高甘油三酯腰围表型

See corresponding editorial on page 3. See corresponding CME exam on page 183. Clustering of metabolic abnormalities in adolescents with the hypertriglyceridemic waist phenotype1–3 Ahmad Esmaillzadeh, Parvin Mirmiran, and Fereidoun Azizi ABSTRACT Background: It remains unknown whether the hypertriglyceride- mic waist (HW) phenotype, an appropriate screening tool in adults, can also be used to screen for metabolic abnormalities in adolescents. Objective: We aimed to evaluate metabolic risk factors identified by the HW phenotype in adolescents. Design: Anthropometric and biochemical measurements were as- sessed in a population-based cross-sectional study of 1413 male and 1623 female Iranian adolescents aged 10–19 y. The HW phenotype was defined as serum triacylglycerol concentrations �110 mg/dL and concurrent waist circumference �90th percentile for age and sex. Elevated fasting glucose (�110 mg/dL), high LDL (�130 mg/ dL) and low HDL (�40 mg/dL) cholesterol, hypercholesterolemia (total cholesterol �200 mg/dL), and hypertension (systolic or dia- stolic blood pressure� 95th percentile for age, sex, and height) were considered as risk factors. Results: Adolescents with the HW phenotype had significantly higher prevalences of all metabolic risk factors except elevated fast- ing glucose than did those without the HW phenotype. After control for potential confounding variables, adolescents with the HW phe- notype were significantly more likely to have high LDL cholesterol (odds ratio: 1.8; 95% CI: 1.3, 2.7), low HDL cholesterol (1.6; 1.3, 2.0), hypercholesterolemia (2.9; 2.0, 4.2), and�1 (1.4; 1.1, 1.7) and �2 (2.2; 1.6, 3.0) risk factors than were those without the HW phenotype. The HW phenotype had a significantly higher percentage of correct prediction of metabolic abnormalities than did over- weight, elevated triacylglycerol concentration, or enlarged waist circumference. Conclusion: This study shows a clustering of metabolic abnormal- ities in adolescents with the HW phenotype and suggests this phe- notype as a simple marker for identifying adolescents at risk of metabolic syndrome and other metabolic abnormalities. Am J Clin Nutr 2006;83:36–46. KEY WORDS Hypertriglyceridemic waist, metabolic syn- drome, adolescents, cardiovascular risk factors, overweight INTRODUCTION Cardiovascular diseases (CVDs) are one of the major causes of mortality in Iran (1), and the prevalence of these disturbances continues to rise (2). Persons with metabolic syndrome are at greater risk of CVD. The metabolic syndrome is defined as a constellation of laboratory and physical findings such as central obesity, insulin resistance, hyperglycemia, dyslipidemia, and hy- pertension (3). The third report of the National Cholesterol Ed- ucation Program Adult Treatment Panel III recognized the met- abolic syndrome as a secondary target of risk-reduction therapy (4). A recent study in Tehran showed that the metabolic syn- drome is highly prevalent in Tehranian adults; the estimated prevalence is �30% (5), which is higher than that in most de- veloped countries, such as the United States (6). Although studies indicated that the process of atherosclerosis starts at an early age and is linked even in childhood to obesity and other components of the metabolic syndrome (7), few studies have reported the prevalence of the metabolic syndrome pheno- type in children and adolescents (8–11). Moreover, at present, there is no globally accepted definition for the metabolic syn- drome in children and adolescents. Research is needed to ascer- tain whether the precursors of the metabolic syndrome in chil- dren and adolescents differ from those in adults, but many investigators assume that insulin resistance is the fundamental metabolic defect underlying the metabolic syndrome (3, 4, 12, 13). The concurrent presence of insulin resistance, increased serum apolipoprotein B concentrations, and high serum concen- trations of small, dense LDL cholesterol has been referred to as a metabolic triad (14) that could be identified by using the inex- pensive screening tool of the hypertriglyceridemic waist (HW) phenotype (15). Some investigators have reported that HW, or waist- triacylglycerol syndrome, predicts the presence of the metabolic syndrome (16). Others recommended this index for the identifi- cation of a syndrome of lipid overaccumulation (17). Subjects with the HW phenotype were nearly 4 times as likely to have angiographically defined coronary artery disease (CAD) as were subjects who did not have the HW phenotype (15). Our previous studies showed that the HW phenotype is highly prevalent in the adult population of Tehran; the estimated prevalence is 19% in 1 From the Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. 2 Supported by grant no. 121 from the National Research Council of the Islamic Republic of Iran and by the combined support of the National Re- search Council of Islamic Republic of Iran and the Endocrine Research Center of Shaheed Beheshti University of Medical Sciences. 