abdominal obesity , characterized by preferential accumulation of intra - abdominal adipose tissue ( iat ) , contributes to cardiovascular and metabolic risk beyond the risk defined by body mass index [ 1 , 2 ] thus , prevention of abdominal obesity is key to reducing cardiometabolic risk .
preferential iat accumulation , as measured by iat adjusted for percent body fat or iat to subcutaneous abdominal adipose tissue ( sat ) ratio , depends on genetic factors ( e.g. , ethnicity or gender ) , smoking , and the hormonal milieu ( e.g. , postmenopausal status ) [ 5 , 6 ] . the iat compartment is highly active during changes in balance between energy intake ( food consumption ) and energy expenditure ( physical activity ) .
rapid iat accumulation occurs in acute overfeeding experiments , and preferential reduction of iat volume is characteristic of immediate and acute weight loss , but mitigated after 1214 weeks of intervention .
we have shown that lack of regular moderate physical activity ( not meeting physical activity guidelines for healthy adults ) is associated with preferential iat accumulation in midlife women , independent of age , menopausal status , income , smoking , and percent body fat , suggesting that  a  sustained change in lifestyle may affect preferential iat accumulation . however , physical activity may not be the only lifestyle target for preventing iat accumulation .
although energy intake is linked to iat in laboratory studies , no population - based studies have been conducted and no studies have determined whether or not energy intake is associated with preferential iat accumulation , independently of physical activity . moreover , there have been no studies that examined whether these relationships are moderated by ethnicity or menopausal status in midlife women .
answers to these questions are important because they can inform the design of lifestyle interventions aimed at decreasing cardiometabolic risk by decreasing preferential accumulation of iat in midlife women .
participants were women who enrolled in an ancillary study of the study of women 's health across the nation ( swan ) at the chicago site .
this ancillary study , the  swan fat patterning study  , was designed to investigate the impact of the menopausal transition on iat accumulation .
swan is a seven - site , multiethnic longitudinal study of women transitioning through menopause , featuring ongoing annual evaluations . at enrollment into the swan , between 1996 and 1997 , eligible women were 4252 years old , reported a menstrual period within the past 3 months , did not use medications known to affect pituitary or ovarian function , and did not use exogenous hormones within the 3 months preceding the baseline interview .
a unique feature of the chicago swan site was that it used a population - based recruitment strategy , drawing on a complete community census , to recruit a representative sample of caucasian and african american women in which the confound between ethnicity and socioeconomic status was minimized .
women enrolled in the chicago swan fat patterning study between august 2002 and december 2005 , coincident with annual swan follow - up visits 4 through 9 .
eligible women did not have diabetes , chronic liver or kidney disease , substance abuse or eating disorders , were not pregnant , had no breast or joint implants , and weighed less than 300 pounds .
of the 386 eligible chicago swan participants , 297 ( 77% ) enrolled in this swan fat patterning study , and they did not differ from the remaining women in any of the baseline characteristics .
four were excluded from analytical sample because of hysterectomy ( due to difficulty assessing natural menopause ) , four were excluded due to diabetes ( as diabetes and treatment for diabetes contribute to iat accumulation ) , two were excluded because they did not have an iat measurement , and 30 ( 10% ) were excluded because they were receiving menopausal hormone therapy ( as estrogen and progesterone use may potentially affect appetite , adipose tissue accumulation , and distribution ) .
the final analytic cohort of eligible women , which consisted of 257 women , represented 86% of the original 297 participants .
iat and subcutaneous abdominal adipose tissue ( sat ) were assessed by a computerized tomography ( ct ) scan of the abdomen using a general electric lightspeed vct scanner ( general electric medical systems , milwaukee , wi ) at the l4-l5 intervertebral space in a single 10  mm thick image .
scanned images were analyzed at the university of colorado health sciences center using their software ( rsi , boulder , co ) , as described previously [ 5 , 6 ] .
a relative index of iat accumulation was calculated as a ratio of iat to sat .
percent body fat ( % ) was calculated as total body fat mass/(total body fat mass + total lean body mass )  100 .
total body fat mass ( in kilograms ) was assessed the same day as iat by dual - energy x - ray absorptiometry , using a general electric lunar prodigy scanner ( ge - lunar , madison , wi ) , and analyzed using encore software ( ge - lunar ) , as described previously . energy intake was self - reported . at baseline ,
year 5 , and year 9 annual visits , women completed a modified version of the 1995 block interviewer - assisted semiquantitative food frequency questionnaire .
