Transcriptional profiles associated with coronary artery disease in type 2 diabetes mellitus.

Background: Coronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses. Methods: The study is a sex- and age-frequency matched case-control design comparing 23 unrelated adult Filipinos with T2DM-CAD to 23 controls (DM with CAD). Healthy controls served as a reference. Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA). Results: The study observed that 458 genes were differentially expressed between T2DM with and without CAD (FDR<0.05). The 5 top genes the transcription factor 3 (TCF3), allograft inflammatory factor 1 (AIF1), nuclear factor, interleukin 3 regulated (NFIL3), paired immunoglobulin-like type 2 receptor alpha (PILRA), and cytoskeleton-associated protein 4 (CKAP4) with AUCs >89%. Pathway analyses show differences in innate immunity activity, which centers on the myelocytic (neutrophilic/monocytic) theme. SNP-module analyses point to a possible causal dysfunction in innate immunity that triggers the CAD injury in T2DM. Conclusion: The study findings indicate the involvement of innate immunity in the development of T2DM-CAD, and potential immunity markers can reflect the occurrence of this injury. Further studies can verify the mechanistic hypothesis and use of the markers.

Current status of diabetes mellitus care and management in the Philippines.

AIMS: In this paper, we discuss the existing data on the burden of diabetes in the Philippines and present the status of management, prevention, and control of diabetes in the country. METHODS: A review of literature was conducted to synthesize the status of diabetes mellitus in the Philippines. RESULTS: An estimated 4.3 million Filipinos were diagnosed with diabetes, while 2.8 million remained undiagnosed in 2021. Diabetic retinopathy is a top cause of preventable blindness in Region 3, Philippines. Diabetic nephropathy contributes to 38% of renal disease cases in the Philippines. The 2021 Philippine Guidelines on Periodic Health Examination (PhEX) advocate for the utilization of fasting blood sugar (FBS) as a screening measure for Type 2 Diabetes Mellitus (T2DM) in healthy adults aged 40 years and older or in those with specified risk factors. The alternative option of hemoglobin A1c is (HbA1c) deemed appropriate but comes with a conditional recommendation due to its uneven accessibility across different regions of the country. Treatment guidelines align between the Philippines and the US. Initial medical nutrition therapy involves healthy habits, progressing to pharmacologic treatment if necessary. Financial constraints, seen in limited insurance coverage and high out-of-pocket costs, impede care, amplifying disease impact. The complex diabetes care, encompassing pharmacotherapy, nutrition, exercise, and monitoring, faced challenges during COVID-19 quarantines. CONCLUSION: In conclusion, the paper outlines diabetes care principles-screening, diagnostics, and multidisciplinary care-alongside economic implications. Local and national initiatives are discussed to mitigate diabetes trends and reduce its burden in the Philippines.

Incidence, Recurrence and Mortality Among Filipinos With Differentiated Thyroid Cancer: A Systematic Review.

Background: The majority of thyroid malignancies are differentiated thyroid carcinomas (DTCs). We examined the incidence, disease extent, recurrence and disease-specific mortality (DSM) of DTC among Filipinos residing in the Philippines and Filipino immigrants. Methodology: In accordance with the 2020 PRISMA statement, we performed a systematic literature search in MEDLINE, Google Scholar, EBSCO, Cochrane and Clinicaltrials.gov for the period January 1, 1980 until January 27, 2022. Pooled incidence rate ratio and pooled proportions of disease extent, recurrence and DSM were determined. Results: Literature search yielded 1,852 studies. Out of 26 articles retrieved, nine retrospective case controls and cohorts were included. Incidence of DTC was significantly higher in female Filipino immigrants compared with non-Hispanic whites (NHW). Distant metastases and recurrence were more common among Filipinos and Filipino immigrants compared with NHW. Limited data showed higher DSM in Filipino immigrants and NHW than Filipinos, which may be influenced by reporting bias. Conclusions: This review supports the trend of increased incidence and recurrence of DTC among Filipinos, although case registries are essential to confirm these findings. In the setting of the newly released Philippine guidelines for DTC, prospective studies with active long-term follow-up will help detect any changes in the outcomes of DTC among Filipinos.

Genetic Variants Associated with Poor Responsiveness to Sulfonylureas in Filipinos with Type 2 Diabetes Mellitus.