3 Reprints not available. Address correspondence to F Azizi, Endocrine Research Center, Shaheed Beheshti University of Medical Sciences, PO Box 19395-4763, Tehran, Iran. E-mail: azizi@erc.ac.ir. Received March 14, 2005. Accepted for publication August 25, 2005. 36 Am J Clin Nutr 2006;83:36–46. Printed in USA. © 2006 American Society for Nutrition by guest on April 5, 2011 w w w .ajcn.org D ow nloaded from men (18) and 32% in women (19). Although the prevalence (15–20) and correlates (21–23) of the HW phenotype have been investigated in adults, comparatively little emphasis was placed on its prevalence and correlates in children and adolescents, and there is no report in the current literature regarding the prevalence of this phenotype in adolescents. It also remains unknown whether, as seen in adults, the HW phenotype is associated with a similar clustering of metabolic risk factors in adolescents. We found in our previous investigation (24) that the HW phenotype is highly prevalent in Tehranian adolescents; ie, the estimated prevalence is 6.5%. In the current study, we aimed to evaluate whether the HW phenotype could be used as a screening tool for metabolic abnormalities in adolescents. SUBJECTS AND METHODS Subjects This study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS), a prospective study performed in a representative sample of residents of one district of Tehran with the aims of ascertaining the prevalence of noncommunica- ble disease risk factors and developing a healthy lifestyle to curtail these risk factors (25). The TLGS provides a representa- tive sample of the population of the city of Tehran (25):�15 000 people aged�3 y who were living in a district of Tehran and were selected by multistage cluster random-sampling method, includ- ing 3265 adolescents aged 10–19 y. In the current population- based cross-sectional study, after the exclusion of subjects taking medications that affect serum lipids, blood pressure, and carbo- hydrate metabolism (n� 23), 3036 adolescents (1413 male and 1623 female) with full relevant data (206 adolescents had incom- plete relevant data) were included in the study. Written informed consent was obtained from each subject. This study was approved by the research council of the Endocrine Research Center of the Shaheed Beheshti University of Medical Sciences. Methods Details of the TLGS protocol and all laboratory procedures were published elsewhere (2, 26, 27). In brief, weight was mea- sured with the use of digital scales while subjects were minimally clothed and not wearing shoes, and it was recorded to the nearest 100 g. Height was measured with the use of a tape measure while subjects were in a standing position and not wearing shoes and while the shoulders were in a normal position. Body mass index (BMI) was calculated as weight (in kg) divided by height (in m2). Waist circumference (WC) was measured at the narrowest level, and hip circumference was measured at the maximum level over light clothing with the use of an unstretched tape measure and without any pressure to body surface; measurements were re- corded to the nearest 0.1 cm. Because the measurements were to be made over light clothing, participants were asked to remove belts and any tight or loose garments that may alter the shape of the body, and the person measuring was asked to ensure that the tape had the proper tension around the subject’s body—ie, nei- ther too loose nor too tight. Although the narrowest waist is easy to identify in most subjects, for some subjects there is no single narrowest waist because of either a large amount of abdominal fat or extreme thinness (28). In the current study, when the narrowest point of waist was difficult to identify (particularly in obese subjects), we measured the WC immediately below the end of the lowest rib, because in most subjects the narrowest waist is at the lowest rib (28). To reduce subjective error, all measurements in all males were taken by the same male technician, and those in all females were taken by the same female technician. There were significant correlations between both the test and retest measure- ments taken by male and female technicians (r� 0.75, P� 0.01 for both). Data on family history of diabetes were collected as the subjects’ oral responses to the previously tested questionnaire. The criterion for family history of diabetes was having�1 first- degree relative with a diagnosis of diabetes after 30 y of age. Data on physical activity, which were reported previously (29), were obtained by using subjects’ oral responses to a previously tested questionnaire, and subjects were categorized into 3 physical ac- tivity groups—light, moderate, and heavy. Between 0700 and 0900, a blood sample was drawn into evac- uated tubes from all study participants after overnight (ie,�10 h) fasting. Blood samples were taken