before modeling prevented HFD-induced blood glucose and plasma TG increases. Mice consuming coffee pulp also had lower body fat and liver TG compared to the model group. qPCR results showed that the expression of transcription factors (Srebp1, PPARγ) and genes (Fasn, CideA, Plin3, Plin4, Plin5) related to DNL and lipid droplets (LD) formation in the liver of mice consuming coffee pulp were significantly lower than those of the control group. Conclusions: Our study demonstrated that coffee pulp can attenuate HFD-induced disorders of glucose and lipid metabolism, and this effect may be related to the key pathways of lipid synthesis DNL and LD formation pathways in the liver.

Background: This study assessed glucometric changes in Type 2 diabetes mellitus (T2DM) patients before, during, and after Ramadan fasting using an intermittently scanned continuous glucose monitoring system (isCGMS). Methods: This prospective comparative study included T2DM patients aged 30–70 years who were receiving nonintensive insulin in Riyadh, Saudi Arabia. In addition to the baseline characteristics, glycated hemoglobin (HbA1c) and ambulatory glucose profile (AGP)-derived metric data were collected at three specific points: pre-, during-, and post-Ramadan. Self-care activities during Ramadan were evaluated using the Diabetes Self-Management Questionnaire (DSMQ). Results: Overall, a total of 93 T2DM patients were enrolled in the study. Their mean age ±SD age was 47.9 ± 7.5 years, and 51.6 % of them were males. Compared with pre- and post-Ramadan, there was a significant decrease in HbA1c (p

Background: High prevalence of metabolic abnormalities and poor bone health in ethnic minorties may stem from differences in body composition and alterations in endocrine milieu. South Asian Indians (SAIs) are at greater risk for metabolic syndrome (MetS) and poor bone health than Caucasians. Often these differences are reported later in life and/or in a resident immigrant population compared to a Caucasian population. In this study, we determined whether vitamin D status, bone, body composition differed in young SAIs and Caucasians. Notably we compared differences amongst recent SAI immigrants and Caucasians. Methods: We examined differences in bone density, body composition, serum 25-hydroxy vitamin D (s25(OH)D), parathyroid hormone (sPTH), vitamin D binding protein (sDBP), osteocalcin (sOC), and dietary intakes in young healthy SAI and Caucasian men. Results: Sixty men (N = 30 SAIs and N = 30 Caucasians) with a mean age of 27.8 ± 7.4 years completed the study. Compared to the Caucasians, SAIs had statistically significantly lower s25(OH)D and higher sPTH (p

Background: This study examines the association between apolipoprotein E (APOE) genotypes and metabolic syndrome (MetS) in an older urban population in South India, as part of the Tata Longitudinal Study on Aging. Methods: A total of 618 participants aged 45 and above were analyzed cross-sectionally for the association between APOE carrier status and MetS (based on both NCEP ATP III and Consensus criteria). Results: Despite the high prevalence of MetS observed in this cohort (51.62 % by NCEP-ATP III and 61.33 % by Consensus criteria), multivariable logistic regression revealed no significant association between APOE genotypes and MetS under both criteria. However, specific associations were noted in age and sex-stratified analyses; notably, E2 carriers under 60 showed 0.42-fold decreased odds (95%CI:0.20,0.89, p-value-0.023) for an increased waist circumference, and E4 carriers above 60 were at 1.85 times increased odds (95 % CI:1.04,3.28, p-value

Background: 25-hydroxy vitamin-D (25(OH)D) deficiency is prevalent worldwide including India. Earlier some cross-sectional studies have discussed 25(OH)D deficiency and its prevalence. The correlation of 25(OH)D with seasonal variation has been reported rarely in India. To determine the 25(OH)D levels and seasonal changes of 25(OH)D status at a tertiary care hospital in North-western India. Materials and methods: 25(OH)D assessments performed in laboratories between 2018 and 2020 was acquired using hospital records. A total of 11,428 assays of serum 25(OH)D were analyzed in the study. Subjects were divided into three groups based on the International Endocrine Society's recommendation for serum 25(OH)D level. The 25(OH)D deficiency

