Journal of the ASEAN Federation of Endocrine Societies最新文献

Objective: To evaluate the Type 2 Diabetes (T2D) risk variants in the Pashtun ethnic population of Khyber Pakhtunkhwa using nascent whole-exome sequencing (WES) to better understand the pathogenesis of this complex polygenic disorder.

Methodology: A total of 100 confirmed patients with T2D of Pashtun ethnicity were included in the study, DNA was extracted from whole blood samples, and paired-end libraries were prepared using the Illumina Nextera XT DNA library kit carefully following the manufacturer's instructions. Illumina HiSeq 2000 was used to obtain sequences of the prepared libraries followed by bioinformatics data analysis.

Results: A total of n=11 pathogenic/likely pathogenic variants were reported in the CAP10, PAX4, IRS-2, NEUROD1, CDKL1 and WFS1. Among the reported variants CAP10/rs55878652 (c.1990-7T>C; p.Leu446Pro) and CAP10/rs2975766 (c.1996A>G; p.Ile666Val) identified were novel, and have not yet been reported for any disease in the database.The variants CAP10/rs7607759 (c.1510A>G, p.Thr504Ala), PAX4/rs712701 (c.962A>C; p.His321Pro), PAX4/rs772936097 (c.748-3delT; p.Arg325Trp), IRS-2/rs1805097 (c.3170G>A; p.Gly1057Asp), NEUROD1/rs1801262 (c.133A>G; p.Thr45Ala), CDKL1/rs77152992 (c.1226C>T; p.Pro409Leu), WFS1/rs1801212 (c.997G>A; p.Val333Ile), WFS1/rs1801208 (c.1367G>A; p.Arg456His), and WFS1/rs734312 (c.1832G>A; p.Arg611His) are previously identified in other ethnic populations. Our study reconfirms the associations of these variants with T2D in the Pakistani Pashtun population.

Conclusion: In-silico analysis of exome sequencing data suggests a statistically substantial association of all (n=11) identified variants with T2D in the Pashtun ethnic population. This study may serve as a foundation for performing future molecular studies aimed at unraveling T2D associated genes.

Objective: To determine whether bisphenol S (BPS), a common substitute for bisphenol A (BPA), induces cell proliferation and migration in human endometrial epithelial cells (Ishikawa) and adult mouse uterine tissues.

Methodology: Human endometrial Ishikawa cells were exposed to low doses of BPS (1 nM and 100 nM) for 72 hours. Cell proliferation was assessed through the viability assays MTT and CellTiter-Glo^®. Wound healing assays were also used to evaluate the migration potential of the cell line. The expression of genes related to proliferation and migration was also determined. Similarly, adult mice were exposed to BPS at a dose of 30 mg/kg body weight/day for 21 days, after which, the uterus was sent for histopathologic assessment.

Results: BPS increased cell number and stimulated migration in Ishikawa cells, in association with the upregulation of estrogen receptor beta (ESR2) and vimentin (VIM). In addition, mice exposed to BPS showed a significantly higher mean number of endometrial glands within the endometrium.

Conclusion: Overall, in vitro and in vivo results obtained in this study showed that BPS could significantly promote endometrial epithelial cell proliferation and migration, a phenotype also observed with BPA exposure. Hence, the use of BPS in BPA-free products must be reassessed, as it may pose adverse reproductive health effects to humans.

Objectives: This research investigates whether there is an association between acute hyperglycemia and diabetes mellitus and the level of circulating platelet-derived microparticles (PDMPs) during an initial episode of acute myocardial infarction (AMI).

Methodology: This was a cross-sectional study involving hospitalized AMI patients. Demographic and clinical data were obtained from hospital records. Diabetes mellitus was defined by the history of the disease, anti-diabetes medication use and/ or level of HbA1C ≥6.5%. Levels of HbA1c, admission random and fasting blood glucose levels were measured. Flow-cytometry method was used to determine the levels of PDMPs from collected venous blood through tagging with CD-41 FITC and CD-62 PE markers and a threshold size of <1 μm. The number of circulating PDMPs was compared according to glucometabolic state, namely acute hyperglycemia (admission random glucose ≥200 mg/dL and fasting glucose ≥140 mg/dL) and diabetes mellitus. The comparative analysis between groups was conducted with Student T-test or Mann-Whitney test, where applicable.

