Insights and implications of sexual dimorphism in osteoporosis

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 18, 2024

Osteoporosis, a metabolic bone disease characterized by low mineral density and deterioration of microarchitecture, has led to high risk fatal osteoporotic fractures worldwide. Accumulating evidence revealed that sexual dimorphism is notable feature osteoporosis, with sex-specific differences in epidemiology pathogenesis. Specifically, females are more susceptible than males while prone disability or death from the disease. To date, sex chromosome abnormalities steroid hormones have been proven contribute greatly osteoporosis regulating functions cells. Understanding its related complications essential for improving treatment strategies tailored women men. This literature review focuses on mechanisms underlying mainly population aging patients, chronic glucocorticoid administration, diabetes. Moreover, we highlight implications developing therapeutics preventive screening approaches Additionally, challenges translating bench research bedside treatments future directions overcome these obstacles will be discussed.

Language: Английский

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Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials

Diabetologia, Journal Year: 2024, Volume and Issue: 67(7), P. 1206 - 1222

Published: April 13, 2024

Abstract Aims/hypothesis We conducted a systematic review and network meta-analysis to compare the efficacy safety of s.c. administered tirzepatide vs semaglutide for adults both sexes with type 2 diabetes mellitus. Methods searched PubMed Cochrane up 11 November 2023 RCTs an intervention duration at least 12 weeks assessing maintenance doses 5 mg, 10 mg or 15 once weekly, 0.5 1.0 2.0 in diabetes, regardless background glucose-lowering treatment. Eligible trials compared any specified against each other, placebo other drugs. Primary outcomes were changes HbA 1c body weight from baseline. Secondary achievement target ≤48 mmol/mol (≤6.5%) <53 (<7.0%), loss 10%, including gastrointestinal adverse events severe hypoglycaemia. used version risk-of-bias tool (ROB 2) assess risk bias, frequentist random-effects meta-analyses evaluated confidence effect estimates utilising Confidence In Network Meta-Analysis (CINeMA) framework. Results A total 28 23,622 participants (44.2% female) included. Compared placebo, was most efficacious treatment reducing (mean difference −21.61 [−1.96%]) followed by (−20.19 [−1.84%]), (−17.74 [−1.59%]), (−17.60 [−1.60%]), (−15.25 [−1.39%]) (−12.00 [−1.09%]). between-drug comparisons, all comparable superior mg. more than weight, reductions ranging 9.57 kg (tirzepatide mg) 5.27 mg). Semaglutide had less pronounced effect, 4.97 (semaglutide 2.52 demonstrated greater respectively. Both drugs increased incidence while neither nor serious Conclusions/interpretation Our data show that on reduction people diabetes. drugs, particularly higher tirzepatide, events. Registration PROSPERO registration no. CRD42022382594 Graphical

Language: Английский

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Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high risk. An assessment the efficacy semaglutide atherosclerotic disease, chronic kidney or both is needed. In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years age older, had glycated hemoglobin level 6.5 to 10.0%, known receive either once-daily (maximal dose, 14 mg) placebo, addition standard care. primary outcome was major adverse events (a composite death from causes, nonfatal myocardial infarction, stroke), assessed time-to-first-event analysis. confirmatory secondary outcomes included disease five-point outcome). Among 9650 undergone randomization, mean (±SD) follow-up 47.5±10.9 months, median 49.5 months. A primary-outcome event occurred 579 4825 (12.0%; incidence, 3.1 per 100 person-years) group, as compared 668 (13.8%; 3.7 placebo group (hazard ratio, 0.86; 95% confidence interval, 0.77 0.96; P = 0.006). results for did not differ significantly between two groups. incidence serious 47.9% 50.3% group; gastrointestinal disorders 5.0% 4.4%, respectively. both, use associated lower risk than without an increase events. (Funded by Novo Nordisk; SOUL ClinicalTrials.gov number, NCT03914326.).

