OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

Abstract Introduction: Type 2 diabetes mellitus (T2DM) is a major global health concern characterized by insulin resistance, hyperglycemia, and chronic inflammation. Interest in natural adjunctive therapies has increased, particularly in mangosteen (Garcinia mangostana), which contains xanthone compounds in the peel with potential antidiabetic properties. Methods: This systematic review followed PRISMA 2020 guidelines. Literature searches were conducted using PubMed, Google Scholar, and ClinicalKey up to December 2022 for studies assessing mangosteen peel extract (MPE) or α-mangostin in diabetic human subjects. Eligible studies included randomized controlled and quasi-experimental trials reporting glycemic or metabolic outcomes. Risk of bias was evaluated using the Cochrane RoB tool. The primary result of this study is to evaluate the effects of mangosteen peel extract supplementation on key glycemic outcomes in patients with T2DM, specifically fasting blood glucose (FBG), HOMA-IR, and HbA1c. Results: A total of two studies (n=2) met the inclusion criteria. A randomized controlled pilot trial reported significant improvement in insulin sensitivity (HOMA-IR −53.2% vs −15.2%; p = 0.004) after 26 weeks of standardized mangosteen extract. A small quasi-experimental study reported a significant reduction in FBG following 7 days of mangosteen peel decoction. Discussion: Limited clinical evidence indicates that mangosteen peel extract may improve insulin sensitivity and lower fasting glucose in T2DM. However, the conclusions are limited by the small number of available studies, the short follow-up duration in one trial, and variability in extract preparation. Conclusion: Mangosteen peel extract demonstrates promising glycemic benefits, including improved insulin sensitivity and reduced fasting glucose. However, the available evidence remains limited by small sample sizes, short follow-up periods, and heterogeneity in extract formulations. Larger randomized controlled trials using standardized preparations are required before clinical recommendations can be made.
Garcinia mangostana ; mangosteen peel extract ; &alpha ; -mangostin ; type 2 diabetes mellitus ; insulin resistance ; oxidative stress

Introduction: Insulin resistance and progressive beta-cell dysfunction are key components of the pathophysiology of type 2 diabetes mellitus (T2DM). The triglyceride-to-highdensity lipoprotein cholesterol (TG/HDL) ratio has been widely used as a marker of insulin resistance. In addition, testosterone deficiency has been associated with adverse metabolic profiles and T2DM. However, the relationship between testosterone levels, insulin resistance, and betacell function in patients with T2DM remains incompletely understood. Methodology: A cross-sectional study was conducted involving 25 male patients with T2DM attending the diabetic clinic at Dr. Mohammad Hoesin General Hospital. Serum testosterone, C-peptide, TG, and HDL levels were obtained from routine clinical data. The TG/HDL ratio was calculated as an index of insulin resistance. Normality was assessed using the Shapiro–Wilk test, and due to the non-normal distribution of key variables, Spearman correlation analysis was applied. Results: A strong inverse correlation was observed between testosterone levels and TG/HDL ratio (r = -0.860, p <0.001), indicating that higher insulin resistance was associated with lower testosterone levels. In addition, TG/HDL ratio showed a strong negative correlation with C-peptide levels (r = -0.741, p <0.001), suggesting reduced beta-cell function in the presence of increased insulin resistance. Conclusion In patients with T2DM, increased insulin resistance is strongly associated with lower testosterone levels and reduced beta-cell function. These findings highlight the interaction between metabolic dysfunction and hormonal status in middle-aged and elderly patients with T2DM
Diabetes Mellitus, Type 2 ; Insulin Resistance ; Testosterone

