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.

Factors Associated with Postoperative Diabetes Insipidus after Pituitary Surgery.

BACKGROUND: Determining risk factors for diabetes insipidus (DI) after pituitary surgery is important in improving patient care. Our objective is to determine the factors associated with DI after pituitary surgery. METHODS: We reviewed records of patients who underwent pituitary surgery from 2011 to 2015 at Philippine General Hospital. Patients with preoperative DI were excluded. Multiple logistic regression analysis was performed and a predictive model was generated. The discrimination abilities of the predictive model and individual variables were assessed using the receiving operator characteristic curve. RESULTS: A total of 230 patients were included. The rate of postoperative DI was 27.8%. Percent change in serum Na (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.15 to 1.69); preoperative serum Na (OR, 1.19; 95% CI, 1.02 to 1.40); and performance of craniotomy (OR, 5.48; 95% CI, 1.60 to 18.80) remained significantly associated with an increased incidence of postoperative DI, while percent change in urine specific gravity (USG) (OR, 0.53; 95% CI, 0.33 to 0.87) and meningioma on histopathology (OR, 0.05; 95% CI, 0.04 to 0.70) were significantly associated with a decreased incidence. The predictive model generated has good diagnostic accuracy in predicting postoperative DI with an area under curve of 0.83. CONCLUSION: Greater percent change in serum Na, preoperative serum Na, and performance of craniotomy significantly increased the likelihood of postoperative DI while percent change in USG and meningioma on histopathology were significantly associated with a decreased incidence. The predictive model can be used to generate a scoring system in estimating the risk of postoperative DI.

Limited cutaneous systemic sclerosis arising in a patient with Graves' disease.

Although Graves' disease and systemic sclerosis are both autoimmune disorders, their relationship is rarely reported. We present the case of a Filipino woman with goitre and thyrotoxic signs and symptoms. Diagnosed with Graves' disease at the outpatient clinic, she took antithyroid medications and underwent radioactive iodine ablation with resultant hypothyroidism after 6 months, during which she began to experience skin tightness over the face, neck and fingers. Workup revealed limited cutaneous systemic sclerosis, and the patient improved with methotrexate. This case highlights the increased prevalence of coincident autoimmune disorders in Graves' disease.

Validation of the oral health screening questionnaire in predicting serious periodontitis among adult Filipinos with type 2 diabetes mellitus / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Periodontitis affects more than half of patients with diabetes. In resource poor areas in the Philippines, access to routine dental visits may be difficult and thus, a selective approach might be needed to identify those who need dental evaluation and management. An easy-to-administer oral health self-report questionnaire was developed in order to predict serious (moderate to severe) periodontitis.<br /><strong>OBJECTIVE:</strong> The study aims to determine the validity of the Oral Health Screening Questionnaire for Persons with Diabetes (OHSQPD) in estimating the prevalence of serious periodontitis.<br /><strong>METHODOLOGY:</strong> A cross-sectional criterion-referenced study of 175 participants with T2DM were included in the study. They were asked to answer the questionnaire and then made to undergo a full dental examination to identify the presence and severity of periodontitis. The validity of the questionnaire was assessed by determining the sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver-operating curve (AUROC) with the dental examination as the gold standard.<br /><strong>RESULTS:</strong> Using the questionnaire, the prevalence of serious periodontitis was 61% (106) based on an optimal cut-off score of ?12. At this score, the questionnaire yielded a sensitivity of 80.4% and a specificity of 70.6%, with an AUROC of 0.83.<br /><strong>CONCLUSION:</strong> The OHSQPD is a valid tool in detecting serious periodontitis</p>