ABSTRACT This review examines whether the relations and

Relation between visceral fat and disease risk in children and
adolescents1–3
Michael I Goran and Barbara A Gower
KEY WORDS
Fat distribution, visceral fat, subcutaneous
fat, intraabdominal adipose tissue, subcutaneous abdominal
adipose tissue, diabetes, cardiovascular disease, heart disease,
dyslipidemia, obesity, development, metabolic risk, disease risk,
children, adolescents, ethnicity, syndrome X
INTRODUCTION
The prevalence of obesity among US children is <22–30%
(1, 2) and has increased at an accelerated rate in the past several years (2, 3). In addition, the prevalence of obesity is > 30%
in some pediatric populations (3, 4). Among schoolchildren in
Birmingham, Alabama (4), the prevalence of obesity (defined
as body weight > 120% of ideal body weight) at age 10 y was
21% in white boys and girls, 26% in African American boys,
and 38% in African American girls. Although the immediate
health implications of childhood obesity have not been examined extensively, obesity in childhood is associated with obesity in adulthood (5, 6), which in turn is associated with
increased morbidity (7), cardiovascular disease (CVD) (8), and
type 2 diabetes (9).
Epidemiologic evidence supports the theory that the relation
between obesity and disease risk begins early in life. For example, in young adults who died in accidents, fatty streaks in the
coronary arteries and aorta that were found at autopsy were
associated with blood lipid profile, blood pressure, and obesity
status obtained at one or more points antemortem (10, 11). Addi-
tional longitudinal data from the Bogalusa Heart Study indicate
that the occurrence of overweight, hypertension, and dyslipidemia in young adults (aged 19–32 y) was associated with these
same risk factors in childhood. More recently, data from Children’s Hospital Medical Center in Cincinnati showed that the
incidence of type 2 diabetes among adolescents increased
10-fold from 1982 to 1994 and virtually all diagnosed cases of
type 2 diabetes occurred in obese individuals (12). These observations are likely to reflect national trends. The group with the
highest prevalence of adolescent type 2 diabetes was African
American females, a group that also showed an increase in obesity (assessed by body mass index) over the study period. Thus,
the evidence indicates that obesity-related disease can begin in
childhood and that risk factors for disease track, or remain at a
similar level, with advancing age, growth, and development.
Adipose tissue stores are heterogeneous with respect to metabolic activity and relation to disease risk. In adults, intraabdominal adipose tissue (IAAT), or visceral fat (body fat located within
the abdominal cavity around the visceral organs), has emerged as
the clinically relevant type of body fat independent of total body
fat (13, 14). The metabolic complications and adverse health
effects of increased IAAT include insulin resistance, type 2 diabetes, dyslipidemia, and CVD (14–17). The relation between
obesity and disease was noted as early as 100–200 BC by
Samhita and Ayurveda, who observed the relation between glycosuria, obesity, and lifestyle (18). In 1717, Morgagni noted the
android fat pattern in the corpse of a woman (19) and in 1947,
Vague described the metabolic risk of android obesity as compared with the protective nature of gynoid obesity (19). With the
use of imaging techniques for direct measurement of IAAT (20),
Kissebah et al (15), Després et al (16, 17), Björntorp (14), and
Vague et al (19) reported in the 1980s and early 1990s that
1
From the Division of Physiology and Metabolism, Department of Nutrition Sciences, University of Alabama at Birmingham.
2
Supported by the National Institute of Child Health and Human Development (R29 HD-32668 and RO1 HD/HL 33064); the US Department of
Agriculture (95-37200-1643); the National Institute on Aging (KO1 AG
00740); and in part by the General Clinical Research Center at the University
of Alabama at Birmingham.