Introduction: Sulfonylureas (SUs) are commonly used drugs for type 2 diabetes mellitus (T2DM) in the Philippines. This study aimed to associate genetic variants with poor response to gliclazide and glimepiride among Filipinos. Methodology: Two independent, dichotomous longitudinal substudies enrolled 139 and 113 participants in the gliclazide and glimepiride substudies, respectively. DNA from blood samples underwent customized genotyping for candidate genes using microarray. Allelic and genotypic features and clinical associations were determined using exact statistical methods. Results: Three months after sulfonylurea monotherapy, 18 (13%) were found to be poorly responsive to gliclazide, while 7 (6%) had poor response to glimepiride. Seven genetic variants were nominally associated (p<0.05) with poor gliclazide response, while three variants were nominally associated with poor glimepiride response. For gliclazide response, 3 carboxypeptidase-associated variants (rs319952 and rs393994 of AGBL4 and rs2229437 of PRCP) had the highest genotypic association; other variants include rs9806699, rs7119, rs6465084 and rs1234315. For glimepiride response, 2 variants were nominally associated: CLCN6-NPPA-MTHFR gene cluster - rs5063 and rs17367504 - and rs2299267 from the PON2 loci. Conclusion: Genetic variants were found to have a nominal association with sulfonylurea response among Filipinos. These findings can guide for future study directions on pharmacotherapeutic applications for sulfonylurea treatment in this population.

Variants of SLC2A10 may be Linked to Poor Response to Metformin.

Purpose: A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin. Methods: Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood samples were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods. Results: Several polymorphisms were nominally associated with poor response to metformin (P uncorr < 0.05). The most notable is the association of multiple variants in the SLC2A10 gene-rs2425911, rs3092412, and rs2425904-with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8). Conclusion: In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.

Practical Guidance on Basal Insulin Initiation and Titration in Asia: A Delphi-Based Consensus.

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM.

A bibliometric analysis of polycystic ovary syndrome research in Southeast Asia: Insights and implications.

BACKGROUND AND AIMS: There has been an increased understanding in the pathophysiology and management of polycystic ovary syndrome (PCOS) in recent years. This study aimed to evaluate the trends and characteristics of PCOS publications in Southeast Asia (SEA) through a bibliometric analysis. METHODS: Systematic review of literature on PCOS in SEA countries between 1975 and 2020 was performed using the Scopus database. All published studies on PCOS conducted in or published by authors from any of the countries in SEA were included in this analysis. Bibliographic information was obtained, and visualization of collaboration networks of countries and keywords was conducted using VOSviewer software. RESULTS: A total of 260 articles were included in this analysis. The number of PCOS publications in SEA continued to increase through the years. The country with the highest number of publications was Thailand while Singapore produced the most publications with the greatest impact. The focus of research in SEA was on PCOS prevalence, risk factors, infertility, and metabolic complications. A country's fertility rate, research and development expenditures (%GDP), number of researchers per million people, and international research collaborations significantly correlated with PCOS research impact in SEA. CONCLUSION: This is the first bibliometric analysis in PCOS research in SEA. Despite the continuing increase in PCOS publications in SEA, it still lags compared to other regions. Countries in SEA should consider policies and strategies directed at increasing research support and encouraging international collaborations for local researchers to produce more meaningful publications and augment PCOS knowledge in the region.

AFES A.S.-O.N.E.: ASEAN Survey Of Needs in Endocrinology in the Time of the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic has made a major impact on hospital services globally, including the care of persons with diabetes and endocrine disorders. The aim of this study is to describe the epidemiology of COVID-19 in the ASEAN Federation of Endocrine Societies (AFES) member countries; to describe challenges, changes and opportunities in caring for patients with endocrine diseases, as well as in fellowship training programs, and endocrinerelated research in the AFES countries. METHODOLOGY: The AFES ASEAN Survey Of Needs in Endocrinology (AFES A.S.-O.N.E.) was an open-ended questionnaire that was sent to the presidents and representatives of the AFES member countries by email. Responses from Societies were collated and synthesized to obtain perspectives on the emergent issues in endocrinology in the Southeast Asian region during this pandemic. RESULTS: The burden of COVID-19 cases varied widely across the AFES member countries, with the least number of cases in Vietnam and Myanmar, and the greatest number of cases in either the most populous countries (Indonesia and the Philippines), or a country with the highest capability for testing (Singapore). The case fatality rate was also the highest for Indonesia and the Philippines at around 6%, and lowest for Vietnam at no fatalities. The percentage with diabetes among patients with COVID-19 ranged from 5% in Indonesia to 20% in Singapore, approximating the reported percentages in China and the United States. The major challenges in managing patients with endocrine diseases involved inaccessibility of health care providers, clinics and hospitals due to the implementation of lockdowns, community quarantines or movement control among the member countries. This led to disruptions in the continuity of care, testing and monitoring, and for some, provision of both preventive care and active management including surgery for thyroid cancer or pituitary and adrenal tumors, and radioactive iodine therapy. Major disruptions in the endocrine fellowship training programs were also noted across the region, so that some countries have had to freeze hiring of new trainees or to revise both program requirements and approaches to training due to the closure of outpatient endocrine clinics. The same observations are seen for endocrine-related researches, as most research papers have focused on the pandemic. Finally, the report ends by describing innovative approaches to fill in the gap in training and in improving patient access to endocrine services by Telemedicine. CONCLUSION: The burden of COVID-19 cases and its case fatality rate varies across the AFES member countries but its impact is almost uniform: it has disrupted the provision of care for patients with endocrine diseases, and has also disrupted endocrine fellowship training and endocrine-related research across the region. Telemedicine and innovations in training have been operationalized across the AFES countries in an attempt to cope with the disruptions from COVID-19, but its over-all impact on the practice of endocrinology across the region will only become apparent once we conquer this pandemic.

