Chitosan Nanoparticles for Intranasal Drug Delivery.

This manuscript explores the use of nanostructured chitosan for intranasal drug delivery, targeting improved therapeutic outcomes in neurodegenerative diseases, psychiatric care, pain management, vaccination, and diabetes treatment. Chitosan nanoparticles are shown to enhance brain delivery, improve bioavailability, and minimize systemic side effects by facilitating drug transport across the blood-brain barrier. Despite substantial advancements in targeted delivery and vaccine efficacy, challenges remain in scalability, regulatory approval, and transitioning from preclinical studies to clinical applications. The future of chitosan-based nanomedicines hinges on advancing clinical trials, fostering interdisciplinary collaboration, and innovating in nanoparticle design to overcome these hurdles and realize their therapeutic potential.

Quantum Dot Research in Breast Cancer: Challenges and Prospects.

The multifaceted role of quantum dots (QDs) in breast cancer research highlights significant advancements in diagnostics, targeted therapy, and drug delivery systems. This comprehensive review addresses the development of precise imaging techniques for early cancer detection and the use of QDs in enhancing the specificity of therapeutic delivery, particularly in challenging cases like triple-negative breast cancer (TNBC). The paper also discusses the critical understanding of QDs' interactions with cancer cells, offering insights into their potential for inducing cytotoxic effects and facilitating gene therapy. Limitations such as biocompatibility, toxicity concerns, and the transition from laboratory to clinical practice are critically analyzed. Future directions emphasize safer, non-toxic QD development, improved targeting mechanisms, and the integration of QDs into personalized medicine, aiming to overcome the current challenges and enhance breast cancer management.

Lipid Nanoparticles in Lung Cancer Therapy.

This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such as doxorubicin and paclitaxel. This manuscript details the design and benefits of various LNP systems, including solid lipid-polymer hybrids, which offer controlled release and enhanced drug encapsulation. Despite achievements in reducing tumor size and enhancing survival, challenges such as manufacturing complexity, biocompatibility, and variable clinical outcomes persist. Future directions are aimed at refining targeting capabilities, expanding combinatorial therapies, and integrating advanced manufacturing techniques to tailor treatments to individual patient profiles, thus promising to transform lung cancer therapy through interdisciplinary collaboration and regulatory innovation.

Epigenetics of the blood pressure reactivity to salt: Is the salt sensitive phenotype correctable?

Salt sensitivity defines a state characterized by a highly reactive blood pressure to changes in salt intake. The salt-sensitive phenotype is strongly associated with hypertension, visceral adiposity/metabolic syndrome, and ageing. Obesity accounts for around 70% of hypertension in young adults, and 30% to 50% of adult hypertensives carry the salt-sensitive phenotype. It is estimated that the salt-sensitive phenotype is responsible for high blood pressure in over 600 million adults. But is the salt-sensitive phenotype correctable? Interventional, controlled, clinical trials in obese adolescents and young obese adults, demonstrated that weight-reducing lifestyle modifications revert the salt-sensitive to the salt-resistant phenotype, and restored the faulty production of nitric oxide. Correction of the salt-sensitive phenotype lowers the blood pressure by reducing its reactivity to dietary salt. In a random sample of obese adults subjected to lifestyle modifications, those who were salt-resistant at baseline, were also normotensive and failed to further lower their blood pressure despite a 12% drop in body weight. The salt-resistant phenotype protects the metabolically healthy obese from hypertension, even if their salt consumption is comparable to that of salt-sensitive obese. In summary, at early stages, the elevated blood pressure of obesity, is determined by epigenetic changes leading to a state of salt-sensitivity.

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality globally. Despite significant advancements in the development of pharmacological therapies, the challenges of targeted drug delivery to the cardiovascular system persist. Innovative drug-delivery systems have been developed to address these challenges and improve therapeutic outcomes in CVDs. This comprehensive review examines various drug delivery strategies and their efficacy in addressing CVDs. Polymeric nanoparticles, liposomes, microparticles, and dendrimers are among the drug-delivery systems investigated in preclinical and clinical studies. Specific strategies for targeted drug delivery, such as magnetic nanoparticles and porous stent surfaces, are also discussed. This review highlights the potential of innovative drug-delivery systems as effective strategies for the treatment of CVDs.

