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Abdominal obesity, hypertriglyceridemia, hypertriglyceridemic waist phenotype and risk of type 2 diabetes in American adults
Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2008) 2, 273—281
http://diabetesindia.com/
ORIGINAL PAPER
Abdominal obesity, hypertriglyceridemia, hypertriglyceridemic waist phenotype and risk of type 2 diabetes in American adults Ike S. Okosun a,*, John M. Boltri b a b
Institute of Public Health, Georgia State University, MSC 2A0875, Atlanta, GA 30303-6879, United States Department of Family Medicine, Mercer University School of Medicine, Macon, GA, United States KEYWORDS Triglyceride; Waist circumference; Abdominal obesity
Summary Background: Hypertriglyceridemic waist (HTGW) phenotype is a marker of atherogenesis whose association with cardiovascular diseases is unclear. Objective: To determine the association of abdominal obesity, hypertriglyceridemia and HTGW with risk of type 2 diabetes in American adults. Methods: Data (n = 1914) From the 2003—2004 United States National Health and Nutrition Examination Surveys (NHANESs) were used in this investigation. The risk of type 2 diabetes associated with HTGW was estimated using odds ratio from the logistic regression model, adjusting for race/ethnicity, age, body mass index (BMI), hypertension, HDL-cholesterol (HDL-C), smoking and alcohol intake. Results: There was a gender and racial/ethnic difference in the association of adiposity phenotypes with type 2 diabetes. In men, abdominal obesity, hypertriglyceridemia and HTGW were associated with 1.59 (95% CI: 1.09—2.79), 2.27 (95% CI: 1.42—3.62), and 2.85 (95% CI: 2.10—2.10) increased odds of type 2 diabetes. The analogous values in women were 2.50 (95% CI: 1.82—4.79), 2.14 (95% CI: 1.30—3.53), and 2.58 (95% CI: 1.48—4.24), respectively. HTGW was associated with 1.24 (95% CI: 1.05—2.39) and 3.94 (95% CI: 2.85—3.90) increased risks of type 2 diabetes. The corresponding risks in White women and Black women were 1.36 (95% CI: 1.23—2.91) and 5.62 (95% CI: 1.04—9.42), respectively. Conclusion: Hypertriglyceridemic waist phenotype is more strongly associated with type 2 diabetes than both hypertriglyceridemia and abdominal obesity alone. Well designed public health strategies to enhance lifestyle modification program to reduce the prevalence of HTGW may be a way to decrease racial/ethnic disparities for type 2 diabetes in the United States. # 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Tel.: +1 404 413 1113; fax: +1 404 413 1140. E-mail address: [email protected] (I.S. Okosun).
Elevated serum triglyceride (TG) and abdominal obesity are components of metabolic syndrome (MS) [1,2] whose joint role in cardiovascular
1871-4021/$ — see front matter # 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dsx.2008.04.003
274 diseases is uncertain. MS is pathophysiologically linked to insulin resistance [3,4]. While some studies have shown a positive association of TG with cardiovascular disease risk factors [5—7], others have shown a negative or lack of association [8—11]. Recent studies however, suggest that TG is an independent risk factor for cardiovascular diseases, leading to speculation about its potential role in identifying subjects at greater risk for coronary events [12,13]. Paradoxically, the prevalence of elevated TG is lower in cardiovascular disease high risk groups such as Blacks as compared to Whites [12—14]. Abdominal adiposity is an independent risk factor for cardiovascular diseases [15—18]. Abdominal adiposity is a gauge of the actual amount of total abdominal fat accumulation and a key correlate of visceral adiposity among obese and overweight subjects [19]. Because TG is a surrogate marker for a variety of atherogenic disturbances in lipoprotein moieties that are found in association with increased abdominal fat (marker of visceral fat) and insulin resistance such as type 2 diabetes [20—22], understanding the role of the joint occurrence of TG and abdominal obesity may provide very useful diabetes prevention clues. The comorbid condition consisting of elevated TG and large waist circumference (surrogate measure of abdominal obesity) was originally described by Lemieux et al. as hypertriglyceridemic waist (HTGW) phenotype [23]. Hypertriglyceridemia and abdominal adiposity are interrelated metabolic disorders [24—26]. TG is a key lipid in chylomicrons and very-low-density lipoprotein particles. A TG level of less than 200 mg/dL is considered normal, while values of 200—400, 401—1000, and 1001 mg/dL or greater are considered borderline, high and extremely high, respectively [7]. Abdominal adiposity is characterized by a waist circumference value of 94 cm or greater in men and 80 cm or greater in women [27]. HTGW is a marker of the atherogenic metabolic triad that consists of hyperinsulinemia, hyperapolipoprotenemia and small density low-density lipoprotein cholesterolemia [15—17]. Studies have shown that the cardiovascular disease risk attributable to glycemia may be explained by the co-occurrence of hypertriglyceridemia and abdominal adiposity [18]. Indeed, results of a study by Lemieux et al. (2000) indicates that in the absence of hypertriglyceridemia and abdominal adiposity comorbidity, hyperglycemia by itself is not predictive of cardiovascular disease risk [23]. A recent analysis of subjects with HTGW and glucose intolerance or type 2 diabetes indicate much earlier occurrences of coronary artery disease symptoms and higher risk for coronary artery disease (hazard
I.S. Okosun, J.M. Boltri ratio 2.0, 95% CI: 1.2—3.7) compared to those without the phenotype [19]. Determination of HTGW is cheap and easy, and a significant marker of cardiovascular disease manifestations at an earlier age in subjects with hyperglycemia, including glucose intolerance and type 2 diabetes [18—21]. To the best of our knowledge there is no study comparing the association of joint occurrence of abdominal obesity (waist circumference of 94 cm or greater in men, and 80 cm of greater in women), of hypertriglyceridemia (200 mg/dL or greater) and HTGW with type 2 diabetes in the US. The aim of this study was to determine the association of abdominal obesity, hypertriglyceridemia and their joint occurrence with risk of type 2 diabetes. We also sought to determine the effect of race/ethnicity on association of these adiposity phenotypes with risk of type 2 diabetes.
Methods Data source The United States National Center for Health Statistics (NCHS) provided the 2003—2004 NHANES data that were used in this study. The 2003—2004 NHANES was a cross-sectional survey carried out among the non-institutionalized US civilian population. Descriptions of the plan and operation of the surveys have been described by other investigators [28,29]. Briefly, the 2003—2004 NHANES conducted by NCHS was based on a complex, multi-stage sampling plan. Approximately 10,000 persons completed the survey that was designed to over sample Mexican Americans and non-Hispanic Blacks in order to improve estimates for these groups. The survey included an in-person home interview, followed by an interview/examination at a mobile examination center. In the survey, waist measurements were done with steel tape at the natural waist midpoint between the lowest aspect of the rib cage and highest point of the iliac crest to the nearest 0.1 cm [30]. Fasting TG was measured only in participants that were examined in the morning session. TG was measured enzymatically in plasma or serum using a sequence of coupled reactions in which TG is hydrolyzed to produce glycerol [30]. Glycerol is subsequently oxidized using glycerol oxidase, and hydrogen peroxide, one of the reaction products, is changed via peroxidase to a phenazone. TG absorbance was measured at 500 nm [30]. In NHANES, serum glucose level was also determined enzymatically in a series of chemical reactions that involves hexokinase and adenosine triphosphate to produce glucose-6-phosphate and other intermediaries [30].
Hypertriglyceridemic waist and diabetes Glucose concentration was measured using spectrophotometer at 340 nm [30]. Only subjects who were identified as non-Hispanic White and non-Hispanic Black Americans between 20 and 85 years old were included in this investigation. Subjects who were on hormones such as estrogen and those with renal diseases and drugs such as glucocorticoids were excluded from this study because these factors are associated with elevated TG values [7]. Those who were excluded due to missing variables of interest were not different from the population examined in our study.