while the subjects were in a sitting position, according to the standard protocol, and were centrifuged within 30–45 min. All blood lipid analyses were done at the TLGS research laboratory on the day of blood col- lection. The analysis of samples was performed by using a Se- lectra 2 autoanalyzer (Vital Scientific, Spankeren, Netherlands). Fasting plasma glucose was measured on the day of blood col- lection by using the enzymatic colorimetric method with glucose oxidase. Serum total cholesterol (TC) and triacylglycerol con- centrations were measured by commercially available enzymatic reagents (Pars Azmoon Inc, Tehran, Iran) adapted to the Selectra autoanalyzer. HDL cholesterol was measured after precipitation of the apolipoprotein B–containing lipoproteins with phospho- tungistic acid. LDL cholesterol was calculated from serum TC, triacylglycerol, and HDL cholesterol concentrations, except when the triacylglycerol concentration was� 400 mg/dL. Assay performance was monitored once every 20 tests by using the lipid control serum Percinorm (normal range) and by using Percipath (pathologic range) whenever applicable [Cat. no. 1446070 (Percinorm) and 171778 (Percipath); Boehringer Mannheim, Mannheim, Germany]. Lipid standard (calibrated for automated systems) (Cat. No. 759350; Boehringer Mannheim) was used to calibrate the Selectra 2 autoanalyzer on each day of laboratory analyses. All samples were analyzed when internal quality con- trol met the acceptable criteria. Interassay and intraassay CVs were 2% and 0.5% for TC and 1.6% and 0.6% for TAG, respec- tively (26). Participants were made to rest for 15 min before their blood pressure was measured. A qualified physician then measured the blood pressure of the seated subject twice by using a standard mercury sphygmomanometer, and thereafter the mean of 2 mea- surements was considered as the participant’s blood pressure. The systolic blood pressure was defined as the appearance of the first sound (Korotkoff phase 1), and the diastolic blood pressure was defined as the disappearance of the sound (Korotkoff phase 5) during deflation of the cuff at a decrement rate of 2–3 mm/s of the mercury column (30). Definition of terms Because no reference values for WC exist for children and adolescents, we established the enlarged WC criteria by analyz- ing all adolescents in the current dataset whose WCs were re- corded. Subjects with a value �90th percentile for age and sex from this sample population were classified as having enlarged HYPERTRIGLYCERIDEMIC WAIST IN ADOLESCENTS 37 by guest on April 5, 2011 w w w .ajcn.org D ow nloaded from WC. The choice of the 90th percentile was based on the associ- ation between truncal fat and WC according to Taylor et al (31). Other investigators also showed that clustering of risk factors was significantly higher in subjects with a WC� 90th percentile than in subjects with a WC� 90th percentile (32). In developing a definition for elevated serum triacylglycerol concentration in adolescents, we considered reference values from the National Cholesterol Education Program’s Pediatric Panel Report (32). In children aged 10–19 y, a borderline high range for triacylglycerol concentrations is given as 90–129 mg/dL (1.02–1.46 mmol/L). Therefore, the midpoint value for triacylglycerol concentrations (�110 mg/dL � 1.24 mmol/L) was taken as the 90th percentile value for age. Subjects were categorized in 4 phenotype groups on the basis of the mentioned cutoffs: normal WC (�90th percentile for age and sex) and normal serum triacylglycerol concentrations (�110 mg/dL); normal WC (�90th percentile for age and sex) and elevated serum triacylglycerol concentrations (�110 mg/dL); enlarged WC (�90th percentile for age and sex) and normal serum tri- acylglycerol concentrations (�110 mg/dL); and enlarged WC (�90th percentile for age and sex) and elevated serum triacyl- glycerol concentrations (�110 mg/dL). Subjects with �3 of the 5 characteristics described in this paragraph were categorized as having the metabolic syndrome. The first characteristic was an enlarged WC (�90th percentile for age and sex), and the second characteristic was an elevated systolic or diastolic blood pressure, which was defined as a value �90th percentile for age, sex, and height based on pub- lished reference data (34). Because the updated report of the Task Force on the Diagnosis and Management of Hypertension does not include adolescents aged 18 and 19 y, we used cutoffs of�130 and�85 mm Hg for systolic and diastolic blood pres- sure, respectively, in those age categories, on the basis of the recommendations of the Joint National Committee on Preven- tion, Detection, Evaluation and Treatment of High Blood Pres- sure (35). The third characteristic was a borderline low HDL cholesterol concentration, in the range of 35–45 mg/dL (0.91– 1.16 mmol/L), as ascertained for all sexes and ages by the Na- tional Cholesterol Education