3
Address reprint requests to MI Goran, Division of Physiology and
Metabolism, Department of Nutrition Sciences, University of Alabama at
Birmingham, Birmingham, AL 35294–3360. E-mail: [email protected]
Am J Clin Nutr 1999;70(suppl):149S–56S. Printed in USA. © 1999 American Society for Clinical Nutrition
149S
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ABSTRACT
This review examines whether the relations and
metabolic parameters necessary for the development of syndrome
X are present in children and whether the metabolic complications
of obesity in children are explained by excess intraabdominal
adipose tissue (IAAT), or visceral fat. Despite the limited use of
imaging techniques in research studies, an increasing number of
studies reported on IAAT and its relation to disease risk in
children and adolescents. For this article we reviewed studies that
documented the early accumulation of IAAT in children and
adolescents and the factors that contribute to variation in the
degree of IAAT accumulation. We also reviewed studies that
showed the clinical relevance of IAAT in children and adolescents
through significant relations with adverse health effects including
dyslipidemia and glucose intolerance in obese and nonobese
children and adolescents of different ethnic groups.
Am J Clin
Nutr 1999;70(suppl):149S–56S.
150S
GORAN AND GOWER
REVIEW OF THE LITERATURE
Measurement of intraabdominal adipose tissue
Because IAAT lies within the abdominal cavity it can only be
directly quantified with imaging techniques. Both computed
tomography (CT) and magnetic resonance imaging (MRI) have
been used in children and adolescents for this purpose (32–35).
With these approaches, adipose tissue is measured in terms of
cross-sectional area (cm2) or volume (cm3). Because these techniques are expensive and CT involves radiation exposure, IAAT
is often measured in a single, cross-sectional slice at an anatomic
landmark, usually the level of the umbilicus or the L3–L4 disk
space. The major advantages of these imaging techniques are the
high resolution of the images and the capability to identify small
deposits of IAAT. In addition, subcutaneous abdominal adipose
tissue (SAAT) is also accurately quantified at the same time.
Some investigators have used multiple-slice CT to measure adipose tissue in multiple slices of the abdominal area or across the
whole body (36) to determine adipose tissue volume. There is
some concern that a single slice of the abdomen may not reflect
total IAAT content (37), and further studies in children and adolescents are needed to explore this issue. Indirect measures of
IAAT include dual energy X-ray absorptiometry (DXA) to measure fat mass in the trunk region and anthropometric measures
(circumferences and skinfold thicknesses). The relations between
IAAT and these indirect measures are reviewed in greater detail
later in this article.
Factors that influence intraabdominal adipose tissue
It is currently unclear whether the amount of IAAT accumulation seen in children is appropriate for their body size, and
whether the observed extremes are related to extremes of general
body fatness. For example, some studies suggest that IAAT in
children increases in proportion to overall fatness (34) as measured in adults (38), whereas other studies showed that obese children tend to accumulate subcutaneous fat and not IAAT (33).
In healthy young children (aged 6.4 ± 1.2 y; 24.8 ± 5.4 kg),
mean IAAT at the level of the umbilicus was 8.3 ± 5.8 cm2 and
mean SAAT was 65.3 ± 44.8 cm2 as measured by CT scanning
(34). In 101 African American and white obese and nonobese
children (aged 7.5 ± 1.7 y; 33.0 ± 12.2 kg body weight; 30 ± 11%
body fat), IAAT averaged 30.0 ± 23.0 cm2 and varied greatly
from 6 to 102 cm2 (35). SAAT averaged 101 ± 95 cm2 and also
varied greatly (range: 8–372 cm 2). When MRI was used in
healthy 11- and 13-y-old girls, IAAT at the level of the umbilicus was 24.1 ± 4.1 and 25.7 ± 4.1 cm2, respectively (39). In a
study of 11-y-olds, IAAT was 17.8 ± 10.0 and 24.8 ± 8.8 cm2 in
boys and girls, respectively (33). These values in children and
adolescents compare with typical values of 100–120 cm 2 of
IAAT in healthy nonobese adults (38), although it is difficult to
compare absolute amounts because of differences in body size.
