OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Introduction: Peripheral arterial disease (PAD) is a common macrovascular complication of type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular morbidity and mortality. The ankle-brachial index (ABI) is a simple, non-invasive method for detecting PAD; however, Doppler devices are not always available in primary care and resource-limited settings. This study aimed to determine the diagnostic accuracy of ABI measurement using a stethoscope compared with the Doppler method among adults with T2DM. Methods: A diagnostic accuracy study was conducted among 200 adults with T2DM recruited through convenience sampling from a private outpatient clinic in Iloilo City. ABI measurements were obtained using both the stethoscope and Doppler methods. An ABI of ≤0.90 was considered indicative of PAD. Diagnostic accuracy measures, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy, and agreement, were calculated. Results: The prevalence of PAD was 30.5% using the stethoscope method and 35.0% using the Doppler method. Compared with Doppler ABI, the stethoscope method demonstrated an overall accuracy of 94.5%, sensitivity of 85.7%, specificity of 99.2%, PPV of 98.4%, and NPV of 92.8%. Agreement between the two methods was excellent (Cohen’s κ = 0.88, p < 0.001). Conclusion Stethoscope-based ABI determination demonstrated high diagnostic accuracy and excellent agreement with Doppler ABI. Given its low cost, accessibility, and non-invasive nature, it may serve as a practical screening tool for PAD among adults with T2DM, particularly in primary care and resource-limited settings where Doppler devices are unavailable
Peripheral arterial disease ; Ankle-brachial index ; Stethoscope ; Doppler ultrasound ; Type 2 diabetes mellitus

Introduction: Endothelial dysfunction (ED) is an early marker of atherosclerosis and plays a role in the pathophysiology of cardiovascular complications in type 2 diabetes mellitus (T2DM). Metabolic factors such as adiposity and insulin resistance contribute to early vascular dysfunction, particularly in patients with preserved kidney function. This study aimed to identify factors associated with ED in T2DM and early-stage chronic kidney disease (CKD) Methodology: This study was conducted at Universiti Teknologi MARA (UiTM), Sungai Buloh, and involved 107 adults with T2DM and estimated glomerular filtration rate ≥60 mL/min/1.73 m&sup2; (CKD stages 1–2). Endothelial function was assessed using ultrasound-based brachial artery flow-mediated dilation (FMD), with ≤7.1% defining ED. Clinical, anthropometric, metabolic, and renal parameters were compared between groups. Logistic regression analyses were performed to identify independent predictors, with p-values <0.05 considered statistically significant. Results: Of the cohort, 48.6% (n = 52) had abnormal FMD. They tended to have higher BMI (31.36 vs 28.38 kg/m&sup2;, p = 0.020), larger waist circumference (100.48 vs 94.53 cm, p = 0.026), and were more likely to be on insulin therapy (71.2 vs 49.1%, p = 0.020). The total daily insulin dose was higher in the abnormal FMD group (0.48 vs 0.35 U/kg), but this difference did not reach statistical significance (p = 0.140). There were no significant differences in hemoglobin A1c, blood pressure, or renal parameters. In multivariate analysis, BMI (adjusted OR 1.07, 95% CI 1.00–1.14, p = 0.037) and insulin therapy (adjusted OR 2.43, 95% CI 1.07–5.51, p = 0.034) remained independently associated. Conclusion In patients with T2DM and early CKD, higher BMI and insulin therapy are independently associated with ED. These findings highlight the role of obesity and insulin resistance in early vascular dysfunction, emphasizing the importance of weighttargeted strategies alongside glycemic control and further identifying high-risk individuals to reduce cardiovascular risk.
Diabetes Mellitus, Type 2 ;

