以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 血脂异常在早期通常没有明显症状，但实际上血管已经在悄悄受损。随着病情进展，脂肪、胆固醇等物质在血管内逐渐沉积，形成"斑块"，导 致血管逐步硬化、变窄，进而大幅提升动脉粥样硬化性心血管疾病的风险。 很多人以为高血脂只是中老年人才需要担心的健康问题。事实上，过去针对动脉粥样硬化的筛查和防控，大多也是聚焦在50岁以上胆固醇偏高 的人群。 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 你最近检测过自己的血脂吗？根据《中国成人血脂管理指南（2023年）》的数据，2018年我国18岁及以上人群血脂异常的总患病率已高达 35.6%。这包括高胆固醇血症、高甘油三酯血症、混合型高脂血症以及低高密度脂蛋白胆固醇血症。 然而，最近《自然》杂志发表的新研究提醒我们，动脉粥样硬化的预防应更早开始，年轻时就要重视血脂管理，尤其要警惕高脂饮食在儿童和 青少年中的摄入。 在这项研究中，剑桥大学心肺研究所的科学家用小鼠做实验，探索高脂饮 ...

以下文章来源于肥胖世界ObesityWorld ，作者欢迎订阅 肥胖世界ObesityWorld . 《肥胖世界》Obesity World - 同步传真肥胖及代谢国际新学术进展，为医学减重临床、教研人员搭建一座与国际接轨的桥梁，「每医健」旗下内容平台。 《柳叶刀》（The Lancet）近日刊登了一项涵盖全球八大地区的研究，聚焦全身及腹部肥胖与高血压之间的关系。该研究深入分析了全球各地 不同人群内部及群体间BMI与腰高比的关联，并对这两个指标在高血压患者与非高血压患者之间的差异进行了量化。结果显示，BMI能够较为 准确地区分腹部脂肪含量高低的中青年人群，准确度达到中等偏高水平；同时，BMI和腰高比这两个指标均可有效区分高血压患者与非高血压 人群。 01 • 背景 肥胖通常通过体重指数（BMI，即体重与身高的比值）以及腹部肥胖指数来评估。本文探讨了全球不同地区人群内部及地区之间的BMI与腰高比 （WHtR，即腰围与身高的比值）的关系，并进一步量化了这两个指标在高血压患者与非高血压人群之间的差异。 02 • 方法 本研究收集了1990至2023年间，全球八大地区20-64岁一般人群中关于BMI、WHtR与高血压 ...

Core Insights - The article highlights a significant medical breakthrough with the FDA approval of the first innovative drug, Tzield (teplizumab), for delaying the onset of Type 1 Diabetes (T1DM), marking a new phase in diabetes treatment in China [4]. Group 1: Disease Overview and Family History - Type 1 Diabetes (T1DM) is an autoimmune disease characterized by the destruction of insulin-producing beta cells in the pancreas, leading to insufficient insulin secretion. Genetic predisposition and environmental factors contribute to its complexity [6]. - The case of Linlin, who has a family history of T1DM, illustrates the high-risk nature of individuals with relatives diagnosed with the disease, as they face a 15-fold increased risk compared to the general population [8]. Group 2: Early Screening and Monitoring - Early screening is crucial for high-risk individuals to identify risks and delay disease progression. The latest guidelines recommend systematic screening for first-degree relatives of T1DM patients aged 1-45 years [8]. - The detection of islet autoantibodies (IAb) is a key component of the screening process, recognized as the most reliable predictor of T1DM. The guidelines emphasize the importance of IAb testing for early diagnosis and reducing the risk of diabetic ketoacidosis (DKA) [8][9]. Group 3: Importance of Follow-Up and Intervention - T1DM progresses gradually, and timely intervention during the early stages can significantly improve outcomes. Research indicates that 44% of stage 1 and 75% of stage 2 patients progress to stage 3 within five years [10]. - Establishing a structured follow-up system can capture the "intervention golden period," delaying disease onset and reducing DKA risk by over 50%. Individualized monitoring plans are essential for patients at different stages of the disease [10][11]. Group 4: Conclusion and Future Outlook - A standardized early screening and dynamic monitoring system is vital for extending the intervention window for T1DM, ultimately improving long-term outcomes. The adoption of personalized treatment plans and innovative therapies offers hope for high-risk populations to overcome genetic predispositions and regain health [11].

