Can We Apply the National Cholesterol Education Program Adult Treatment Panel Definition of the Metabolic Syndrome to Asians?
Chee-Eng Tan , PHD, MMED 1 ,
Stefan Ma , PHD 2 ,
Daniel Wai , MRCP 1 ,
...Suok-Kai Chew , MSC 2 and
E.-Shyong Tai , MRCP 1
1 Department of Endocrinology, Singapore General Hospital, Singapore
2 Ministry of Health, College of Medicine Building, Singapore
Address correspondence and reprint requests to Dr. C.E. Tan, Department of Endocrinology, Singapore General Hospital, Block
6 Level 6, Outram Road, Singapore 169608, Republic of Singapore. E-mail: ce_tan{at}sgh.com.sg
Abstract
OBJECTIVE —Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using
waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference
for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population.
RESEARCH DESIGN AND METHODS —We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese,
Malay, and Asian-Indian ethnicity aged 18–69 years. Receiver operating characteristic analysis suggested that waist circumference
>80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence
of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP
ATP III) criteria with and without the modified waist circumference criteria.
RESULTS —In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using
the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18–30 years to 31.0%
in those aged 60–69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001).
CONCLUSIONS — NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference
cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely
to exist between populations across Asia.
CVD, cardiovascular disease
IGT, impaired glucose tolerance
NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III
NHANES III, Third National Health and Nutrition Examination Survey
ROC, receiver operating characteristic
WHO, World Health Organization
Footnotes
Accepted January 19, 2004.
Received October 13, 2003.
DIABETES CARE
Epidemiology and control of SARS in Singapore Goh, Kee-Tai; Cutter, Jeffery; Heng, Bee-Hoon ...
Annals of the Academy of Medicine, Singapore,
05/2006, Volume:
35, Issue:
5
Journal Article
Peer reviewed
Open access
Severe acute respiratory syndrome (SARS) was imported into Singapore in late February 2003 by a local resident who returned from a holiday in Hong Kong and started an outbreak in the hospital where ...she was admitted on 1 March 2003. The disease subsequently spread to 4 other healthcare institutions and a vegetable wholesale centre. During the period between March and May 2003, 238 probable SARS cases, including 8 imported cases and 33 deaths, were reported. Transmission within the healthcare and household settings accounted for more than 90% of the cases. Factors contributing to the spread of infection included the failure to recognise the high infectivity of this novel infection, resulting in a delay in isolating initial cases and contacts and the implementation of personal protective measures in healthcare institutions; and the super-spreading events by 5 index cases, including 3 with co-morbid conditions presenting with atypical clinical manifestations of SARS. Key public health measures were directed at prevention and control within the community and hospitals, and the prevention of imported and exported cases. An isolated laboratory-acquired case of SARS was reported on 8 September 2003. Based on the lessons learnt, Singapore has further strengthened its operational readiness and laboratory safety to respond to SARS, avian flu and other emerging diseases.
FTO Variants Are Associated With Obesity in the Chinese and Malay Populations in Singapore
Jonathan T. Tan 1 ,
Rajkumar Dorajoo 2 ,
Mark Seielstad 2 ,
Xue Ling Sim 1 ,
Rick Twee-Hee Ong 2 ,
Kee Seng ...Chia 1 ,
Tien Yin Wong 3 4 ,
Seang Mei Saw 3 5 ,
Suok Kai Chew 6 ,
Tin Aung 3 and
E-Shyong Tai 1 7
1 Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore
2 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
3 Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
4 Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
5 Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore,
Singapore, Singapore
6 Ministry of Health, Singapore, Singapore
7 Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
Corresponding author: Tai E. Shyong, eshyong{at}pacific.net.sg
Abstract
OBJECTIVE— Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans.
The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations.
RESEARCH DESIGN AND METHODS— We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese,
785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore
Malay Eye Study (SiMES).
RESULTS— All nine SNPs exhibited strong linkage disequilibrium ( r 2 = 0.6–0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging
from 0.42 to 0.68 kg/m 2 ( P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m 2 ( P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m 2 ( P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also
associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17–1.22;
P ≤ 0.026).
CONCLUSIONS— FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data
do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association
observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus
may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 3 July 2008.
J.T.T. and R.D. contributed equally to this study.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted June 19, 2008.
Received February 15, 2008.
DIABETES
We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996-2003. Influenza A (H3N2) was the predominant circulating influenza virus ...subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8-19.8), 2.9 (1.0-5.0), and 11.9 (8.3-15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.