Results: A total of 108 subjects were included and their data analyzed. The level of circulating PDMPs was significantly lower in subjects with admission random glucose ≥200 mg/dL as compared to those with below level [median (interquartile range (IQR)]: 2,710.0 (718.0-8,167.0) count/mL vs. 4,452.0 (2,128.5-14,499.8) count/mL, p = 0.05) and in subjects with fasting glucose ≥140 mg/dL as compared to those with below level (median (IQR): 2,382.0 (779.0-6,619.0) count/mL vs. 5,972.0 (2,345.7-14,781.3) count/mL, p = 0.006). The level of circulating PDMPs was also significantly lower in patients with diabetes mellitus as compared to those without (median (IQR): 2,655.0 (840.0-5,821.0) count/mL vs. 4,562.0 (2,128.5-15,055.8) count/mL; p = 0.007).

Conclusion: Acute hyperglycemia and diabetes mellitus are significantly associated with a lower circulating PDMP level during an initial AMI episode.

Objective: Obesity is known to be associated with left ventricular diastolic dysfunction due to its effect on blood pressure and glucose tolerance. We aimed to investigate whether weight loss after bariatric surgery might improve diastolic dysfunction through in-depth echocardiographic examination.

Methodology: We recruited twenty-eight patients who were about to undergo bariatric surgery by purposive sampling. They underwent echocardiography at baseline and 6 months after surgery with a focus on diastolic function measurements and global longitudinal strain (GLS). They also had fasting serum lipid and glucose measurements pre- and post-surgery.

Results: The mean weight loss after surgery was 24.1 kg. Out of the 28 subjects, fifteen (54%) initially had diastolic dysfunction before surgery. Only two had persistent diastolic dysfunction 6 months after surgery. The mean indexed left atrial volume 6 months post-surgery was 27.1 from 32 ml/m² prior to surgery. The average E/e' is 11.78 post-surgery from 13.43 pre-surgery. The left ventricular GLS became (-)25.7% after surgery from (-)21.2% prior to surgery. Their post-surgery fasting serum lipid and glucose levels also showed significant improvement.

Conclusion: Our study reinforced the existing evidence that bariatric surgery significantly improved echocardiographic parameters of diastolic function and left ventricular global longitudinal strain, along with various metabolic profiles.

Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.

Objective: This study aimed to explore the prevalence and associated factors of thyroid dysfunction among cancer patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).

Methodology: A cross-sectional study was done in patients who received TKIs at Rajavithi Hospital in 2019. For patients treated with ICI, a retrospective chart review for patients seen in 2018 to 2019 was conducted. If there were abnormal thyroid function tests (TFT), thyroid autoantibodies were tested.

Results: There were 144 patients on TKIs with a mean age of 56.0 years. Thyroid dysfunction was found in 14.6% of patients and most had subclinical hypothyroidism (n = 16, 11.1%). Imatinib (n = 11, 10.8%) and sunitinib (n = 4, 100%) were the 2 most common TKIs given to patients with thyroid dysfunction. Thyroid dysfunction was associated with male sex, chronic kidney disease and hepatitis B virus infection but not with previous thyroid disease and presence of thyroid autoantibodies.There were 18 patients who received ICIs. The mean age was 63.3 years. Twelve patients (66.7%) used programmed cell death protein-1 antibody (anti-PD1), mainly nivolumab. Thyroid dysfunction was found in 50%, which occurred at a median duration of 46 days. Most patients had overt hypothyroidism and 55.6% needed levothyroxine replacement.

Conclusion: Thyroid dysfunctions from TKIs were mostly asymptomatic and mild in severity. Some types of TKIs might be associated with thyroid dysfunction. On the other hand, thyroid dysfunction from ICIs usually occurs within 6 months and requires levothyroxine replacement.

Objective: This study aims to characterize the presentation, biochemical status of children with T1DM at diagnosis, the type of subcutaneous insulin regimens initiated, and to determine the incidence of T1DM in Bruneian children aged 18 years and younger.

Methodology: A retrospective electronic and paper medical chart review was performed on patients aged 18 years and younger diagnosed with T1DM from 2013 to 2018 in Brunei Darussalam.

Results: A total of 31 children with a mean age of 10.2 ± 3.6 years old were diagnosed with T1DM, of which 66.7% presented with diabetic ketoacidosis (DKA), a majority in severe DKA with an intercurrent illness (p = 0.021). The mean HbA1c was 13.6 ± 2.7% with a mean serum glucose of 37.0 ± 14.9 mmol/L at diagnosis. In the majority of the children (67.7%), multiple daily injections of subcutaneous insulin were initiated. The incidence of T1DM in children aged 18 years and younger was 4.9 per 100,000 for the year 2018.

Conclusions: The majority of the patients in this study presented with severe DKA with an intercurrent illness. This highlights the importance of childhood T1DM awareness among the public and healthcare providers. The incidence of childhood T1DM in Brunei Darussalam is similar to other countries in the Asian region, being relatively low, compared to the rest of the world.