整理 | GLP1减重宝典内容团队 哥本哈根大学的一组研究人员发现，运动结合减肥药物可以帮助维持健康的体重。这项《柳叶刀》旗下的 eClinicalMedicine 研究比较 了停止使用胰高血糖素样肽-1 (GLP-1) 受体激动剂、监督锻炼计划或两者结合进行主动干预一年后减肥效果的维持程度。 与单一减肥治疗相比，GLP-1 受体激动剂利拉鲁肽和监督锻炼计划的联合治疗表现出更好的减肥维持效果和更好的身体成分。 在治疗 终止后的一年内（第52-104周），接受利拉鲁肽+定期运动的参与者反弹比仅接受利拉鲁肽的参与者更少。 ▍ 研究背景 肥胖是一种与体内多余脂肪堆积有关的健康状况。多项研究表明，肥胖会影响多种健康状况的发病率，包括 2 型糖尿病和心血管事件。 近年来，已经开发出许多治疗方法和减肥计划来减少肥胖。例如，GLP-1 受体激动剂已获得全球监管机构批准用于治疗肥胖和 2 型糖 尿病。已证明 GLP-1 受体激动剂可以减少食欲，从而减少食物摄入量。 与安慰剂对照组相比， GLP-1 受体激动剂（如司美格鲁肽和替尔泊肽）分别在治疗 68 周和 72 周后导致体重减轻 。尽管多项研究报 告了这些肥胖干预措施的积极 ...

Core Insights - The article discusses the recent price reduction agreements between AstraZeneca and Pfizer with the U.S. government, which are expected to reshape the weight loss drug market, particularly focusing on GLP-1 medications [2][4]. Group 1: Price Reduction Agreements - AstraZeneca announced an agreement with the U.S. government to offer up to an 80% discount on its medications for eligible patients with chronic diseases through direct-to-consumer channels [2]. - Pfizer has also reached a similar agreement, indicating a trend among major pharmaceutical companies to lower drug prices in response to government pressure [4]. Group 2: Impact of U.S. Drug Pricing - The U.S. has the highest drug prices globally, often 3 to 4 times higher than in Europe and up to ten times higher than in China [5]. - GLP-1 weight loss drugs, previously costing patients up to thousands of dollars monthly, are now being targeted for price negotiations to alleviate the financial burden on healthcare systems [5]. Group 3: Market Dynamics and Competition - The shift towards government negotiations may lead to significant revenue and profit impacts for pharmaceutical companies, particularly smaller firms that may exit the market [7]. - Long-term competition in the weight loss drug market is expected to focus on product value rather than price, emphasizing efficacy, safety, and convenience [7]. Group 4: Global Supply Chain Changes - Companies like AstraZeneca and Novo Nordisk are investing heavily in domestic production in the U.S. to avoid tariffs and pricing pressures, potentially reshaping the global supply chain for GLP-1 drugs [8]. - This strategy may lead to a ripple effect in international drug pricing, with potential increases in prices in some countries and challenges to the current innovation and return on investment models [8].

