Core Viewpoint - The research highlights the need for high-throughput, high-resolution functional genomics platforms based on human normal cells to systematically reveal the pathogenic mechanisms of complex diseases like Type 2 Diabetes (T2D) and provide new paradigms for therapeutic target discovery [3]. Group 1: Research Findings - A study published in Nature Metabolism utilized single-cell perturbation sequencing to decode the functions of genes related to T2D and insulin production in human pancreatic β cells, identifying the previously unknown gene ZZEF1 [4]. - The research team identified 21 significant functional genes affecting β cells, including known genes like ABCC8 and PCSK1, as well as the novel ZZEF1 gene [6]. - ZZEF1's perturbation was found to impact pathways related to β cell homeostasis, MAPK/JNK stress response, protein secretion, and endoplasmic reticulum stress response, indicating its potential as a key regulatory factor [7]. Group 2: Mechanistic Insights - The study constructed cell-specific knockout mouse models to validate ZZEF1's function, revealing that ZZEF1 knockout mice exhibited impaired glucose tolerance and reduced insulin secretion under high-fat diet conditions [8]. - ZZEF1 deficiency led to decreased insulin protein levels without significant transcriptional reduction, suggesting issues in insulin translation or post-translational modifications [8]. - The research categorized β cells into four functional subgroups based on their activity and stress levels, demonstrating that ZZEF1 deficiency shifts these subgroups towards a high-stress state [8]. Group 3: Therapeutic Implications - The research tested various intervention strategies, including the use of adeno-associated virus (AAV) to restore EDF1 expression, which significantly improved insulin secretion in ZZEF1 knockout mice [10]. - The small molecule drug Azoramide was shown to enhance the degradation of misfolded proteins, improving glucose tolerance and partially restoring insulin secretion function in ZZEF1 knockout mice [10]. - These findings suggest that targeting ribosomal stress, protein homeostasis, and the elimination of misfolded protein accumulation could be new strategies for protecting β cells and treating T2D [10]. Group 4: Conclusion - The study demonstrates the advantages of single-cell functional genomics in the genetic analysis of complex diseases, establishing a new paradigm for systematically elucidating the molecular mechanisms and targets of T2D [12].

Core Viewpoint - The research reveals the atomic structure of pathological human islet amyloid polypeptide (hIAPP) fibrils, providing a significant foundation for understanding the mechanisms of type 2 diabetes (T2D) and developing treatment strategies [7]. Group 1: Research Findings - The study analyzed hIAPP fibrils extracted from pancreatic tissues of three T2D patients using cryo-electron microscopy (cryo-EM) [4]. - The hIAPP fibrils exhibited a uniform morphology, consisting of two symmetrical protofibrils, containing amino acid residues 2-37, and forming an Ω-shaped spatial fold [4]. - Additional electron density observed in pancreatic hIAPP fibrils suggests potential ligand binding, which may significantly impact the pathogenesis of T2D [4][5]. Group 2: Structural Insights - The core findings include the atomic structure of hIAPP fibrils derived from T2D patients [5]. - The hIAPP fibrils display an unprecedented Ω-shaped folding structure with a conserved core region [5]. - Structural similarities were observed between pathological hIAPP fibrils and Aβ fibrils [5].

Core Viewpoint - The increasing consumption of sugar-free beverages, often perceived as a healthier choice, is linked to rising health risks, including diabetes and accelerated brain aging. Group 1: Health Risks of Sugar-Free Beverages - Regular consumption of sugar-free drinks is associated with a 38% increased risk of developing type 2 diabetes compared to those who rarely consume them [1] - Drinking artificial sweetener beverages daily can lead to a 21% increase in obesity risk and a 15% increase in type 2 diabetes risk [4] - A study indicates that daily consumption of sugar-free soda can accelerate brain aging by 1.6 years [2] Group 2: Mechanisms and Recommendations - Artificial sweeteners may disrupt the body's metabolic processes, leading to increased cravings for sweet foods and poor dietary choices [5] - The World Health Organization advises against using non-sugar sweeteners for weight control or reducing non-communicable disease risks [3] - For individuals with cardiovascular disease history, caution is advised with sugar alcohols, particularly xylitol and erythritol, due to potential risks [6] Group 3: General Dietary Recommendations - The recommended daily limit for added sugars is no more than 50 grams, ideally below 25 grams, which includes sugars from beverages and other food sources [6] - Healthier alternatives to sugar-free beverages include water, unsweetened tea, and coffee [6]