Adropin, a peptide discovered in 2008, has gained recognition as a key regulator of cardiovascular health and metabolic balance. Initially identified for its roles in energy balance, lipid metabolism, and glucose regulation, adropin has also been found to improve cardiovascular health by enhancing endothelial function, modulating lipid profiles, and reducing oxidative stress. These protective mechanisms suggest that adropin may be able to help prevent conditions such as atherosclerosis, hypertension, and other cardiovascular diseases. Research has established connections between adropin and cardiovascular risk factors, such as obesity, insulin resistance, and dyslipidemia, positioning it as a valuable biomarker for evaluating cardiovascular disease risk. New studies highlight adropin's diagnostic and prognostic significance, showing that higher levels are linked to better cardiovascular outcomes, while lower levels are associated with a higher risk of cardiovascular diseases. This review aims to summarize current knowledge on adropin, emphasizing its significance as a promising focus in the intersection of cardiovascular health and metabolic health. By summarizing the latest research findings, this review aims to offer insights into the potential applications of adropin in both clinical practice and research, leading to a deeper understanding of its role in maintaining cardiovascular and metabolic health.

Background: While prevalence estimates differ by definition of metabolic syndrome (MetS), it is less clear how different definitions affect associations with alcohol consumption. Methods: We included 3051 adults aged 25–77 from the baseline examination of the Swedish INTERGENE cohort (2001–2004). Using multiple logistic regression, we investigated cross-sectional associations between ethanol intake and MetS defined according to the Adult Treatment Panel III (ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). Alcohol exposure categories comprised abstinence, and low, medium, and high consumption defined via sex-specific tertiles of ethanol intake among current consumers. Covariates included sociodemographics, health, and lifestyle factors. Results: MetS prevalence estimates varied between 13.9 % (ATP III) and 25.3 % (JIS), with higher prevalence in men than women. Adjusted for age and sex, medium-high alcohol consumption was associated with lower odds of MetS compared to low consumption, while no difference was observed for abstainers. Only the most specific (and thus severe) definition of MetS (ATP III) showed decreasing odds for ethanol intake when adjusted for all covariates. Conclusion: Our study shows that alcohol-related associations differ by definition of MetS. The finding that individuals with the most stringently defined MetS may benefit from alcohol consumption calls for further well-controlled studies.

Background: In sub-Saharan African nations, there's a documented shortfall in the utilization of statins, despite established clinical guidelines advocating their use for reducing cardiovascular risks and overall mortality among Type 2 diabetes patients aged 40–75 years old. Most clinical guidelines recommend prescribing statins to individuals with type 2 diabetes to reduce the chances of cardiovascular disease. There is currently a lack of extensive research on statin utilization specifically for primary prevention of cardiovascular disease in Africa. Thus, this study aimed to assess the prescription patterns of statins for preventing cardiovascular disease in type 2 diabetes patients. Methods: The findings of the review were presented following the guidelines outlined in the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA-2020) checklist. We conducted searches on electronic databases including PubMed, EMBASE, Cochrane Library, Science Direct, African Journal Online, and Google Scholar. This systematic review and meta-analysis included articles that met specific inclusion criteria: observational studies such as cross-sectional, cohort, and case-control studies focusing on determinants, risk factors, or correlates associated with statin prescription within Africa. Only published articles up to June 2, 2024, published in English, and conducted in either community or healthcare facility settings were considered. Data import was initially conducted using Microsoft Excel, and statistical analysis was performed using STATA software. Cochran's Q test was employed to assess whether there was a significant variance in prevalence among the studies. Additionally, the I2 statistic was utilized to quantify the extent of heterogeneity. A funnel plot, a visual tool, was utilized to evaluate publication bias. Results: The search strategy resulted in 7695 published original articles. The full texts of the 89 papers were assessed for eligibility and quality. Moreover, some articles were rejected due to inaccuracies in the outcome variable. Ultimately, only ten studies focusing on the prevalence of statin prescription were examined. The research suggests that the pooled prevalence of statin prescription among Type 2 diabetic individuals in Africa is found to be 48.82% (95% CI: 35.41–63.24). Age greater than 65 years (AOR = 3.56, 95% CI: 1.70–7.45; I2 = 54.7%), comorbidity (AOR = 1.13, 95% CI: 0.27–4.63, I2 = 96.4%), dyslipidemia (AOR = 3.15, 95% CI: 1.54–6.44, I2 = 61.7%), DM duration greater than ten years (AOR = 1.36, 95% CI: 0.81–2.28, I2 = 77.3%), and government insurance (AOR = 8.85, 95% CI: 2.72–28.76, I2 = 81.5%) were factors associated with statin prescription among type 2 diabetic patients. Conclusions: In general, the extent of statin prescriptions for individuals with type 2 diabetes who are eligible for statin therapy was below the target outlined by clinical practice guidelines. Being over 65 years old, having comorbidities, experiencing dyslipidemia, having type 2 diabetes for more than ten years, and having government insurance were all identified as independent factors predicting the prescription of statins. This finding is concerning and underscores the urgent need to enhance adherence to clinical practice guidelines for the well-being of this vulnerable population at high risk.