Core Insights - The article discusses the metabolic reprogramming that occurs during critical illness, emphasizing the role of inflammation and immune response in altering energy distribution and substrate utilization within the body [6][9][27]. Metabolic Regulation Principles - The priority of substrate utilization shifts during critical illness, with the body first consuming glucose and glycogen, followed by fats and proteins. This shift is crucial for supporting immune and inflammatory cell needs, leading to significant breakdown of muscle and fat tissues [10][13]. - The liver and kidneys enhance gluconeogenesis during critical illness, utilizing lactate, glycerol, and amino acids as substrates, which is vital for maintaining glucose levels [13]. Immune and Inflammatory Cell Metabolism - Immune cells, particularly M1 macrophages and activated T cells, primarily rely on aerobic glycolysis (Warburg effect) for rapid ATP production and biosynthetic precursors, supporting inflammatory responses despite lower energy efficiency [16][18]. - Metabolic intermediates can epigenetically regulate gene expression, influencing inflammation and immune responses [17]. Muscle and Fat Tissue Metabolic Remodeling - In critical illness, white adipose tissue may convert to brown adipose tissue, enhancing thermogenic capacity, while obesity paradox suggests that obese individuals may have better survival rates due to greater energy reserves and anti-inflammatory factors [20][22]. - Muscle protein breakdown is significantly increased due to enhanced ubiquitin-proteasome and autophagy mechanisms, leading to muscle wasting [22][26]. Conclusion - The body adapts through metabolic reprogramming during critical illness to enhance immune protection and survival, with a focus on the roles of immune cell metabolism and the breakdown of muscle and fat tissues. Future research should explore innovative interventions targeting metabolic pathways to improve clinical outcomes for critically ill patients [27].

以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 深度分享内分泌用药经验、病例剖析、指南专业解读并紧跟国内外内分泌领域前沿进展，「每医健」旗下内容平台。 还在为体重数字焦虑？科学评估肥胖有妙招！这份指南教你用对指标，精准掌握健康体重。 ▍ 一、全身肥胖的黄金标准：BMI 2. 腰臀比 - ＜1 8.5 低体重 - 18.5 - 23 .9 正常 - 24- 2 7.9 超重 - ≥2 8 肥胖（分四级） ✓ 全球通用，数据可比 ✓ 与体脂率相关性良好 ✓ 肥胖并发症预警性强 2024版《肥胖症诊疗指南》明确指出，BMI（体质指数）仍是评估肥胖的核心指标。只需用体重（kg）除以身高（m）的平方，就能 快速判断体重状态： 这个沿用30年的指标有何优势？ 但要注意3个"不完美"： 【关键结论】BMI仍是首选筛查工具，但需结合个体情况综合判断！ 二、隐形杀手：中心性肥胖三大指标 亚洲人更需警惕"苹果型身材"！腰围、腰臀比、腰高比是检测内脏脂肪的利器： 1. 腰围（最常用） 男性≥9 0cm、女性≥8 5cm即超标 1. 肌肉达人易"误伤"（运动员可能被误判） 2. 老年人适用性降低 3. 青少年评估需 ...

Core Viewpoint - The article discusses the current landscape of weight loss medications in China, focusing on the differences between new-generation GLP-1 drugs and traditional weight loss medications, highlighting their mechanisms, efficacy, and safety profiles [4][7]. Group 1: Overview of Weight Loss Medications - There are six weight loss drugs currently approved in China, including three new-generation GLP-1 drugs: Semaglutide, Tirzepatide, and Mounjaro, and three traditional drugs: Benaglutide, Liraglutide, and Orlistat [4][7]. - New-generation GLP-1 drugs have longer action times and more significant weight loss effects compared to first-generation drugs [4][6]. Group 2: Mechanisms and Administration - The six weight loss drugs differ in their mechanisms of action and target populations, with new-generation drugs showing better safety and efficacy [7]. - All approved GLP-1 weight loss medications are currently available only as subcutaneous injections, with no oral versions available yet [6]. Group 3: Indications and Contraindications - Weight loss medications should be considered for patients who have not achieved a weight loss of at least 5% after three months of lifestyle intervention, even for those who are merely overweight without complications [9]. - A comprehensive assessment is necessary before starting medication, especially for high-risk populations such as the elderly or those with liver and kidney dysfunction [10]. Group 4: Clinical Application Process - Diagnosis of obesity or overweight should consider BMI, metabolic indicators, and related comorbidities, with obesity defined as BMI ≥ 28 kg/m² [12]. - The selection of medications should prioritize those with additional clinical benefits for patients with comorbid conditions like type 2 diabetes or cardiovascular diseases [13]. Group 5: Monitoring and Management - Regular monitoring of body composition and metabolic indicators is essential, with evaluations occurring monthly during the initial three months and quarterly thereafter [16]. - For elderly patients, careful consideration of muscle mass and potential drug interactions is crucial, with recommendations for dose adjustments based on renal and hepatic function [19].