Other variables included in the study Other variables from the 2003—2004 NHANES that were employed in this study include: systolic (SBP) and diastolic (DBP) blood pressure, HDL-cholesterol, total cholesterol, body mass index (BMI), smoking and alcohol intake. The protocol for blood pressure (BP) measurement in 2003—2004 NHANES was in accordance with standard procedures as developed by the American Heart Association. BP was measured three or four times manually by trained personnel using a mercury sphygmomanometer [30]. Excluding the first BP reading, the average of the remaining values was used for determining hypertension status in this study. Total cholesterol was measured enzymatically in serum in a series of coupled reactions that hydrolyze cholesteryl esters and oxidize the 3-OH group of cholesterol while HDL-cholesterol (HDL-C) was measured directly in serum. Height and weight were measured in a mobile examination center using standardized procedures and equipment. In this study BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). During the mobile examination center interview/ examination, participants were asked questions about smoking and alcohol use. Specifically, participants were asked if they had smoked at least 100 cigarettes in their lifetime. Those who responded in the affirmative were asked if they smoked ‘‘now’’. In this study, those who answered yes to the second question were considered as current smokers while others were considered as nonsmokers. Participants who were 20 years of age or older were also asked questions regarding usual alcohol consumption in the past year. In this study, participants who had consumed at least 12 drinks in any year or in their entire life, and had consumed alcohol on at least 1 day in the past year were considered as current drinkers. Those who had consumed at least 12 drinks in any year or in their entire life, and had not consumed alcohol in the past year and those who had no drinks at all in their lifetime were considered to be nondrinkers.
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Definition of terms Hypertriglyceridemia was defined as TG levels of 200 mg/dL or greater [22]. Abdominal obesity was defined as waist circumference values of 94 cm or greater and 80 cm or greater in men and women, respectively [19]. Hypertriglyceridemic waist phenotype was defined as co-occurrence of hypertriglyceride, and abdominal obesity [18—21]. Type 2 diabetes was defined as diagnosed diabetes on insulin or other hypoglycemic agents or fasting blood glucose value 126 mg/dL or an oral tolerance test glucose level of 200 mg/dL [31]. Hypertension was defined as an average BP 140/90 mmHg or if the participant was taking antihypertensive medications or had been diagnosed with hypertension.
Statistical analysis Statistical programs that are available in SAS for Windows [32], and SUDAAN [33] were utilized in this analysis. To account for unequal probabilities of selection, over sampling, and non-response, appropriate sample weights were utilized for the analyses. Standard errors were estimated using the SUDAAN statistical program method [33]. All analysis were stratified by gender, and gender differences in age, waist circumference, lipids, and other continuous variables were assessed by independent ttests. Gender differences for frequency variables were determined by Pearson’s chi-square tests. Odds ratios from logistic regression analyses were used to estimate the risk of type 2 diabetes that was associated with abdominal obesity, hypertriglyceridemia and HGTW. Gender specific multivariate logistic regression analyses were used to determine the association of each adiposity phenotype with type 2 diabetes. In the analyses, type 2 diabetes was used as the dependent and independent variable. Effects of race/ethnicity were determined by statistically adjusting for race/ethnicity, including other covariates, including age, body mass index, hypertension, HDL-cholesterol, smoking, and alcohol intake. To determine the impact of abdominal obesity, hypertriglyceridemia, and HGTW on type 2 diabetes, we calculated race/ethnic specific population attributable risks. [34] The results of all analyses were evaluated for statistical significance using P <.05 and the 95% confidence intervals.
Results The basic characteristics of eligible men (n = 937) and women (n = 977) for this study are shown in Table 1. Men were taller and heavier, and presented
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Table 1 Characteristics of studied populations Variables
Men
Women
P-Value
n Age (y) Height (cm) Weight (kg) Waist (cm) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Triglyceride (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Abdominal obesity (%) Hypertriglyceridemia (%) Hypertriglyceridemic waist (%) Diabetes (%) Smoking (%) Alcohol use (%)
937 50.9 19.3 175.1 8.0 86.2 18.8 100.6 14.6 28.0 5.4 70.4 14.4 125.3 18.9 48.7 13.2 117.7 39.1 163.0 141.1 197.2 45.0 108.3 39.8 43.5 22.5 13.1 15.0 26.1 17.5
977 50.4 19.2 161.8 7.5 76.4 19.2 97.3 15.1 29.2 6.9 67.8 13.8 124.3 22.8 59.9 16.7 117.1 36.1 143.8 118 205.6 45.2 101.6 39.9 56.3 19.1 14.9 12.5 17.5 41.9
.629 <.001 <.001 <.001 <.001 <.001 .298 <.001 .734 <.001 <.001 <.001 <.001 .069 .253 .104 <.001 <.001
Race/ethnicity (%) White Black
80.5 19.5
79.3 20.7
.532
with larger waist girth compared to women (P <.001). Men also presented with higher values of DBP, triglyceride, and fasting blood glucose compared to women (P <.001). The prevalences of generalized obesity (body mass index of 30 kg/m2 or greater) abdominal obesity, alcohol intake, and blood concentrations of TG were higher in women compared to men (P <.001). In Table 2, anthropometric and clinical differences between subjects with hypertriglyceridemic waist phenotype were compared with those with abdominal obesity and hypertriglyceridemia and subjects without abdominal obesity or hypertriglyceridemia (normal). In men, subjects with hypertriglyceridemic waist phenotype were more obese and had higher values of fasting blood glucose compared with normal subjects and those with abdominal obesity or hypertriglyceridemia (P <.05). Prevalences of diabetes and alcohol use were also greater in subjects with hypertriglyceridemic waist phenotype than normal subjects and those with abdominal obesity and hypertriglyceridemia (P <.05). In women, subjects with hypertriglyceridemic waist phenotype also had higher values of body mass index and fasting blood glucose compared with normal subjects and those with abdominal obesity or hypertriglyceridemia (P <.05). The prevalences of diabetes and alcohol use were greater in subjects with hypertriglyceridemic waist phenotype as compared with normal subjects and those with either abdominal obesity or hypertriglyceridemia (P <.05).