Total fat mass is an important determinant of IAAT (38). It is
currently unclear whether increasing adiposity in children and
adolescents is related to increasing deposition of IAAT. Fox et al
(33) found that differences in adiposity between obese and
nonobese children are predominately found in SAAT; in obese as
compared with control adolescents, the majority of excess abdominal adipose tissue was subcutaneous (353 ± 94 and 79 ± 61 cm2,
respectively), although IAAT was still greater in the obese than
the control children (49 ± 21 and 22 ± 11 cm2, respectively). It is
clear that a portion of the variance in IAAT is explained by total
fat mass, although interpretation of findings is complicated by
strong multicollinearity among IAAT, SAAT, and total body fat
(36). In 101 prepubertal children, the correlation between IAAT
and total fat was 0.81 (36), similar to that seen in 206 adult
women (40). However, the relation between IAAT and total body
fat is not significant after adjusting for SAAT and there is no
relation between IAAT and percentage body fat (35). Thus, the
relation between IAAT and body fat may be explained by multicollinearity, and a major portion of the variance in IAAT is independent of total body fat.
Ethnicity is known to affect fat distribution. Results from previous studies that used anthropometric measures suggested that
African Americans, Mexican Americans, and Mohawk Indians
have more central fat than whites (41, 42). Because prior studies of
ethnic differences in fat distribution have been limited to skinfold thickness data, it is not known whether the findings represent differences in SAAT or IAAT. More recent data based on
direct measurement of IAAT in women (37) and prepubertal
children (43, 35) suggest, however, that African Americans have
less IAAT and that this is apparent early in life. However, the
important issue in terms of health risk is whether ethnicity influences the strength or magnitude of the relations between IAAT
and the subsequent development of disease risk factors as discussed later in this article.
The hormonal environment plays a key role in determining
body fat distribution (44). Because sex hormones are known to
affect regional fat deposition (45), the changing hormonal environment during puberty may contribute to the development of sex
differences and large individual changes in fat distribution (32,
46). To date, no studies have used imaging to track or compare
children at different stages of maturation and relate differences in
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excess IAAT explains the relation between obesity and metabolic
complications in adults.
The mechanism or mechanisms underlying the relations among
obesity, IAAT, insulin action, and dyslipidemia are unknown. In
1988, Reaven (21) characterized the interrelations of insulin resistance, dyslipidemia, and hypertension as syndrome X; this description was later expanded to include excess IAAT (22). However, the
specific effects of excess IAAT have not yet been identified and it
is also unknown whether insulin resistance precedes and causes
dyslipidemia or vice versa. It was postulated that because IAAT is
more sensitive to lipolytic stimuli than is adipose tissue stored at
other sites, turnover of triacylglycerols and release of fatty acids
into the portal circulation are increased. Increased hepatic release
of fatty acids leads to excess hepatic exposure to fatty acids, which
may increase hepatic gluconeogenesis and secretion of LDLs and
inhibit hepatic clearance of insulin, leading to hyperinsulinemia
and peripheral insulin resistance (14). In prospective studies, fasting hyperinsulinemia was a risk factor for future metabolic abnormalities (23) and for ischemic heart disease in men, independent of
altered lipid levels (24). On the other hand, some research suggested that inherent abnormalities in fat oxidation in the obese state
cause changes in insulin sensitivity (25). According to the Randle
hypothesis (26), an increase in fat oxidation reduces the need for
glucose oxidation leading to reduced glucose uptake and insulin
resistance. However, there is controversy concerning the existence
of an inherent abnormality in fat oxidation in the obese state. Some
studies support the theory that there is an alteration in fat oxidation
due to obesity (27, 28) whereas others do not (29–31).
VISCERAL FAT AND DISEASE RISK
151S
and the ratio of trunk-to-extremity skinfold thicknesses explain
62% of the variation in IAAT. In adolescent girls, there were no
significant correlations between IAAT area as measured by MRI
and either waist circumference, waist-to-hip ratio, or trunk-toextremity skinfold thickness ratio (39). Similarly, in 11-y-old boys
and girls, waist-to-hip ratio was not significantly correlated with
IAAT (33). In these studies of adolescents, anthropometric indexes
explained only 25–50% of the variation in IAAT (33, 39).