Introduction: Multiple daily insulin injections, while effective for glycemic control, impose considerable costs on healthcare systems and carry inherent risks including hypoglycemia, weight gain, and poor treatment adherence. This study evaluates the glycemic effects of insulin regimen de-escalation from multiple daily injections in poorly controlled type 2 diabetes mellitus (T2DM) patients and explores the predictors of successful insulin de-escalation. Methodology: This is a multi-centred, prospective observational study of adult T2DM patients on multiple daily insulin injections with hemoglobin A1c (HbA1c) 7–12% who underwent de-escalation to one or two injections. Patients were reassessed at 3 months and 6 months. Primary endpoint was change in HbA1c from baseline. Secondary endpoints were changes in body weight, hypoglycemia frequency, treatment adherence and predictors of successful insulin de-escalation defined by at least a 0.3% reduction in HbA1c while on de-escalated regimen. Results: A total of 80 patients were included. HbA1c improved from 9.23 to 8.52% (p <0.001) with total daily insulin dose reduction from 0.81 + 0.35 units per kg to 0.46 + 0.24 units per kg. Symptomatic hypoglycemia decreased from 22.5 to 5.0%. Insulin adherence improved from 50.0 to 92.3%. Body weight decreased by 1.4 kg. Forty-nine patients (61.3%) were successfully de-intensified. Factors associated with successful insulin de-escalation included a high baseline HbA1c, high fasting blood glucose and higher estimated glomerular filtration rate, while increased age, disease duration and being Indian were associated with unsuccessful insulin de-escalation. After adjustment of the confounders, only HbA1c (OR 2.07, 95% CI 1.23–3.46, p = 0.006) and the status of being Indian (OR 0.21, 95% CI 0.05–0.94, p = 0.041) remained as significant positive and negative predictors respectively for successful insulin de-intensification. Conclusion Insulin regimen de-escalation, when combined with optimized oral glucose-lowering agents, improved glycemic control and treatment adherence while reducing hypoglycemia and body weight. These findings support insulin therapy deescalation as a safe, effective strategy for poorly controlled T2DM patients taking multiple daily insulin injections.
Diabetes Mellitus, Type 2 ; Prospective Studies ; Insulins

Introduction: Current education on diabetes self-management is time-consuming as it is conducted face-to-face. This study aimed to evaluate the effectiveness of diabetes education via mobile application on hemoglobin A1c (HbA1c). Methodology: This was a double-blinded randomized controlled study conducted in the Department of Endocrinology, Hospital Pulau Pinang and Hospital Raja Permaisuri Bainun. Participants were stratified randomized according to HbA1c to intervention group (using T-Manis) and control group. The primary objective was to assess the difference in HbA1c between the groups. Secondary objectives were to assess the difference in body weight, hospitalization related to diabetes, diabetes knowledge between groups and usability and satisfaction of T-Manis. Laboratory investigations and questionnaires were conducted at baseline, 4 months and 8 months. Results: A total of 112 participants were randomized into two groups each with 56 participants. Mean age was 51 years with similar diabetes duration of 16 years in both groups. Participants comprised of 61.6% females with ethnic distribution of 49.1% Malay, 30.4% Chinese, 19.6% Indian and 0.9% Siamese. Baseline HbA1c levels were comparable between intervention and control groups (10.04% versus 9.91%; mean difference 0.13%; 95% CI −0.56 to 0.81; p = 0.718). At 4 months, HbA1c of the intervention group demonstrated a significant reduction compared to the control group (8.93% versus 9.80%; mean difference −0.86; 95% CI −1.59 to −0.14; p = 0.02). Sustained reduction of HbA1c in the intervention group was observed at 8 months (mean difference −1.01; 95% CI −1.85 to −0.16; p = 0.02). Baseline body weight was 77 kg, with no betweengroup differences in body weight, hospitalization related to diabetes and diabetes knowledge scores, although diabetes knowledge scores improved at 4 months in the intervention group. 89.3% of participants reported satisfaction with T-Manis Conclusion The T-Manis mobile application aided in significantly improving glycemic control with high user satisfaction, supporting its feasibility as an adjunct to standard diabetes care.
Diabetes Mellitus, Type 2 ; Glycemic Control ; Mobile Applications ; Pangolins

Introduction: Swyer syndrome (46, XY gonadal dysgenesis) is a rare disorder of sex development, characterized by a phenotypic female with streak gonads and hypergonadotropic hypogonadism. It presents with primary amenorrhea and delayed puberty. Overlapping clinical features with Turner syndrome may cause diagnostic uncertainty, highlighting the role of karyotypic evaluation in diagnosis. Case: A 35-year-old phenotypic female was first evaluated at age 27 during admission for an acute viral illness, when incidental findings of primary amenorrhea, short stature (height 131 cm), webbed neck, pectus excavatum, and absent secondary sexual characteristics raised suspicion of Turner syndrome. She had hypertension, with initial imaging suggesting coarctation of the thoracic aorta. CT angiography showed focal narrowing of the descending aorta; multidisciplinary review favored aortic folding, and she was managed conservatively. Endocrine evaluation demonstrated hypergonadotropic hypogonadism, with markedly elevated follicle-stimulating hormone (FSH 108.6 IU/L) and luteinizing hormone (LH 23.16 IU/L) in the presence of low estradiol levels. Pelvic imaging revealed an atrophic uterus with absence of bilateral ovaries, consistent with gonadal dysgenesis. Karyotypic analysis was performed, demonstrating a 46, XY genotype with confirmed SRY gene presence, establishing the diagnosis of Swyer syndrome. DEXA scan demonstrated osteoporosis, in keeping with prolonged hypogonadism. She was commenced on hormone replacement therapy, resulting in the development of secondary sexual characteristics and regular withdrawal bleeding. She remains under structured multidisciplinary follow-up, with endocrine-led management of hypothyroidism and osteoporosis, alongside cardiology follow-up and gynecological surveillance. Conclusion This case highlights the diagnostic complexity of disorders of sex development with overlapping phenotypes and the need for re-evaluation when clinical progression is atypical. Diagnosis enables hormone replacement therapy for induction of secondary sexual characteristics and preservation of bone health. Integration of clinical, biochemical, and genetic data within a multidisciplinary framework is essential to achieve diagnostic accuracy and optimize outcomes.
Turner Syndrome