Conductive polymers for cardiac tissue engineering and regeneration.

Cardiovascular diseases, such as myocardial infarction, are considered a significant global burden and the leading cause of death. Given the inability of damaged cardiac tissue to self-repair, cell-based tissue engineering and regeneration may be the only viable option for restoring normal heart function. To maintain the normal excitation-contraction coupling function of cardiac tissue, uniform electronic and ionic conductance properties are required. To transport cells to damaged cardiac tissues, several techniques, including the incorporation of cells into conductive polymers (CPs) and biomaterials, have been utilized. Due to the complexity of cardiac tissues, the success of tissue engineering for the damaged heart is highly dependent on several variables, such as the cell source, growth factors, and scaffolds. In this review, we sought to provide a comprehensive overview of the electro CPs and biomaterials used in the engineering and regeneration of heart tissue.

Antiviral and anti-inflammatory drugs to combat COVID-19: Effects on cardiac ion channels and risk of ventricular arrhythmias.

Introduction: Drugs with no indication for the treatment of cardiovascular diseases (e.g., drugs employed to treat COVID-19) can increase the risk of arrhythmias. Of interest, a six-fold increase in the number of arrhythmic events was reported in patients with severe COVID-19. In this study, we reviewed (i) the pro-arrhythmic action of drugs given to patients with COVID-19 infection, and (ii) the effects of inflammatory cytokines on cardiac ion channels and possible generation of arrhythmias. Methods: We conducted a literature search on the drugs with purported or demonstrated efficacy against COVID-19 disease, emphasizing the mechanisms by which anti-COVID-19 drugs and inflammatory cytokines interfere with cardiac ion channels. Results: Antibiotics (azithromycin), antimalarials (hydroxychloroquine, chloroquine), antivirals (ritonavir/lopinavir, atazanavir), and some of the tyrosine kinase inhibitors (vandetanib) could induce long QT and increase risk for ventricular arrhythmias. The pro-arrhythmic action results from drug-induced inhibition of Kv11.1 (hERG) channels interfering with the repolarizing potassium IKr currents, leading to long QT and increased risk of triggered arrhythmias. At higher concentrations, these drugs may interfere with IKs, IK1, and/or Ito potassium currents, and even inhibit sodium (INa) and calcium (ICa) currents, inducing additional cardiac toxicity. Ibrutinib, an inhibitor of Bruton's TK, increased the incidence of atrial fibrillation and ventricular tachycardia associated with a short QT interval. Inflammatory cytokines IL-6 and TNF-α inhibit IKr and Ito repolarizing potassium currents. High levels of inflammatory cytokines could contribute to the arrhythmic events. For remdesivir, favipiravir, dexamethasone, tocilizumab, anakinra, baricitinib, and monoclonal antibodies (bamlanivimab, etesevimab, and casirivimab), no evidence supports significant effects on cardiac ion channels, changes in the QT interval, and increased risk for ventricular arrhythmias. Conclusion: This study supports the concept of hERG channel promiscuity. Different drug classes given to COVID-19 patients might delay repolarization, and increase the risk of ventricular arrhythmias. The presence of comorbid pro-arrhythmic disease states, and elevated levels of pro-arrhythmic cytokines, could increase the risk of ventricular arrhythmias. Discontinuation of nonessential drugs and correction of electrolyte abnormalities could prevent severe ventricular arrhythmias. Altogether, the most effective therapies against COVID-19 (remdesivir, dexamethasone, monoclonal antibodies) lack pro-arrhythmic activity.

A Comparison of SARS-COV-2 Neutralizing Antibody Therapies in High-Risk Patients with Mild to Moderate COVID-19 Disease at a Single Academic Hospital.