In 101 prepubertal white and African American children the
strongest anthropometric correlates of IAAT were abdominal
skinfold thickness (r = 0.88), subscapular skinfold thickness
(r = 0.85), suprailiac skinfold thickness (r = 0.85), and waist circumference (r = 0.84); the strongest correlates of SAAT were
waist circumference (r = 0.93), triceps skinfold thickness
(r = 0.92), abdominal skinfold thickness (r = 0.91), suprailiac
skinfold thickness (r = 0.91), and axillary skinfold thickness
(r = 0.84) (36). There were much lower correlations between
IAAT or SAAT and the traditional indexes of central fat distribution, such as trunk-to-extremity skinfold thickness ratio (r = 0.49
for IAAT; r = 0.50 for SAAT) and waist-to-hip ratio (r = 0.32 for
IAAT; r = 0.40 for SAAT). In forward multiple regression analysis, abdominal skinfold thickness, ethnicity, and subscapular
skinfold thickness explained 82% of the variance in IAAT whereas
waist circumference, subscapular skinfold thickness, height, and
abdominal skinfold thickness explained 92% of the variance in
SAAT. Based on this information, prediction equations were
developed that estimated accurately IAAT and SAAT as measured
by CT in an independent sample of 12 children (36).
DXA measurements of total abdominal fat do not distinguish
SAAT from IAAT. IAAT has been estimated in adults with reasonable accuracy by combining measures of total abdominal fat
by DXA with skinfold thickness and anthropometric data (as an
index of subcutaneous fat) (40, 60). In 101 prepubertal children,
the combination of trunk and total fat by DXA and abdominal
skinfold thickness predicted IAAT as measured with CT scanning (model R2, 0.85; SEE, ± 9 cm2) (36). However, this approach
only marginally improved the prediction power of the anthropometric equation that included abdominal skinfold thickness, ethnicity (white compared with African American), and subscapular
skinfold thickness (model R2, 0.82; SEE, ± 10 cm2).
Thus, combinations of skinfold thicknesses and circumferences can be modeled to yield relatively accurate estimates of
IAAT and SAAT in the absence of direct measurement by imaging techniques. The addition of regional measures of trunk fat by
DXA only marginally improves the prediction of IAAT.
Relation between IAAT and anthropometric indexes
Regional adiposity and insulin action in children and
adolescents
CT and MRI are accurate imaging techniques for assessing
body fat distribution, but their disadvantages are cost, radiation
exposure (for CT), and limited availability outside of research
settings. Thus, based on the relation between IAAT and anthropometric measures, other indirect indicators of body fat distribution were used. For example, in adults the waist-to-hip ratio and
waist circumference are often used as markers of IAAT (58, 59).
However, in children (34) and adolescents (33, 39) the correlation between these markers and IAAT as measured by imaging
techniques is not strong. To identify an accurate alternative
index, it is important to study the relations between IAAT and
both anthropometry and body composition.
In young children (34) waist-to-hip ratio is not significantly correlated with IAAT, whereas individual trunk skinfold thicknesses
In general, obesity in children and adolescents is related to
differences in insulin action. Although relatively few studies
have examined fat distribution in children, epidemiologic data
from the Bogalusa Heart Study provide evidence of a link
between central body fat (measured by skinfold thicknesses) and
fasting insulin level (61). Research with predominantly obese
white adolescents indicated that IAAT is associated with both
insulin secretion and insulin sensitivity. Among 21 obese children and adolescents (62), IAAT assessed with MRI (x– ± SD:
49 ± 21 cm2) tended to be associated with insulin area-under-thecurve (AUC) during an oral glucose tolerance test (OGTT) (r = 0.44,
P = 0.07). In contrast, SAAT was not associated with insulin
AUC (r = 0.04, P = 0.88). Neither index of central adiposity
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fat distribution to hormone concentrations. However, cross-sectional
studies that used DXA showed that during growth, white girls
store more fat in the trunk than girls of other ethnic backgrounds
as adiposity increases (47). Also, when comparing girls of different Tanner pubertal stages (48), it was shown that puberty was
associated with greater gains in fat than lean tissue and the accumulation of fat was greatest in the trunk region.
The earlier onset of puberty in the United States (49) implies
that the development of an adult body-fat pattern will occur at an
accelerated pace and that this in turn may lead to earlier onset of
diseases of adulthood.
