Pub Date : 2025-12-01DOI: 10.1016/j.disamonth.2025.102015
Rishabh Chaudhary Ph.D. , Alpana Singh MS
Danon disease (DD) represents a rare and complex X-linked disorder, characterized by hypertrophic cardiomyopathy, skeletal muscle deterioration, and cognitive deficits. At its core, the disease stems from mutations in the LAMP2 (lysosome-associated membrane protein 2) gene, which result in a critical deficiency of LAMP-2, particularly the LAMP-2B isoform. This loss destabilizes normal autophagic clearance, leading to the buildup of dysfunctional autophagic vacuoles that ultimately disrupt cellular homeostasis. Although accurately modeling the full range of DD symptoms remains challenging, patient-specific induced pluripotent stem cells and innovative LAMP-2-deficient animal models have provided valuable insights into the disease’s molecular and cellular basis. Recent research points decisively to mitochondrial dysfunction and fragmentation as pivotal contributors to disease progression, shifting our understanding of DD beyond lysosomal defects alone. These mechanistic revelations have inspired new therapeutic directions, with gene therapy emerging as a particularly promising candidate based on encouraging preclinical results and ongoing clinical studies. Moving forward, a deeper integration of molecular insights with therapeutic innovation will be essential to developing effective strategies that address the multifaceted pathology of DD and improve outcomes for affected individuals. In this review, we provide a comprehensive analysis of DD, focusing on its genetic and molecular underpinnings, particularly the role of LAMP-2 deficiency in disrupting autophagy and mitochondrial integrity. We critically evaluate experimental models that have advanced our understanding of DD pathogenesis. Additionally, we discuss emerging therapeutic strategies, with an emphasis on gene therapy and other innovative approaches aimed at restoring cellular homeostasis and mitigating cardiomyopathy and neuromuscular symptoms.
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Pub Date : 2025-11-26DOI: 10.1016/j.disamonth.2025.102043
Sneha Annie Sebastian MD , Inderbir Padda MD, MPH , Tia Bimal MD , Shalendra Varma MD, MBA, FACC , Jessicah Collins MD , Zahid Ahmad MD , Maya S. Safarova MD, PhD, FNLA, FACC, FAHA
<div><h3>Background</h3><div>Continuous glucose monitoring (CGM) is extensively studied for its role in glycemic control, but evidence regarding its effects on cardiometabolic and clinical outcomes in type 2 diabetes (T2D) is limited. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the impact of patient-accessible CGM on cardiometabolic risk factors and examine its potential for improving cardiovascular health and integration into T2D care.</div></div><div><h3>Methods</h3><div>We performed a systematic review by searching MEDLINE, Scopus, ScienceDirect, the Cochrane Library, and ClinicalTrials.gov up to April 2025. We included RCTs comparing real-time continuous glucose monitoring (rtCGM) or intermittently scanned continuous glucose monitoring (isCGM) versus self-monitoring of blood glucose (SMBG) or usual care in adults with T2D. Statistical analysis was conducted using RevMan 5.4, applying an inverse variance random effects model to compute mean differences (MD) for continuous outcomes and odds ratios (OR) for dichotomous outcomes. Our study protocol is registered with PROSPERO (CRD42024578002).</div></div><div><h3>Results</h3><div>Thirty RCTs (19 rtCGM, 11 isCGM) with 3133 participants (mean age 60.2 years; baseline HbA1c 8.5 %) were included. CGM use reduced HbA1c by –0.48 % (95 % CI: 0.68 to –0.29; <em>p</em> < 0.001), with greater reductions for rtCGM (–0.65 %) than isCGM (–0.25 %). Mean glucose decreased by –14.72 mg/dL (<em>p</em> < 0.001), and TIR increased by 10.76 % (<em>p</em> < 0.001). Subgroup analysis showed greater HbA1c reduction in non–insulin-treated individuals (–0.57 %) versus insulin-treated (–0.46 %). CGM lowered non-HDL cholesterol (–9.31 mg/dL), triglycerides (–32.17 mg/dL), systolic blood pressure (–3.47 mmHg), weight (–3.26 kg), and BMI (–0.87 kg/m²). No significant differences were found in MACE or hypoglycemia. Treatment satisfaction and physical activity were higher with CGM versus SMBG.</div></div><div><h3>Conclusions</h3><div>Patient-accessible CGM significantly impacts cardiometabolic risk reduction, emphasizing the need for further RCTs with extended follow-ups focusing on these outcomes as primary endpoints. Integrating CGM into clinical practice may enhance personalized care and cardiovascular health for individuals with T2D.