Archives of internal medicine research最新文献

{"title":"Heart Failure with Reduced versus Preserved Ejection Fraction: Molecular Mechanisms, Immunologic Pathways, Current Therapies, and Future Directions.","authors":"Erin Kim, Devendra K Agrawal","doi":"10.26502/aimr.0254","DOIUrl":"10.26502/aimr.0254","url":null,"abstract":"<p><p>Heart failure remains a major clinical and public health challenge due to its rising prevalence, heterogeneous biology, and persistent burden of morbidity, mortality, and healthcare utilization. Although left ventricular ejection fraction remains central to classification and treatment selection, it incompletely captures the molecular and clinical diversity of heart failure syndromes. Heart failure with reduced ejection fraction is commonly characterized by cardiomyocyte injury, impaired systolic force generation, neurohormonal activation, and adverse ventricular remodeling, which has enabled development of a standardized guideline-directed medical therapy framework. In contrast, heart failure with preserved ejection fraction is driven by more heterogeneous and overlapping mechanisms, including cardiometabolic stress, endothelial dysfunction, coronary microvascular disease, inflammation, myocardial fibrosis, and impaired physiologic reserve. This narrative review synthesizes current evidence on the fundamental pathophysiology, cellular and molecular mechanisms, immunologic pathways, and contemporary therapeutic strategies in HFrEF and HFpEF. Emphasis is placed on the translational gap between mechanistic discovery and clinically actionable treatment selection. Emerging evidence suggests that future progress, especially in HFpEF, may depend on integrating molecular phenotyping with biomarkers, imaging, hemodynamics, comorbidity profiles, and social determinants of health. A more precise and equitable approach to heart failure care may improve risk stratification, therapeutic selection, and patient-centered outcomes across the full spectrum of disease.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"251-268"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Assessment of Optimal Timing to Initiate Post-Stroke Rehabilitation.","authors":"Sumanjali Reddy Kanmantha Reddy, Marcel P Fraix, Devendra K Agrawal","doi":"10.26502/aimr.0258","DOIUrl":"10.26502/aimr.0258","url":null,"abstract":"<p><p>Early rehabilitation following stroke is widely advocated to prevent complications associated with immobility and promote neuroplasticity. However, the optimal timing of rehabilitation remains unclear, as clinical evidence regarding very early mobilization is inconsistent with its biological rationale. This review examines the biological rationale for early post-stroke rehabilitation, compares outcomes associated with early versus delayed rehabilitation, and evaluates factors that influence the optimal timing of post-stroke rehabilitation. Early rehabilitation may reduce immobility-related complications, cardiovascular deconditioning, and muscle atrophy, while promoting neuroplasticity during a narrow window in early stroke recovery. However, these biological benefits do not consistently translate into improved clinical outcomes. The AVERT trial demonstrated that high-dose, very early mobilization initiated within 24 hours of stroke onset can decrease the chance of favorable functional outcomes, highlighting the role of rehabilitation intensity in addition to timing. In contrast, other studies have demonstrated that earlier mobilization may improve activities of daily living (ADLs), functional independence, and hospital length of stay. The discrepancy in these findings suggests that post-stroke rehabilitation should be individualized according to stroke type, severity, hemodynamic and neurological stability, and patient-specific functional and psychosocial factors. Further research is needed to determine the optimal timing, intensity, and frequency of rehabilitation for different stroke populations. Personalized rehabilitation interventions may help maximize functional recovery, minimize harm, and improve overall quality of life.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 4","pages":"317-324"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Use of Medical Cannabis Beyond Pain Management in Physical Medicine and Rehabilitation.","authors":"Andrew Cameron, Marcel P Fraix, Devendra K Agrawal","doi":"10.26502/aimr.0246","DOIUrl":"10.26502/aimr.0246","url":null,"abstract":"<p><p>Medical cannabis has emerged as a rapidly evolving therapeutic modality with expanding clinical interest beyond its traditional role in pain management. Particularly relevant to Physical Medicine and Rehabilitation (PM&R), where the focus extends beyond symptom control to functional restoration and optimal quality of life, key non-pain indications described in the literature include management of spasticity, neurologic and seizure disorders, sleep disturbances, and chemotherapy-induced nausea and vomiting (CINV). This PM&R-centered narrative review synthesizes current evidence on the efficacy, mechanisms, and clinical implications of cannabis use for non-pain conditions, with emphasis on its interaction with the endocannabinoid system, including CB1- and CB2-receptor-mediated pathways influencing neuromodulation, inflammation, and homeostasis. Across multiple conditions, cannabinoids demonstrate modest benefits in symptom reduction, including improvements in patient-reported spasticity in multiple sclerosis, significant seizure reduction in treatment-resistant pediatric epileptic syndromes, antiemetic effects in refractory