Hormone and Metabolic Research最新文献

This study aims to establish a random forest model for detecting the severity of Graves Orbitopathy (GO) and identify significant classification factors. This is a hospital-based study of 199 patients with GO that were collected between December 2019 and February 2022. Clinical information was collected from medical records. The severity of GO can be categorized as mild, moderate-to-severe, and sight-threatening GO based on guidelines of the European Group on Graves’ orbitopathy. A random forest model was constructed according to the risk factors of GO and the main ocular symptoms of patients to differentiate mild GO from severe GO and finally was compared with logistic regression analysis, Support Vector Machine (SVM), and Naive Bayes. A random forest model with 15 variables was constructed. Blurred vision, disease course, thyroid-stimulating hormone receptor antibodies, and age ranked high both in mini-decreased gini and mini decrease accuracy. The accuracy, positive predictive value, negative predictive value, and the F1 Score of the random forest model are 0.83, 0.82, 0.86, and 0.82, respectively. Compared to the three other models, our random forest model showed a more reliable performance based on AUC (0.85 vs. 0.83 vs. 0.80 vs. 0.76) and accuracy (0.83 vs. 0.78 vs. 0.77 vs. 0.70). In conclusion, this study shows the potential for applying a random forest model as a complementary tool to differentiate GO severity.

The aim of the study was to explore the clinical features related to early hypothyroidism and the relationship between the changes of thyrotropin receptor antibodies (TRAb) and early hypothyroidism in the course of ¹³¹I treatment for Graves’ disease. This study was a retrospective observation, including 226 patients who received the first ¹³¹I treatment. The general information and laboratory tests were collected before and after ¹³¹I treatment, and the laboratory data affecting the difference in disease outcome were analyzed. According to the changes of antibodies in the third month, whether the changes of antibodies were involved in the occurrence of early-onset hypothyroidism was analyzed. Early onset hypothyroidism occurred in 165 of 226 patients, and the results showed that the incidence of early hypothyroidism was higher in patients with low baseline TRAb level (p=0.03) and increased TRAb after treatment (p=0.007). Both baseline TRAb levels (p<0.001) and the 24-hour iodine uptake rate (p=0.004) are significant factors influencing the changes in TRAb. The likelihood of a rise in TRAb was higher when the baseline TRAb was less than 18.55 U/l and the 24-hour iodine uptake level exceeded 63.61%. Low baseline and elevated post-treatment levels of TRAb were significantly associated with early-onset hypothyroidism after ¹³¹I treatment. Monitoring this index during RAI treatment is helpful in identifying early-onset hypothyroidism and mastering the clinical outcome and prognosis of Graves’ disease.

The aim was to compare the lipid profile of patients with GD treated with anti-thyroid drugs (ATDs) using a titration regimen versus a block and replace regimen. This is an 18-month prospective observational study. In this study were included 149 medically treated GD patients, aged+>+18 years. Pregnant women and patients treated with radioactive iodine therapy or partial/total thyroidectomy were excluded. Patients were divided into 2 subgroups: titration (A) and block and replace (B) therapy, according to the ATD regimen used. Thyroid and metabolic profile was measured at baseline and at least one visit during medical treatment. The whole group included 122 (81.87%) females (F) and 27 (18.12%) males (M), ratio F:M=4.5:1. As expected, at the time of diagnosis, thyrotoxic patients were with normal lipid profile. During medical treatment, in patients who achieved euthyroidism, the cholesterol levels increased as follows: in subgroup A: by 52.9 mg/dl (95% CI: 26.4–79.3), p<0.001 for total cholesterol (T-C), by 33.3 mg/dl (95% CI: 10.3–56.3), p=0.007 for low-density lipoprotein cholesterol (LDL-C) and by 11.44 mg/dl (95% CI: 3.08–19.79), p=0.009 for high-density lipoprotein cholesterol (HDL-C); in subgroup B T-C increased by 45.1 mg/dl (95% CI: 22.2–68), p<0.001 and for LDL-C by 33.57 mg/dl (95% CI: 12.72–54.42), p=0.003. No statistically significant increase in triglyceride levels was determined. Medical treatment of hyperthyroidism due to Graves’ disease increased cholesterol levels regardless of the ATD regimen used.