Language: Английский

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Global, regional, and national burden of type 2 diabetes mellitus caused by high BMI from 1990 to 2021, and forecasts to 2045: analysis from the global burden of disease study 2021

Frontiers in Public Health, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 23, 2025

Objective To produce estimates of the global burden type 2 diabetes mellitus (T2DM) caused by high body mass index (high BMI) and its impact for 2021 projections 2045. Methods We downloaded data from Global Burden Disease Study 2021(GBD 2021) to estimate disease T2DM BMI. Secondary analyses were performed year, age, gender, region, socio-demographic (SDI). Results Globally, all-ages number T2DM-related deaths has increased significantly 238.1 thousand 723.7 thousand, representing a 203.9% increase since 1990. And T2DM-raleted DALYs raised 10.4 million 39.3 million, 276.7% The was expected continue 1296.7 2045 deaths, 85.5 DALYs. curves showed an intersection different genders around age 60, beyond which women exhibit higher burden, compared men. BMI shows significant upward trend across all SDI groups, with heavier on women, especially in postmenopausal female population. In 2021, among 204 countries territories, top 3 largest occurred China, India, United States. three highest rate Fiji, Marshall Islands, Kiribati. Conclusion Our study reveals that is increasing rising future. Women bear particularly there are differences geographical regions, socioeconomic statuses. Targeted considerations specific strategies essential address these disparities, thereby improving public health reducing burden.

Language: Английский

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Diabetes and gut microbiome

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Diabetes mellitus represents a significant global health problem. The number of people suffering from this metabolic disease is constantly rising and although the incidence heterogeneous depending on region, country, economic situation, lifestyle, diet level medical care, it increasing worldwide, especially among youths children, mainly due to lifestyle environmental changes. pathogenesis two most common subtypes diabetes mellitus, type 1 (T1DM) 2 (T2DM), substantially different, so each form characterized by different causation, etiology, pathophysiology, presentation, treatment. Research in recent decades increasingly indicates potential role gut microbiome initiation, development, progression disease. Intestinal microbes their fermentation products have an important impact host metabolism, immune system, nutrient digestion absorption, barrier integrity protection against pathogens. This review summarizes current evidence changes microbial populations both types mellitus. Attention focused abundance specific bacterial groups at taxonomic levels humans, shift also assessed relation geographic location, age, antidiabetic drug. causal relationship between bacteria still unclear, future studies applying new methodological approaches broader range microorganisms inhabiting digestive tract are urgently needed. would not only provide better understanding disease, but use beneficial species probiotics for treatment diabetes.

Language: Английский

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Comparative efficacy of incretin drugs on glycemic control, body weight, and blood pressure in adults with overweight or obesity and with/without type 2 diabetes: a systematic review and network meta-analysis

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 4, 2025

Background The rapid development of multi-receptor drugs targeting glucagon-like peptide-1 receptor (GLP-1R) is driving significant advancements in the treatment individuals with type 2 diabetes and obesity. This systematic review network meta-analysis aims to compare efficacy safety adults overweight or obesity, without diabetes. Methods A search was conducted PubMed, Cochrane, Web Science, Embase, CNKI, WanFang databases up May 12, 2024. Randomized controlled trials (RCTs) an intervention duration at least 12 weeks were included. population interest consisted Eligible studies compared placebo other drugs. primary outcomes weight reduction, glycated hemoglobin (HbA 1c ), fasting plasma glucose (FPG), blood pressure changes, adverse events. Risk bias assessed using version Cochrane risk-of-bias tool (ROB2), a random-effects performed frequentist approach. Confidence effect estimates evaluated In Network Meta-Analysis (CINeMA) framework. Results total 24 trials, involving 9165 participants, Retatrutide (mean difference (MD): -11.91 kg, 95% CI: -19.00 -4.82, P-score: 0.80, p: 0.0003) Tirzepatide (MD: -12.78 -16.10 -9.46, 0.89, p &lt; 0.0001) exhibited superior reducing body weight, all agents except Mazdutide -5.31 -9.78 -0.84, 0.37, 0.0189) achieving reductions over 8 kg. patients diabetes, reduced HbA by 1%, -1.87%, -2.15 -1.59, 0.87, -1.89%, -2.43 -1.35, 0.88, showing greatest effects on glycemic control. For management, significantly systolic -6.69 mmHg, -7.62 -5.75, 0.84, diastolic -3.73 -4.75 -2.71, 0.92, 0.0001), nearly lowering more than 5 mmHg. Non-diabetic participants showed pronounced improvements both pressure. Safety analysis revealed that had favorable profile no impact serious events placebo. Conclusions Multi-receptor demonstrated substantial therapeutic potential control, regulation generally profile. Systematic registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42024554005.

