The association of waist circumference with bone mineral density and risk of osteoporosis in US adult: National health and nutrition examination survey.

PURPOSE: Obesity and osteoporosis (OP) are receiving increasing attention. Waist circumference (WC) is an effective indicator for assessing central obesity. Currently, there is controversy regarding the relationship between WC and bone mineral density (BMD), as well as OP. Therefore, our study aims to utilize data from the National Health and Nutrition Examination Survey (NHANES) to evaluate the relationship between WC and BMD, as well as OP, in US adults. METHODS: This cross-sectional study included subjects aged ≥18 years from the NHANES 1999-2018. Multivariate linear regression models were performed to investigate the association between WC and BMD. Multivariate logistic regression models were employed to assess the relationship between WC and OP. Restricted cubic spline curves were used to assess potential nonlinear association between WC and BMD, OP. Subgroup analysis and sensitivity analysis were performed to assess the robustness of the results. RESULTS: Finally, 11,165 participants (non-OP, n = 10,465; OP, n = 700) were included in the final analysis. The results showed that WC was positively associated with total femur (TF), femoral neck (FN), and lumbar spine (LS) BMD, and might be a protective factor for OP, independent of traditional confounding factors. For each 1 cm increased in WC, TF BMD, FN BMD and LS BMD increased by 0.004 g/cm2, 0.003 g/cm2 and 0.003 g/cm2, respectively, and the risk of OP decreased by 3.1 %. Furthermore, there was a non-linear relationship between WC and BMD, OP. The association remained robust in sensitivity and subgroup analyses. CONCLUSION: In US adults, there is a positive association between WC and BMD, and WC may be a protective factor for the risk of OP. The association between WC and BMD as well as OP exhibits a non-linear relationship.

Liddle syndrome presenting with normal aldosterone levels: A case report.

INTRODUCTION: Liddle syndrome is an autosomal dominant disorder characterized by hypertension, hypokalemia, low aldosterone levels, and reduced renin activity. Atypical Liddle syndrome can be easily misdiagnosed due to its clinical phenotypes resembling hyperaldosteronism. PATIENT CONCERN: The patient was diagnosed with primary aldosteronism due to hypertension and hypokalemia, and underwent left adrenalectomy. After the operation, the patient still had hypertension and hypokalemia that were not easy to control and correct, and had acute cerebral infarction. DIAGNOSIS: The genetic test showed that the base duplication in the coding region of SCN1B gene caused a frameshift mutation:c.1789dupC (p.Arg597fs), Liddle syndrome was diagnosed. INTERVENTION AND OUTCOMES: The patient was treated with a low-sodium diet and oral triamterene. The serum potassium level returned to normal and the blood pressure was controlled. LESSONS: Some Liddle syndrome may present with normal aldosterone levels, genetic testing is necessary for the diagnosis. If the diagnostic test of primary aldosteronism is positive, but the treatment with spironolactone is ineffective, we should actively search for other causes.

Trabecular bone score in type 1 diabetes: a meta-analysis of cross-sectional studies.

BACKGROUND: Bone fragility is a recognized complication of type 1 diabetes (T1D). Thus, lower trabecular bone score (TBS) measurements in T1D patients can be predicted. However, the results of current studies on TBS in patients with T1D are inconsistent. In this context, the present study aimed to test the hypothesis that T1D is associated with lower TBS through a meta-analysis. METHODS: An electronic search of the literature was conducted using PubMed, Embase and Web of science databases to identify studies related to TBS and T1D, supplemented by an additional manual check of the reference list of relevant original and review articles. All data was analyzed using a random effects model. Results were compared using standardized mean differences (SMD) and 95% confidence intervals (CI). P ≤ 0.05 was considered statistically significant. Review Manager 5.4 software and Stata 17.0 software were used for statistical analysis. RESULTS: Seven cross-sectional studies involving 848 participants were included. TBS was lower in T1D patients than in healthy controls on random effects analysis, with no heterogeneity (SMD = - 0.39, 95% CI [- 0.53, - 0.24], P < 0.001; I2 = 0%). In addition, by subgroup analysis, T1D patients were strongly associated with reduced TBS in different regions and age groups, and the results were independent of covariate adjustment. CONCLUSION: This study showed that TBS was lower in patients with T1D than in healthy individuals with normal blood glucose levels, suggesting that TBS may be a useful measure to assess fracture risk in T1D.

The association between prediabetes and bone mineral density: A meta-analysis.

