Nur Lisa Zaharan

Statins and risk of treated incident diabetes in a primary care population

AIMS (i) To examine the incidence of new onset treated diabetes in patients treated with different types of statins and (ii) the relationship between the duration and dose of statins and the subsequent development of new onset treated diabetes. METHODS A retrospective cohort study was performed using the Irish Health Services Executive Primary Care Reimbursement Services national pharmacy claims database. Individuals who received any medicines were identified from January 2001 to January 2009 (n = 1 235 671). Patients newly treated with statins from 1 January 2002 to 31 December 2007 were identified (n = 239 628). Cases were identified as individuals newly treated with antidiabetic medication (n = 38 503). Adjusted hazards ratios (HR) with 95% confidence intervals (CI) were calculated to examine the association between statins (any vs. none) and time to new onset treated diabetes using Cox proportional hazard regression. The dose and duration response relationship between statins and new onset treated diabetes was examined using restricted spline functions to assess the linearity of the relationship. RESULTS Statin use was associated with an increased risk of new onset treated diabetes (HR = 1.18, 95% CI 1.15, 1.22). Increased risk of new onset treated diabetes was found with rosuvastatin (HR = 1.41, 95% CI 1.31, 1.52), atorvastatin (HR = 1.23, 95% CI 1.19, 1.27) and simvastatin (HR = 1.15, 95% CI 1.05, 1.25). There were statistically significant overall dose and duration effects for all statins, excepting fluvastatin, which only demonstrated a duration effect. CONCLUSION An increased risk of new onset treated diabetes was found in those treated with statins showing significant duration and dose effect. Further study is required to confirm this association.

Eating Behaviour among Multi-Ethnic Adolescents in a Middle-Income Country as Measured by the Self-Reported Children’s Eating Behaviour Questionnaire

Background Escalating weight gain among the Malaysian paediatric population necessitates identifying modifiable behaviours in the obesity pathway. Objectives This study describes the adaptation and validation of the Children’s Eating Behaviour Questionnaire (CEBQ) as a self-report for adolescents, investigates gender and ethnic differences in eating behaviour and examines associations between eating behaviour and body mass index (BMI) z-scores among multi-ethnic Malaysian adolescents. Methodology This two-phase study involved validation of the Malay self-reported CEBQ in Phase 1 (n = 362). Principal Axis Factoring with Promax rotation, confirmatory factor analysis and reliability tests were performed. In Phase 2, adolescents completed the questionnaire (n = 646). Weight and height were measured. Gender and ethnic differences in eating behaviour were investigated. Associations between eating behaviour and BMI z-scores were examined with complex samples general linear model (GLM) analyses, adjusted for gender, ethnicity and maternal educational level. Results Exploratory factor analysis revealed a 35-item, 9-factor structure with ‘food fussiness’ scale split into two. In confirmatory factor analysis, a 30-item, 8-factor structure yielded an improved model fit. Reliability estimates of the eight factors were acceptable. Eating behaviours did not differ between genders. Malay adolescents reported higher Food Responsiveness, Enjoyment of Food, Emotional Overeating, Slowness in Eating, Emotional Undereating and Food Fussiness 1 scores (p<0.05) compared to Chinese and Indians. A significant negative association was observed between BMI z-scores and Food Fussiness 1 (‘dislike towards food’) when adjusted for confounders. Conclusion Although CEBQ is a valuable psychometric instrument, adjustments were required due to age and cultural differences in our sample. With the self-report, our findings present that gender, ethnic and weight status influenced eating behaviours. Obese adolescents were found to display a lack of dislike towards food. Future longitudinal and qualitative studies are warranted to further understand behavioural phenotypes of obesity to guide prevention and intervention strategies.

Sugar‐sweetened beverage intake and its associations with cardiometabolic risks among adolescents

Investigations on sugar‐sweetened beverage (SSB) intake and cardiometabolic risks among Asians are scant.

Comprehensive evaluation of the neuropeptide-Y gene variants in the risk of obesity: a case-control study and meta-analysis.

Background Orexigenic actions mediated by neuropeptide-Y (NPY) promote body weight regulation. Genetic variations in the NPY gene could therefore influence susceptibility to obesity, but results have been conflicting. We have carried out, for the first time, a case–control study to examine the effect of NPY rs16147 and rs5574 variants with the risk of obesity in Asians and also a meta-analysis to summarize the effect of these variants including that of the widely studied rs16139. Materials and methods Genotypes and biochemistry data were determined for 942 children (262 cases and 680 controls) recruited from 23 randomly selected schools in Malaysia. Relevant articles were identified from Pubmed, Embase, Web of Science and Google Scholar. Data were extracted and summary estimates of the association between the NPY variants and obesity were examined. Results The frequency of the rs16147 T allele was significantly higher in the cases than controls (odds ratio 1.27, 95% confidence interval 1.04–1.55, P=0.022), whereas the rs5574 T allele was significantly higher in the controls (odds ratio 0.76, 95% confidence interval 0.61–0.96, P=0.020). In addition, NPY rs16147 was significantly correlated with obesity parameters including BMI, waist circumference, triglyceride and body fat percentage (P<0.05). Meta-analysis including nine case–control studies further confirmed the findings of the association of the two variants with the risk of obesity and also found that rs16139 was associated with increased risk. Conclusion This study suggests that NPY rs16147 T and rs16139 C minor alleles are associated with increased risk, whereas the minor allele T of the rs5574 is associated with a reduced risk of obesity.

Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland

AIMS (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing. METHODS The Irish HSE-Primary Care Reimbursement Services database was used to identify patients ≥16 years old co-prescribed ACEIs and ARBs between January 2000 and April 2009 (n= 266 554 prescriptions). The rate of prescribing per 1000 general medical services (GMS) scheme population was calculated for each month. Patients with diabetes, hypertension, heart failure and ischaemic heart disease were also identified by prescribing of certain medications. A linear trend test was used to examine prescribing trends. Logistic regression was used to examine prescribing according to patient characteristics. The effects of the major trials on prescribing were examined using segmented regression analysis for 12 months pre- and post-trials. RESULTS There was a significant linear trend in overall ACEI and ARB co-prescribing over the study period (P < 0.001). Rate of co-prescribing in January 2000 and April 2009 was 0.16 and 5.72, per 1000 eligible population, respectively. Those 45-64 years old (OR = 2.88, 95% confidence interval (CI) 2.71, 3.06) and ≥65 years (OR = 2.52, 95% CI 2.36, 2.68) were more likely to receive dual therapy compared with those <45 years old. Those with hypertension (OR = 8.85, 95% CI 8.45, 9.27), diabetes (OR = 4.10, 95% CI 3.97, 4.23) and heart failure (OR = 1.78, 95% CI 1.72, 1.84) were more likely to receive dual therapy compared with the general population. Significant increases in prescribing were observed only after the CALM (P= 0.03) and VALIANT (P= 0.007) trials. CONCLUSION Increased co-prescribing of ACEIs and ARBs was observed in Ireland during 2000-09. Prescribing patterns did not appear to be affected by results from major trials.

Irish Medicines Board safety warnings: do they affect prescribing rates in primary care?

To examine the impact of safety warnings issued between 2005 and 2007 by the Irish Medicines Board (IMB) on the rate of prescribing of clopidogrel, co‐amoxiclav, celecoxib and haloperidol by primary care physicians in the General Medical Services (GMS) scheme across Ireland.

Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

BACKGROUND The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients. METHODS Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes. RESULTS There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05). CONCLUSIONS The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.

The associations between VDR BsmI polymorphisms and risk of vitamin D deficiency, obesity and insulin resistance in adolescents residing in a tropical country

Background The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. Aims This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country. Methods Thirteen-year-old adolescents were recruited via multistage sampling from twenty-three randomly selected schools across the city of Kuala Lumpur, Malaysia (n = 941). Anthropometric measurements were obtained. Obesity was defined as body mass index higher than the 95th percentile of the WHO chart. Levels of fasting serum vitamin D (25-hydroxyvitamin D (25(OH)D)), glucose and insulin were measured. HOMA-IR was calculated as an indicator for insulin resistance. Genotyping was performed using the Sequenom MassARRAY platform (n = 807). The associations between BsmI and vitamin D, anthropometric parameters and HOMA-IR were examined using analysis of covariance and logistic regression. Result Those with AA genotype of BsmI had significantly lower levels of 25(OH)D (p = 0.001) compared to other genotypes. No significant differences was found across genotypes for obesity parameters. The AA genotype was associated with higher risk of vitamin D deficiency (p = 0.03) and insulin resistance (p = 0.03) compared to GG. The A allele was significantly associated with increased risk of vitamin D deficiency compared to G allele (adjusted odds ratio (OR) = 1.63 (95% Confidence Interval (CI) 1.03–2.59, p = 0.04). In those with concurrent vitamin D deficiency, having an A allele significantly increased their risk of having insulin resistance compared to G allele (adjusted OR = 2.66 (95% CI 1.36–5.19, p = 0.004). Conclusion VDR BsmI polymorphism was significantly associated with vitamin D deficiency and insulin resistance, but not with obesity in this population.

Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents

Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = −0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents.

Disparities in health‐related quality of life among healthy adolescents in a developing country – the impact of gender, ethnicity, socio‐economic status and weight status

BACKGROUND Physical functioning and psychological resilience in adulthood is shaped during adolescence. Self-reported health-related quality of life (HRQoL) assessments during this life phase are important first-hand accounts of their well-being. This study aimed, firstly, to identify differences in HRQoL according to gender, ethnicity, socio-economic status and weight status; and secondly, to examine associations between weight status and HRQoL among an urban sample of multi-ethnic adolescents in Kuala Lumpur, Malaysia. METHODS A cross-sectional study involving 652 adolescents (aged 13 years) was conducted in Kuala Lumpur. Weight and height were measured. Body mass index z-scores were categorized according to the International Obesity Task Force criteria. HRQoL was assessed using the Malay version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. Univariate analyses of differences in HRQoL according to gender, ethnicity (Malays, Chinese and Indians), maternal education level and weight status were performed. Complex samples general linear model was used to examine the associations between HRQoL and weight status, adjusted for confounders. RESULTS Female adolescents reported significantly lower emotional functioning scores (mean, 95% confidence interval: 59.25, 57.33-61.17). When the three main ethnic groups were studied, Malay adolescents scored significantly lower emotional functioning scores (59.00, 57.13-60.87) compared with their Chinese peers. Adolescents with tertiary-educated mothers reported lower emotional functioning scores (57.45, 53.85-61.06) compared with those with primary-educated mothers. Obese adolescents reported poorer HRQoL scores with significantly impaired physical and social functioning after controlling for confounders. CONCLUSIONS These findings detected disparities in HRQoL among the adolescents when gender, ethnicity, maternal education level and weight status were considered. Further studies should address these health inequalities by implementing gender-specific and culturally appropriate measures to attain optimal well-being and avoid potential burden of disease.