BACKGROUND: Bamlanivimab and casirivimab/imdevimab are recombinant neutralizing monoclonal antibodies that decrease viral load in patients with coronavirus disease 2019 (COVID-19) and can decrease hospitalizations. Few data exist comparing these two therapies. OBJECTIVE: Our aim was to compare the efficacy and safety of bamlanivimab and casirivimab/imdevimab in emergency department (ED) patients with COVID-19 who met criteria for monoclonal antibody therapy. METHODS: We performed a single-center, open-label, prospective study in adult ED patients with confirmed COVID-19 and high-risk features for hospitalization. Enrolled patients received bamlanivimab or casirivimab/imdevimab, depending on the day of the week that they arrived. We observed patients for post-infusion-related reactions and contacted them on days 5, 10, and 30. The primary outcome was the number of hospitalizations through day 30. In addition, we compared groups with regard to return visits to the ED, symptom improvement, antibody-induced adverse events, and deaths. RESULTS: Between December 17, 2020 and January 17, 2021, 321 patients completed the study. We found no statistically significant difference in the rate of subsequent hospitalization between groups (bamlanivimab: n = 18 of 201 [8.9%] and casirivimab/imdevimab: n = 13 of 120 [10.8%]; p = 0.57). In addition, we found no statistically significant differences between groups regarding return visits to the ED or symptom improvement. One patient had a possible adverse reaction to the treatment, and 1 patient died. Both of these events occurred in the bamlanivimab group. CONCLUSIONS: We found no statistically significant differences in rates of subsequent hospitalization or other outcomes for ED patients with COVID-19 when they received bamlanivimab as opposed to casirivimab/imdevimab. Adverse events were rare in both groups.

Emergency Physician Survey on Firearm Injury Prevention: Where Can We Improve?

INTRODUCTION: Firearm injury and death is increasingly prevalent in the United States. Emergency physicians (EP) may have a unique role in firearm injury prevention. The aim of this study was to describe EPs' beliefs, attitudes, practices, and barriers to identifying risk of and counseling on firearm injury prevention with patients. A secondary aim was assessment of perceived personal vulnerability to firearm injury while working in the emergency department (ED). METHODS: We conducted a cross-sectional survey of a national convenience sample of EPs, using questions adapted from the American College of Surgeons' Committee on Trauma 2017 survey of surgeons. Descriptive statistics and chi-square tests were calculated as appropriate. RESULTS: A total of 1901 surveys were completed by EPs from across the United States. Among respondents, 42.9% had a firearm at home, and 56.0% had received firearm safety training. Although 51.4% of physicians in our sample were comfortable discussing firearm access with their high-risk patients, more than 70% agreed or strongly agreed that they wanted training on procedures to follow when they identify that a patient is at high risk of firearm injury. Respondents reported a variety of current practices regarding screening, counseling, and resource use for patients at high risk of firearm injury; the highest awareness and self-reported screening and counseling on firearm safety was with patients with suicidal ideation. Although 92.3% of EPs reported concerns about personal safety associated with firearms in the ED, 48.1% reported that there was either no protocol for dealing with a firearm in the ED, or if there was a protocol, they were not aware of it. Differences in demographics, knowledge, attitudes, and behavior were observed between respondents with a firearm in the home, and those without a firearm in the home. CONCLUSIONS: Among respondents to this national survey of a convenience sample of EPs, approximately 40% had a firearm at home. The majority reported wanting increased education and training to identify and counsel ED patients at high risk for firearm injury. Improved guidance on personal safety regarding firearms in the ED is also needed.

Cell proliferation and anti-oxidant effects of oxytocin and oxytocin receptors: role of extracellular signal-regulating kinase in astrocyte-like cells.