CINV, and appetite stimulation in cachectic states. Additionally, subjective improvements in sleep quality have been observed, though objective changes in sleep architecture remain inconsistent. However, there remains limited evidence supporting meaningful improvements in functional outcomes and quality of life. Cannabis use may negatively impact rehabilitation through dose-dependent cognitive impairment, sedation, impaired motor learning, and increased fall risk. Significant challenges persist, including lack of standardized dosing, variability in formulations and THC:CBD ratios, inconsistent product labeling, and limited high-quality randomized controlled trials assessing long-term functional outcomes. Regulatory barriers, including discrepancies between federal and state laws, further complicate clinical implementation and research. This review highlights the gap between symptomatic relief and functional recovery, emphasizing the need for PM&R-specific research focused on rehabilitation-relevant outcomes that objectively measure functional independence and quality of life. Bridging this gap will be critical to defining a role for medical cannabis within rehabilitation medicine and optimizing patient-centered care that maximizes function.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13409867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Management of Guillain-Barré Syndrome: A Narrative Review.","authors":"Andrew Cameron, Devendra K Agrawal","doi":"10.26502/aimr.0256","DOIUrl":"10.26502/aimr.0256","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is a rapidly progressive immune-mediated polyradiculoneuropathy that can cause respiratory failure, autonomic dysfunction, and significant long-term disability. This narrative review examines the acute management of GBS, including supportive care, established immunotherapies, and emerging treatment strategies. Early recognition and close monitoring of respiratory and autonomic function remain essential, particularly during the progressive phase of disease. Intravenous immunoglobulin (IVIg) and plasma exchange remain the primary disease-modifying treatments and have similar overall efficacy, although both primarily accelerate recovery rather than prevent ongoing nerve injury. Their limitations, including treatment-related fluctuations, adverse effects, cost, supply limitations, and the logistical challenges of plasma exchange, highlight the need for more effective therapies. Emerging treatments are increasingly targeting specific mechanisms involved in GBS pathophysiology. Although the C5 inhibitor eculizumab failed to improve outcomes in a phase 3 trial, early results with the upstream C1q inhibitor ANX005 suggest that earlier complement inhibition may reduce nerve injury and improve functional outcomes. Other investigational approaches include IgG-degrading enzymes such as imlifidase, FcRn inhibitors such as efgartigimod, regulatory T-cell therapies, and regenerative strategies. However, most of these treatments lack adequately powered randomized clinical trial data. Important gaps also remain in subtype-specific treatment, nerve regeneration, long-term rehabilitation, treatment-related fluctuations, and access to care. Future research should focus on more targeted and individualized therapies that address both immune-mediated injury and subsequent nerve damage.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"294-308"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overview of IgG4-Related Disease.","authors":"Amy Phu, Lannhi Nguyen, Daniel Mashiach, Ryan Afrahim, Devendra K Agrawal","doi":"10.26502/aimr.0259","DOIUrl":"https://doi.org/10.26502/aimr.0259","url":null,"abstract":"<p><p>IgG4-related disease is a chronic inflammatory condition that has been formally described and extensively researched only in the recent few decades, making it a relatively new clinical entity. Furthermore, IgG4- related disease has been highly underreported and misdiagnosed as other similarly presenting conditions. In this article, we discuss the variable presentation, diagnosis process and criteria of IgG4-related disease and Sjogren's syndrome in consideration of the literature currently available. In IgG4- related disease patients, an accurate diagnosis is crucial to timely treatment and circumvention of serious adverse outcomes such as irreversible organ damage. This critical review article provides an overview of IgG4-related disease with a primary focus on (i) current understanding of its pathophysiological mechanisms, (ii) most recognized clinical phenotypes, (iii) current diagnostic guidelines, and (iv) current treatments available.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"325-330"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cloning of human DING: Developmental expression and downregulation by EtOH in-utero.","authors":"Nune Darbinian, Armine Darbinyan, Tin Htwe Thin, Nana Merabova, Tamara Tatevosian-Geller, Laura Goetzl, Malgorzata Simm, Eric Chabriere, Shohreh Amini, Michael E Selzer","doi":"10.26502/aimr.0249","DOIUrl":"10.26502/aimr.0249","url":null,"abstract":"<p><strong>Introduction: </strong>An estimated 15-20% of women consume alcohol (EtOH) during pregnancy. Women with alcohol use in early pregnancy are likely to have a child with fetal alcohol spectrum disorders (FASD). Recently, we reported neuroprotective effects of human DING (a member of the DING family of phosphatases) against EtOH-mediated toxicity in rats and in human fetal cortical neurons in vitro. Now, we report the sequencing and developmental expression patterns of endogenous DING in human fetal brain.