We compared the association of abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype with risk of type 2 diabetes, in sexspecific multiple logistic regression models (Model I of Tables 3 and 4) adjusting for age, BMI, HDL-C, hypertension, smoking and alcohol intake. As shown (Table 3) the risk of type 2 diabetes differ by adiposity types. Abdominal obesity (OR = 1.59; 95% CI: 1.09—2.79), hypertriglyceridemia (OR = 2.27; 95% CI: 1.42—3.62) and hypertriglyceridemic waist phenotype (OR = 2.85; 95% CI: 2.10—3.11) were associated with increased odds of type 2 diabetes in men. As similar increased odds of type 2 diabetes due to abdominal obesity (OR = 2.50; 95% CI: 1.82— 4.79), hypertriglyceridemia (OR = 2.14; 95% CI: 1.30—3.53) and hypertriglyceridemic waist phenotype (OR = 2.58; 95% CI: 1.48—4.24) were also evident in women (Table 4). In order to determine the effect of race/ethnicity on the association between abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype with risk of type 2 diabetes, we further adjusted for race/ethnicity (coded as 1 = White, 2 = Black) in gender specific logistic regression analyses (Model II of Tables 3 and 4) adjusting for age, BMI, HDL-C, hypertension, smoking and alcohol intake. Compared to Whites, Black race/ethnicity was associated with increased odds of type 2 diabetes, adjusting for each adiposity phenotype and other independent variables. In men, adjusting for each adiposity phenotype, Black
Hypertriglyceridemic waist and diabetes
277
Table 2 Anthropometric and clinical differences between subjects with abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist in adult US population Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
Normal
Men n Age (y) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Diabetes (%) Smoking (%) Alcohol use (%)
408 54.6 17.4 32.3 4.6 72.4 15.2 127.4 17.2 45.0 10.8 119.3 34.2 200.6 43.4 115.5 47.1 22.5 20.6 19.0
211 52.8 17.1 29.7 5.2 71.0 16.3 125.2 19.2 39.8 8.9 122.1 52.0 221.0 56.7 124.2 64.2 26.1 30.3 16.8
123 55.2 16.4 32.6 4.5 73.0 16.4 127.6 18.0 39.7 8.3 117.2 32.6 220.4 51.2 129.0 69.7 31.7 24.4 21.2
440 47.9 20.7 24.6 3.2 69.1 13.1 124.0 19.4 54.0 13.9 114.5 35.7 189.2 39.6 99.7 24.1 7.5 28.8 17.4
Women n Age (y) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Diabetes (%) Smoking (%) Alcohol use (%)
550 52.0 18.7 33.0 6.2 69.0 13.7 126.8 22.2 55.8 15.1 120.2 36.9 208.7 47.3 107.8 37.3 18.5 16.7 44.6
187 53.2 19.1 31.1 6.2 67.9 17.0 129.2 23.9 51.3 14.3 125.4 45.9 234.2 58.6 111.1 41.7 12.5 15.5 47.5
146 51.8 19.6 33.3 5.6 68.0 15.3 127.7 22.7 50.1 13.7 124.8 46.0 231.9 60.1 11.4.8 45.1 26.0 15.1 47.9
386 47.2 19.7 23.8 3.1 66.2 12.8 119.7 22.3 66.2 17.0 111.6 34.8 199.0 38.4 93.1 24.0 4.1 18.7 37.4
race/ethnicity was associated with approximately twofold increased odds of type 2 diabetes compared to White men, and in women approximately threefold increased odds type 2 diabetes compared to White women. We estimated the impact of race/ ethnicity on the relationship between each adiposity phenotype and risk of type 2 diabetes by comparing Model I with Model 2. In men, adjustment for race/ethnicity was associated with 8.8, 5.7 and 2.1% greater odds of type 2 diabetes that may be attributable to abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist phenotype, respectively. The corresponding values in women were 4.4, 7.9 and 5.0%, respectively. Race/ethnic and gender specific associations of hypertriglyceridemic waist phenotype with risk of type 2 diabetes were determined, adjusting for age, BMI, HDL-C, hypertension, smoking, and alcohol intake (Table 5). In both men and women, hypertriglyceridemic waist phenotype was significantly associated with increased odds of type 2 diabetes in the total population, adjusting for confounding variables. In White men and Black men, hypertriglyceridemic waist phenotype was also associated with increased odds of type 2 diabetes, adjusting for age,
BMI, HDL-C, hypertension, smoking, and alcohol intake. The greatest risk of type 2 diabetes was in Black men (OR = 3.94; 95% CI: 2.85—3.90) compared to White men (OR = 1.24; 95% CI: 1.05—2.39). Among women, the greatest risk of type 2 diabetes was also in Black women (OR = 5.62; 95% CI: 1.04— 9.42) compared to White (OR = 1.36; 95% CI: 1.23— 2.91) women. Similar to the results of the association between abdominal adiposity, hypertriglyceridemia, and hypertriglyceridemic waist phenotype with type 2 diabetes, increased age and BMI were also associated with increased risk of type 2 diabetes in White and Black men and women.
Discussion The independent and combined roles of TG and abdominal adiposity in the development of cardiovascular diseases are unclear. Although some studies have described the independent roles of these metabolic profiles in cardiovascular diseases, findings have been inconsistent. The Honolulu Heart Program found that the risk of cardiovascular disease was amplified in subjects with low HDL-cholesterol and elevated TG
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Table 3 Impact of race/ethnicity in the association of abdominal adiposity, hypertriglyceridemia and hypertriglyceridemic waist with type 2 diabetes in men Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
OR
[95% CI]
OR
[95% CI]
OR
[95% CI]
Model I Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
1.59 1.06 1.07 0.99 0.76 1.51 1.04
1.09—2.79 1.04—1.07 1.02—1.13 0.97—1.01 0.48—1.21 0.90—2.54 0.63—1.73
2.27 1.06 1.10 1.00 0.75 1.45 1.07
1.42—3.62 1.04—1.07 1.05—1.14 0.99—1.02 0.47—1.20 0.87—2.43 0.64—1.79
2.85 1.06 1.09 0.99 0.75 1.47 1.02
2.10—3.11 1.04—1.07 1.05—1.14 0.98—1.01 0.47—1.19 0.88—2.46 0.61—1.69
Model II Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
1.73 1.06 1.07 0.99 0.72 1.41 1.09
1.43—5.33 1.04—1.07 1.04—1.12 0.98—1.01 0.58—1.51 1.05—3.54 0.66—1.58
2.40 1.06 1.10 0.99 0.70 1.34 1.10
1.50—3.86 1.04—1.08 1.05—1.14 0.98—1.01 0.44—1.13 0.80—2.27 0.65—1.85
2.91 1.06 1.09 0.99 0.70 1.37 1.06
2.18—3.41 1.05—1.08 1.05—1.13 0.97—1.01 0.43—1.12 0.81—2.30 0.63—1.77
Race/ethnicity b Black
1.94
1.11—3.41
2.09
1.19—3.68
2.00
1.14—3.52
a
Abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist; OR, odds ratio, CI, confidence intervals from multivariate logistic regression models. b Reference group was White; Model II, adjustment for race/ethnicity.
Table 4 Impact of race/ethnicity in the association of abdominal adiposity, hypertriglyceridemia and hypertriglyceridemic waist with type 2 diabetes in women Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
OR
[95% CI]
OR
[95% CI]
OR
[95% CI]
Model I Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
2.50 1.05 1.04 0.99 0.78 1.84 1.03
1.82—4.79 1.04—1.07 1.00—1.08 0.98—1.01 0.60—1.08 1.00—3.39 0.66—1.61
2.14 1.06 1.09 1.00 0.92 2.08 1.04
1.30—3.53 1.04—1.07 1.05—1.13 0.98—1.01 0.57—1.49 1.13—3.84 0.67—1.61
2.58 1.06 1.09 0.99 0.92 2.09 1.04
1.48—4.24 1.04—1.07 1.05—1.12 0.98—1.01 0.57—1.49 1.13—3.85 0.67—1.61
Model II Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
2.61 1.06 1.03 0.99 0.80 2.21 0.97
1.79—3.62 1.05—1.08 0.99—1.07 0.98—1.01 0.48—1.32 1.17—4.18 0.61—1.52
2.31 1.06 1.08 0.99 0.74 2.55 0.98
1.37—3.90 1.05—1.09 1.04—1.12 0.98—1.01 0.45—1.21 1.35—4.81 0.63—1.54
2.71 1.06 1.07 0.99 0.73 2.54 0.98
1.57—4.67 1.05—1.09 1.03—1.11 0.98—1.01 0.44—1.21 1.35—4.80 0.62—1.54
Race/ethnicity b Black
2.78
1.54—5.00
3.15
1.74—5.70
3.16
1.75—5.71
a
Abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist; OR, odds ratio, CI, confidence intervals from multivariate logistic regression models. b Reference group was White; Model II, adjustment for race/ethnicity.