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Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and ...epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.
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OBJECTIVE:--The International Diabetes Federation (IDF) proposes that central obesity is an "essential" component of the metabolic syndrome, while the American Heart Association/National Heart, Lung, ...and Blood Institute (AHA/NHLBI) proposes that central obesity is an "optional" component. This study examines the effect of the metabolic syndrome with and without central obesity in an Asian population with ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS--From the population-based cohort study (baseline 1992-1995), 4,334 healthy individuals were grouped by the presence or absence of the metabolic syndrome and central obesity and followed up for an average of 9.6 years by linkage with three national registries. Cox's proportional hazards model was used to obtain adjusted hazard ratios (HRs) for risk of a first IHD event. RESULTS:--The prevalence of metabolic syndrome was 17.7% by IDF criteria and 26.2% by AHA/NHLBI criteria using Asian waist circumference cutoff points for central obesity. Asian Indians had higher rates than Chinese and Malays. There were 135 first IHD events. Compared with individuals without metabolic syndrome, those with central obesity/metabolic syndrome and no central obesity/metabolic syndrome were at significantly increased risk of IHD, with adjusted HRs of 2.8 (95% CI 1.8-4.2) and 2.5 (1.5-4.0), respectively. CONCLUSIONS:--Having metabolic syndrome either with or without central obesity confers IHD risk. However, having central obesity as an "optional" rather than "essential" criterion identifies more individuals at risk of IHD in this Asian cohort.
OBJECTIVE:--To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by ...macronutrient intake. RESEARCH DESIGN AND METHODS--A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization-recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18-69 years) were studied. Genetic (PLIN 11482Grightward arrowA and 14995Arightward arrowT), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects. RESULTS:--We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482Grightward arrowA/14995Arightward arrowT polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482Grightward arrowA, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8-19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1-9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (-24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups. CONCLUSIONS:--PLIN 11482Grightward arrowA/14995Arightward arrowT polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.
Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma ...triacylglycerol.
We investigated the combined effects of the GCKR rs780094C→T, APOA5 −1131T→C, and APOA5 56C→G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions.
We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = 1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes).
Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001).
SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment.
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Context: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, ...the association in other East Asian populations is less well characterized.
Objective: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore.
Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.
Results: In Chinese, SNPs in CDKAL1 odds ratio (OR) = 1.19; P = 2 × 10−4, HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 × 10−4) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 × 10−4), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19–1.25; P = 0.003–2.5 × 10−4) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 × 10−4), CDKN2A/B (OR = 1.16; P = 9 × 10−5), HHEX (OR = 1.14; P = 6 × 10−4), and KCNQ1 (OR = 1.16–1.20; P = 3 × 10−4 to 3 × 10−6) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.
Conclusions: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.
Combined data from multiple Asian populations show that common variants associated with type 2 diabetes, identified in populations of European ancestry, are also associated in East Asians.
Summary
Objective This study assesses the effect of the metabolic syndrome on all‐cause and cardiovascular disease (CVD) mortality in healthy Chinese, Malays and Asian Indians in Singapore. The ...utility of the metabolic syndrome is also compared with the Framingham risk score for prediction of mortality.
Methods Healthy participants (n = 5699) were grouped by the presence or absence of the metabolic syndrome, and followed up (mean 14·1 years) by data linkage with the National Death Register. Risk of mortality was obtained by Cox's proportional hazards model with adjusted hazard ratios (HRs). Area under receiver operating characteristic (ROC) curves were used to compare the metabolic syndrome and Framingham risk score for prediction of mortality.
Results During a follow‐up of 80 236 person‐years, there were 382 deaths, of which 128 were due to CVD. Individuals with the metabolic syndrome had an increased risk of mortality for ‘all‐causes’ (males: HR 1·4, 95% confidence intervals (95%CI) 1·1–1·8; and females: HR 1·8, 95%CI 1·3–2·6). There was also an increased risk of mortality due to CVD (males: HR 3·0, 95%CI 1·9–4·8; and females: HR 2·1, 95%CI 1·1–4·0). The area under ROC for Framingham risk score was higher for both all‐cause and CVD mortality than metabolic syndrome.
Conclusions Although an increased risk of ‘all‐cause’ and CVD mortality due to the metabolic syndrome was found, the Framingham risk function still performed better than the metabolic syndrome in an Asian population. However, the metabolic syndrome should not be disregarded as it is a clinically useful entity for identifying individuals for management of its component CVD risk factors.
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