individual energy intake  per  day  was  calculated  using  dietsys  software ( http://appliedresearch.cancer.gov/dietsys/software.html ) .
pearson correlations between initial measures with repeated measures of ffq energy intake were 0.70 , and the coefficient of variation was 2.7% .
measurement error that occurs when assessing person 's usual diet with a food frequency questionnaire generally involves bias related to true intake in addition to random variation .
bias related to true intake often occurs as the  flattened - slope phenomenon  ( consumers with high levels of intake tend to underreport and low - level consumers tend to overreport ) , which biases the beta - coefficient upward .
energy intake is derived from the food frequency questionnaire , and thus subject to measurement error . because biomarker validation studies were not performed in swan , we adjusted energy intake , using factors previously shown in other studies using biomarkers   to correct for measurement error  :  income , ethnicity , age , physical activity , and a measure of body size .
we did not use exact regression coefficients derived from other studies , as the patient population and food frequency questionnaire differed in our study .
it was administered at the swan follow - up visits 3 , 5 , 6 , and 9 .
the assessment selected for analysis was the one that was closest to the adipose tissue assessment , as described previously .
a total activity score was created by summing across kaiser physical activity survey ( kpas ) domains ( sports / exercise , active living habits , housework / caregiving ) , with a higher score indicating higher activity , as described previously .
the women were grouped into ( a ) pre-/perimenopausal ( pre- , early peri- , and late perimenopause ) and ( b ) postmenopausal groups .
the postmenopausal women had their final menstrual period more than 12 months prior to the iat assessment .
height , weight , and waist girth were measured using a standard anthropometric measurement protocol .
weight was measured to the nearest 0.1  kg at each annual examination on digital scale while participants stood in stocking feet and light clothing .
waist girth was measured annually to the nearest 0.1  cm with a measuring tape placed horizontally around the participant at the narrowest part of the torso , and an average of two measurements was reported .
self - administered and interviewer - administered questionnaires were used to assess social , economic , behavioral , psychological , health , and lifestyle characteristics .
age ( in years ) was a variable created as the difference between iat assessment date and self - reported date of birth and modeled continuously in all analyses .
participant 's annual household income was classified into three levels  :  less than $ 50,000 , $ 50,000 to $ 75,000 , or greater than $ 75,000 .
data for the principal outcome ( iat area ) were collected at the baseline of the ancillary swan fat patterning study , which corresponded to swan annual visit 4 , 5 , or 6 , dependent on the timing of recruitment .
however , data for the primary predictor variable ( energy intake ) were collected only at the swan study baseline , visit 5 , and visit 9 . to handle differences in the timing of assessments of iat and energy intake , we used an interpolation technique for the energy intake variable [ 18 , 19 ] . after checking for linearity of energy intake trends over time
, we used a random effects model with random intercept and slope to estimate energy intake over time in the swan study ( between baseline , year 5 and year 9 ) .
these models yielded participant - specific intercepts and slopes , which were weighted averages of the regression coefficients for the full sample and the regression coefficients from each participant 's data . these slopes were used to estimate energy intake at the time of iat assessment . to assess the performance of these interpolation models , we compared fitted values with observed values from baseline , visit 5 , and
we ran the pearson correlations between fitted and observed values which produced r = 0.89 ( p < 0.0001 ) , indicating a strong agreement .
in addition , linear regressions of observed values on fitted values indicated no systematic bias , as intercepts were close to 0 and slopes were close to 1 .
descriptive statistics were used to summarize the participants ' energy intake , age , ethnicity , income , education , menopausal status , physical activity , smoking , body mass index , waist girth , and other adipose tissue measurements .
logarithmic transformation of iat area was used in linear regression models , as this primary outcome did not follow a normal distribution .
we employed a series of linear regression models using log - transformed iat as a dependent variable and interpolated energy intake as our primary predictor with adjustments for ethnicity , age , income , percent body fat , menopausal status , smoking , and physical activity .
the energy intake was reported in 500  kcal increments and percent body fat was reported in 5% increments in body fat . to adjust for possible nonlinear association between ( i ) iat and percent body fat and ( ii ) iat and age
, these covariates were entered in the model as both linear and centered quadratic terms .