Hypertriglyceridemic waist and diabetes
279
Table 5 Association between hypertriglyceridemic waist phenotype and type 2 diabetes in white, and black American adults Variables
White
Black
OR
[95% CI]
OR
[95% CI]
Men Hypertriglyceridemic waist Age BMI HDL-C Hypertension Smoking Alcohol intake
1.24 1.06 1.09 0.97 0.85 1.21 0.71
1.05—2.39 1.04—1.08 1.03—1.15 0.94—1.00 0.44—1.63 0.54—2.73 0.39—1.61
3.94 1.07 1.09 1.02 0.30 2.99 3.53
2.85—3.90 1.04—1.11 1.01—1.19 0.99—1.07 0.21—1.15 0.91—9.85 1.12—5.14
Women Hypertriglyceridemic waist Age BMI HDL-C Hypertension Smoking Alcohol intake
1.36 1.06 1.06 0.99 0.70 1.29 1.39
1.23—2.91 1.03—1.09 1.01—1.12 0.96—1.01 0.32—1.52 0.51—3.26 0.72—2.69
5.62 1.10 1.12 1.02 0.69 6.07 0.53
1.04—9.42 1.06—1.15 1.03—1.21 0.99—1.06 0.23—2.07 1.50—9.48 0.17—1.62
OR, odds ratio, CI, confidence intervals from multivariate logistic regression models.
when the total cholesterol level was borderline high or elevated [35]. However, the Prospective Cardiovascular Munster Study, which investigated the risk of coronary artery disease in more than 4500 men, found that TG was not an independent predictor of risk [10]. In the study, subjects with TG serum concentrations of 200 mg/dL or greater had more than two times the number of coronary artery disease events as those with TG values below 200 mg/dL [10]. A similar observation was noted in the Helsinki Heart Study. The Helsinki Heart Study found a threefold increased risk of cardiac events in subjects with a high LDL/HDL cholesterol ratio and TG greater than 200 mg/dL [36]. Previous studies have shown the independent role of abdominal obesity [25,37—39]. This study was designed to lend further insight into the role of hypertriglyceridemic waist phenotype on the risk of type 2 diabetes in American men and women. In this study, subjects with hypertriglyceridemic waist phenotype presented with poorer metabolic profiles such as elevated serum cholesterol and fasting blood glucose compared to non-hypertriglyceridemic waist subjects. The risk of type 2 diabetes as estimated from odds ratio was stronger for hypertriglyceridemic waist phenotype compared to abdominal obesity or hypertriglyceridemia in men and women. In men, the odds ratios for type 2 diabetes due to abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype were 1.59, 2.27 and 2.85, respectively. The corresponding values in women were 2.50, 2.14, and 2.58, respectively. The risk of type 2 diabetes due to hypertriglyceridemic waist phenotype was much
stronger in Black men (OR = 3.94) compared to White (OR = 1.24) and higher in Black women (OR = 5.62) compared to their White (OR = 1.36) counterparts. In this study, Black men (129.7 mg/dL) and Black women (110.7 mg/dL) had lower serum concentrations of TG compared to their White men (168.1 mg/ dL) and Black women (143 mg/dL). This finding is consistent with results of others [9,40]. The lower concentration of TG in Blacks compared to Whites may be explained by distinct racial/ethnic differences in lipoprotein lipase activity [8]. Lipoprotein is a key regulator of plasma TG levels and high concentrations of lipoprotein are associated with elevated TG levels [41]. Unlike Whites, where lipoprotein lipase activity is down graded in the presence of insulin resistance, in Blacks insulin resistance is not associated with a decrease in lipoprotein lipase activity [42]. The racial/ethnic differences in lipase activity may be one of the reasons for the concomitant presence of insulin resistance and low TG in Blacks. The independent role of abdominal adiposity for type 2 diabetes as shown in this study is consistent with the physiological and endocrinological bases of visceral adiposity [43—45]. Abdominal adiposity is a surrogate marker for visceral adiposity and is highly sensitive to lipolytic stimulation with diminished antilipolytic effect on cardiovascular diseases [45]. It has been shown that visceral fat depot is strongly regulated by endocrine mechanisms. Due to higher blood flow and abundant innervations, hormonal effects on adipose tissues are more pronounced in visceral
280 than other fat depots. Thus, any systemic change in available lipid substrate or hormone secretion has marked consequences on the visceral fat microenvironment [45]. Also, the density of hormone receptors is higher in visceral fat than in other depots [45]. The mechanism associated with the increased risk of type 2 diabetes due to coexistence of hypertriglyceridemia and abdominal obesity is not known and warrants investigation. To our knowledge, no studies have described the impact of hypertriglyceridemic waist phenotype in White and Black American adults. Understanding racial/ethnic differences in the association between risk factors and type 2 diabetes is vital for implementing efficient diabetes management in different population groups. Being nationwide and representative in scope, NHANES represents an excellent data source for investigating racial/ethnic risk factors for cardiovascular diseases. The quality control measures instituted in NHANES give an added credence to the data. Some limitations are noteworthy in the interpretation of results from this study. First, bias because of survey non-response and missing values for some variables cannot be ruled out. However, previous studies of NHANES have shown little bias because of non-response [46]. Second, several well-known factors that can have an impact on diabetes (e.g., diet and exercise) were not examined. Also, several genetic factors known to be associated with hypertriglyceridemia were not controlled for [47]. These unmeasured risk factors may have significant implications in the magnitude of the observed differences of the association between hypertriglyceridemic waist phenotype and diabetes. Third, as a cross-sectional study, cause and effect relationships cannot be established.
Conclusion Data from this national survey document that type 2 diabetes is associated with hypertriglyceridemic waist phenotype in American adults. The much higher odds for type 2 diabetes due to hypertriglyceridemic waist phenotype in Blacks suggests the need to develop strategies to reduce the prevalences of co-occurrence of hypertriglyceridemia and abdominal adiposity in these at-risk populations. Given the pervasive sedentary lifestyles and consumption of high fat foods in the US, particularly among non-Whites [48], it is reasonable to assume a much higher prevalence of this hypertriglyceridemic waist phenotype and its associated sequalae in the future. Racial/ethnic public health strategies to adequately enhance modification change necessary
I.S. Okosun, J.M. Boltri to reduce hypertriglyceridemia and abdominal obesity in this population may offer a way of reducing the risk of type 2 diabetes in the United States.
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Hypertriglyceridemic waist and diabetes [17] Haffner SM, Valdez RA, Hazed HP, Mitchell BD, Morales PA, Stern MP. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715—22. [18] Despres J-P. Abdominal obesity as an important component of insulin-resistance syndrome. Nutrition 1993;9: 452—545. [19] Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK, et al. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982;54:254—60. [20] Lamarche B, Tchernof A, Mauriege P, Cantin B, Dagenais GR, Lupien PJ, et al. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA 1998;279:1955—61. [21] Durrington PN. Seminar: dyslipidaemia. Lancet 2003;362: 717—31. [22] Onat A, Hergenc G, Karabulut A, Albayrak S, Can G, Kaya Z. Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women. Metabolism 2007;56:1356—62. [23] Lemieux I, Pascot A, Couillard C, Lamarche B, Tchernof A, Almeras N, et al. Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men? Circulation 2000;102:179—84. [24] St-Pierre J, Lemieux I, Perron P, Brisson D, Santure ´ M, Vohl MC, et al. Relation of the ‘‘hypertriglyceridemic waist’’ phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus. Am J Cardiol 2007;99:369—73. [25] Gazi IF, Filippatos TD, Tsimihodimos V, Saougos VG, Liberopoulos EN, Mikhailidis DP, et al. The hypertriglyceridemic waist phenotype is a predictor of elevated levels of small, dense LDL cholesterol. Lipids 2006;41:647—54. [26] Esmaillzadeh A, Mirmiran P, Azizi F. Clustering of metabolic abnormalities in adolescents with the hypertriglyceridemic waist phenotype. Am J Clin Nutr 2006;83:36—46. [27] National Institute of Health/National Heart Lungs and Blood. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults (1998). The Evidence Report. Obes Res 1998;6:51S—209S. [28] Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States 1999—2004. JAMA 2006;295:1549—55. [29] Ong KL, Cheung BM, Man YB, Lau CP, Lam KS. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999—2004. Hypertension 2007;49: 69—75. [30] http://www.cdc.gov/nchs/about/major/nhanes/ nhanes2003-2004/nhanes03_04.htm (assessed October 15, 2007). [31] Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002;55:65—85. [32] SAS . Institute. SAS Release 8. 02. Cary, NC: SAS Institute; 1999
281 [33] Shah BV, Barnwell BG, Bieler GS. SUDAAN User’s Manual. Research Triangle Park, NC: Research Triangle Institute; 1995. [34] Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic Research. Principles and Quantitative Methods. Belmont, CA: Livetime Learning Pub; 1988. [35] Burchfiel CM, Laws A, Benfante R, Goldberg RJ, Hwang LJ, Chiu D, et al. Combined effects of HDL cholesterol, triglyceride, and total cholesterol concentrations on 18-year risk of atherosclerotic disease. Circulation 1995;92:1430—6. [36] Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 2001;104:3046—51. [37] Okosun IS. Ethnic differences in the risk of type 2 diabetes attributable to differences in abdominal adiposity in American women. J Cardiovasc Risk 2000;7:425—4230. [38] Okosun IS, Boltri JM, Anochie LK, Chandra KM. Racial/ethnic differences in prehypertension in American adults: population and relative attributable risks of abdominal obesity. J Hum Hypertens 2004;18:849—55. [39] Okosun IS, Chandra KM, Choi S, Christman J, Dever GE, Prewitt TE. Hypertension and type 2 diabetes comorbidity in adults in the United States: risk of overall and regional adiposity. Obes Res 2001;9:1—9. [40] Brown SA, Hutchinson R, Morrisett J, Boerwinkle E, Davis CE, Gotto Jr AM, et al. Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb 1993;13:1139—58. [41] Eckel RH. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989;320:1060—8. [42] Eckel RH, Yost TJ, Jensen DR. Alterations in lipoprotein lipase in insulin resistance. Int J Obes Relat Metab Disord 1995;19(Suppl 1):S16—21. [43] Salans LB, Knittle JL, Hirsch J. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J Clin Invest 1968;47:153—65. [44] Bjorntorp P. Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Curr Opin Lipidol 1994;5:166—74. [45] Evans DJ, Murray R, Kissebah AH. Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding: effects of obesity and body fat topography. J Clin Invest 1984;74:1515—25. [46] Landis JR, Lepkowski JM, Eklund SA, Stehouwer SA. A statistical methodology for analyzing data from a complex survey: the first National Health and Nutrition Examination Survey. Vital Health Stat 1982;2(92):1—5. [47] Assmann B, Brewer HB. Genetic (primary) forms of hypertriglyceridemia. Am J Carliol 1991;68:13A—6A. [48] Atienza AA, Yaroch AL, Masse LC, Moser RP, Hesse BW, King AC. Identifying sedentary subgroups: the National Cancer Institute’s Health Information National Trends Survey. Am J Prev Med 2006;31:383—90.