Core Viewpoint - The article emphasizes the significant health benefits of natural daylight exposure in office environments, particularly for managing type 2 diabetes, as supported by recent research findings [2][3]. Group 1: Research Findings - A study published in Cell Metabolism indicates that exposure to natural light during office hours improves glucose control and whole-body substrate metabolism in type 2 diabetes patients [2][3]. - The research involved 13 type 2 diabetes patients working in two different office environments: one with natural light and the other with artificial light, maintaining consistent dietary and activity conditions [6][8]. - Results showed that patients in natural light environments had 50.9% of their time with blood glucose levels in the normal range (4.4-7.2 mmol/L), compared to 43.3% in artificial light environments, equating to nearly 2 additional hours of normal blood glucose time daily [10]. Group 2: Metabolic Changes - Natural light exposure led to a significant increase in fat oxidation rates, indicating a shift in the body's energy source from carbohydrates to fats [12]. - The study also found that participants had higher evening melatonin levels in natural light, which is crucial for regulating the sleep-wake cycle and maintaining metabolic health [15]. Group 3: Molecular Insights - Multi-omics analysis revealed that beneficial metabolites like choline, glutamate, and threonine increased in natural light conditions, while harmful lipids such as cholesterol esters and ceramides decreased, aligning with improved glucose control [17]. Group 4: Practical Implications - The findings suggest that simple environmental adjustments, such as working near windows to increase natural light exposure, could provide significant clinical benefits for type 2 diabetes and obesity patients [19][21].

Financial Data and Key Metrics Changes - The company reported a strong second quarter in 2025, driven by the incretin teams on Mounjaro and Zepbound in the U.S. and Mounjaro outside the U.S. [2] - The U.S. opportunity in type 2 diabetes is significant, with a reported HbA1c reduction of 1.8 and weight loss of 10.5 in the obese population with type 2 diabetes [7][10] Business Line Data and Key Metrics Changes - The composition of the U.S. business is currently different from that outside the U.S., with 25% of incretin performance coming from type 2 diabetes and 75% from chronic weight management outside the U.S. [11] - The company expects a gradual growth in the second half of the year, with no major launches comparable to Q2 [16] Market Data and Key Metrics Changes - The company launched Mounjaro in Brazil, Mexico, India, and China, with a significant channel build at the time of launch [10] - The oral type 2 diabetes market in the U.S. is substantial, with approximately 4 million patients on orals every month [7] Company Strategy and Development Direction - The company is preparing submissions for chronic weight management and type 2 diabetes for Orforglipron, with a focus on appealing safety and tolerability profiles [3][4] - The management believes that outcome data will help in gaining access to reimbursement for chronic weight management, emphasizing the need for evidence that obesity is a chronic disease [14][15] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the underlying performance and growth opportunities, particularly in international markets [17] - The company is optimistic about the future, with expectations for significant growth in type 2 diabetes and chronic weight management markets [11][30] Other Important Information - The company is currently negotiating with several agencies globally for type 2 diabetes reimbursement, which is expected to impact in 2026 [11] - The management highlighted the importance of differentiating their products in competitive markets, particularly in China [33][34] Q&A Session Summary Question: How is the product profile of Orforglipron fitting in the marketplace? - Management indicated that Orforglipron has a very appealing safety and tolerability profile, with significant weight loss and HbA1c reduction, and is preparing for regulatory submissions [3][4] Question: What are the expectations for the rest of the year regarding growth drivers? - Management noted that while Q2 saw significant channel build, they expect more gradual growth in the second half of the year due to fewer major launches [16] Question: How is the impact of the CVS change being tracked? - Management reported that the impact of the CVS change has been seen, but they have returned to strong growth in market share for Zepbound [22][23] Question: What is the outlook for access in 2026? - Management stated that they expect gradual improvement in employer opt-in rates for chronic weight management, with ongoing discussions for broader coverage [30] Question: How is the competitive landscape evolving in international markets? - Management acknowledged increased competition in markets like China but emphasized their product differentiation and premium pricing strategy [33][34]