The influence of dietary factors on IAAT accumulation has not
been extensively studied. One study of healthy, white, nonobese
men examined the relations between CT measures of IAAT and
SAAT and dietary factors (50). Fat intake explained only 2% of
the variance in general adiposity after adjusting for fat-free mass,
age, sex, physical activity, and intake of energy from nutrients
other than fat. Dietary fat accounted for only 1.4% of the variance
in SAAT (and this effect disappeared after adjusting for age, sex,
and physical activity) and none of the variance in IAAT before or
after adjustment (50). Thus, in agreement with other studies
reviewed by Lissner and Heitmann (51), dietary fat appears to play
a minor role in determining general adiposity and is not related to
IAAT when measured in cross-sectional studies (50). We are not
aware of any studies of the link between diet and regional adiposity in children and adolescents based on direct measures of IAAT.
Finally, physical activity is an important determinant of IAAT.
In adults, physical inactivity is associated with elevated IAAT
(13, 52, 53) and IAAT is selectively reduced after aerobic (54)
and strength-training exercise (55). In adults, the effect of physical inactivity on CVD risk factors is mediated in part by the
effects of inactivity on IAAT (56). To our knowledge, only 2 studies of children or adolescents examined the interrelations among
physical activity, IAAT, and increased risk of disease by using
sophisticated measurement techniques. In an intervention study
in obese girls, strength training (3 times/wk for 5 mo) had no
effect on IAAT despite significant increases in body weight, total
body fat, and SAAT (57). In another study in 7–11-y-old obese
children there was no significant change in IAAT but a significant
loss of SAAT after a 4-mo aerobic training program, whereas
there were significant increases in both IAAT and SAAT in a control group that received no exercise intervention (B Gutin, unpublished observations, 1998). Thus, both strength training and aerobic exercise appear to slow the time-related increase in IAAT in
obese children.
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GORAN AND GOWER
TABLE 1
Summary of studies that examined relations between adiposity and metabolic risk factors by using direct measures of IAAT and SAAT in children and
adolescents1
Study
Major findings
Brambilla et al (62)
21 white obese children and adolescents
(aged 10–15 y)
Caprio et al (63, 67)2,4
13 obese and 9 nonobese adolescent girls
Yanovski et al (43)2,3,5
40 normal-weight white and African
American 7–10-y-old girls
74 obese and nonobese white and African
American prepubertal boys and girls
IAAT but not SAAT was associated with insulin AUC (P = 0.07), IAAT and
SAAT were not correlated with fasting insulin concentration, and IAAT but
not SAAT was related to blood lipid concentrations.
In obese subjects, IAAT correlated with fasting insulin concentration, insulin
secretion, and insulin sensitivity; IAAT was related to triacylglycerol (+)
and HDL cholesterol (2) concentrations; and SAAT was related to LDL
cholesterol concentration (2).
In nonobese subjects, IAAT was not related to any index of insulin action and
SAAT was related to insulin-stimulated glucose metabolism.
In African Americans, SAAT but not IAAT was related to basal and 2-h insulin
concentrations. In whites, SAAT and IAAT were not related to insulin action.
IAAT, SAAT, and total fat were all correlated with all parameters of insulin
action; total fat was related to fasting insulin concentration independent of
IAAT and SAAT; SAAT was related to insulin AUC independent of total fat
and IAAT; and IAAT was related to 30-min insulin concentration independent
of SAAT and total fat (only in whites). Ethnicity effects: Fasting and 30-min
insulin concentrations and insulin AUC were higher in African Americans
independent of any adiposity index.
Gower et al (64)3,5,6
1
IAAT, intraabdominal adipose tissue; SAAT, subcutaneous abdominal adipose tissue; MRI, magnetic resonance imaging; CT, computed tomography;
DXA, dual energy X-ray absorptiometry; OGTT, oral glucose tolerance test; AUC, area-under-the-curve.
2–6
Study methods included measurement of: 2 IAAT and SAAT by MRI, 3 insulin action by OGTT, 4 insulin action by hyperglycemic and euglycemic
clamps, 5 total fat by DXA, and 6 IAAT and SAAT by CT.
was associated with fasting insulin. Among 13 obese adolescents, IAAT assessed with MRI (x– ± SEM for total volume = 160 ± 16 cm3), but not SAAT, was highly and significantly
correlated with fasting insulin (r = 0.89), stimulated insulin
secretion (r = 0.61), and insulin sensitivity as assessed with a
euglycemic clamp (r = 20.63) (63). Nonobese adolescents in
this study (n = 9) showed no association between IAAT volume
and indexes of glucose metabolism. However, among nonobese
adolescents, SAAT was significantly correlated with insulinstimulated glucose metabolism (r = 20.60). These data suggest
that the contribution of IAAT and SAAT to the metabolic profile
may differ in lean compared with obese children.