OBJECTIVES: Oxytocin (OXT) participates in various physiological functions ranging from reproduction to social and non-social behaviors. Recent studies indicate that OXT affects cell growth and metabolism. Here we characterized the growth stimulating and antioxidant actions of OXT and of OXT receptors (OXTR) in a glial cell-line (U-87MG). METHODS: We developed an OXTR-knockdown cell-line (U-87MG KD) to establish the receptor specificity of OXT's actions, and the impact of lacking OXTR on growth and survival in glial cells. The role Extracellular-Signal Regulated Kinases (ERK1/2) on glial cell protection against consequences of oxidative stress, and cell proliferation was investigated. RESULTS: In U-87MG cells, OXT stimulated cell proliferation and increased ERK1/2 phosphorylation. The specific ERK1/2 inhibitor, PD098059, produced marked inhibition of cell proliferation, and antagonized the stimulating effect of OXT on ERK1/2 phosphorylation and on cell proliferation. Slower growth rates and lower levels of phosphorylated ERK1/2 were observed in OXTR-knockdown cells and in U-87MG cells treated with an OXTR antagonist (L-371,257). In addition to increasing cell proliferation, OXT significantly blunted the rise in reactive oxygen species induced by H2O2, and antagonized the reductions in cell viability induced by H2O2 and camptothecin. The cell protective and antioxidant actions of OXT in U-87MG cells were not observed in the OXTR-knockdown cells. CONCLUSION: OXT stimulates the growth of astrocyte-like cells acting on OXTR via ERK1/2 phosphorylation. The protection against apoptosis and the antioxidant capacity of OXT may contribute to the observed increase in cell proliferation. Oxytocin and OXTR appear to be fundamental for cell growth and viability of glial cells.

Can Prehospital Personnel Accurately Triage Patients for Large Vessel Occlusion Strokes?

BACKGROUND: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) score was developed in the hospital setting to be used in the prehospital setting. It has been shown to have higher predictive value than comparable stroke scales, including the National Institutes of Health Stroke Scale, for identifying large vessel occlusion strokes. OBJECTIVE: We sought to determine whether prehospital FAST-ED scores are comparable with FAST-ED scores determined by emergency physicians. METHODS: Emergency Medical Services (EMS) personnel were trained to calculate a FAST-ED score for any patient suspected of having a stroke in the field. When the patient arrived at our ED, an emergency physician generated a FAST-ED score. RESULTS: One hundred and thirty-five patients were studied and large vessel occlusions were detected in 23.7%. There was no significant difference between median FAST-ED scores from EMS personnel (3; interquartile range [IQR] 1-5) and emergency physician (2; IQR 1-6). The difference between paired scores was not significantly different from 0 (median of paired differences was 0). In addition, prehospital FAST-ED scores were significantly and positively correlated with physician FAST-ED scores (r2 = 0.26). Comparable receiver operator curve area under the curve values were obtained for EMS FAST-ED (0.727; 95% confidence interval [CI] 0.638-0.816) and ED FAST-ED (0.769; 95% CI 0.669-0.868). CONCLUSIONS: The findings validate that prehospital FAST-ED scores are comparable in predictive value to FAST-ED scores calculated in the ED for prediction of large vessel occlusion strokes.

Emergency Medicine Resident-Driven Point of Care Ultrasound for Suspected Shoulder Dislocation.

OBJECTIVE: To determine the impact of implementing a musculoskeletal in-service educational intervention for emergency medicine (EM) residents on the use of point-of-care ultrasound (POCUS) to diagnose and manage shoulder dislocations in the emergency department (ED). METHODS: This study was conducted in the ED of an academic teaching hospital in Miami, Florida. It consisted of a short in-service educational intervention on how to perform and interpret POCUS, followed by an open, prospective convenience sample study in patients with clinical suspicion of shoulder dislocation. Twenty EM residents, with no prior shoulder scanning training, participated in the study. In all of the cases, the findings of the shoulder US were compared with radiographs, which were considered the reference standard. EM residents enrolled patients, and obtained and interpreted the shoulder US images. RESULTS: Seventy-eight patients were evaluated to rule out shoulder dislocation and/or fracture. Diagnosis of the dislocated shoulder was made in 55 of 78 patients, 53 of whom had anterior dislocations. Resident-driven POCUS had a sensitivity and specificity of 100% to diagnose and rule out, respectively, shoulder dislocations and relocations. There were no differences in the number of dislocations diagnosed and relocated by early and advanced EM residents. Results from a POCUS were available 22 ± 2.8 minutes sooner than x-ray for initial diagnosis and 27 ± 2.9 minutes (P < 0.0001) sooner than x-ray for assessment of reduction. CONCLUSIONS: EM resident physicians, with no previous training in shoulder US imaging, exposed to a brief in-service musculoskeletal education intervention, were able to diagnose shoulder dislocations via POCUS with high sensitivity and specificity. Shoulder US for dislocation should be a core component in EM training.