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ORIGINAL PAPER
Abdominal obesity, hypertriglyceridemia, hypertriglyceridemic waist phenotype and risk of type 2 diabetes in American adults Ike S. Okosun a,*, John M. Boltri b a b
Institute of Public Health, Georgia State University, MSC 2A0875, Atlanta, GA 30303-6879, United States Department of Family Medicine, Mercer University School of Medicine, Macon, GA, United States KEYWORDS Triglyceride; Waist circumference; Abdominal obesity
Summary Background: Hypertriglyceridemic waist (HTGW) phenotype is a marker of atherogenesis whose association with cardiovascular diseases is unclear. Objective: To determine the association of abdominal obesity, hypertriglyceridemia and HTGW with risk of type 2 diabetes in American adults. Methods: Data (n = 1914) From the 2003—2004 United States National Health and Nutrition Examination Surveys (NHANESs) were used in this investigation. The risk of type 2 diabetes associated with HTGW was estimated using odds ratio from the logistic regression model, adjusting for race/ethnicity, age, body mass index (BMI), hypertension, HDL-cholesterol (HDL-C), smoking and alcohol intake. Results: There was a gender and racial/ethnic difference in the association of adiposity phenotypes with type 2 diabetes. In men, abdominal obesity, hypertriglyceridemia and HTGW were associated with 1.59 (95% CI: 1.09—2.79), 2.27 (95% CI: 1.42—3.62), and 2.85 (95% CI: 2.10—2.10) increased odds of type 2 diabetes. The analogous values in women were 2.50 (95% CI: 1.82—4.79), 2.14 (95% CI: 1.30—3.53), and 2.58 (95% CI: 1.48—4.24), respectively. HTGW was associated with 1.24 (95% CI: 1.05—2.39) and 3.94 (95% CI: 2.85—3.90) increased risks of type 2 diabetes. The corresponding risks in White women and Black women were 1.36 (95% CI: 1.23—2.91) and 5.62 (95% CI: 1.04—9.42), respectively. Conclusion: Hypertriglyceridemic waist phenotype is more strongly associated with type 2 diabetes than both hypertriglyceridemia and abdominal obesity alone. Well designed public health strategies to enhance lifestyle modification program to reduce the prevalence of HTGW may be a way to decrease racial/ethnic disparities for type 2 diabetes in the United States. # 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Tel.: +1 404 413 1113; fax: +1 404 413 1140. E-mail address: [email protected] (I.S. Okosun).
Elevated serum triglyceride (TG) and abdominal obesity are components of metabolic syndrome (MS) [1,2] whose joint role in cardiovascular
1871-4021/$ — see front matter # 2008 Diabetes India. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dsx.2008.04.003
274 diseases is uncertain. MS is pathophysiologically linked to insulin resistance [3,4]. While some studies have shown a positive association of TG with cardiovascular disease risk factors [5—7], others have shown a negative or lack of association [8—11]. Recent studies however, suggest that TG is an independent risk factor for cardiovascular diseases, leading to speculation about its potential role in identifying subjects at greater risk for coronary events [12,13]. Paradoxically, the prevalence of elevated TG is lower in cardiovascular disease high risk groups such as Blacks as compared to Whites [12—14]. Abdominal adiposity is an independent risk factor for cardiovascular diseases [15—18]. Abdominal adiposity is a gauge of the actual amount of total abdominal fat accumulation and a key correlate of visceral adiposity among obese and overweight subjects [19]. Because TG is a surrogate marker for a variety of atherogenic disturbances in lipoprotein moieties that are found in association with increased abdominal fat (marker of visceral fat) and insulin resistance such as type 2 diabetes [20—22], understanding the role of the joint occurrence of TG and abdominal obesity may provide very useful diabetes prevention clues. The comorbid condition consisting of elevated TG and large waist circumference (surrogate measure of abdominal obesity) was originally described by Lemieux et al. as hypertriglyceridemic waist (HTGW) phenotype [23]. Hypertriglyceridemia and abdominal adiposity are interrelated metabolic disorders [24—26]. TG is a key lipid in chylomicrons and very-low-density lipoprotein particles. A TG level of less than 200 mg/dL is considered normal, while values of 200—400, 401—1000, and 1001 mg/dL or greater are considered borderline, high and extremely high, respectively [7]. Abdominal adiposity is characterized by a waist circumference value of 94 cm or greater in men and 80 cm or greater in women [27]. HTGW is a marker of the atherogenic metabolic triad that consists of hyperinsulinemia, hyperapolipoprotenemia and small density low-density lipoprotein cholesterolemia [15—17]. Studies have shown that the cardiovascular disease risk attributable to glycemia may be explained by the co-occurrence of hypertriglyceridemia and abdominal adiposity [18]. Indeed, results of a study by Lemieux et al. (2000) indicates that in the absence of hypertriglyceridemia and abdominal adiposity comorbidity, hyperglycemia by itself is not predictive of cardiovascular disease risk [23]. A recent analysis of subjects with HTGW and glucose intolerance or type 2 diabetes indicate much earlier occurrences of coronary artery disease symptoms and higher risk for coronary artery disease (hazard
I.S. Okosun, J.M. Boltri ratio 2.0, 95% CI: 1.2—3.7) compared to those without the phenotype [19]. Determination of HTGW is cheap and easy, and a significant marker of cardiovascular disease manifestations at an earlier age in subjects with hyperglycemia, including glucose intolerance and type 2 diabetes [18—21]. To the best of our knowledge there is no study comparing the association of joint occurrence of abdominal obesity (waist circumference of 94 cm or greater in men, and 80 cm of greater in women), of hypertriglyceridemia (200 mg/dL or greater) and HTGW with type 2 diabetes in the US. The aim of this study was to determine the association of abdominal obesity, hypertriglyceridemia and their joint occurrence with risk of type 2 diabetes. We also sought to determine the effect of race/ethnicity on association of these adiposity phenotypes with risk of type 2 diabetes.