In a heterogeneous sample of 74 obese and nonobese, prepubertal, white and African American children (aged 5–10 y;
11–47% body fat; 7.0–114.4 cm2 IAAT), we examined several
indexes of insulin secretion and action in data obtained from a
3-h OGTT (64). Total fat, IAAT, and SAAT were all significantly
correlated with fasting insulin, incremental 30-min insulin, and
incremental insulin AUC in both white and African American
children (r ranged from 0.40 to 0.81). After multiple regression
analysis, total fat remained independently related to fasting
insulin after adjusting for IAAT and SAAT. This finding supports
the general notion that simple obesity is commonly associated
with fasting hyperinsulinemia, even in individuals without visceral obesity (22). In multiple regression analysis, SAAT was
independently related to incremental insulin AUC in the group as
a whole (P < 0.05) after adjusting for other indexes of adiposity
(64). This finding suggests that subcutaneous upper-body fat,
rather than IAAT, may be the primary determinant of insulin
resistance in children. In adults, SAAT has greater lipolytic
responsiveness than does peripheral adipose tissue (65, 66) and
thus shares some of the metabolic features of IAAT. Therefore,
in subjects with relatively low amounts of IAAT (such as children), SAAT may have a greater effect on insulin resistance.
Studies that used direct measures of IAAT and SAAT to
explore their relations with insulin action in children and adolescents are summarized in Table 1. Collectively, the results of
these studies show that central fat is associated with indexes of
insulin resistance in children and adolescents, as in adults. However, the precise depot associated with insulin resistance differs
with obesity status; in lean children it is subcutaneous whereas
in obese children it is intraabdominal. Further research will be
required to determine whether cause-and-effect relations exist
between IAAT or SAAT and insulin action in obese and nonobese
adolescents, respectively.
Regional adiposity, lipids, and insulin action
Several studies have used circumferences and skinfold thicknesses to determine whether fat distribution is related to CVD
risk factors in children (68–74). However, most of these studies
were cross-sectional and in those studies that showed a link
between body fat and cardiovascular risk, the correlations were
weak (r values of 0.1–0.3). The weak correlations may have been
due to the fact that body fat and fat distribution were usually estimated from crude anthropometric indexes (33, 39).
In the Bogalusa Heart Study, among children and adolescents
aged 6–18 y, those with high LDL- and VLDL-cholesterol concentrations had more trunk fat and less thigh fat (after adjusting
for total adiposity) than those with low concentrations of these
lipids (75). In early pubertal white girls (aged 10 ± 0.1 y, Tanner
stage 1 or 2), waist-to-hip ratio was positively associated with
total cholesterol, LDL cholesterol, and apolipoprotein B and
inversely associated with the apolipoprotein A-I to apolipoprotein B ratio after adjusting for the sum of 4 skinfold thicknesses
(76). In contrast, regional subcutaneous adiposity as assessed
with skinfold thicknesses (adjusted for total adiposity) was not
associated with the lipid profile. These data support the hypothesis that deposition of relatively greater amounts of IAAT
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Subject characteristics
2,3
VISCERAL FAT AND DISEASE RISK
the leading cause of death (85). These studies are reviewed in
more detail below.
Ethnic differences in the association between central
adiposity and disease risk
A number of studies found that African Americans differ from
whites with respect to the regulation of several metabolic risk factors. Healthy, nonobese African Americans were found to have
higher fasting and postchallenge insulin concentrations, lower
insulin sensitivity, and lower hepatic insulin extraction when compared with whites of similar body mass index and waist-to-hip
ratio (86). In contrast, fasting glucose concentrations (37) and glucose AUC (87) were lower, HDL-cholesterol concentrations were
higher (37, 87, 88), and triacylglycerol concentrations were lower
(37, 89) in African Americans. The health implications of these
differences in risk factors for African Americans are not clear.