The knowledge about the features of energy metabolism in MAFLD in the population living at different climatic and geographic heights is lacking. The goal of this study is to explore the biochemical parameters of blood and erythrocyte energy consumption in patients with MAFLD with and without DM2 living in the low- and moderate-altitude regions of Central Asia. Our study was carried out on patients living in low-altitude mountains: Bishkek, altitude=750-800 m; n=67 (MAFLD with DM 2: n=24; MAFLD without DM2: n=25; control: n=18), and At-Bashy District, Naryn Region, altitude=2046-2300 m; n=58 (MAFLD with DM2: n=28; MAFLD without DM2: n=18; control: n=12). Non-alcoholic fatty liver disease was diagnosed according to history, laboratory tests, liver ultrasound, and exclusion of other liver diseases. The level of liver fibrosis was determined using the FIB-4 score. Blood adenosine 5'-triphosphate (ATP) was determined using the CellTiter-Glo method. Healthy residents living in moderate altitudes have significantly higher levels of cytosolic ATP in their blood (p+≤+0.05) than residents living in low mountains. MAFLD is characterized by an increase in the level of ATP concentration in their blood. ATP concentration decreased significantly in patients with MAFLD with DM2 living in moderate-altitude in comparison to those living in low-altitude mountains. The results suggest that chronic altitude hypoxia leads to a breakdown in adaptive mechanisms of energy metabolism of ATP in patients with MAFLD with type 2 DM.

β-Thalassemia major is a congenital hemoglobin disorder that requires regular blood transfusion. The disease is often associated with iron overload and diabetes mellitus, among other complications. Pancreatic iron overload in β-thalassemia patients disrupts β-cell function and insulin secretion and induces insulin resistance. Several risk factors, including family history of diabetes, sedentary lifestyle, obesity, gender, and advanced age increase the risk of diabetes in β-thalassemia patients. Precautionary measures such as blood glucose monitoring, anti-diabetic medications, and healthy living in β-thalassemia patients notwithstanding, the prevalence of diabetes in β-thalassemia patients continues to rise. This review aims to address the relationship between β-thalassemia and diabetes in an attempt to understand how the pathology and management of β-thalassemia precipitate diabetes mellitus. The possible employment of surrogate biomarkers for early prediction and intervention is discussed. More work is still needed to better understand the molecular mechanism(s) underlying the link between β-thalassemia and diabetes and to identify novel prognostic and therapeutic targets.

COVID-19 disease, caused by the severe acute respiratory syndrome virus 2 (SARS-CoV-2), induces a broad spectrum of clinical symptoms ranging from asymptomatic cases to fatal outcomes. About 10-35% of all COVID-19 patients, even those with mild COVID-19 symptoms, continue to show symptoms, i. e., fatigue, shortness of breath, cough, and cognitive dysfunction, after initial recovery. Previously, we and others identified red blood cell precursors as a direct target of SARS-CoV-2 and suggested that SARS-CoV-2 induces dysregulation in hemoglobin- and iron-metabolism contributing to the severe systemic course of COVID-19. Here, we put particular emphasis on differences in parameters of clinical blood gas analysis and hematological parameters of more than 20 healthy and Long-COVID patients, respectively. Long-COVID patients showed impaired oxygen binding to hemoglobin with concomitant increase in carbon monoxide binding. Hand in hand with decreased plasma iron concentration and transferrin saturation, mean corpuscular hemoglobin was elevated in Long-COVID patients compared to healthy donors suggesting a potential compensatory mechanism. Although blood pH was within the physiological range in both groups, base excess- and bicarbonate values were significantly lower in Long-COVID patients. Furthermore, Long-COVID patients displayed reduced lymphocyte levels. The clinical relevance of these findings, e. g., as a cause of chronic immunodeficiency, remains to be investigated in future studies. In conclusion, our data suggest impaired erythrocyte functionality in Long-COVID patients, leading to diminished oxygen supply. This in turn could be an explanation for the CFS, dyspnea and anemia. Further investigations are necessary to identify the underlying pathomechanisms.

