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.

A Filipino woman with autoimmune polyglandular syndrome.

A 47-year-old Filipino woman presented with goitre of 3 months' duration. She had no symptoms of thyrotoxicosis or hypothyroidism. Her thyroid was diffusely enlarged. Thyrotropin was elevated and free thyroxine was low. Ultrasound revealed slightly enlarged thyroid with diffuse parenchymal disease. Antithyroid peroxidase antibody was elevated. She was started on levothyroxine at 1.6 mcg/kg body weight/day and dose was adjusted to maintain the thyrotropin level within normal limits. Four years after the diagnosis of Hashimoto's thyroiditis was made, the patient started to experience malaise, generalised weakness and fatigue. Functional screening for other autoimmune endocrinopathy was done. Fasting 8 a.m serum cortisol was noted to be markedly decreased. She was diagnosed with autoimmune polyglandular syndrome type 2 (Schmidt syndrome). Physiologic dose of prednisone was started which afforded significant improvement in the patient's symptoms. The patient is on regular follow-up and clinically well.

Prevalence of undiagnosed autoimmune thyroid disease and thyroid dysfunction in Filipino patients with autoimmune rheumatic disorders / Journal of the ASEAN Federation of Endocrine Societies

OBJECTIVES:(1) To determine the prevalence of autoimmune thyroid disease among patients with autoimmune rheumatic disorders seen at the Philippine General Hospital. (2) To determine clinical features that are associated with the occurrence of autoimmune thyroid disease in these patient.METHODOLOGY:This is a cross sectional analytical study that included 155 adult Filipinos diagnosed with an autoimmune rheumatic disorder. Clinical characteristics were recorded. Serum thyrotropin, thyroxine, triiodothyronine, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody and urinary iodide excretion were determined. The prevalence of autoimmune thyroid disease was computed. Associations between clinical factors and autoimmune thyroid disease were determined.RESULTS:Overall 21.94% of the population had autoimmune thyroid disease. There was significant association between duration of the autoimmune rheumatic disorder and autoimmune thyroid disease (p-= 0.018). No significant association was noted with the other clinical factors although there was an almost significant association observed for the presence of goiter (p=0.054).CONCLUSION:Autoimmune thyroid disease commonly occurs in patients with autoimmune rheumatic disorders. As such, it is important to consider screening these patients for the coexistence of thyroid disease to help prevent the complications associated with thyroid dysfunction and avoid adding up to the morbidity of the existing autoimmune rheumatic disorder.

University of the Philippines-Philippine General Hospital revised clinical practice guidelines for the management of well-differentiated thyroid carcinoma of follicular cell origin / Journal of the ASEAN Federation of Endocrine Societies

In an effort to unify treatment approaches to patients with well-differentiated thyroid cancer of follicular cell origin, the Section of Endocrinology, Section of Nuclear Medicine, Department of Surgery, and Department of Otorhinolaryngology of the Philippine General Hospital formulated and published a clinical practice guideline on the management of well-differentiated thyroid cancer in 2008. In recognition of the new literature on thyroid cancer, as well as the questions that have arisen from the use of the guideline, the group reconvened in 2011 to review and update the clinical practice guideline designed for patients seen at the Philippine General Hospital. This article summarizes the latest revisions and recommendations.