The basis of some of the ethnic differences in risk factors may
be differences in visceral adiposity. Recent studies in women
have shown that, at any given degree of adiposity, African Americans may have less IAAT (37, 87). No ethnic differences were
found in the slopes of the regressions between IAAT and glucose
AUC, insulin AUC, insulin sensitivity, triacylglycerol concentration, and HDL cholesterol concentration (87, 89). However,
SAAT was significantly correlated with insulin sensitivity in
African American but not white women (89). Thus, a given
amount of IAAT appears to confer the same risks for both white
and African American women, but for any given amount of total
body fat, African American women have less IAAT. Although
this observation may explain the lower triacylglycerol and higher
HDL cholesterol concentrations observed in African Americans,
the greater degree of hyperinsulinemia and insulin resistance
seen in this group remains unexplained. Possible ethnic differences in the relation of SAAT to insulin, particularly among
women, deserve further attention.
Few studies have addressed ethnic differences in the metabolic
correlates of obesity or central obesity in children. Yanovski et al
(43) found that, among normal-weight African American girls
aged 7–10 y, SAAT but not IAAT as assessed with MRI was
related to basal and 2-h insulin during an OGTT. In contrast, neither measure of adiposity was related to these insulin values in
white girls matched for age, bone age, body mass index, and body
weight. No relations between serum lipids or blood pressure and
IAAT or SAAT were found in either group of girls. Gutin et al
(77) found that percentage body fat, but not fat distribution as
assessed with waist-to-hip ratio, was correlated with fasting
insulin and triacylglycerol concentrations and the atherogenic
index in a group of 7–11-y-old African American and white children. No effects of sex or ethnicity on the relations between adiposity and these risk factors were detected in multiple regression
analysis. However, African American children had higher fasting
insulin than white children, before and after adjusting for total
adiposity. Likewise, in the Bogalusa Heart Study, African American children (mean age <12 y) had higher 30-min insulin concentrations than white children during an OGTT (61). In this
study, central fat as assessed with skinfold thickness measurements was related to postchallenge insulin concentrations in both
whites and African Americans. From these limited observations,
it is difficult to draw any conclusions regarding the influence of
ethnicity on the relation between central adiposity and metabolism
in children, although it appears that basal insulin is significantly
higher in African American children.
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adversely affects circulating lipid and lipoprotein concentrations
in young females. The data did not indicate that regional adiposity influences the lipid profile in early pubertal males. Another
study of early pubertal and prepubertal children showed that
waist-to-hip ratio was not a useful index of metabolic dysfunction (77). As discussed earlier, lack of agreement among studies
is likely due to the poor correlations between some of the frequently used anthropometric indexes and IAAT in children.
Two studies have used direct measures of IAAT and SAAT to
examine relations between regional adiposity and blood lipids. In
obese, predominantly white adolescent girls, fat distribution was
measured with MRI and the results showed that: 1) IAAT was
positively correlated with triacylglycerol and basal insulin
concentrations and inversely correlated with HDL-cholesterol
concentrations, 2) SAAT was inversely correlated with LDL-cholesterol concentrations, and 3) femoral adipose tissue was inversely
correlated with triacylglycerol and LDL-cholesterol concentrations (67). The inverse association between femoral adipose tissue and lipid risk factors has been observed in adults (78, 79) and
may suggest that deposition of lipid in this low-flux depot actually protects against CVD. In obese boys and girls aged 10–15 y,
IAAT as determined by MRI was positively associated with totaland LDL-cholesterol and triacylglycerol concentrations but
SAAT was not associated with any lipid or lipoprotein index (62).
Taken together, the results of these 2 studies suggest that, at least
among obese adolescents, IAAT is the only adipose tissue depot
associated with lipid risk factors; SAAT and femoral fat appear to
have either no effect or a protective effect.
Changes in lipid and lipoprotein concentrations may result
from insulin resistance and the accompanying hyperinsulinemia.
