Siew Pheng Chan

CLINICOPATHOLOGIC STUDIES OF THYMIC CARCINOIDS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

&NA; Abbreviations used in this article: ACTH, adrenocorticotropic hormone; CT, computed tomography; LOH, loss of heterozygosity; MEN, multiple endocrine neoplasia; MRI, magnetic resonance imaging; NSE, neuron‐specific enolase.

Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids.

Aim:  To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone‐active medication.

Hypoglycemic symptoms in patients with type 2 diabetes in Asia-Pacific—Real-life effectiveness and care patterns of diabetes management: The RECAP-DM study

Symptoms of hypoglycemia were reported by 35.8% of patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region. Symptoms were severe in 11.6% and very severe in 8.2% of patients experiencing hypoglycemia.

Genome-wide scan identifies novel modifier loci of acromegalic phenotypes for isolated familial somatotropinoma

Isolated familial somatotropinoma (IFS) accounts for 18% of familial isolated pituitary adenoma (FIPA) cases. Recently, germline mutations of the aryl hydrocarbon receptor-interacting protein gene (AIP) have been found in families with pituitary adenoma predisposition, FIPA, and IFS. In this study, we investigate the AIP mutation status and perform a genome-wide scan to search for the modifier regions of acromegalic phenotypes in an IFS family of 31 aborigines from Borneo. Complete endocrine diagnosis and data could not be collected due to logistical and cultural reasons. AIP mutation screening was carried out by direct sequencing and the genome-wide scan was performed using 400 microsatellites. Non-parametric linkage analysis was performed to obtain the logarithm of odds (LOD) scores. A novel AIP frameshift mutation in exon 4 (c.500delC) (p.P167HfsX3) was identified in all members with acromegalic features, as well as in 15 members without acromegalic features, revealing incomplete penetrance of AIP. The data showed that patients with the same mutation may express acromegalic features of differing severity, suggesting the existence of modifier genes. The highest LOD score of 2.2 was obtained near D19S571 (19q13.41). We also found weak linkages on chromosomes 3q28, 8q12.1, and 21q22.13, with LOD scores of 1.1, 1.8, and 1.4 respectively. Our results show the first genome-wide scan that identifies novel modifier loci for acromegalic phenotypes in an IFS family. Identification of modifier loci may provide further insight into the disease mechanism and explain the clinical variability observed in its patients.

Non-alcoholic fatty liver disease in Malaysia: a demographic, anthropometric, metabolic and histological study.

BACKGROUND AND OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing rapidly in the Asia–Pacific region. There has been a paucity of studies from the region. The aims of this study were to define the demographic, anthropometric, metabolic and histological characteristics of patients with NAFLD in our local population and to determine independent predictors of severe liver fibrosis.

Hypoglycemia is associated with increased worry and lower quality of life among patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region☆

AIMS We examined the relationship of hypoglycemic symptoms with health-related quality of life and worry about hypoglycemia among type 2 diabetic patients using oral antihyperglycemic agents (AHA) in the Asia-Pacific region. METHODS A total of 2257 type 2 diabetic patients with at least 6 months of oral AHA were enrolled in China, Korea, Malaysia, Thailand, and Taiwan. Quality of life was measured with the EuroQol Visual Analog Scale (EQ-VAS) and EuroQol-5 Dimensions questionnaire (EQ-5D), and worry about hypoglycemia with the worry subscale of the Hypoglycemic Fear Survey-II (HFS). RESULTS The mean (SD) age was 58.7 (10.2) years and HbA(1c) was 7.5% (1.5). The proportion of patients with an HbA(1c) <6.5% and <7% was 24.9% and 41.8%, respectively. Hypoglycemic symptoms in the prior 6 months were reported by 35.8% of patients. Mean scores on the EQ-VAS and the EQ-5D were significantly lower for patients who had hypoglycemic symptoms compared to those who did not (73.6 vs. 76.9, p<0.001; 0.88 vs. 0.90, p<0.0001, respectively), whereas mean score on the HFS was significantly higher (12.5 vs. 6.3, p<0.001). In multivariate models, hypoglycemic symptoms were independently associated with scores on the EQ-5D, EQ-VAS, and HFS (all p ≤ 0.01-0.001). Symptom severity was positively associated with fear of hypoglycemia (all p ≤ 0.001). CONCLUSION Hypoglycemic symptoms were associated with reduced quality of life and increased patient worry in patients with type 2 diabetes treated with AHA.

Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women

What is known and Objective:  Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy, but the association between adherence and bone turnover markers (BTMs) has never been studied. Therefore, the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence (and its effects on BTMs), as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates.

Managing diabetes in Asia: overcoming obstacles and the role of DPP-IV inhibitors.

Asia bears the worlds greatest burden of type 2 diabetes (T2DM) and prevalence is increasing rapidly. Compared to other races, Asians develop T2DM younger, at a lower degree of obesity, suffer longer from its complications and die earlier. Curbing this epidemic requires an integrated, risk-based, and multidisciplinary approach. Inadequately managed T2DM has macrovascular and microvascular sequelae, Asians with T2DM being particularly susceptible to diabetic nephropathy. Earlier and more intensive monitoring and management of risk factors are required, especially for patients with, or at risk of, renal impairment. Particular challenges of T2DM management in Asia include: lack of access to specialist healthcare, insufficient clinical evaluation and delayed diagnosis. As in Caucasians, conventional treatment modalities are limited by deteriorating glycaemic control with disease progression and there is an unmet need for efficacious, safe, cost-effective and convenient pharmacotherapies for treating different stages of T2DM and preventing its complications, particularly in high-risk patients. There is a trend towards increasing use of DPP-IV inhibitors, which are no less efficacious and safe in Asians than Caucasians and may have some advantages over existing oral antidiabetic agents, particularly for certain high-risk groups. Such agents may play a significant future role in the management of T2DM.

Effects of sun exposure on 25(OH) vitamin D concentration in urban and rural women in Malaysia.

Ultraviolet B sunlight exposure is a primary source of vitamin D. There have been reports of low vitamin D status amongst the Malaysian population despite it being a tropical country. This study was conducted to determine the influence of sun exposure on 25(OH)D concentrations in urban and rural women in Malaysia and factors predicting 25(OH)D concentrations. Women aged above 45 years were recruited from urban (n=107) and rural areas (n=293). Subjects were interviewed regarding their outdoor activities and usual outdoor attire over the previous week. 25(OH)D concentrations were analyzed using the vitamin D3 (25-OH) electrochemiluminescence immunoassay. Median (Q1-Q3) age of the participants was 57 (53-61) years old. Median (Q1-Q3) 25(OH)D concentration of rural women was significantly higher [69.5 (59.0-79.1) nmol/L] compared to urban women [31.9 (26.1- 45.5) nmol/L] (p<0.001). Rural women spent more time in the sun compared to urban women (7.83 (3.67-14.7) vs 2.92 (1.17-4.92) hours, p<0.001), although the fraction of body surface area (BSA) exposed to sunlight was significantly higher in the urban group [0.21 (0.21-0.43) vs 0.12 (0.07-0.17), p<0.001]. The calculated sun index (hours of sun exposure per week × fraction of BSA) was significantly higher in rural [0.89 (0.42-1.83)] compared to urban women [0.72 (0.26-1.28)], p=0.018. In the stepwise linear regression, rural dwelling increased the serum 25(OH)D by 31.74 nmol/L and 25(OH)D concentrations increased by 1.93 nmol/L for every unit increment in sun index. Urban women in Malaysia had significantly lower vitamin D status compared to rural women. Rural dwelling and sun index were key factors influencing vitamin D status in Malaysian women.

Genetic Polymorphisms in LDLR, APOB, PCSK9 and Other Lipid Related Genes Associated with Familial Hypercholesterolemia in Malaysia

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in Low Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB) or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the LDLR gene, seven in the APOB gene and three in the PCSK9 gene. SNP rs12720762 in APOB gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management.