Introduction: Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM), with nerve conduction studies recognized as the diagnostic gold standard. Serum neuron-specific enolase (NSE) has been linked with DPN. This study aims to determine the prevalence of DPN among T2DM patients, evaluate clinical characteristics, and explore the relationship between NSE and DPN. Methodology: A cross-sectional study was conducted at Universiti Teknologi MARA Specialist Centre Sungai Buloh and Hospital Al-Sultan Abdullah, involving patients aged 18–60 years, diagnosed with T2DM for more than 5 years (n = 132). All participants underwent anthropometric measurement, completed the Michigan Neuropathy Screening Instrument evaluation, and biochemical parameters, including lipid profile, hemoglobin A1c, and serum creatine and NSE. The diagnosis of DPN was made based on positive NCS findings. Logistic regression was used to identify factors associated with DPN. Results: The study population had a mean age of 60.16 ± 10.28 years and a mean duration of diabetes of 14.82 ± 6.66 years. The prevalence of DPN was 51.5% (n = 68). Serum NSE levels were significantly higher (p = 0.003) and independently associated with the presence of DPN (adjusted odds ratio [OR] 1.033, 95% confidence interval [CI] 1.009–1.058, p = 0.006). Participants with DPN were also more likely to be on insulin therapy (p = 0.040). In addition, retinopathy (adjusted OR 3.567, 95% CI 1.528–8.329, p = 0.013) and elevated Urine Albumin-to-Creatinine Ratio levels indicating albuminuria (adjusted OR 1.031, 95% CI 1.002– 1.061, p = 0.037) were significantly associated with DPN. Conclusion More than half of the study population had DPN, which was significantly associated with both retinopathy and nephropathy, as well as with elevated serum NSE. This emphasizes the importance of early screening and highlights the role of NSE as a surrogate marker for neuropathy in diabetes.
Humans ; Diabetes Mellitus, Type 2 ; Diabetic Neuropathies ; Prevalence ; Phosphopyruvate Hydratase

Introduction: Sodium-glucose-linked-transporter inhibitors (SGLT2-i) have demonstrated cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM), but patients aged ≥75 years remain underrepresented in major trials, creating uncertainty regarding their risk–benefit profile. Real-world data show mixed safety signals. In Malaysia, local evidence is limited despite a growing elderly diabetic population. This study evaluates the glycemic efficacy and safety of SGLT2-i in advanced elderly patients in a real-world public hospital setting. Methodology: We conducted a retrospective observational cohort study of patients aged ≥75 years with T2DM initiated on SGLT2-i in Hospital Putrajaya (2020–2024). Electronic records were reviewed for demographics, comorbidities, medications, and biochemical parameters. Outcomes at 6–12 months assessed glycemic control and safety. Adverse events and discontinuation rates were recorded. Patients with incomplete data, type 1 diabetes, active malignancy, or severe renal impairment were excluded. Results: A total of 104 patients (mean age 78.2 years; 54% female) were included with a high proportion (76.9%) classified as at high cardiovascular risk due to established macrovascular disease (57.7%) or nephropathy (53.8%). Indications for SGLT2-i initiation were glycemic control alone (69.2%) and together with cardiorenal protection (58.7%). Glycemic control remained stable (hemoglobin A1c: 7.66–7.45%; p = 0.076), with preserved renal function (estimated glomerular filtration rate: 58.65–58.11 mL/min/1.73 m&sup2;; p = 0.575). Overall safety was favorable, with 90.4% experiencing no adverse events. Minor adverse events included urinary tract infections (2.9%) and polyuria (1.9%). ASCVD-related hospitalizations occurred in 4.8% of patients, with a low discontinuation rate (7.7%). A statistically significant weight reduction was observed (baseline 66.67 kg, −1.01 kg; p = 0.005) but was not clinically significant. Proteinuria improvement was noted in 15.7% of patients. Conclusion SGLT2-i are safe and well-tolerated in elderly T2DM patients (≥75 years), with stable glycemic control, preserved renal function, and minimal adverse events, supporting their use in very elderly Asian populations.
Aged ; Diabetes Mellitus, Type 2 ; Sodium-Glucose Transporter 2 Inhibitors