the continuous variables in the model were iat area , percent body fat ( and its centered quadratic transformation ) , age ( and its centered quadratic transformation ) , and physical activity .
the categorical variables in the models were income , ethnicity , smoking , and menopausal status .
reference groups for these variables were  caucasian for ethnicity ; pre-/perimenopause for menopausal status ; and nonsmokers for smoking status .
the high - income group was the reference group for the categorical ( trichotomous ) income variable .
model 1 was constructed to evaluate the relationship between energy intake and iat after adjustment for ( i ) confounders ( ethnicity and menopausal status ) , and ( ii ) correction factors ( age , percent body fat , smoking , and income ) .
model 2 was constructed to evaluate the relationship between energy intake and iat after adjustment for ( i ) physical activity in addition to covariates used in the first model .
model 3 was designed to explore interactions of energy intake with ethnicity and menopausal status , adjusting for the factors in model 2 .
analogous models 1 through 3 were constructed using iat  :  sat ratio as a dependent variable to assess the predictors of iat per quantity of sat . to interpret the coefficients from the linear model , we estimated the percentage change in the average value of iat area per unit increase in energy intake multiplied by 100 ( 100   ) .  
all analyses were conducted using sas , pc version 9.2 ( sas institute inc . , cary , nc ) .
48% ( n = 123 ) were african american and 52% ( n = 134 ) were caucasian .
fifty - three percent had an annual household income above $ 75,000 , and 61% had a college education or higher degree . at the time of iat assessments ,
women were on average 52 years old ( ranging from 47 to 61 ) , 46% were obese ( body mass index ( bmi )  30.0  kg / m ) , and 30% were overweight ( bmi  =  25.029.9  kg/ m ) .
forty - nine percent ( n = 125 ) were postmenopausal , and the remaining participants were pre- or perimenopausal .
participants ' self - reported energy intake corresponding to the respective swan fat patterning study visit was an average of 1608  470  kcal/24  h. 
 table 2 , model 1 shows that self - reported energy intake was associated with preferential iat accumulation  :  every 500 calories of energy intake were related to a 6% higher iat ( p = 0.025 ) , after adjustment for ethnicity , menopausal status , smoking , income , age , and percent body fat . 

table 2 , model 2 shows that both energy intake and physical activity contributed independently to iat .
the addition of physical activity into the model did not weaken the association between energy intake and iat . 

table 2 , model 3 shows a significant interaction between self - reported energy intake and ethnicity ( p = 0.02 ) . as depicted in figure 1 , the association between energy intake and preferential iat accumulation was considerably stronger in caucasian women compared to african american women .
the relationship between energy intake and iat was not significantly moderated by physical activity or menopausal status .
an alternative approach to explore preferential iat accumulation is to use the ratio iat  :  sat as the outcome .
this is a relative index of iat accumulation , which is associated with higher cardiometabolic risk . 

table 3 contains models 1 , 2 , and 3 with iat  :  sat ratio as a dependent variable .
the results are virtually identical to those obtained using iat as the outcome . however , the model for iat  :  sat ratio explains less of the variance , as indicated by r. in models with sat as a dependent variable ( not shown ) , energy intake did not have an independent contribution to sat accumulation beyond that explained by percent body fat .
this finding is not surprising , as sat correlated very closely with percent body fat ( pearson correlation r = 0.88 , p < .0001 ) .  
our principal finding was that self - reported energy intake was associated with higher iat in this diverse and well - defined , naturalistic , community - based cohort of women undergoing the menopausal transition .
this relationship of energy intake and iat was independent of self - reported physical activity and menopausal status and was stronger in caucasian than in african american women .
however , further studies are needed to explore the allometric relationships between iat and body size in weight gain .
however , during positive energy balance iat is hypothesized to be a secondary fat storage pool that accumulates only after subcutaneous stores are full .
our cross - sectional data suggest preferential iat accumulation at higher self - reported caloric intake in mid - life women .
this finding should be confirmed in longitudinal explorations of the allometric relationship between iat and body fat . to our knowledge , this is the first study in a naturalistic community - based cohort to analyze the joint associations of self - reported energy intake and physical activity with preferential iat accumulation .
our current findings extend the previous work conducted by our group demonstrating that that regular moderate physical activity ( meeting physical activity guidelines for healthy adults ) was associated with lower iat area in midlife women , independent of total adiposity .
