BACKGROUND:Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare but clinically compelling cause of hyperinsulinemic hypoglycemia in individuals without prior insulin exposure. Antibody-mediated sequestration of insulin followed by delayed dissociation produces marked glycemic variability, often mimicking insulinoma or factitious hypoglycemia. Increasing global recognition has linked IAS to medications, nutritional supplements, and autoimmune conditions. OBJECTIVE:This review summarizes current evidence on the epidemiology, immunogenetic susceptibility, pathophysiology, clinical presentation, diagnostic evaluation, and management of IAS, with emphasis on mechanisms that explain glycemic variability and practical strategies for accurate diagnosis. METHODS:A structured narrative review was conducted using major biomedical databases to identify publications describing IAS, insulin autoantibodies, or antibody-mediated hypoglycemia. Case reports, case series, mechanistic studies, and reviews were included. Evidence was synthesized to highlight consistent clinical patterns, immunologic mechanisms, and management approaches. RESULTS:IAS is driven by high-capacity, low-affinity insulin autoantibodies that bind endogenous insulin after meals and release it unpredictably, producing postprandial hyperglycemia followed by delayed hypoglycemia. HLA-DR4-related alleles, particularly DRB1×0406, increase susceptibility, while sulfhydryl-containing medications and alpha-lipoic acid are common triggers. Diagnostic challenges arise from immunoassay interference, disproportionately elevated insulin levels, and negative imaging for insulinoma. Most cases improve with withdrawal of triggering agents, dietary modification, and supportive care; persistent hypoglycemia may require glucocorticoids, acarbose, diazoxide, or antibody-directed therapies. CONCLUSION:IAS is an underrecognized immune-mediated cause of hyperinsulinemic hypoglycemia. Early consideration of IAS in patients with discordant insulin-C-peptide results or recent exposure to high-risk medications can prevent unnecessary imaging and guide effective, mechanism-based treatment.
The respiratory tract (i.e., airways and alveoli) is in close contact with the milieu that is outside the human body and thus, in addition to its role in exchange of gases, it is needed to protect the human being from outside threats such as microbes and pollution. Respiratory tract diseases can have major detrimental effects on human health with increased risks for morbidity and mortality. An example of this dilemma is the orphan disease, primary ciliary dyskinesia (PCD), a complex genetic disorder linked with myriad genetic mutations involving over 50 genes and over 2000 pathogenic variants that lead to dysfunction of vital human components including the respiratory tract, auditory system, mechanisms of fertility and others. The core defect involves abnormal function and motion of microscopic organelles called cilia found throughout the human body with abnormal mucociliary clearance (i.e., aberrant mucociliary escalator). The regulation of motile cilia that are involved in various aspects of physiology such as respiration and reproduction is via thousands of genes. PCD pathophysiology, genetic underpinnings, diagnosis and principles of treatment are considered in this review of primary ciliary dyskinesia in pediatric persons (i.e., newborns, children and adolescents). Primary ciliary dyskinesia (PCD) is one of many ciliopathies that is identified as a condition with remarkable phenotypic and genetic variability. In this fluid fluctuation phenomenon, some PCD patients exhibit classic features such as chronic respiratory disease, situs abnormalities, and infertility, while others may present with milder or atypical disease. In certain cases, ultrastructural analysis of cilia may appear normal despite underlying dysfunction. Disease severity can range from early-onset bronchiectasis to relatively preserved pulmonary function into adulthood, reflecting perplexing genotype-phenotype diversity. Testing for PCD requires an experienced team with expertise in sophisticated technology that includes nasal nitric oxide (nNO) analysis, transmission electron microscopy (TEM), immunofluorescence analysis (IFA), high-speed video-microscopy analysis (HSVMA), three-dimensional explant spheroid formation (3D-E; ex vivo technique), genetic studies and others. Genetic testing is recommended for those suspected of having PCD, as for example in certain neonates (i.e., persistent respiratory distress, unexplained rhinorrhea with chronic cough, situs inversus), at-risk children (i.e., having persistent wet cough, chronic sinusitis, unexplained bronchiectasis, recurrent otitis media with airway symptomatology) and adults with early childhood respiratory symptoms often associated with infertility. The medical evaluation is complicated by various factors including the absence of a gold standard for a precise diagnosis. Also, as the clinician or clinical team considers a patient with possible PCD, the testing that is done should keep in mind the differential diagnoses of PCD; these conditions include cystic fibrosis (CF), various immune disorders, numerous infections (i.e., tuberculosis, aspergillosis, others), alpha-1-antitrypsin deficiency (AATD) and others as noted in this article. As emerging cutting-edge 21st century research seeks treatment of PCD via gene therapy, current management involves intense therapy of upper and lower respiratory tract infections (i.e., rhinosinusitis, otitis media, pneumonia) as well as bronchiectasis with focused efforts at dealing with impaired mucus clearance. Primary ciliary dyskinesia is a classic example of how microscopic (electron microscopic) maladies can lead to major macroscopic maladies in newborns, children, adolescents and adults.