The Relationship Between Physician/Nurse Gender and Patients' Correct Identification of Health Care Professional Roles in the Emergency Department.

Background: A 2006 study of emergency medicine (EM) patients found male physicians were more often recognized as doctors that were female physicians. We sought to identify gender awareness of EM physicians and nurses by patients to see whether there has been a reduction in gender bias during the past 12 years. Materials and Methods: Before emergency department (ED) discharge or hospital admission, a convenience sample of 150 patients in an urban academic ED was anonymously surveyed to determine their awareness of the role of the health personnel involved in their care. Results: Our patients recognized male attending physicians as physicians 75.7% of the time and female attending physicians as physicians 58.1% of the time (p < 0.01). No differences were observed for resident physicians. Patients recognized male nurses as nurses 77.1% of the time, and female nurses as nurses 91.1% of the time (p < 0.01). Conclusions: These data indicate that patients continue to exhibit gender bias in the recognition of lead physicians and nurses.

Patients' Perceptions of the Role of Physicians in Questioning and Educating in Firearms Safety: Post-FOPA Repeal Era.

OBJECTIVES: In this study, we determined patients' attitudes toward discussing firearms and issues of firearms safety with emergency department physicians. We assessed whether patients feel discriminated against should physicians discuss firearms safety, and whether they believed that physician counseling may change how patients store firearms. METHODS: From June to October 2017, we conducted a cross-sectional institutional review board-approved survey of 200 consenting adult patients (convenience sample) not requiring critical care presenting to the emergency department of Mount Sinai Medical Center in Miami Beach, Florida. The survey consisted of 22 questions about perceptions of physicians inquiring about firearms, demographics, firearms statistics, and firearms knowledge. Results on firearms owners and nonowners were compared with the Fisher exact test. P < 0.05 was considered significant. RESULTS: Ninety percent of patients said they felt comfortable discussing firearms safety with a physician (firearms vs no firearms owner, 100% vs 87.5%, P = 0.028). Ninety percent (firearms 90.7% vs no firearms owners 89.9%, P = 1.0) of patients did not believe that physicians were discriminating against patients who are firearms owners when discussing firearms safety. Seventy-six percent (firearms 76.4% vs no firearms owners 77.3%, P = 0.367) of patients believed that physicians should be educating their patients about firearms safety, and 71% (n = 142) believed that education provided by physicians will change how people store their firearms (firearms 75% vs no firearms owners 70.2%, P = 0.67). CONCLUSIONS: Firearms safety is a difficult but important public health matter that requires significant intervention to help prevent future firearms incidents. This study supports physicians' efforts to help educate patients about the dangers of firearms, along with proper firearms storage techniques, showing that patients are largely open to this discussion. We propose that training of physicians in strategies for initiating clinical discourse and addressing firearms safety is needed.

Breaking the Barriers in Resident Education: A Quality Improvement Initiative.

INTRODUCTION: In 2013, the American College of Cardiology and American Heart Association updated the cholesterol guideline. Despite strong evidence supporting the recommendations, a discernible gap exists in the number of residents who practice them. Our study aimed to identify barriers hindering residents from guideline implementation. METHODS: Twenty eight residents were administered a preintervention and postintervention questionnaire to identify barriers in guideline application. The questionnaire was categorized into three barriers: knowledge, attitude, and behavior. A multifaceted educational intervention consisting of directed teaching sessions and supervised patient encounters was conducted. RESULTS: Our analysis showed that our residents lacked awareness, familiarity, and self-efficacy in using the cholesterol guideline. The intervention led to significant improvements in awareness (79% vs. 43%, p = .0129), familiarity (61% vs. 29%, p = .0306), and self-efficacy (65% vs. 16%, p = .0018) and achieved a 31% increase in knowledge (p = .0001), 38% in attitude (p = .0001), and 20% in behavior (p = .019). The overall improvement in scores averaged 30% (p = .0001). CONCLUSION: Our quality improvement initiative successfully improved our resident's comprehension and applicability of the 2013 ACC/AHA cholesterol guideline. We recommend a multifaceted educational approach tailored toward addressing specific barriers to improve the practice of evidence-based medicine.

Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy.

BACKGROUND: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. AIM: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. METHODS: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. RESULTS: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). CONCLUSION: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes.

Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias.

Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended.

Association of traits of metabolic syndrome with glucose abnormalities.

The association of glucose abnormalities (GAs) with the early appearance of traits of the metabolic syndrome (MS) was studied in an unselected sample of apparently healthy Urban Hispanics. GAs were defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes mellitus (DM). Overall, GAs were associated with older age, abdominal obesity, low high-density lipoprotein cholesterol levels, hypertriglyceridemia, hyperinsulinemia, hypertension, and MS. Prevalence of MS defined as per NCPE-ATPIII was the greatest in subjects with DM (54.3%) and with combined abnormalities (IFG + IGT) (54.1%; P > 0.5). Similar prevalence of MS was found in subjects with isolated IFG (34.3%) and isolated IGT (36.8%) but higher than in normal fasting-glucose tolerant individuals (23.3%) (P < 0.01). The average number of traits of the MS coexisting in normal fasting glucose-tolerant individuals was 1.6 [95% confidence interval (CI), 1.5-1.8; median 2], in isolated IFG: 2.05 (95% CI, 1.8-2.2; median 2); isolated IGT: 2.16 (95% CI, 1.8-2.3; median 2); combined IFG + IGT: 2.7 (95% CI, 2.3-3.1; median 3); and DM: 2.7 (95% CI, 2.25-3.1; median 3) (P < 0.01). Postload insulin levels were higher in isolated IGT than in isolated IFG, whereas HOMA-IR was higher in IFG. Indices of early and total insulin secretion were markedly reduced in DM, IFG-IGT, and IGT. In conclusion, GAs are strongly associated with the number and severity of traits of the MS, defects in insulin secretion, and sustained hyperinsulinemia in response to oral glucose. Subjects with combined GA and newly diagnosed type 2 DM had not only an increased prevalence of MS, but also the MS was characterized by the presence of more than 3 traits, and by a greater severity of each of the coexisting traits.

Prevalence of glucose abnormalities and diagnostic value of fasting glucose and fasting insulin in urban Hispanics.

The prevalence of glucose abnormalities (GAs) and the diagnostic value of fasting plasma glucose and insulin in detecting impaired glucose tolerance (IGT) and diabetes mellitus (DM) were determined in urban Latin Americans. An oral glucose tolerance test was conducted in 592 subjects after administration of 75 g of glucose. Employing American Diabetes Association (ADA) and World Health Organization guidelines, GAs were found in 34% of the subjects, defined as impaired fasting glucose (IFG) (13.3%), IGT (6.9%), combined IFG + IGT (7.8%), and newly diagnosed type-2-DM (6.5%). All newly diagnosed diabetics had 2-hour glucose levels ≥200 mg/dL, but only 46.1% had fasting glucose ≥126 mg/dL. In addition, nearly half of the subjects with IGT (47%) had fasting glucose levels <100 mg/dL. The sensitivity, specificity, positive and negative predictive values of IFG in predicting IGT was 52.9%, 83%, 36.8%, and 90.4 %, respectively. Fasting insulin levels were not sensitive for differentiating glucose tolerant, from IFG and IGT; only the subjects with combined IFG + IGT had increased fasting insulin levels (22% above IFG) (P < 0.01). Two-hour insulin was increased by 30% in IGT and newly diagnosed diabetics, and by 46% in the subjects with combined IFG + IGT. In summary, the very high prevalence of undetected GA encountered in "healthy" subjects living in Caracas, Venezuela, requires immediate sanitary attention. With 50% of diabetic patients being unaware of their condition, half of IGT and DM not detected by ADA guidelines, and the poor sensitivity/specificity of fasting glucose in predicting 2-hour abnormalities, we recommend that 2-hour postload glucose be included when screening for GAs. Measurements of fasting and/or postload insulin are not cost effective for the diagnosis of GA, because they provide little additional clinical information in this context.