Core Viewpoint - The article discusses the recent acceptance of the new drug application for Idaglutide α injection by the China NMPA, developed by Shiyao Group's subsidiary, aimed at long-term weight management for overweight or obese adults [2][4]. Group 1: Drug Details - Idaglutide α injection is a recombinant human glucagon-like peptide-1 (hGLP-1) Fc fusion protein that requires weekly administration [2]. - The drug works by selectively binding and activating GLP-1 receptors, leading to appetite suppression and reduced food intake, thereby aiding in weight loss [4]. - It also lowers blood glucose levels in a glucose-dependent manner and improves cardiovascular and metabolic indicators [4]. Group 2: Clinical Trial Results - The new drug application is based on a pivotal Phase 3 clinical trial involving overweight adults with at least one weight-related comorbidity [4]. - Results showed that Idaglutide α significantly reduced body weight compared to a placebo, along with reductions in waist circumference, blood glucose, blood pressure, and blood lipids, providing cardiovascular and metabolic benefits [4]. - The drug demonstrated good safety and tolerability, with lower rates of gastrointestinal adverse events and treatment interruptions due to adverse events, and a quicker, simpler dose escalation scheme that reaches the target maintenance dose in just four weeks [4].

Core Viewpoint - The article discusses the development of ASC35, a novel GLP-1/GIP receptor dual agonist by the company, which is expected to enhance patient compliance and reduce production costs due to its long-acting formulation and improved pharmacokinetics [4][5]. Group 1: Drug Development and Characteristics - ASC35 is a monthly subcutaneous injection candidate for obesity treatment, with an IND application planned for submission to the FDA in 2026 [4]. - The drug shows approximately 4 times higher activity on GLP-1R and GIPR compared to Tirzepatide in vitro [4]. - ASC35 has a longer half-life and higher bioavailability, requiring only 1 milliliter or less for administration, which supports monthly dosing [4]. Group 2: Pharmacokinetics and Efficacy - In non-human primate studies, ASC35's average half-life is about 14 days, which is 6 times longer than that of Tirzepatide [5]. - Drug exposure (measured by AUC) shows ASC35 has approximately 80% higher exposure via intravenous injection and 70% higher via subcutaneous injection compared to Tirzepatide [5]. - The estimated half-life of ASC35 in humans could reach 30 days or longer, supporting its monthly dosing feasibility [5]. Group 3: Weight Loss Efficacy - In a diet-induced obesity mouse model, ASC35 led to a weight reduction of 33.6% at equimolar doses, compared to 19.6% for Tirzepatide, representing a 71% relative efficacy improvement [7]. - The higher weight loss efficiency per milligram of peptide is advantageous for large-scale production [7]. Group 4: Combination Therapy Potential - The company plans to explore ASC35 as both a monotherapy and in combination with other candidates for treating various cardiometabolic diseases, including obesity and diabetes [8]. - Potential combination therapies include ASC36, a GLP-1 receptor agonist, and ASC47, a THRβ agonist, both designed for monthly subcutaneous administration [8]. - The company utilizes its AISBDD and ULAP technology platforms to design and optimize long-acting peptide drugs, aiming to improve clinical efficacy by controlling subcutaneous release rates [8].