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is common among patients with type 2 diabetes (T2D) and increases the risk of cirrhosis, yet fibrosis often remains clinically silent until hepatic decompensation occurs. Current diabetes guidelines recommend noninvasive fibrosis risk stratification, such as the fibrosis-4 index (FIB-4), during routine diabetes care, but real-world adoption remains unclear. This study aimed to evaluate the implementation of FIB-4 as a risk stratification tool in patients with T2D. Methodology: This was a retrospective study of consecutive patients with T2D who were seen in the Diabetes Clinic of University of Malaya Medical Centre in 2023. Patients were identified as having a higher risk of future cirrhosis based on elevated FIB-4 ≥1.3. Results: The data for 1,009 patients were analyzed, median age 62 (52–71) years, 40.7% male. Elevated FIB-4 was seen in 28.8% (291/1,009). Only 12.0% (35/291) with elevated FIB-4 were referred for further hepatology evaluation, whereas 3.3% (24/718) with low FIB-4 were referred. Among the patients with elevated FIB-4, those referred were more likely known to have hepatic steatosis, had higher alanine aminotransferase, aspartate aminotransferase, gammaglutamyl transferase, and lower low-density lipoprotein cholesterol and platelet count. Over a median follow-up of 1.71 (0.99–1.95) years, totaling 1,440 person-years, two liverrelated events (0.2%) occurred (one each in the elevated and low FIB-4 group, respectively). Sixteen patients (4.0%) experienced cardiovascular events, including one patient (0.6%) in the elevated FIB-4 group and 15 (2.9%) in the low FIB-4 group. Conclusion Despite automated FIB-4 reporting, this risk stratification tool was underutilized in T2D, resulting in missed opportunities for early identification and management of more severe liver disease. Integration of FIB-4 into diabetes care workflows, alongside structured referral pathways and clinician education, may improve early detection and reduce long-term hepatic complications in T2D.
Diabetes Mellitus, Type 2 ; Risk Assessment ; Liver Diseases ; Referral and Consultation

Introduction: Diabetic nephropathy is a major complication of type 1 diabetes mellitus (T1DM) and a leading cause of endstage renal disease. This study aims to correlate long-term glycemic control and disease duration with renal decline, measured via estimated glomerular filtration rate (eGFR) and urinalysis proteinuria. Methodology: A retrospective cohort study was conducted among 15 patients with T1DM at Hospital Bentong. Independent variables were 3-year mean glycated hemoglobin A1c (HbA1c) and duration of diabetes. Dependent variables included the change in eGFR derived from baseline and latest serum creatinine (calculated using the CKD-EPI 2021 equation), and the shift in urine protein severity, mapped to an ordinal scale, over a 3-year follow-up. Multivariate linear regression and Spearman’s rank correlation were utilized for analysis. Results: The cohort consisted of 5 male patients and 10 female patients with a mean initial presentation HbA1c of 11.4%, a mean 3-year HbA1c of 9.15%, and a median disease duration of 11 years. Baseline eGFR was preserved (mean 117.15 mL/ min/1.73 m&sup2;). Regression analysis revealed that for every 1% increase in mean HbA1c, eGFR declined significantly by 9.6 mL/min/1.73 m&sup2; (p = 0.002). Furthermore, each additional year of disease duration independently reduced eGFR by 1.1 units (p = 0.008). Spearman validation confirmed the strong negative correlation between HbA1c and eGFR (Rho = -0.664, p = 0.006). Conversely, the correlation between 3-year mean HbA1c and worsening proteinuria was not statistically significant (Rho = -0.067, p = 0.827), and patient gender did not significantly impact progression (p = 0.129). Conclusion Poor long-term glycemic control and longer duration of diabetes mellitus are strong independent predictors of decline in functional glomerular filtration in T1DM. While worsening proteinuria may not be detected during a short 3-year window using a standard urinalysis (UFEME), a more sensitive test such as Urine Albumin-to-Creatinine Ratio may better detect early structural kidney damage.
Diabetes Mellitus, Type 1 ; Proteinuria