Hypovitaminosis D is highly prevalent in critically ill patients, and it has been suggested to be a risk factor for infections, sepsis and higher mortality. We sought to investigate whether serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in critically ill patients with new onset sepsis are associated with severity and outcome. We prospectively included 50 consecutive critically ill adult cases with new onset sepsis and 50 healthy controls matched for age and sex. PTH and 25(OH)D were determined in serum via electrochemiluminescence immunoassays at inclusion in the study in all cases and controls, and one week after sepsis onset in cases. Patients had reduced 25(OH)D compared to controls at sepsis onset (7.9 ± 3 vs 24.6 ± 6.7 ng/mL, p 0.05). 25(OH)D was positively correlated with ionized calcium (r = 0.46, p

Background/Aims: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM). This study aimed to investigate the association between genetic polymorphisms, specifically AGTR1 (rs5186) and TGF-β1 (rs1800470), and the risk of developing Diabetic nephropathy (DN) in type 2 diabetes mellitus patients, compared to those without DN and healthy controls. Methods: A case-control study was conducted on 165 diabetic patients (59 with diabetic nephropathy (DN) and 54 without DN (DM)), and 52 healthy controls (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Age, gender, and duration of diabetes were matched across groups. Clinical parameters including FBS, RBS, HbA1C, creatinine, urea, SBP, DBP, total cholesterol, triglycerides, LDL, and BMI were assessed. Results: Diabetic patients with nephropathy exhibited significantly higher levels of clinical parameters compared to those without nephropathy and healthy controls. The risk allele of AGTR1 , C (p

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements. It has been suggested that autophagy promotes β-cell survival by delaying apoptosis and providing adaptive responses to mitigate the detrimental effects of ER stress and DNA damage, which is directly related to oxidative stress. As people with diabetes are now living longer, they are more susceptible to a different set of complications. There has been a diversification in causes of death, whereby a larger proportion of deaths among individuals with diabetes is attributable to nonvascular conditions; on the other hand, the proportion of cancer-related deaths has remained stable or even increased in some countries. Due to the increasing cases of both T1D and T2D, these diseases become even more socially significant. Hence, we believe that search for any opportunities for control of this disease is an overwhelmingly important target for the modern science. We focus on two differences that are characteristic of the development of diabetes’s last periods. One of them shows that all-cause death rates have declined in several diabetes populations, driven in part by large declines in vascular disease mortality but large increases in oncological diseases. Another hypothesis is that some T2D medications could be repurposed to control glycemia in patients with T1D.