Language: Английский

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Relationship between advanced lung cancer inflammation index and long-term all-cause, cardiovascular, and cancer mortality among type 2 diabetes mellitus patients: NHANES, 1999–2018

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 28, 2023

Background Type 2 diabetes mellitus (T2DM) was a major global health threat. As chronic low-grade inflammatory disease, the prognosis of associated with inflammation. The advanced lung cancer inflammation index (ALI) served as comprehensive to assess This study aimed estimate association between ALI and all-cause, cardiovascular disease (CVD), mortality in T2DM patients. Methods We extracted cohort data from National Health Nutrition Examination Survey (NHANES) spanning 1999-2018 for analysis. weighted Kaplan-Meier analysis multivariate-adjusted Cox were utilized evaluate relationship CVD, Restricted cubic spline (RCS) employed their non-linear relationship. Stratified interaction conducted enhance robustness results. Results incorporated total 3,888 An increase reduced risk all-cause CVD patients, but not related mortality. There J-shaped L-shaped relationships respectively. inflection points 90.20 93.06, For values below point, every 10U ALI, both decreased by 9%. Beyond rose 3%, while remained unaffected. Gender-stratified RCS indicated linear negative female whereas trend males aligned overall population. Conclusion Our research initially identified significant correlation increased levels there relation These findings suggested that maintaining (for example, control body weight keep albumin normal range) within certain range clinical settings crucial improving

Language: Английский

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Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(2), P. 189 - 201

Published: Jan. 25, 2024

Background Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs).

Language: Английский

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Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet

Nutrients, Journal Year: 2024, Volume and Issue: 16(10), P. 1408 - 1408

Published: May 8, 2024

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic disease. Lifestyle modifications dieting strategies that can prevent dysfunction-associated (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD has been recommended people affected by obesity; we evaluated effect gender on steatosis fibrosis in cohort 112 overweight or obese patients undergoing an eight-week with VLCKD. Differences between genders terms anthropometric measures, body composition, indicators were examined before, during, after nutritional intervention. At baseline, there significant differences men women parameters, blood pressure, Homeostatic Model Assessment Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, lipid profile. Men had considerably higher levels (measured CAP) stiffness E) under basal conditions than women. After VLCKD, reductions both controlled attenuation parameter (CAP), weight, mass index (BMI), waist circumference, systolic diastolic insulin resistance, fat (FM), free (FFM), glucose, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) alanine transaminase (ALT), gamma-glutamyl transferase (γGT), uric acid levels. Only men, stiffness, aspartate aminotransferase (AST), creatinine, C-reactive protein (CRP) significantly decreased. Moreover, greater steatosis: male featured increase 23.96 points Fibroscan CAP. exhibited women, these persist despite These gender-specific variations could be caused hormonal factors, suggesting different therapeutic might required depending gender.

Language: Английский

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Association of triglyceride glucose index and triglyceride glucose-body mass index with sudden cardiac arrest in the general population

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 18, 2024

Abstract Background Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear. Methods This prospective cohort analysis included 355,242 UK Biobank participants available TyG TyG-BMI data no history of CVD. Cox proportional risk models assessed the association between index, SCA risk. Additionally, Accelerated Failure Time (AFT) were employed investigate timing onset. The impact dynamic increases in levels on was examined using restricted cubic spline. Results Over a median follow-up period 165.4 months (interquartile range 156.5–174 months), 1,622 cases recorded. Multivariate regression revealed 9% increase per standard deviation (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04–1.15) an 14% (aHR 1.14, CI 1.09–1.2). AFT indicated earlier times occurrence increasing quintiles compared lowest quintile (P trend < 0.05). linearly 0.54) non-linearly 0.007) correlated gradual levels, respectively. Sex-stratified analyses showed stronger associations women. Conclusions Higher associated increased onset, particularly

Language: Английский

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