Ferroptosis was recently identified as a non-apoptotic, iron-dependent cell death mechanism that is involved in various pathologic conditions. There is first evidence for its significance also in the context of islet isolation and transplantation. Transplantation of pancreatic human islets is a viable treatment strategy for patients with complicated diabetes mellitus type 1 (T1D) that suffer from severe hypoglycemia. A major determinant for functional outcome is the initial islet mass transplanted. Efficient islet isolation procedures and measures to minimize islet loss are therefore of high relevance. To this end, better understanding and subsequent targeted inhibition of cell death during islet isolation and transplantation is an effective approach. In this study, we aimed to elucidate the mechanism of ferroptosis in pancreatic islets. Using a rodent model, isolated islets were characterized relating to the effects of experimental induction (RSL3) and inhibition (Fer1) of ferroptotic pathways. Besides viability, survival, and function, the study focused on characteristic ferroptosis-associated intracellular changes such as MDA level, iron concentration and the expression of ACSL4. The study demonstrates that pharmaceutical induction of ferroptosis by RSL3 causes enhancement of oxidative stress and leads to an increase of intracellular iron, zinc and MDA concentration, as well as the expression of ACSL4 protein. Consequently, a massive reduction of islet function, viability, and survival was found. Fer1 has the potential to inhibit and attenuate these cellular changes and thereby protect the islets from cell death.

Hypokalemia plays an important role in the diagnosis and management of primary aldosteronism (PA). While the hypokalemic variant of the disease accounts for about one third of all cases, little is known about the incidence of PA in hypokalemic populations. The IPAHK+ study is an epidemiological, cross-sectional trial to provide evidence on the incidence of PA in hypokalemic patients from a university hospital outpatient population. Recruitment of outpatients with hypokalemia≤3 mmol/l is carried out on a continuous referral-basis through an automated data delivery system. Up to an interim data closure, 66 patients underwent the study protocol. The mean age of the participants was 52.9±1.5 years with an equal sex ratio of 1:1 women to men, a mean potassium value of 2.78±0.31 mmol/l [1.8;3.0] and a prevalence of arterial hypertension of 72.7%. PA was diagnosed in 46.6% of all participants, all of whom had a history of hypertension. Incidence of PA increased continuously with decreasing potassium levels with proportions of 26.7%, 50% and 57.1% in the subgroups of 3.0 mmol/l (n=15), 2.8-2.9 mmol/l (n=22) and≤2.7 mmol/l (n=21), respectively. Prior to testing, 59.1% of all patients presented at least with one plausible other cause of hypokalemia. The incidence of PA in the investigated outpatient population was more than 4 out of 10 and inversely correlated with baseline potassium levels. Moderate or severe hypokalemia, regardless of its cause, should therefore prompt evaluation for PA in hypertensive individuals. Normotensive hypokalemic PA was not observed in this cohort.

The preservation of pancreatic islet β-cells is crucial in diabetes mellitus, encompassing both type 1 and type 2 diabetes. β-cell dysfunction, reduced mass, and apoptosis are central to insufficient insulin secretion in both types. Research is focused on understanding β-cell characteristics and the factors regulating their function to develop novel therapeutic approaches. In type 1 diabetes (T1D), β-cell destruction by the immune system calls for exploring immunosuppressive therapies, non-steroidal anti-inflammatory drugs, and leukotriene antagonists. Islet transplantation, stem cell therapy, and xenogeneic transplantation offer promising strategies for type 1 diabetes treatment. For type 2 diabetes (T2D), lifestyle changes like weight loss and exercise enhance insulin sensitivity and maintain β-cell function. Additionally, various pharmacological approaches, such as cytokine inhibitors and protein kinase inhibitors, are being investigated to protect β-cells from inflammation and glucotoxicity. Bariatric surgery emerges as an effective treatment for obesity and T2D by promoting β-cell survival and function. It improves insulin sensitivity, modulates gut hormones, and expands β-cell mass, leading to diabetes remission and better glycemic control. In conclusion, preserving β-cells offers a promising approach to managing both types of diabetes. By combining lifestyle modifications, targeted pharmacological interventions, and advanced therapies like stem cell transplantation and bariatric surgery, we have a significant chance to preserve β-cell function and enhance glucose regulation in diabetic patients.