Background/Aims: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells. Methods: To pursue this goal, we performed bioinformatic analyses of public datasets. Results: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire. Cluster 1 expressed higher levels of enzymes for S1P formation than cluster 0 which was characterized by enzymes that lead to ceramide formation, which represent the opposite metabolic direction. Inference analysis showed that cluster 1 was higher populated by monocytes, CD4+ T and B cells than cluster 0. Of particular interest was the phenotype of the monocytes in cluster 1 which showed an immunosuppressive nature compared to those in cluster 0. The role of S1P signature in healthy PBMCs was confirmed with other dataset analyses, supporting that circulating monocytes positive to the ceramidase, unlike the negative ones, had an immunosuppressive phenotype characterized by hub immunosuppressive markers (i.e. TYROBP, FCER1G, SYK, SIRPA, CSF1R, AIF1, FCGR2A, CLEC7A, LYN, PLCG2, LILRs, HCK, GAB2). This hub genes well discriminated the immunotype of healthy subjects. Conclusion: In conclusion this study highlights that S1P-associated hub markers can be useful to discriminate subjects with pronounced immunosuppression.

Background/Aims: Extracellular acidic conditions impair cellular activities; however, some cancer cells drive cellular signaling to adapt to the acidic environment. It remains unclear how ovarian cancer cells sense changes in extracellular pH. This study was aimed at characterizing acid-inducible currents in an ovarian cancer cell line and evaluating the involvement of these currents in cell viability. Methods: The biophysical and pharmacological properties of membrane currents in OV2944, a mouse ovarian cancer cell line, were studied using the whole-cell configuration of the patch-clamp technique. Viability of this cell type in acidic medium was evaluated using the MTT assay. Results: OV2944 had significant acid-sensitive outwardly rectifying (ASOR) Cl− currents at a pH50 of 5.3. The ASOR current was blocked by pregnenolone sulfate (PS), a steroid ion channel modulator that blocks the ASOR channel as one of its targets. The viability of the cells was reduced after exposure to an acidic medium (pH 5.3) but was slightly restored upon PS administration. Conclusion: These results offer first evidence for the presence of ASOR Cl− channel in ovarian cancer cells and indicate its involvement in cell viability under acidic environment.

Nephrogenic diabetes insipidus is a heterogeneous disease in the etiopathogenesis of which are involved acquired and congenital factors. In this case, the kidneys do not respond to vasopressin and continue to produce large concentrated volumes of urine. Distinctive features in the pathology of central genesis are the fact of trauma, brain tumor with involvement of pituitary gland, response to intranasal vasopressin in the form of decreased diuresis.For diagnosis it is important to perform a series of differential diagnostic tests.In this article we present a unique clinical case of a patient with a long-term course of diabetes insipidus with the development a spectrum of comorbid conditions, metabolic disorders, required kidney transplantation.