In a group of obese adolescents of mixed sex and ethnicity, both
insulin sensitivity and percentage body fat showed simple correlations with the lipid profile, but only insulin sensitivity predicted
LDL-cholesterol, HDL-cholesterol, and triacylglycerol concentrations in a stepwise multiple regression analysis (80). In a large
sample of Finnish children and adolescents, fasting insulin at baseline was higher in those who subsequently showed a clustering of
high triacylglycerol and low HDL-cholesterol concentrations and
high systolic blood pressure at a 6-y follow-up examination (81).
In addition, fasting insulin was independently related with the
development of hypertriglyceridemia after adjusting for either
baseline obesity or the change in obesity status. In a different
study of white children and adolescents, insulin sensitivity was
associated with triacylglycerol, VLDL concentrations, and diastolic blood pressure, and basal insulin was associated with triacylglycerol and VLDL concentrations (82). Although no measure of
fat distribution was available, percentage body fat was strongly
correlated with insulin sensitivity (r = 20.82). In a longitudinal
study of obese Japanese children (boys and girls aged 7–15 y at
baseline), fasting insulin was independently related to the development of lipid abnormalities and hypertension after adjusting for
body mass index (in kg/m2) and waist-to-hip ratio (83).
Thus, the picture that is beginning to emerge shows that central adiposity, insulin, and lipids are interrelated in children and
adolescents. However, few studies have examined children before
the onset of puberty, a phase of development in which normal
changes in metabolism and body fat distribution may confound
the interpretation of results. In addition, only a few studies have
examined childhood markers of metabolic health in conjunction
with IAAT in African Americans, a population with a disproportionately high rate of type 2 diabetes (84) and for which CVD is
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SUMMARY AND CONCLUSIONS
IAAT, or visceral fat, begins to accumulate in early childhood.
IAAT can be quantified directly only with imaging techniques,
although various anthropometric indexes are highly correlated and
therefore may provide indirect measures. Even before puberty
there is tremendous variation in the amount of IAAT in children.
Some of the interindividual variation is explained by multicollinearity with other adipose tissue stores, but a portion of the
variance in IAAT appears to be completely independent of these
stores. Ethnic differences in IAAT exist; in African American, prepubertal children, relatively less adipose tissue is deposited within
the abdominal cavity and relatively more is deposited subcutaneously. Sex differences in IAAT begin to emerge during pubertal
development, with boys having more IAAT than girls. Some studies suggested that the rate of IAAT accumulation can be slowed in
children by using exercise interventions.
Significant findings regarding the relation between obesity
indexes and metabolic risk factors, based on direct measures of
IAAT and SAAT, are summarized in Table 1. A positive correlation between IAAT and insulin resistance has been observed in
obese (but not nonobese) adolescents and in prepubertal children
with a range of body fat values. In the latter, IAAT was not independently associated with insulin AUC after adjusting for total
body fat and SAAT. SAAT was associated with insulin resistance
in children (an independent association) and in nonobese adolescents (a simple correlation). Thus, obesity status may affect rela-
tions between regional adiposity and disease risk such that
SAAT may have more of an effect on metabolic health in
nonobese children, in whom IAAT deposits are quite low. Further research will be required to determine whether cause-andeffect relations exist between IAAT or SAAT and insulin action
in obese or nonobese adolescents.
Data suggest that the visceral adiposity and insulin resistance syndrome may have its origins in childhood. Among predominantly obese, white adolescents, IAAT is the only adipose
tissue depot associated with lipid risk factors; SAAT and
femoral fat appear to have either no effect or a protective effect.
In children and adolescents, insulin sensitivity and hyperinsulinemia are independently related to circulating lipids after
adjusting for adiposity. Thus, the relations necessary for the
development of syndrome X are apparent at an early age and
may be exacerbated by accumulation of IAAT.
In children, ethnic differences in aspects of insulin metabolism
parallel those observed in adults. As in adults, SAAT is related to
insulin in African American but not white girls. Also as in adults,
higher insulin concentrations in African American children are
independent of total and regional adiposity. The adiposity-independent hyperinsulinemia or insulin resistance among African Americans could be genetically based or could be secondary to lifestyle
factors such as diet and physical activity.
The assistance of study coordinator Tena Hilario and the staff of the
GCRC, and the participation of the children and their families, are gratefully acknowledged.
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