Core Viewpoint - The article emphasizes the significant role of flavonoid-rich foods in reducing the risk of type 2 diabetes, based on a large-scale study from the UK Biobank that tracked over 500,000 individuals for 12 years [5][6][12]. Summary by Sections Global Diabetes Burden - Type 2 diabetes has become a major public health issue, with over 415 million patients globally, 90% of whom have type 2 diabetes, leading to over 4 million deaths annually [5]. Flavonoid Intake and Diabetes Prevention - A groundbreaking study published in "Nutrition & Diabetes" confirmed that increasing flavonoid intake through daily diet can significantly lower the risk of developing type 2 diabetes [6][12]. - Flavonoids, found in foods like tea, apples, berries, dark chocolate, and red wine, play a crucial role in diabetes prevention [6]. Research Methodology - The study utilized a novel Flavonoid Diet Score (FDS) to assess the relationship between flavonoid-rich food consumption and type 2 diabetes incidence [8][9]. - The research involved a comprehensive baseline assessment of participants aged 40-69, collecting extensive health data to ensure reliability [10]. Key Findings - Participants consuming about 6 servings of flavonoid-rich foods daily had a 28% lower risk of developing type 2 diabetes compared to those with lower intake [11][12]. - Specific flavonoid subclasses, such as anthocyanins and flavan-3-ols, showed significant protective effects, with risk reductions ranging from 19% to 28% [11]. - Daily consumption recommendations include 4 cups of tea (21% risk reduction), 1 serving of berries (15% risk reduction), and 1 apple (12% risk reduction) [11][12]. Implications for Public Health - The findings provide strong evidence for dietary guidelines aimed at diabetes prevention, highlighting the importance of incorporating flavonoid-rich foods into daily diets [12].

Core Viewpoint - A groundbreaking study conducted by Xi'an Jiaotong University and Harvard University provides authoritative guidance on beverage choices for diabetes patients, revealing significant differences in health impacts among various drinks [6][9]. Group 1: Research Overview - The study tracked 15,486 type 2 diabetes patients over 38 years, utilizing validated food frequency questionnaires to assess beverage intake and its correlation with all-cause mortality and cardiovascular outcomes [6][12]. - The research highlights the urgent need for dietary interventions in diabetes management, given the rising global diabetes prevalence, projected to reach 783 million by 2045 [9]. Group 2: Key Findings - High intake of sugar-sweetened beverages (SSBs) is significantly associated with increased all-cause mortality and adverse cardiovascular outcomes, while coffee, tea, plain water, and low-fat milk show protective effects [6][10]. - Specifically, the highest consumption group of SSBs had a 20% higher risk of all-cause mortality compared to the lowest intake group, while coffee drinkers had a 26% lower risk [13]. Group 3: Clinical Implications - The study suggests that reducing SSB intake and increasing consumption of healthier beverages like coffee, tea, or plain water could be a viable strategy for improving long-term outcomes and reducing mortality risk in type 2 diabetes patients [14]. - The findings provide high-quality evidence for personalized dietary guidance, emphasizing the importance of beverage choices in diabetes management [14].

Core Viewpoint - The National Health Commission of China has issued notifications prohibiting the use of two surgical procedures: "cervical deep lymphatic vessel/vein anastomosis" for Alzheimer's disease and "jejunum-ileum anastomosis" for type 2 diabetes treatment, due to concerns over their safety and efficacy [1][4][12]. Group 1: Alzheimer's Disease and Surgical Procedure - The "cervical deep lymphatic vessel/vein anastomosis" (LVA) is deemed to be in the early exploratory stage of clinical research, lacking clear indications and contraindications, as well as high-quality evidence supporting its safety and effectiveness [4][10]. - The procedure has been evaluated by experts, who concluded that its application in treating Alzheimer's disease is not supported by sufficient clinical evidence, and it poses potential risks that may outweigh benefits for patients with mild symptoms [9][10]. - The National Health Commission has mandated local health authorities to ensure that medical institutions cease the use of LVA for Alzheimer's treatment and to provide follow-up services for affected patients [11]. Group 2: Type 2 Diabetes and Surgical Procedure - The "jejunum-ileum anastomosis" has been evaluated and found to have uncertain safety and effectiveness for treating type 2 diabetes, with potential severe complications such as liver failure and malnutrition [12][14]. - Although some studies suggest that this procedure may improve blood sugar levels post-surgery, the overall clinical evidence remains limited, and it has not been included in the latest diabetes treatment guidelines [13][14]. - The National Health Commission has instructed health authorities to monitor and regulate the clinical application of this procedure, ensuring that institutions stop its use for diabetes treatment and enhance public health education [14].