Program’s Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (33). Therefore, the midpoint value for HDL cholesterol (�40 mg/dL� 1.03 mmol/L) was used as a 10th percentile value. The fourth characteristic was an elevated serum triacylglycerol con- centration (�110 mg/dL). The fifth characteristic was a refer- ence value of�110 mg/dL (�6.1 mmol/L) for elevated fasting plasma glucose, which was taken from the American Diabetes Association guideline (36). Hypercholestrolemia was defined as TC �200 mg/dL and high LDL cholesterol as �130mg/dL (33). Hypertension was defined as systolic or diastolic blood pressure of�95th percen- tile for sex, age, and height (34) and, in adolescents aged 18 and 19 y, as a systolic blood pressure �140 mm Hg or a diastolic blood pressure� 90 mm Hg (35). The presence of�1 and�2 of the 5 major risk factors for CVD (ie, elevated fasting glucose, high LDL cholesterol, low HDL cholesterol, hypercholesterol- emia, and hypertension) was also evaluated. On the basis of the standardized percentile curves of BMI suggested for Iranian children and adolescents, overweight was defined as�95th percentile of BMI for age and sex (37). Risk of overweight was defined as�85th to�95th percentile of BMI for age and sex, and normal weight was defined as�85th percentile of BMI for age and sex. Statistical analysis We used SPSS software (version 9.05; SPSS Inc, Chicago IL) for all statistical analyses. The prevalence of the HW phenotype and its 95% CI was calculated overall, by sex, by sex and family history of diabetes, and by sex and BMI status. There was a significant interaction between sex and age with regard to the prevalence of HW (P� 0.05). Therefore, the prevalences of the HW phenotype in boys and girls were examined by age. Preva- lence values were compared by using the chi-square test. Signif- icant differences in general characteristics across different phe- notypes of serum triacylglycerol concentrations and WC were searched by using 2-factor (enlarged WC versus normal WC and elevated triacylglycerol versus normal triacylglycerol) analysis of variance (ANOVA), and the main effects of WC and triacyl- glycerol concentrations and the WC � triacylglycerol concen- tration interaction were tested. We also used 2-factor ANOVA to detect significant differences in the distribution of subjects across different phenotypes of serum triacylglycerol concentra- tion and WC with regard to the prevalence of metabolic abnor- malities. We ascertained age- and sex-adjusted means of meta- bolic risk factors across different phenotypes of serum triacylglycerol concentrations and WC by using general linear models. These models were further adjusted for BMI. Analysis of covariance was used to compare these means. To determine the association of the HW phenotype with metabolic abnormalities, we used logistic regression models. Because the ORs estimated from logistic regression models in cross-sectional studies are not valid estimators of the rate ratios when the binary outcome vari- able has a higher prevalence (38, 39), we used the formula sug- gested by Zhang and Yu (39) to correct the adjusted ORs obtained from logistic regression so that we could derive an estimate of association that better represents the true relative risk. All models were controlled for age (y), sex, and physical activity level (light, moderate, and heavy). When a significant association with the HW phenotype was observed, we further examined whether overweight associated with the HW phenotype would explain the associations by adjusting for BMI. In all multivariate models, subjects with normal serum triacylglycerol concentrations and normal WCs were considered as a reference. McNemar’s chi- square statistic was used to ascertain whether significant differ- ences were present between the HW phenotype and overweight with respect to accuracy in classifying individuals according to the presence or absence of risk factors. Such analyses were also repeated by comparing the HW phenotype with the metabolic syndrome, enlarged WC, or elevated triacylglycerol concentra- tion alone. The frequency of subjects with and without CVD risk factors in established cutoffs of the screening measures (HW phenotype, overweight, and the metabolic syndrome) was ascer- tained by cross-tabulation, and sensitivity and specificity were calculated. The sensitivity of each screening measure was de- fined as the proportion of the total number of subjects with a given risk factor who were identified correctly by the same in- dicator. The specificity of each screening measure was defined as the proportion of the total subjects without the risk factor who were correctly identified by the same measure. 38 ESMAILLZADEH ET AL by guest on April 5, 2011 w w w .ajcn.org D ow nloaded from RESULTS Of the 3036 adolescents, 358 (11.8%) had a family history of diabetes, 382 (12.5%) were overweight, and 399 (13.1%) were at risk of overweight. The prevalence of the HW phen