</p><p><strong>Methods: </strong>DING cDNA was cloned from human U87MG astrocytoma cells with primers specific to the plant DING gene and known prokaryotic DING genes. This cDNA was used to prepare antibodies. The full-length human DING gene p38hu (1095 nucleotide bases) is flanked by the first initiating codon, ATG, and the last, stop codon, TAA. Post-mortem fetal tissues and maternal blood were collected during pregnancy between 8 and 37 weeks' gestation. The developmental, spatial, and temporal expression of DING protein in fetal brain tissue was analyzed by immunohistochemistry. Developmental expression of DING in fetal brain and placenta was quantified by qWestern blots. DING promoter expression was assayed by ddPCR. Statistical analysis included ANOVA.</p><p><strong>Results: </strong>Sequencing revealed different-sized genomic DNA clones. The anti-DING antibody detected proteins ranging in size from 35 to 40 kDa, and high molecular weight precursor protein in fetal brain and placenta. DING protein was present in fetal brain at early stages and its level was increased at later gestational ages. The DING promoter was expressed in fetal brain, neurospheres, and fetal brain-derived exosomes. DING levels were reduced in samples exposed to maternally consumed alcohol.</p><p><strong>Conclusions: </strong>Because DING is neuroprotective, its reduced expression in fetuses exposed to alcohol may suggest a mechanism that contributes to the pathogenesis of FASD, which could lead to the development of therapeutic tools aimed at preventing, ameliorating or reversing this prevalent group of syndromes that are implicated in as many as 5% of births world-wide.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"184-204"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of the Mechanisms and Therapeutic Applications of GHK-Cu (Glycyl-L-Histidyl-L-Lysine-Copper Complex) in Topical Microneedle Delivery: A Case for Expanded Clinical Trials.","authors":"Niayesh Najafi, Hussein Maatouk, Karapet Gary Vardanyan, Kevin Babakhan Vartanian, Devendra K Agrawal","doi":"10.26502/aimr.0255","DOIUrl":"10.26502/aimr.0255","url":null,"abstract":"<p><p>GHK-Cu, the copper-bound form of the human tripeptide glycyl-L-histidyl-L-lysine has accumulated more than four decades of pre-clinical evidence for tissue regeneration, anti-inflammatory action, antioxidant capacity, and broad gene-expression remodeling. Yet despite this volume, the clinical literature in humans remains thin and fragmented: most randomized trials are small, conducted on facial cosmetic creams, and rarely paired with delivery technologies capable of reliably crossing the stratum corneum. The microneedle-mediated delivery route which has been shown in vitro and in porcine ex vivo models to dramatically enhance GHK-Cu skin uptake has yet to be evaluated in a single registered, adequately powered human randomized controlled trial published in the peer-reviewed literature. This systematic review synthesizes the body of GHK-Cu literature published between 2005 and 2026, mapped against the PRISMA framework. Searches across PubMed, Elsevier ScienceDirect, and the Cochrane CENTRAL Registry yielded 1,247 records; after deduplication and screening, 64 records were retained for qualitative synthesis. Studies were stratified by study model (in vitro, ex vivo, in vivo rodent, in vivo non-rodent, and human) so that comparator therapies could be matched on equivalent footing. A critical discussion is provided on the physiology and underlying mechanistic foundation of GHK-Cu activity, including its role as an endogenous matricryptin released from collagen Iα2 and SPARC, copper's essential cofactor function for the lysyl oxidase family of cross-linking enzymes, decorin and glycosaminoglycan organization of newly deposited matrix, TGF-β3-mediated reduction of fibrosis, and ferritin-iron-modulated antioxidant defense. A dedicated surgical wound healing section addresses the evidence base for GHK-Cu in CO₂ laser resurfacing, irradiated tissue and post-radiation reconstruction, Mohs micrographic surgery wounds, skin grafts, and hair transplant sites. The synthesis confirms a deep, mechanistically coherent body of preclinical evidence and reveals a defined evidence gap: well-designed human trials of GHK-Cu delivered via microneedle or microneedle-adjacent platforms (dissolvable patches, hollow microneedle arrays, dermaroller-assisted serums) are needed to translate the strong cellular and animal data into validated clinical practice. Specific recommendations for trial design stratified by indication (photoaging, androgenetic alopecia, atrophic acne scarring, chronic wound healing, post-Mohs cosmetic outcomes, post-radiation surgical reconstruction) are provided.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"269-293"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic Effects of Traditional South Asian Diets and the Growing Burden of Metabolic Syndrome.","authors":"Akshay Bharadwaj, Meghana Kaipa, Devendra K Agrawal","doi":"10.26502/aimr.0248","DOIUrl":"10.26502/aimr.0248","url":null,"abstract":"<p><p>Metabolic syndrome is defined as a set of metabolic abnormalities that increase the risk of cardiovascular disease. South Asians are at a disproportionately high risk for metabolic syndrome due to their genetic profile as well as lifestyle and cultural factors. One main lifestyle factor adding to their increased prevalence is their dietary patterns, which include many high-risk food items like refined carbohydrates, oils, and saturated fats. These dietary components are interconnected with their cardiometabolic profiles which can lead to increasingly adverse outcomes across future South Asian generations. This paper evaluates the intricate relationship between metabolic syndrome and cardiovascular disease, specifically focusing on the dietary components that drive disease progression. Furthermore, this paper examines the protective cardiometabolic elements already inherent to the regional diet, exploring how traditional South Asian dietary patterns can be strategically modified to optimize preventive care. Ultimately, this review stresses the need for individually tailored, culturally centered dietary interventions to optimize preventive care and mitigate the metabolic burden in both native and diaspora South Asian communities.