Core Viewpoint - The article emphasizes the potential of strawberries as a dietary intervention for managing prediabetes and improving metabolic health, supported by clinical research findings that demonstrate significant benefits in blood sugar control and cardiovascular health indicators [4][11][17]. Group 1: Clinical Research Findings - A recent clinical study published in *The Journal of Nutrition* indicates that consuming 2.5 servings of strawberries daily for 12 weeks significantly improves blood glucose metabolism and various cardiovascular metabolic indicators in adults with prediabetes [4][11]. - The study involved a randomized controlled trial design, confirming a causal relationship between strawberry intake and metabolic improvements, rather than mere correlation [4][9]. - Key metabolic improvements observed include an average reduction of 8.9 mg/dl in fasting blood glucose, a 0.2% decrease in glycated hemoglobin, and a 6.9 μIU/ml reduction in serum insulin levels [11]. Group 2: Mechanisms of Action - Strawberries contain various bioactive compounds, such as anthocyanins and ellagic acid, which may enhance insulin sensitivity and reduce chronic inflammation, critical factors in the development of type 2 diabetes [4][13]. - The health benefits of strawberries are attributed to their high polyphenol content, which exhibits antioxidant properties, reduces oxidative stress, and modulates inflammatory pathways [14][15]. - Strawberries also improve lipid metabolism by downregulating key enzymes involved in fat synthesis, leading to favorable changes in cholesterol levels [15]. Group 3: Practical Implications - From a public health perspective, strawberries could provide a palatable and sustainable dietary option for high-risk populations to prevent diabetes [5][17]. - Recommendations suggest a daily intake of approximately 250-300 grams of fresh strawberries for individuals with prediabetes, emphasizing the importance of incorporating them into a balanced diet [16]. - The article highlights the need for further research with larger sample sizes and longer observation periods to establish optimal intake levels and long-term effects of strawberries on metabolic health [5][16].

Core Viewpoint - The overall prevalence of diabetes among adults in China is on the rise, significantly influenced by daily habits such as late dinners, excessive red meat consumption, and high intake of sugary beverages [1][3][4]. Group 1: Eating Habits - Habit 1: Eating dinner too late increases the risk of type 2 diabetes, with a study indicating that late dinners can lead to a 6.7% decrease in insulin and an 8.3% increase in glucose levels [1]. - Habit 2: High consumption of red meat correlates with a higher risk of type 2 diabetes, with those consuming two or more servings per week at greater risk compared to those who eat less [3]. - Habit 3: Daily intake of sugary beverages raises diabetes risk by 41% for those consuming two or more cups daily, and 11% for those drinking artificially sweetened beverages [4][5]. Group 2: Alcohol Consumption - Habit 4: Regular alcohol consumption, particularly beer, can lead to increased blood sugar levels due to its high glycemic index, which is comparable to that of glucose [7][9]. Group 3: Sleep and Lifestyle - Habit 5: Sleeping with lights on can exacerbate insulin resistance, potentially leading to diabetes [10]. - Habit 6: Insufficient sleep (less than 6 hours) is linked to a higher risk of type 2 diabetes, as it can impair insulin sensitivity [12]. - Habit 7: Prolonged sedentary behavior (over 6 hours daily) increases the risk of diabetes by 26.7% compared to those who sit less than 2 hours [14]. - Habit 8: Lack of regular exercise contributes to obesity and diabetes, with recommendations for a mix of aerobic, resistance, and flexibility training [16][17].