Introduction: Acromegaly is usually diagnosed by elevated age- and sex-adjusted insulin-like growth factor-1 (IGF-1) levels reflecting chronic growth hormone (GH) excess. IGF-1 is preferred as a screening biomarker due to its longer half-life and reduced pulsatility compared with GH. However, IGF1 levels may be disproportionately low or only modestly elevated in certain clinical contexts, leading to diagnostic uncertainty. Pituitary apoplexy is one such condition in which acute tumor hemorrhage or infarction may disrupt sustained GH secretion and attenuate IGF-1 production Case: A 48-year-old female with hypertension, type 2 diabetes mellitus, and dyslipidemia presented with a 2-day history of severe headache, vomiting, and visual disturbance, on a background of progressive acral enlargement over 2 years. Examination revealed coarse facial features, prognathism, enlarged hands, and cranial nerve involvement. Magnetic resonance imaging demonstrated an invasive sellar– suprasellar pituitary macroadenoma with optic chiasmal compression and cavernous sinus encasement. Intravenous dexamethasone was initiated pre-operatively due to a significant mass effect. Biochemical evaluation showed markedly elevated random GH levels (>50 ng/mL) with only mildly elevated IGF-1 at 1.19 times the upper limit of normal, below the threshold at which confirmatory oral glucose tolerance testing may be omitted according to current guidelines. Other pituitary axes suggested evolving hypopituitarism. During admission, she developed severe hyperglycemia with marked insulin resistance, requiring high-dose insulin therapy (approximately 1.5 U/kg/day). She underwent urgent transsphenoidal surgery, with histopathology confirming a pituitary neuroendocrine tumor with extensive hemorrhage and infarction, consistent with pituitary apoplexy. Postoperatively, GH levels were suppressed to <5 ng/mL, insulin requirements decreased markedly, and hormone replacement was initiated for secondary adrenal insufficiency and central hypothyroidism. Conclusion This case highlights that IGF-1 levels below conventional diagnostic thresholds do not exclude clinically significant acromegaly, particularly in the setting of pituitary apoplexy. Integration of clinical phenotype, GH levels, and imaging findings is essential to avoid diagnostic delay and ensure timely management.
Acromegaly ; Insulin Resistance ; Pituitary Apoplexy

BACKGROUND

Invasive candidiasis is defined by the growth of Candida species in the bloodstream or other internal organs. It is a global concern due to increasing multidrug resistance and high mortality rates. This study aimed to update prevalence data on Candida infections in the Philippines, analyzing demographic factors (age, sex), specimen sources, and associated risk factors. We compared antifungal resistance patterns against CLSI epidemiological cutoff values (ECVs) and clinical breakpoints and examined MIC variations by underlying disease to inform potential standardized empiric therapies.

METHODOLOGY

We conducted a retrospective analytical cross-sectional study (SLMC-IERC approval, minimal risk) reviewing one year of Candida speciation and susceptibility results from January 2024 to December 2024 at a private tertiary hospital. All aseptically collected samples that tested positive for Candida species were included. Respiratory and wound specimens required a Gram stain demonstrating yeasts and hyphae prior to culture, while urine cultures were included only if they yielded ≥100,000 CFU/mL. Identification and susceptibility testing were performed using the VITEK 2 system, with results interpreted using CLSI breakpoints and ECVs.

RESULTS

Among 266 patients with Candida infections, invasive candidiasis predominated in those aged ≥60 years (66.4%). Candida albicans (21.7%) and Candida tropicalis (13.5%) were more frequent in females, while Candida parapsilosis (13.2%) and Candida glabrata (5.3%) were more common in males. Blood and CSF samples strongly correlated with invasive disease and underlying risk factors. C. albicans was linked to infection-related conditions (13.9%), malignancy (9.0%), and cardiovascular disease (6.8%). C. parapsilosis(23.3%) and C. tropicalis (20.7%) were frequently associated with infection, malignancy, and metabolic disorders. C. glabrata (7.5%), noted for antifungal resistance, was isolated in patients with direct infections (3.4%) and malignancies (1.9%). Among azoles, fluconazole demonstrated greater susceptibility against Candida species, requiring lower concentrations for inhibition, despite a higher resistance rate (13.22%) compared to voriconazole (8.95%). Among echinocandins, micafungin showed better susceptibility than caspofungin. Amphotericin B demonstrated the highest overall susceptibilit y (93 –10 0%), though MICs approached ECV limits. Most susceptible MIC values were fluconazole 0.5 μg/mL for C. albicans and C. parapsilosis, 1.0 μg/mL for C. tropicalis; voriconazole and caspofungin 0.12 μg/mL; micafungin 0.06 μg/mL; amphotericin B 0.5 μg/mL; and flucytosine

CONCLUSION

These findings support a species-specific, risk-adapted approach to antifungal therapy, incorporating demographic and clinical variables. Continuous surveillance of invasive candidiasis prevalence and antifungal MIC trends, with periodic breakpoint updates, is crucial to preserve therapeutic efficacy. Effective management of multidrug-resistant Candidainfections also requires close collaboration between clinicians and pharmacists, as well as the development of new dosing strategies based on pharmacokinetic/pharmacodynamic (PK/PD) principles.