</div><div>Layman Summary:</div><div>Our study analyzed 30 randomized controlled trials involving over 3000 adults with type 2 diabetes to evaluate the effects of continuous glucose monitoring (CGM) on metabolic and cardiovascular health. Compared with traditional finger-stick glucose testing, CGM use led to significant improvements in blood glucose control, with reductions in HbA1c, average glucose levels, cholesterol, triglycerides, blood pressure, and body weight. Participants using CGM also spent more time in the target glucose range and reported higher treatment satisfaction and physical activity. Overall, CGM use was associated with improved cardiom
{"title":"Patient-accessible continuous glucose monitoring for cardiometabolic risk reduction in type 2 diabetes: A meta-analysis of randomized controlled trials","authors":"Sneha Annie Sebastian MD , Inderbir Padda MD, MPH , Tia Bimal MD , Shalendra Varma MD, MBA, FACC , Jessicah Collins MD , Zahid Ahmad MD , Maya S. Safarova MD, PhD, FNLA, FACC, FAHA","doi":"10.1016/j.disamonth.2025.102043","DOIUrl":"10.1016/j.disamonth.2025.102043","url":null,"abstract":"<div><h3>Background</h3><div>Continuous glucose monitoring (CGM) is extensively studied for its role in glycemic control, but evidence regarding its effects on cardiometabolic and clinical outcomes in type 2 diabetes (T2D) is limited. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the impact of patient-accessible CGM on cardiometabolic risk factors and examine its potential for improving cardiovascular health and integration into T2D care.</div></div><div><h3>Methods</h3><div>We performed a systematic review by searching MEDLINE, Scopus, ScienceDirect, the Cochrane Library, and ClinicalTrials.gov up to April 2025. We included RCTs comparing real-time continuous glucose monitoring (rtCGM) or intermittently scanned continuous glucose monitoring (isCGM) versus self-monitoring of blood glucose (SMBG) or usual care in adults with T2D. Statistical analysis was conducted using RevMan 5.4, applying an inverse variance random effects model to compute mean differences (MD) for continuous outcomes and odds ratios (OR) for dichotomous outcomes. Our study protocol is registered with PROSPERO (CRD42024578002).</div></div><div><h3>Results</h3><div>Thirty RCTs (19 rtCGM, 11 isCGM) with 3133 participants (mean age 60.2 years; baseline HbA1c 8.5 %) were included. CGM use reduced HbA1c by –0.48 % (95 % CI: 0.68 to –0.29; <em>p</em> < 0.001), with greater reductions for rtCGM (–0.65 %) than isCGM (–0.25 %). Mean glucose decreased by –14.72 mg/dL (<em>p</em> < 0.001), and TIR increased by 10.76 % (<em>p</em> < 0.001). Subgroup analysis showed greater HbA1c reduction in non–insulin-treated individuals (–0.57 %) versus insulin-treated (–0.46 %). CGM lowered non-HDL cholesterol (–9.31 mg/dL), triglycerides (–32.17 mg/dL), systolic blood pressure (–3.47 mmHg), weight (–3.26 kg), and BMI (–0.87 kg/m²). No significant differences were found in MACE or hypoglycemia. Treatment satisfaction and physical activity were higher with CGM versus SMBG.</div></div><div><h3>Conclusions</h3><div>Patient-accessible CGM significantly impacts cardiometabolic risk reduction, emphasizing the need for further RCTs with extended follow-ups focusing on these outcomes as primary endpoints. Integrating CGM into clinical practice may enhance personalized care and cardiovascular health for individuals with T2D.</div><div>Layman Summary:</div><div>Our study analyzed 30 randomized controlled trials involving over 3000 adults with type 2 diabetes to evaluate the effects of continuous glucose monitoring (CGM) on metabolic and cardiovascular health. Compared with traditional finger-stick glucose testing, CGM use led to significant improvements in blood glucose control, with reductions in HbA1c, average glucose levels, cholesterol, triglycerides, blood pressure, and body weight. Participants using CGM also spent more time in the target glucose range and reported higher treatment satisfaction and physical activity. Overall, CGM use was associated with improved cardiom","PeriodicalId":51017,"journal":{"name":"Dm Disease-A-Month","volume":"72 3","pages":"Article 102043"},"PeriodicalIF":4.3,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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