BACKGROUND:Obesity-related heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and limited therapeutic options. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated reductions in cardiovascular mortality and worsening heart failure events in a recent randomized controlled trial. However, pooled evidence for tirzepatide's cardiovascular and clinical effects in HFpEF remains limited. Moreover, head-to-head comparisons of tirzepatide with semaglutide, another incretin-mimetic therapy shown to be beneficial in HFpEF, are sparse. This meta-analysis aims to systematically analyze the efficacy and safety of tirzepatide in patients with HFpEF. METHODS:We conducted a systematic review by searching multiple databases up to December 5, 2025 evaluating tirzepatide versus standard therapy and semaglutide for cardiovascular outcomes in patients with obesity-related HFpEF. Statistical analysis was performed using RevMan 5.4, with an inverse variance random effects model to calculate hazard ratios (HR) and odds ratios (OR). Heterogeneity was assessed using the Higgins I² test. The study protocol is registered in PROSPERO (CRD420251170117). RESULTS:Our final analysis included five studies, including RCTs and observational studies with a total of 47,710 patients with HFpEF and BMI ≥ 30 kg/m2, a mean age of 64.7 years, and follow-up ranging from 52 to 146 weeks. Tirzepatide was associated with a significant reduction in the composite outcome of cardiovascular mortality and worsening heart failure events compared with standard therapy (HR 0.50; 95% CI: 0.42-0.60; p < 0.001). A significant reduction in heart failure exacerbation events alone was also observed with tirzepatide versus standard therapy (HR 0.75; p = 0.04), whereas no significant difference was seen when compared with semaglutide (HR 0.95; p = 0.31). Heart failure hospitalization and all-cause mortality did not differ significantly between tirzepatide and either standard therapy or semaglutide. No statistically significant difference in adverse drug reactions was observed. CONCLUSION:In this meta-analysis, tirzepatide was associated with a significant reduction in the composite outcome of cardiovascular mortality and worsening heart failure events in patients with HFpEF and obesity. When compared to semaglutide, there were no significant differences in heart failure hospitalization or all-cause mortality.
BACKGROUND: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. METHODS: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). RESULTS: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; p < 0.001), with greater reductions for rtCGM (-0.65 %) than isCGM (-0.25 %). Mean glucose decreased by -14.72 mg/dL (p < 0.001), and TIR increased by 10.76 % (p < 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. CONCLUSIONS: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. Layman Summary: 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 cardiometabolic health and may contribute to better cardiovascular outcomes in type 2 diabetes beyond glycemic control alone.
BACKGROUND:Takotsubo cardiomyopathy (TTC) is an acute, reversible cardiac syndrome triggered by physical or emotional stress, involving complex multi-system interactions, with unclear mechanisms and variable prognosis across patient subgroups. OBJECTIVES:To synthesize current evidence on comorbidities, biomarkers, genetic predispositions, prognostic factors, and management strategies in TTC, highlighting clinical implications and research gaps for improved diagnosis, prevention, and patient outcomes. METHODS:A systematic review was conducted on studies published between January 2015 and July 2025. Search was performed across Embase, PubMed, Web of Science, Scopus and Google Scholar using predefined MeSH terms and keywords. Twenty-five studies were included in this review. Quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS:TTC was associated with psychiatric disorders, malignancies, endocrine and inflammatory conditions, and neurological insults. Apical ballooning morphology predicted worse outcomes. Biomarkers (NT-proBNP/TnI) and echocardiography improved diagnostic accuracy. Adrenergic receptor polymorphisms (GRK5 L41Q, α2CDel322-325) increased susceptibility in select populations, though genetic findings were inconsistent. Psychological support and beta-blockers improved recovery, while machine learning models enhanced prognostic prediction. ICU-based early echocardiographic screening identified high-risk patients. Multi-disciplinary approaches integrating cardiovascular, psychological, and genetic considerations yielded better patient outcomes. Evidence was limited by heterogeneity, small genetic cohorts, and inconsistent follow-up durations, highlighting the need for standardized diagnostic criteria and prospective, multicenter studies. CONCLUSION:TTC is a multifactorial syndrome requiring integrated diagnostic, therapeutic, and preventive strategies. Early detection, comorbidity management, and personalized care improve prognosis. Standardized research is needed to refine understanding and optimize management.