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"175-183"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stiff Person Syndrome: Bridging Neuroimmunology and Rehabilitation for Improved Patient Outcomes.","authors":"Colleen C Mercado, Marcel P Fraix, Devendra K Agrawal","doi":"10.26502/aimr.0252","DOIUrl":"10.26502/aimr.0252","url":null,"abstract":"<p><p>Stiff person syndrome (SPS) is a rare autoimmune neurologic disorder characterized by progressive muscle rigidity, painful stimulus-triggered spasms, and impaired inhibitory neurotransmission. Once considered a singular entity, SPS is now recognized as part of a broader spectrum of autoimmune neurologic disorders with diverse clinical phenotypes, antibody profiles, and functional outcomes. Although advances in neuroimmunology have improved understanding of disease mechanisms and expanded therapeutic options, the functional consequences of SPS and the role of rehabilitation remain comparatively underrepresented in the literature. This comprehensive review provides the current evidence regarding the epidemiology, immunopathogenesis, clinical spectrum, diagnosis, treatment, functional outcomes, and rehabilitation considerations of stiff person syndrome and stiff person spectrum disorders. A review of the literature was conducted using peer-reviewed publications identified through PubMed and Google Scholars. Priority was given to original research, clinical trials, systematic reviews, and landmark studies, with an emphasis on contemporary literature published within the past five years. Additional studies were included to provide historical context and highlight the evolution of current concepts. SPS is increasingly recognized as a heterogeneous autoimmune disorder associated with anti-glutamic acid decarboxylase, glycine receptor, and amphiphysin antibodies, including rituximab, hematopoietic stem cell transplantation, and chimeric antigen receptor T-cell therapy, offer promise for refractory disease. Despite advances in medical management, SPS continues to impose substantial functional limitations affecting mobility, activities of daily living, and quality of life. Rehabilitation interventions, including physical and occupational therapy, spasticity management, neuromodulation, and multidisciplinary care, demonstrate potential to improve functional outcomes, although evidence remains limited. SPS is a complex autoimmune disorder requiring multidisciplinary management that extends beyond immunotherapy alone. Continued advances in biomarker discovery, targeted immunotherapies, standardized functional outcome measures, and evidence-based rehabilitation strategies are essential to improve diagnosis, optimize functional recovery, and enhance long-term quality of life.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 3","pages":"227-240"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiorenal Protective Effects of Finerenone in Patients with Type 2 Diabetes Mellitus.","authors":"Talia Radparvar, Ilana Radparvar, Devendra K Agrawal","doi":"10.26502/aimr.0241","DOIUrl":"10.26502/aimr.0241","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and progressive β-cell dysfunction, resulting in persistent hyperglycemia and long-term vascular complications. The global prevalence of T2DM continues to rise and is strongly associated with cardiovascular disease, chronic kidney disease, and the broader cardiovascular-kidney-metabolic (CKM) syndrome. This review summarizes the pathophysiology of T2DM, with emphasis on insulin resistance, endothelial dysfunction, oxidative stress, and activation of the renin-angiotensin-aldosterone system, all of which contribute to progressive end-organ damage. Chronic hyperglycemia further promotes inflammatory and fibrotic pathways that accelerate diabetic kidney disease and atherosclerotic cardiovascular disease. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has emerged as a therapeutic option for patients with T2DM and chronic kidney disease. Clinical trial data demonstrate that finerenone reduces albuminuria and provides cardiovascular and renal protection by reducing inflammation and fibrosis. Its use is associated with a generally acceptable safety profile, although hyperkalemia remains an important adverse effect requiring routine monitoring. Overall, T2DM is a multifactorial disease that requires comprehensive management targeting metabolic dysregulation as well as inflammatory and hormonal pathways. Finerenone represents an important advancement in cardiorenal protection. Understanding the interconnected mechanisms underlying CKM syndrome is essential for improving long-term outcomes in individuals with T2DM.</p>","PeriodicalId":519871,"journal":{"name":"Archives of internal medicine research","volume":"9 2","pages":"94-106"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}