although exercise has been regarded as a specific therapy to reduce iat accumulation , our findings suggest that lower energy intake also has significant independent protective effects on preferential iat deposition beyond those of physical activity , and these effects are independent of total adiposity .
higher self - reported energy intake is related to iat to sat ratio higher at all body sizes in mid - life women .
thus , excess energy appears to be preferentially partitioned into intra - abdominal rather than subcutaneous abdominal area at all body sizes .
although , caucasian women have more iat adjusted for percent body fat than african american women [ 20 , 2628 ] , over the past 10 years , the largest increase in abdominal obesity occurred in the african american population .
the association between self - reported energy intake and iat appears stronger in caucasian than in african american women . during energy intake restriction ,
caucasian women tend to lose more iat than african american women , however , the differences disappear after adjustment for baseline iat or the amount of total fat lost [ 30 , 31 ]
. the quantitative differences in energy intake do not explain why african american women partition proportionally less fat into the iat compartment .
these ethnic differences in the association between self - reported energy intake and iat can be a result of differential reporting bias among caucasian and african american women .
since the problem of abdominal obesity may be growing more extreme for african american women , it is urgent to determine factors associated with this increasing risk .
the findings in our study are congruent with a recently published small longitudinal study suggesting preferential iat increase related to menopause in caucasian women .
however , longitudinal study of african american women suggested that the greatest iat accumulation occurs during young adulthood ; no significant 5-year iat change was observed in women between ages 50 to 69 .
the strength of our study is that the women were studied in their naturalistic , community - based environment , they were demographically similar , and their menopausal status was well defined . unlike the majority of previous studies exploring correlates of iat distribution [ 26 , 27 , 3437 ] , we adjusted our multivariable models for income . a limitation of our study is the lack of longitudinal followup of iat , which would clarify the effects of menopause on iat accumulation and factors associated with iat gain during the menopausal transition .
measurement error , a result of self - reporting energy intake without biomarker validation for the food frequency questionnaire , may have affected the association between energy intake and iat .
we made our best effort to adjust the energy intake , derived from the food frequency questionnaire , using factors previously shown to correct for the measurement error :  relative body fat mass , ethnicity , age , physical activity , smoking , and annual income .
since measurements error biases toward the null hypothesis , and since these data show strong and significant associations for energy intake , measurement error is unlikely to be a serious problem in this report . in summary ,
higher self - reported energy intake in mid - life women was associated with preferential compartmentalization of fat into the iat depot , particularly for caucasian women .
a longitudinal follow - up study is needed to explore the allometric relationship between iat and body fat , as well as the effects of diet quality ( such as macronutrient composition ) , socioeconomic and lifestyle risk factors , menopause , insulin resistance , and other atherosclerosis risk markers on increases in iat , particularly in african american women .
 we have previously shown that physical activity predicts intra - abdominal adipose tissue ( iat ) , but it is unknown whether energy intake predicts iat independently of physical activity in a community - based , naturalistic environment . 
 the association of energy intake with iat was explored cross - sectionally in women , recruited between 2002 and 2005 for a study of fat patterning in midlife . 
 iat at l4-l5 vertebral interspace was assessed by computed tomography , energy intake by the block food frequency questionnaire , and physical activity by the kaiser physical activity survey . 
 linear regression models were used for the principal analyses . 
 among the 257 women , 48% were african american and 52% were caucasian . 
 women were 52  3 years old , and 49% were postmenopausal . 
 every 500 kcal increase in energy intake was associated with a 6% higher iat ( p = 0.02 ) , independent of physical activity ( p = 0.02 ) , after adjustment for ethnicity , menopausal status , age , smoking , income , and dxa - assessed percent body fat . 
 energy intake had a significant interaction with ethnicity ( p = 0.02 ) , but not with physical activity . 
 models using the iat to subcutaneous abdominal adipose tissue ratio as an outcome had similar associations . in conclusion , 
 self - reported ei was associated with preferential iat accumulation in midlife women , independent of physical activity . 
 this association was significantly stronger in caucasian than african american women . 
 future longitudinal studies are needed to explore lifestyle predictors of iat accumulation during the menopausal transition . 
1. Introduction
2. Methods and Procedures
3. Design and Data Analysis
4. Results
5. Relative Index of Intraperitoneal Abdominal Adipose Tissue Accumulation