Human ; Candidiasis ; Antifungal Agents ; Drug Resistance ; Candida ; Azoles

Objective:Multi-drug resistant bacterial infection（MRSA） complications occurring in cochlear implant recipients is rare and of serious consequence. This paper aimed to summarize the treatment experience of a patient with MRSA infection after cochlear implantation. A patient with nasopharyngeal malignant tumor after radiotherapy developed to severe sensorineural deafness. She suffered MRSA infection nine days after cochlear implantation. Since the wound failed to heal after weeks of topical and systemic sensitive antibiotic therapy, the patient underwent surgery for wound debridement. The stimulator-receiver and the electrode of the implant was removed, negative pressure wound therapy was applied, and systemic anti-infection treatment with sensitive antibiotics for weeks, the patients recovered and was discharged from hospital 69 days after infection.
Humans ; Cochlear Implantation/adverse effects* ; Female ; Drug Resistance, Multiple, Bacterial ; Staphylococcal Infections/therapy* ; Methicillin-Resistant Staphylococcus aureus ; Cochlear Implants ; Anti-Bacterial Agents/therapeutic use* ; Postoperative Complications ; Middle Aged

Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

Nasopharyngeal carcinoma（NPC） is a distinct type of head and neck cancer closely associated with Epstein-Barr virus（EBV） infection and exhibits significant geographic variations in its incidence. Despite recent advancements in radiotherapy techniques and precision medicine for NPC, the overall survival rate remains unsatisfactory due to tumor metastasis, recurrence, and drug resistance. Single-cell RNA sequencing（scRNA-seq） is an emerging technology that allows for the analysis of gene expression at single-cell resolution, providing a clearer understanding of tumor cell subpopulations, the evolutionary trajectory of tumor cells, and the functional roles and interactions of cells within the tumor microenvironment. This provides new ideas for the development of precision medicine in NPC. Here, we review the applications of scRNA-seq in exploring the mechanisms of NPC pathogenesis, tumor heterogeneity, the tumor microenvironment, drug resistance, and therapeutic response.
Humans ; Nasopharyngeal Neoplasms/genetics* ; Tumor Microenvironment ; Nasopharyngeal Carcinoma ; Single-Cell Analysis ; Sequence Analysis, RNA ; Precision Medicine ; Drug Resistance, Neoplasm ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Single-Cell Gene Expression Analysis

OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

OBJECTIVES: To investigate how larval feeding regimens influence development and deltamethrin resistance of Aedes albopictus to provide evidence for standardizing larval feeding protocols in studies of insecticide resistance. METHODS: Aedes albopictus larvae of a laboratory resistant strain were divided into 3 groups (n=500) and reared with high, medium, and low food availability (100, 50, or 25 mg daily for the 1st and 2nd instars, and 500 mg 250, or 125 mg daily for 3rd and 4th instars). The developmental time, pupation rate, adult emergence rate, adult body weight, and wing length were recorded in each group, and deltamethrin resistance of the mosquitoes was assessed using larval bioassays and contact tube tests for adults. RESULTS: Significant developmental differences were observed across the 3 feeding groups. Larval development time decreased as the food availability increased, and both high- and low-food groups showed reduced pupation rates (χ²=16.282, 7.440) and emergence rates (χ²=4.093, 6.977) compared to the medium-food group. Adult body weight and wing length were positively correlated with the amount of larval food intake (P<0.05). In high, medium and low food intake groups, larval LC₅₀ values for deltamethrin were 0.110, 0.072 and 0.064 mg/L, adult KDT50 values were 97.404, 68.964 and 65.005 min, and adult mosquitoe mortality rates at 24 h after deltamethrin exposure were 12%, 16% and 19%, respectively. CONCLUSIONS The feeding amount during larval stage significantly impacts the development and deltamethrin resistance of Aedes albopictus, suggesting the importance of standardization of larval nutrition for ensuring comparability of resistance test data across laboratories.
Animals ; Aedes/physiology* ; Pyrethrins/pharmacology* ; Nitriles/pharmacology* ; Larva/physiology* ; Insecticide Resistance ; Insecticides/pharmacology* ; Feeding Behavior