Clinical Characterization of Post-parathyroidectomy Patients with Primary Hyperparathyroidism and the Concordance of Preoperative Localization Imaging with Histopathology at a Tertiary Hospital in Manila, Philippines.

BACKGROUND: Philippine studies on primary hyperparathyroidism (PHPT) and preoperative localization are scarce, making improvements on detection and recognition particularly difficult. OBJECTIVE: Describe the clinical profile of post-parathyroidectomy PHPT patients at The Medical City (TMC) and assess localization rates and concordance of neck ultrasound (UTZ) and 99mTc-sestamibi scan (MIBI) with surgical histopathologic findings. METHODOLOGY: Retrospective chart review of PHPT Filipino patients who underwent parathyroidectomy at The Medical City from January 2004 to August 2018. Clinical profile and presentations were described and compared with international data. Imaging results were compared with surgical histopathology findings and the level of agreement was determined. RESULTS: Thirty-five patients were analyzed with female predominance (63%) and an average age of 53 years. Our population had more overt manifestations including skeletal abnormalities (51%), renal calculi (49%) and musculoskeletal symptoms (43%) prior to surgery compared to western countries, where symptoms were noted in less than 20%. MIBI had higher rates of detection than UTZ (80% versus 58%) but had similar localization rates (96.4% versus 94%). When performed together, given a positive result from either test, a much higher yield (93.8%) was observed. The level of agreement between MIBI and surgery was 72.5% (κ=0.54) while UTZ and surgery was 54.1% (κ=0.38). CONCLUSION: Our Filipino subjects had predominantly overt symptomatic hyperparathyroidism upon diagnosis prior to surgery as opposed to more asymptomatic surgical patients in western countries. Combining UTZ and MIBI is a more successful preoperative localization approach in our setting than performing either imaging alone, especially in patients with nodular goiter.

The Modified Ferriman-Gallwey Score and Hirsutism among Filipino Women.

BACKGROUND: The modified Ferriman-Gallwey (mFG) score is the gold standard for the clinical evaluation of hirsutism. However, racial variations in terminal hair growth limit this tool. This study aimed to determine the mFG cut-off score among Filipino women and its association with biochemical hyperandrogenism. METHODS: A total of 128 Filipino women were included in this prospective cross-sectional study and were divided into two groups: a polycystic ovary syndrome (PCOS) group (n=28) and a non-PCOS group (n=100). The participants underwent mFG score determination, ovarian ultrasound conducted by a single sonographer, and hormone testing. The mFG cut-off score was determined based on the 95th percentile of the non-PCOS group. Logistic regression was used to analyze the relationship between mFG score and biochemical hyperandrogenism. RESULTS: Although the mFG score was generally low in both the PCOS and non-PCOS groups, the former exhibited a higher mean score than the latter (4.3±3.0 vs. 2.0±2.2, P<0.001). Normal values for the total mFG score ranged from 0 to 7. Using a cut-off score of 7, a higher proportion of hirsute women (mFG score ≥7) was observed in the PCOS group versus the non-PCOS group (17.9% vs. 5.0%, P=0.025). Elevated calculated free testosterone (FT) was also found to be significantly associated with hirsutism (odds ratio, 6.2; 95% confidence interval, 1.2 to 32.4 pmol/L; P=0.030). CONCLUSION: A score of 7 and above constitutes hirsutism in this population of Filipino women. Hirsute women are more likely than non-hirsute women to have elevated calculated FT.

Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP.

While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3' UTR, H3K36me3 histone markings and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3' UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the USA and found three DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP2K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.