Methods Data source The United States National Center for Health Statistics (NCHS) provided the 2003—2004 NHANES data that were used in this study. The 2003—2004 NHANES was a cross-sectional survey carried out among the non-institutionalized US civilian population. Descriptions of the plan and operation of the surveys have been described by other investigators [28,29]. Briefly, the 2003—2004 NHANES conducted by NCHS was based on a complex, multi-stage sampling plan. Approximately 10,000 persons completed the survey that was designed to over sample Mexican Americans and non-Hispanic Blacks in order to improve estimates for these groups. The survey included an in-person home interview, followed by an interview/examination at a mobile examination center. In the survey, waist measurements were done with steel tape at the natural waist midpoint between the lowest aspect of the rib cage and highest point of the iliac crest to the nearest 0.1 cm [30]. Fasting TG was measured only in participants that were examined in the morning session. TG was measured enzymatically in plasma or serum using a sequence of coupled reactions in which TG is hydrolyzed to produce glycerol [30]. Glycerol is subsequently oxidized using glycerol oxidase, and hydrogen peroxide, one of the reaction products, is changed via peroxidase to a phenazone. TG absorbance was measured at 500 nm [30]. In NHANES, serum glucose level was also determined enzymatically in a series of chemical reactions that involves hexokinase and adenosine triphosphate to produce glucose-6-phosphate and other intermediaries [30].
Hypertriglyceridemic waist and diabetes Glucose concentration was measured using spectrophotometer at 340 nm [30]. Only subjects who were identified as non-Hispanic White and non-Hispanic Black Americans between 20 and 85 years old were included in this investigation. Subjects who were on hormones such as estrogen and those with renal diseases and drugs such as glucocorticoids were excluded from this study because these factors are associated with elevated TG values [7]. Those who were excluded due to missing variables of interest were not different from the population examined in our study.
Other variables included in the study Other variables from the 2003—2004 NHANES that were employed in this study include: systolic (SBP) and diastolic (DBP) blood pressure, HDL-cholesterol, total cholesterol, body mass index (BMI), smoking and alcohol intake. The protocol for blood pressure (BP) measurement in 2003—2004 NHANES was in accordance with standard procedures as developed by the American Heart Association. BP was measured three or four times manually by trained personnel using a mercury sphygmomanometer [30]. Excluding the first BP reading, the average of the remaining values was used for determining hypertension status in this study. Total cholesterol was measured enzymatically in serum in a series of coupled reactions that hydrolyze cholesteryl esters and oxidize the 3-OH group of cholesterol while HDL-cholesterol (HDL-C) was measured directly in serum. Height and weight were measured in a mobile examination center using standardized procedures and equipment. In this study BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). During the mobile examination center interview/ examination, participants were asked questions about smoking and alcohol use. Specifically, participants were asked if they had smoked at least 100 cigarettes in their lifetime. Those who responded in the affirmative were asked if they smoked ‘‘now’’. In this study, those who answered yes to the second question were considered as current smokers while others were considered as nonsmokers. Participants who were 20 years of age or older were also asked questions regarding usual alcohol consumption in the past year. In this study, participants who had consumed at least 12 drinks in any year or in their entire life, and had consumed alcohol on at least 1 day in the past year were considered as current drinkers. Those who had consumed at least 12 drinks in any year or in their entire life, and had not consumed alcohol in the past year and those who had no drinks at all in their lifetime were considered to be nondrinkers.
275
Definition of terms Hypertriglyceridemia was defined as TG levels of 200 mg/dL or greater [22]. Abdominal obesity was defined as waist circumference values of 94 cm or greater and 80 cm or greater in men and women, respectively [19]. Hypertriglyceridemic waist phenotype was defined as co-occurrence of hypertriglyceride, and abdominal obesity [18—21]. Type 2 diabetes was defined as diagnosed diabetes on insulin or other hypoglycemic agents or fasting blood glucose value 126 mg/dL or an oral tolerance test glucose level of 200 mg/dL [31]. Hypertension was defined as an average BP 140/90 mmHg or if the participant was taking antihypertensive medications or had been diagnosed with hypertension.
Statistical analysis Statistical programs that are available in SAS for Windows [32], and SUDAAN [33] were utilized in this analysis. To account for unequal probabilities of selection, over sampling, and non-response, appropriate sample weights were utilized for the analyses. Standard errors were estimated using the SUDAAN statistical program method [33]. All analysis were stratified by gender, and gender differences in age, waist circumference, lipids, and other continuous variables were assessed by independent ttests. Gender differences for frequency variables were determined by Pearson’s chi-square tests. Odds ratios from logistic regression analyses were used to estimate the risk of type 2 diabetes that was associated with abdominal obesity, hypertriglyceridemia and HGTW. Gender specific multivariate logistic regression analyses were used to determine the association of each adiposity phenotype with type 2 diabetes. In the analyses, type 2 diabetes was used as the dependent and independent variable. Effects of race/ethnicity were determined by statistically adjusting for race/ethnicity, including other covariates, including age, body mass index, hypertension, HDL-cholesterol, smoking, and alcohol intake. To determine the impact of abdominal obesity, hypertriglyceridemia, and HGTW on type 2 diabetes, we calculated race/ethnic specific population attributable risks. [34] The results of all analyses were evaluated for statistical significance using P <.05 and the 95% confidence intervals.
Results The basic characteristics of eligible men (n = 937) and women (n = 977) for this study are shown in Table 1. Men were taller and heavier, and presented
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Table 1 Characteristics of studied populations Variables
Men
Women
P-Value
n Age (y) Height (cm) Weight (kg) Waist (cm) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Triglyceride (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Abdominal obesity (%) Hypertriglyceridemia (%) Hypertriglyceridemic waist (%) Diabetes (%) Smoking (%) Alcohol use (%)
937 50.9 19.3 175.1 8.0 86.2 18.8 100.6 14.6 28.0 5.4 70.4 14.4 125.3 18.9 48.7 13.2 117.7 39.1 163.0 141.1 197.2 45.0 108.3 39.8 43.5 22.5 13.1 15.0 26.1 17.5
977 50.4 19.2 161.8 7.5 76.4 19.2 97.3 15.1 29.2 6.9 67.8 13.8 124.3 22.8 59.9 16.7 117.1 36.1 143.8 118 205.6 45.2 101.6 39.9 56.3 19.1 14.9 12.5 17.5 41.9
.629 <.001 <.001 <.001 <.001 <.001 .298 <.001 .734 <.001 <.001 <.001 <.001 .069 .253 .104 <.001 <.001
Race/ethnicity (%) White Black
80.5 19.5
79.3 20.7
.532
with larger waist girth compared to women (P <.001). Men also presented with higher values of DBP, triglyceride, and fasting blood glucose compared to women (P <.001). The prevalences of generalized obesity (body mass index of 30 kg/m2 or greater) abdominal obesity, alcohol intake, and blood concentrations of TG were higher in women compared to men (P <.001). In Table 2, anthropometric and clinical differences between subjects with hypertriglyceridemic waist phenotype were compared with those with abdominal obesity and hypertriglyceridemia and subjects without abdominal obesity or hypertriglyceridemia (normal). In men, subjects with hypertriglyceridemic waist phenotype were more obese and had higher values of fasting blood glucose compared with normal subjects and those with abdominal obesity or hypertriglyceridemia (P <.05). Prevalences of diabetes and alcohol use were also greater in subjects with hypertriglyceridemic waist phenotype than normal subjects and those with abdominal obesity and hypertriglyceridemia (P <.05). In women, subjects with hypertriglyceridemic waist phenotype also had higher values of body mass index and fasting blood glucose compared with normal subjects and those with abdominal obesity or hypertriglyceridemia (P <.05). The prevalences of diabetes and alcohol use were greater in subjects with hypertriglyceridemic waist phenotype as compared with normal subjects and those with either abdominal obesity or hypertriglyceridemia (P <.05).