BACKGROUND: Overweight and obesity have a significant impact on the course and results of treatment of many diseases, including cancer. One of the modern types of antitumor therapy is immune checkpoint inhibitors. Taking into account the high effectiveness of immune checkpoint inhibitors for various types of tumors, it seems interesting to study the initial anthropometric data of patients and assess the possible influence of nutritional status on the development of endocrine immune-mediated adverse events.AIM: To compare groups of patients with different starting body mass index (BMI) before the first administration of the immune checkpoint inhibitors drug and analyze the risk of developing endocrine immune-mediated adverse events in the future.MATERIALS AND METHODS: The single-center study included 172 patients who were recommended antitumor therapy immune checkpoint inhibitors at the N.N. Blokhin National Medical Research Center of Oncology and Moscow City Oncology Hospital №62 in 2020–2022. Measurement of height and body weight with further calculation of BMI was carried out before the first administration of the drug immune checkpoint inhibitors.Depending on the subsequent occurrence of immune-mediated adverse events, patients were divided into groups: those with developed immune-mediated adverse events (any, cutaneous, thyroid) and those without immune-mediated adverse events (any, cutaneous, thyroid).RESULTS: According to the results of our study, in 38 patients (37.3%) out of 102, for whom data on the presence/absence of any immune-mediated adverse events were obtained, the following were recorded: thyropathies (n=13, 12.7%), skin lesions (n=13, 12.7%), gastrointestinal toxicity (n=7, 6.9%), hepatotoxicity (n=4, 3.9%), hypophysitis (n=2, 2%), nephritis (n=2, 2%), diabetes mellitus (DM) (n=1, 1%), hematological toxicity (n=1, 1%), pneumonitis (n=1, 1%), Guillain-Barré syndrome (n=1, 1%). At the same time, in most patients only one immune-mediated adverse event was encountered (n=31, 81.6%), two immune-mediated adverse events were detected significantly less frequently (n=7, 18.4%).When conducting a comparative analysis of groups of patients with developed immune-mediated adverse events, including dermatological ones, or their absence, a statistical trend in differences in BMI was obtained. Using ROC analysis, a BMI cut-off point was determined equal to 28.16 kg/m² for all immune-mediated adverse events and 25.39 kg/m² for skin immune-mediated adverse events, below which, contrary to the available data, the risk of developing immune-mediated adverse events increased, but the diagnostic sensitivity (DS) and diagnostic specificity (DS) turned out to be low.CONCLUSION: We identified a statistical trend in the risk of developing immune-mediated adverse events (primarily dermatological) with a lower BMI before the start of antitumor immunotherapy immune checkpoint inhibitors. More research is required to find a more reliable relationship.

Androgen insensitivity syndrome is a genetic disorder characterized by complete or partial androgen insensitivity in individuals with a 46XY genotype. It is also the most common cause of disorders of sexual differentiation in patients with a 46XY karyotype. This condition is caused by a defect in the androgen receptor gene (AR), leading to abnormal development of male genitalia, impaired formation of male secondary sexual characteristics, and phenotypic features resembling the female sex.One of the important aspects related to the management of androgen insensitivity syndrome is the necessity of preventive gonadectomy. However, the rationale for prophylactic removal of gonads remains a subject of debate. This article presents a clinical case of a 37-year-old woman with complete androgen insensitivity syndrome who, despite recommendations for gonadectomy based on suspicious MRI characteristics of the gonads, made the decision to decline surgical intervention, justifying her choice by the positive impact of gonadal hormonal activity on her external appearance and physical characteristics. This clinical case highlights the complexity of decision-making in the management of androgen insensitivity syndrome, where patient preferences and needs may play a significant role, despite potential risks and concerns surrounding the preservation of gonads.

The prevalence of obesity and type 2 diabetes continues to grow, which determines the need to develop new methods of prevention in order to reduce the population risks of developing these diseases. The current direction is to limit the consumption of easily digestible carbohydrates and use low-calorie or non-calorie sweeteners instead. Currently, there is an increase in the use of non-calorie sweeteners in the manufacture of food. In this regard, the study of their possible effects on metabolic processes is of great importance.This review presents studies that have shown different effects of non-calorie sweeteners on carbohydrate and fat metabolism, body weight, the composition of intestinal microbiota, as well as the regulation of eating behavior. Some studies show that low-calorie sugar substitutes can be used in obese people as part of a comprehensive weight loss program, as well as in patients with type 2 diabetes mellitus with the aim of reducing postprandial hyperglycemia. Other studies demonstrate the negative effect of a number of low-calorie sweeteners on carbohydrate metabolism.The main search for materials was carried out in Pubmed databases, eLIBRARY.ru, Google Scholar. Temporary search criteria 2012–2023 The relevant additional literature was included after a manual search in the literature lists of the included articles.