BACKGROUND: Prediabetes is an intermediate metabolic state between euglycaemia and diabetes, including three different definitions: impaired fasting glucose, impaired glucose tolerance, and mildly elevated glycated haemoglobin (HbA1c) (range 5.7%-6.4%). The effect of prediabetes on bone mineral density (BMD) has not been established. Therefore, we performed a meta-analysis to evaluate the association between prediabetes and BMD. METHODS: We retrieved studies related to prediabetes and BMD from PubMed, Web of Science, and Embase databases from January 1990 to December 2022. All data were analysed using the random effects model. Statistical heterogeneity was tested by I2 . Subgroup analysis was performed after each study-level variable was pre-defined by meta-regression. RESULTS: A total of 17 studies were included involving 45,788 patients. We detected a significant overall association of prediabetes with increased spine BMD (weighted mean difference [WMD] = 0.01, 95% CI [0.00, 0.02], p = 0.005; I2  = 62%), femur neck (FN) BMD (WMD = 0.01, 95% CI [0.00, 0.01], p < 0.001; I2  = 19%), and femur total (FT) BMD (WMD = 0.02, 95% CI [0.01, 0.03], p < 0.001; I2  = 51%). Several variables leading to heterogeneity were defined by meta-regression, including age, sex, region, study type, dual-energy X-ray absorptiometry scanner manufacturer, and prediabetes definition. Subgroup analyses indicated that the association of prediabetes with increased BMD was stronger in men, Asians, and older adults over 60 years of age. CONCLUSIONS: Current evidence shows that prediabetes is strongly associated with increased BMD of the spine, FN, and FT. The association was stronger among males, Asians, and older adults over 60 years of age.

Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: Type 2 diabetes mellitus(T2DM) is closely related to sarcopenic obesity(SO). Body composition measurement including body weight, body mass index, waist circumference, percentage body fat, fat mass, muscle mass, visceral adipose tissue and subcutaneus adipose tissue, plays a key role in evaluating T2DM and SO. The weight reduction effect of sodium-glucose cotransporter 2(SGLT-2) inhibitors has been demonstrated. However, there are warnings that SGLT-2 inhibitors should be used with caution because they may increase the risk of sarcopenia. The effect of SGLT-2 inhibitors on body composition in T2DM is inconclusive. In this work, a meta-analysis of randomized controlled trials was conducted to evaluate the effect of SGLT-2 inhibitors on body composition in T2DM. METHODS: PubMed, the Cochrane Library, EMbase and Web of Science databases were searched by computer. All statistical analyses were carried out with Review Manager version 5. 3. Results were compared by weight mean difference(WMD), with 95% confidence intervals(CI) for continuous outcomes. A random effects model was applied regardless of heterogeneity. The I2 statistic was applied to evaluate the heterogeneity of studies. Publication bias was assessed using Funnel plots. RESULTS: 18 studies with 1430 participants were eligible for the meta-analysis. SGLT-2 inhibitors significantly reduced body weight(WMD:-2. 73kg, 95%CI: -3. 32 to -2. 13, p<0. 00001), body mass index(WMD:-1. 13kg/m2, 95%CI: -1. 77 to -0. 50, p = 0. 0005), waist circumference(WMD:-2. 20cm, 95%CI: -3. 81 to -0. 58, p = 0. 008), visceral fat area(MD:-14. 79cm2, 95%CI: -24. 65 to -4. 93, p = 0. 003), subcutaneous fat area(WMD:-23. 27cm2, 95% CI:-46. 44 to -0. 11, P = 0. 05), fat mass(WMD:-1. 16kg, 95%CI: -2. 01 to -0. 31, p = 0. 008), percentage body fat(WMD:-1. 50%, 95%CI:-2. 12 to -0. 87, P<0. 00001), lean mass(WMD:-0. 76kg, 95%CI:-1. 53 to 0. 01, P = 0. 05) and skeletal muscle mass(WMD:-1. 01kg, 95%CI:-1. 91 to -0. 11, P = 0. 03). CONCLUSION: SGLT-2 inhibitors improve body composition in T2DM including body weight, body mass index, waist circumference, visceral fat area, subcutaneous fat area, percentage body fat and fat mass reduction, but cause adverse effects of reducing muscle mass. Therefore, until more evidence is obtained to support that SGLT-2 inhibitors increase the risk of sarcopenia, not only the benefit on body composition, but also the adverse effect of the reduction in muscle mass by SGLT-2 inhibitors in T2DM should be considered.