We compared the association of abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype with risk of type 2 diabetes, in sexspecific multiple logistic regression models (Model I of Tables 3 and 4) adjusting for age, BMI, HDL-C, hypertension, smoking and alcohol intake. As shown (Table 3) the risk of type 2 diabetes differ by adiposity types. Abdominal obesity (OR = 1.59; 95% CI: 1.09—2.79), hypertriglyceridemia (OR = 2.27; 95% CI: 1.42—3.62) and hypertriglyceridemic waist phenotype (OR = 2.85; 95% CI: 2.10—3.11) were associated with increased odds of type 2 diabetes in men. As similar increased odds of type 2 diabetes due to abdominal obesity (OR = 2.50; 95% CI: 1.82— 4.79), hypertriglyceridemia (OR = 2.14; 95% CI: 1.30—3.53) and hypertriglyceridemic waist phenotype (OR = 2.58; 95% CI: 1.48—4.24) were also evident in women (Table 4). In order to determine the effect of race/ethnicity on the association between abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype with risk of type 2 diabetes, we further adjusted for race/ethnicity (coded as 1 = White, 2 = Black) in gender specific logistic regression analyses (Model II of Tables 3 and 4) adjusting for age, BMI, HDL-C, hypertension, smoking and alcohol intake. Compared to Whites, Black race/ethnicity was associated with increased odds of type 2 diabetes, adjusting for each adiposity phenotype and other independent variables. In men, adjusting for each adiposity phenotype, Black
Hypertriglyceridemic waist and diabetes
277
Table 2 Anthropometric and clinical differences between subjects with abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist in adult US population Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
Normal
Men n Age (y) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Diabetes (%) Smoking (%) Alcohol use (%)
408 54.6 17.4 32.3 4.6 72.4 15.2 127.4 17.2 45.0 10.8 119.3 34.2 200.6 43.4 115.5 47.1 22.5 20.6 19.0
211 52.8 17.1 29.7 5.2 71.0 16.3 125.2 19.2 39.8 8.9 122.1 52.0 221.0 56.7 124.2 64.2 26.1 30.3 16.8
123 55.2 16.4 32.6 4.5 73.0 16.4 127.6 18.0 39.7 8.3 117.2 32.6 220.4 51.2 129.0 69.7 31.7 24.4 21.2
440 47.9 20.7 24.6 3.2 69.1 13.1 124.0 19.4 54.0 13.9 114.5 35.7 189.2 39.6 99.7 24.1 7.5 28.8 17.4
Women n Age (y) BMI (kg/m2) DBP (mmHg) SBP (mmHg) HDL-C (mg/dL) LDL-C (mg/dL) Total cholesterol (mg/dL) Fasting glucose (mg/dL) Diabetes (%) Smoking (%) Alcohol use (%)
550 52.0 18.7 33.0 6.2 69.0 13.7 126.8 22.2 55.8 15.1 120.2 36.9 208.7 47.3 107.8 37.3 18.5 16.7 44.6
187 53.2 19.1 31.1 6.2 67.9 17.0 129.2 23.9 51.3 14.3 125.4 45.9 234.2 58.6 111.1 41.7 12.5 15.5 47.5
146 51.8 19.6 33.3 5.6 68.0 15.3 127.7 22.7 50.1 13.7 124.8 46.0 231.9 60.1 11.4.8 45.1 26.0 15.1 47.9
386 47.2 19.7 23.8 3.1 66.2 12.8 119.7 22.3 66.2 17.0 111.6 34.8 199.0 38.4 93.1 24.0 4.1 18.7 37.4
race/ethnicity was associated with approximately twofold increased odds of type 2 diabetes compared to White men, and in women approximately threefold increased odds type 2 diabetes compared to White women. We estimated the impact of race/ ethnicity on the relationship between each adiposity phenotype and risk of type 2 diabetes by comparing Model I with Model 2. In men, adjustment for race/ethnicity was associated with 8.8, 5.7 and 2.1% greater odds of type 2 diabetes that may be attributable to abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist phenotype, respectively. The corresponding values in women were 4.4, 7.9 and 5.0%, respectively. Race/ethnic and gender specific associations of hypertriglyceridemic waist phenotype with risk of type 2 diabetes were determined, adjusting for age, BMI, HDL-C, hypertension, smoking, and alcohol intake (Table 5). In both men and women, hypertriglyceridemic waist phenotype was significantly associated with increased odds of type 2 diabetes in the total population, adjusting for confounding variables. In White men and Black men, hypertriglyceridemic waist phenotype was also associated with increased odds of type 2 diabetes, adjusting for age,
BMI, HDL-C, hypertension, smoking, and alcohol intake. The greatest risk of type 2 diabetes was in Black men (OR = 3.94; 95% CI: 2.85—3.90) compared to White men (OR = 1.24; 95% CI: 1.05—2.39). Among women, the greatest risk of type 2 diabetes was also in Black women (OR = 5.62; 95% CI: 1.04— 9.42) compared to White (OR = 1.36; 95% CI: 1.23— 2.91) women. Similar to the results of the association between abdominal adiposity, hypertriglyceridemia, and hypertriglyceridemic waist phenotype with type 2 diabetes, increased age and BMI were also associated with increased risk of type 2 diabetes in White and Black men and women.
Discussion The independent and combined roles of TG and abdominal adiposity in the development of cardiovascular diseases are unclear. Although some studies have described the independent roles of these metabolic profiles in cardiovascular diseases, findings have been inconsistent. The Honolulu Heart Program found that the risk of cardiovascular disease was amplified in subjects with low HDL-cholesterol and elevated TG
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Table 3 Impact of race/ethnicity in the association of abdominal adiposity, hypertriglyceridemia and hypertriglyceridemic waist with type 2 diabetes in men Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
OR
[95% CI]
OR
[95% CI]
OR
[95% CI]
Model I Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
1.59 1.06 1.07 0.99 0.76 1.51 1.04
1.09—2.79 1.04—1.07 1.02—1.13 0.97—1.01 0.48—1.21 0.90—2.54 0.63—1.73
2.27 1.06 1.10 1.00 0.75 1.45 1.07
1.42—3.62 1.04—1.07 1.05—1.14 0.99—1.02 0.47—1.20 0.87—2.43 0.64—1.79
2.85 1.06 1.09 0.99 0.75 1.47 1.02
2.10—3.11 1.04—1.07 1.05—1.14 0.98—1.01 0.47—1.19 0.88—2.46 0.61—1.69
Model II Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
1.73 1.06 1.07 0.99 0.72 1.41 1.09
1.43—5.33 1.04—1.07 1.04—1.12 0.98—1.01 0.58—1.51 1.05—3.54 0.66—1.58
2.40 1.06 1.10 0.99 0.70 1.34 1.10
1.50—3.86 1.04—1.08 1.05—1.14 0.98—1.01 0.44—1.13 0.80—2.27 0.65—1.85
2.91 1.06 1.09 0.99 0.70 1.37 1.06
2.18—3.41 1.05—1.08 1.05—1.13 0.97—1.01 0.43—1.12 0.81—2.30 0.63—1.77
Race/ethnicity b Black
1.94
1.11—3.41
2.09
1.19—3.68
2.00
1.14—3.52
a
Abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist; OR, odds ratio, CI, confidence intervals from multivariate logistic regression models. b Reference group was White; Model II, adjustment for race/ethnicity.