The article discusses certain aspects of the relationship between neurological diseases and metabolic disorders that are extremely relevant in connection with the pandemic spread of obesity. The pathogenesis of damage to the nervous system (NS) is considered in detail. The influence of the main metabolic factors on the development of cerebrovascular diseases (CVD), incl. neuroinflammation, changes in hemostasis, etc. is demonstrated. The problem of the development of cognitive dysfunction against the background of obesity due to the formation of atrophic processes in brain structures is highlighted. Modern possibilities of evaluation and modulation of eating behavior due to brain stimulation using functional magnetic resonance imaging (fMRI) and navigational rhythmic transcranial magnetic stimulation (rTMS) are described.The problem of cerebrometabolic health is presented as a continuum of metabolic and cerebral disturbances. The mechanisms of interaction between the two most important systems of the body allow us to consider the changes that occur in them as an integral neuroendocrine alteration.

BACKGROUND: A special role in the development of obesity is given to the genetic polymorphism of lipid metabolism enzymes, which include triacylglycerol lipase. However, there is still no information about the relationship between the single nucleotide polymorphism (snp) of the triacylglycerol lipase (LIPC) gene and the state of the endocrine function of mesenchymal tissues in childhood and adolescence obesity.AIM: The aim of the work was to study the relationship between snp LIPC for rs2070895 and changes in the content of adipokines, myokines, and the values of blood lipid metabolism in obese children and adolescents with different sexes.MATERIALS AND METHODS: In 96 healthy children and adolescents of different sexes and 98 obese peers, a study was conducted to assess the snp of the LIPC by rs2070895. In the blood serum of the examined, the content of total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triacylglycerols, glucose, activity of alanine aminotransferase and aspartate aminotransferase, as well as the level of leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrine, oncostatin M , insulin and asprosin.RESULTS AND DISCUSSION: It has been established that obesity in boys is accompanied by hyperleptinemia, the occurrence of insulin resistance and disorders of blood lipid metabolism. In carriers of the heterozygous allele -250G/A, dyslipidemia and atherogenesis decrease in obesity, but alteration of internal organs increases. In girls with different LIPC genotypes for rs2070895, with obesity, there is an increase in the level of leptin and apelin, as well as irisin and insulin in the blood. In girls with the homozygous allele -250G/G, in addition to that, the content of resistin, asprosin and prolactin decreases in the blood, which is not are typical for girls with the heterozygous allele -250G/A. In obese girls with the heterozygous allele, the levels of adipsin, FGF-21, oncostatin M, and osteocrine increase, which are not typical for obese girls with the homozygous allele. Against the background of changes in the content of adipokines and myokines in girls homozygous for LIPC, obesity occurs dyslipemia, which is not typical for girls with the heterozygous allele -250G/A.CONCLUSION: The snp of LIPC at rs2070895 has sex-dependent effects on the levels of adipokines, myokines, and parameters lipid metabolism in the blood.

AIM: assessment of the diagnostic accuracy of a 3% hypertonic saline infusion test in relation to a set of clinical and laboratory data (including a water deprivation test and MRI data) for differential diagnoses of diabetes insipidus (DI) and primary polydipsia (PP).METHODS: An interventional cross-sectional study was carried out at Endocrinology Research Centre From September 2021 to September 2023 ninety patients with polyuria-polydipsia syndrome were included. In order to assess the diagnostic characteristics, all the subjects underwent two tests with osmotic stimulation: a 3% hypertonic saline infusion test and a water deprivation test. Adverse events were assessed.RESULTS: Based on the results of clinical, anamnestic, laboratory and instrumental data, and the results of a water deprivation test, a final diagnosis of DI was made in 48 (53%) patients and PP in 42 (47%) patients. The agreement between the two samples is significant — Kappa = 0.823, 95% CI (0.707, 0.939). The operational parameters of the 3% hypertonic saline infusion test are: sensitivity 98% (95% CI: 89%; 100%); specificity 98% (95% CI: 87%; 100%), positive and negative predictive values 98% (95% CI: 89%–100%) and 98% (95% CI: 87%–100%). Respectively. Chills occurred significantly more often (31% vs. 12%), and dizziness and headache were more pronounced during the 3% hypertonic saline infusion test. The median duration of the water deprivation test in patients was 11 hours, and median duration of 3% hypertonic saline infusion test was 1.5 hour (P