A Three-gene-based Type 1 Diabetes Diagnostic Signature.

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease featured by insulin deprivation caused by pancreatic ß-cell loss, followed by hyperglycaemia. OBJECTIVE: Currently, there is no cure for this disease in clinical treatment, and patients have to accept a lifelong injection of insulin. The exploration of potential diagnosis biomarkers through analysis of mass data by bioinformatics tools and machine learning is important for type 1 diabetes. METHODS: We collected two mRNA expression datasets of type 1 diabetes peripheral blood samples from GEO, screened differentially expressed genes (DEGs) by R software, and conducted GO and KEGG pathway enrichment using the DEGs. Moreover, the STRING database and Cytoscape were used to build PPI network and predict hub genes. We constructed a logistic regression model by using the hub genes to assess sample type. RESULTS: Bioinformatic analysis of the GEO dataset revealed 92 and 75 DEGs in GSE50098 and GSE9006 datasets, separately, and 10 overlapping DEGs. PPI network of these 10 DEGs showed 7 hub genes, namely EGR1, LTF, CXCL1, TNFAIP6, PGLYRP1, CHI3L1 and CAMP. We built a logistic regression model based on these hub genes and optimized the model to 3 genes (LTF, CAMP and PGLYRP1) based logistic model. The values of the area under the curve (AUC) of training set GSE50098 and testing set GSE9006 were 0.8452 and 0.8083, indicating the efficacy of this model. CONCLUSION: Integrated bioinformatic analysis of gene expression in type 1 diabetes and the effective logistic regression model built in our study may provide promising diagnostic methods for type 1 diabetes.

Treatment of refractory gout with TNF-α antagonist etanercept combined with febuxostat.

A male patient, diagnosed as acute gouty arthritis with hypertension, gastrointestinal fungal infection, gastric ulcer, and other diseases, received the following treatment: low purine diet, alkalization of urine, omeprazole to inhibit gastric acid secretion, low-dose colchicine to relieve joint pain, febuxostat to reduce uric acid synthesis, losartan potassium to reduce blood pressure, atorvastatin calcium tablet to lower lipid, cefmendoxime proxetil to resist infection, and TNF-α antagonist etanercept 25 mg subcutaneous injection two times a week (with 72 hours interval) for two weeks. As a result, the patient responded well to TNF antagonist etanercept. The joint pain was significantly relieved one day after treatment and completely relieved after five days. Two weeks later, the results of C-reaction protein (CRP) and blood routine examination returned to normal. We drawed conclusions as follows: TNF antagonists etanercept can alleviate the acute inflammatory response of gouty arthritis and ensure uric acid-lowering therapy. However, the safety and effectiveness of the drug in the treatment of acute, complex, and refractory gout still need to be confirmed by randomized, multi-center, large sample clinical controlled study. This case report only supplies a new reference scheme for the treatment of similar diseases.

IRS-1 targets TAZ to inhibit adipogenesis of rat bone marrow mesenchymal stem cells through PI3K-Akt and MEK-ERK pathways.

Gene modification of mesenchymal stem cells (MSCs) offers a promising approach for clinical stem cell therapy. Transcriptional co-activator with PDZ-binding motif (TAZ) plays a vital role in MSCs' differentiation. We aim to explore the interaction of insulin receptor substrate-1 (IRS-1) with TAZ to regulate MSCs' adipogenesis in this study. Initially, IRS-1 and TAZ followed similar decreasing expression pattern at the early stage of adipogenesis. And, overexpression of IRS-1 decreased the CCAAT/enhancer binding protein ß (C/EBPß) and peroxi-some proliferator-activated receptor gamma (PPARγ) expression with TAZ upregulation. Accordingly, knockdown of IRS-1 induced the upexpression of C/EBPß and PPARγ with TAZ downregulation. Indeed, IRS-1 targeted TAZ to downregulate the C/EBPß and PPARγ expression, while knockdown of TAZ attenuated the IRS-1 inhibited adipogenesis. Furthermore, both LY294002 (the PI3K-Akt inhibitor) and U0126 (the MEK-ERK inhibitor) blocked the regulation of IRS-1 on TAZ during adipogenesis. Additionally, IRS-1 and TAZ influenced the cell proliferation in the above process. Taken together, this study suggests for the first time that IRS-1 is a key regulator of the MSCs' adipogenesis and may serve as a potential therapeutic target for differential alterations in bone marrow.