Table 4 Impact of race/ethnicity in the association of abdominal adiposity, hypertriglyceridemia and hypertriglyceridemic waist with type 2 diabetes in women Variables
Abdominal obesity
Hypertriglyceridemia
Hypertriglyceridemic waist
OR
[95% CI]
OR
[95% CI]
OR
[95% CI]
Model I Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
2.50 1.05 1.04 0.99 0.78 1.84 1.03
1.82—4.79 1.04—1.07 1.00—1.08 0.98—1.01 0.60—1.08 1.00—3.39 0.66—1.61
2.14 1.06 1.09 1.00 0.92 2.08 1.04
1.30—3.53 1.04—1.07 1.05—1.13 0.98—1.01 0.57—1.49 1.13—3.84 0.67—1.61
2.58 1.06 1.09 0.99 0.92 2.09 1.04
1.48—4.24 1.04—1.07 1.05—1.12 0.98—1.01 0.57—1.49 1.13—3.85 0.67—1.61
Model II Phenotype a Age BMI HDL-C Hypertension Smoking Alcohol intake
2.61 1.06 1.03 0.99 0.80 2.21 0.97
1.79—3.62 1.05—1.08 0.99—1.07 0.98—1.01 0.48—1.32 1.17—4.18 0.61—1.52
2.31 1.06 1.08 0.99 0.74 2.55 0.98
1.37—3.90 1.05—1.09 1.04—1.12 0.98—1.01 0.45—1.21 1.35—4.81 0.63—1.54
2.71 1.06 1.07 0.99 0.73 2.54 0.98
1.57—4.67 1.05—1.09 1.03—1.11 0.98—1.01 0.44—1.21 1.35—4.80 0.62—1.54
Race/ethnicity b Black
2.78
1.54—5.00
3.15
1.74—5.70
3.16
1.75—5.71
a
Abdominal obesity, hypertriglyceridemia, and hypertriglyceridemic waist; OR, odds ratio, CI, confidence intervals from multivariate logistic regression models. b Reference group was White; Model II, adjustment for race/ethnicity.
Hypertriglyceridemic waist and diabetes
279
Table 5 Association between hypertriglyceridemic waist phenotype and type 2 diabetes in white, and black American adults Variables
White
Black
OR
[95% CI]
OR
[95% CI]
Men Hypertriglyceridemic waist Age BMI HDL-C Hypertension Smoking Alcohol intake
1.24 1.06 1.09 0.97 0.85 1.21 0.71
1.05—2.39 1.04—1.08 1.03—1.15 0.94—1.00 0.44—1.63 0.54—2.73 0.39—1.61
3.94 1.07 1.09 1.02 0.30 2.99 3.53
2.85—3.90 1.04—1.11 1.01—1.19 0.99—1.07 0.21—1.15 0.91—9.85 1.12—5.14
Women Hypertriglyceridemic waist Age BMI HDL-C Hypertension Smoking Alcohol intake
1.36 1.06 1.06 0.99 0.70 1.29 1.39
1.23—2.91 1.03—1.09 1.01—1.12 0.96—1.01 0.32—1.52 0.51—3.26 0.72—2.69
5.62 1.10 1.12 1.02 0.69 6.07 0.53
1.04—9.42 1.06—1.15 1.03—1.21 0.99—1.06 0.23—2.07 1.50—9.48 0.17—1.62
OR, odds ratio, CI, confidence intervals from multivariate logistic regression models.
when the total cholesterol level was borderline high or elevated [35]. However, the Prospective Cardiovascular Munster Study, which investigated the risk of coronary artery disease in more than 4500 men, found that TG was not an independent predictor of risk [10]. In the study, subjects with TG serum concentrations of 200 mg/dL or greater had more than two times the number of coronary artery disease events as those with TG values below 200 mg/dL [10]. A similar observation was noted in the Helsinki Heart Study. The Helsinki Heart Study found a threefold increased risk of cardiac events in subjects with a high LDL/HDL cholesterol ratio and TG greater than 200 mg/dL [36]. Previous studies have shown the independent role of abdominal obesity [25,37—39]. This study was designed to lend further insight into the role of hypertriglyceridemic waist phenotype on the risk of type 2 diabetes in American men and women. In this study, subjects with hypertriglyceridemic waist phenotype presented with poorer metabolic profiles such as elevated serum cholesterol and fasting blood glucose compared to non-hypertriglyceridemic waist subjects. The risk of type 2 diabetes as estimated from odds ratio was stronger for hypertriglyceridemic waist phenotype compared to abdominal obesity or hypertriglyceridemia in men and women. In men, the odds ratios for type 2 diabetes due to abdominal obesity, hypertriglyceridemia and hypertriglyceridemic waist phenotype were 1.59, 2.27 and 2.85, respectively. The corresponding values in women were 2.50, 2.14, and 2.58, respectively. The risk of type 2 diabetes due to hypertriglyceridemic waist phenotype was much
stronger in Black men (OR = 3.94) compared to White (OR = 1.24) and higher in Black women (OR = 5.62) compared to their White (OR = 1.36) counterparts. In this study, Black men (129.7 mg/dL) and Black women (110.7 mg/dL) had lower serum concentrations of TG compared to their White men (168.1 mg/ dL) and Black women (143 mg/dL). This finding is consistent with results of others [9,40]. The lower concentration of TG in Blacks compared to Whites may be explained by distinct racial/ethnic differences in lipoprotein lipase activity [8]. Lipoprotein is a key regulator of plasma TG levels and high concentrations of lipoprotein are associated with elevated TG levels [41]. Unlike Whites, where lipoprotein lipase activity is down graded in the presence of insulin resistance, in Blacks insulin resistance is not associated with a decrease in lipoprotein lipase activity [42]. The racial/ethnic differences in lipase activity may be one of the reasons for the concomitant presence of insulin resistance and low TG in Blacks. The independent role of abdominal adiposity for type 2 diabetes as shown in this study is consistent with the physiological and endocrinological bases of visceral adiposity [43—45]. Abdominal adiposity is a surrogate marker for visceral adiposity and is highly sensitive to lipolytic stimulation with diminished antilipolytic effect on cardiovascular diseases [45]. It has been shown that visceral fat depot is strongly regulated by endocrine mechanisms. Due to higher blood flow and abundant innervations, hormonal effects on adipose tissues are more pronounced in visceral
280 than other fat depots. Thus, any systemic change in available lipid substrate or hormone secretion has marked consequences on the visceral fat microenvironment [45]. Also, the density of hormone receptors is higher in visceral fat than in other depots [45]. The mechanism associated with the increased risk of type 2 diabetes due to coexistence of hypertriglyceridemia and abdominal obesity is not known and warrants investigation. To our knowledge, no studies have described the impact of hypertriglyceridemic waist phenotype in White and Black American adults. Understanding racial/ethnic differences in the association between risk factors and type 2 diabetes is vital for implementing efficient diabetes management in different population groups. Being nationwide and representative in scope, NHANES represents an excellent data source for investigating racial/ethnic risk factors for cardiovascular diseases. The quality control measures instituted in NHANES give an added credence to the data. Some limitations are noteworthy in the interpretation of results from this study. First, bias because of survey non-response and missing values for some variables cannot be ruled out. However, previous studies of NHANES have shown little bias because of non-response [46]. Second, several well-known factors that can have an impact on diabetes (e.g., diet and exercise) were not examined. Also, several genetic factors known to be associated with hypertriglyceridemia were not controlled for [47]. These unmeasured risk factors may have significant implications in the magnitude of the observed differences of the association between hypertriglyceridemic waist phenotype and diabetes. Third, as a cross-sectional study, cause and effect relationships cannot be established.
Conclusion Data from this national survey document that type 2 diabetes is associated with hypertriglyceridemic waist phenotype in American adults. The much higher odds for type 2 diabetes due to hypertriglyceridemic waist phenotype in Blacks suggests the need to develop strategies to reduce the prevalences of co-occurrence of hypertriglyceridemia and abdominal adiposity in these at-risk populations. Given the pervasive sedentary lifestyles and consumption of high fat foods in the US, particularly among non-Whites [48], it is reasonable to assume a much higher prevalence of this hypertriglyceridemic waist phenotype and its associated sequalae in the future. Racial/ethnic public health strategies to adequately enhance modification change necessary
I.S. Okosun, J.M. Boltri to reduce hypertriglyceridemia and abdominal obesity in this population may offer a way of reducing the risk of type 2 diabetes in the United States.
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