Department of Medicine, and Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont 05405
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ABSTRACT |
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Controversy exists regarding the relative
importance of adiposity, physical fitness, and physical activity in the
regulation of insulin-stimulated glucose disposal. To address this
issue, we measured insulin-stimulated glucose disposal
[mg · kg fat-free mass
(FFM)1 · min
1; oxidative and
nonoxidative components] in 45 nondiabetic, nonobese, premenopausal
women (mean ± SD; 47 ± 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU · m
2 · min
1) and
[6,6-2H2]glucose dilution techniques. We also
measured body composition, abdominal fat distribution, thigh muscle fat
content, maximal oxygen consumption
(
O2 max), and physical activity energy expenditure (2H218O kinetics) as
possible correlates of glucose disposal.
O2 max was the strongest correlate of
glucose disposal (r = 0.63, P < 0.01),
whereas whole body and abdominal adiposity showed modest associations
(range of r values from
0.32 to
0.46, P < 0.05 to P < 0.01). A similar pattern of
correlations was observed for nonoxidative glucose disposal. None of
the variables measured correlated with oxidative glucose disposal. The
relationship of
O2 max to glucose
disposal persisted after statistical control for FFM, percent body fat,
and intra-abdominal fat (r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity
measures to insulin sensitivity were no longer significant after
statistical adjustment for
O2 max.
O2 max was the only variable to enter
stepwise regression models as a significant predictor of total and
nonoxidative glucose disposal. Our results highlight the importance of
O2 max as a determinant of glucose
disposal and suggest that it may be a stronger determinant of variation
in glucose disposal than total and regional adiposity in nonobese,
nondiabetic, premenopausal women.
aerobic fitness; body composition; body fat distribution; euglycemic clamp
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INTRODUCTION |
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CONSIDERABLE ATTENTION
HAS FOCUSED on the role of adiposity as a determinant of insulin
sensitivity. The association between increased adiposity and decreased
insulin sensitivity has been recognized for some time (33)
and has been well characterized with the use of glucose clamp
techniques (6, 52). In the past two decades, the
hypothetical role of adiposity in the development of insulin resistance
has evolved to consider the anatomic distribution of body fat,
specifically, that increased abdominal adiposityintra-abdominal fat in particular
has potent effects to reduce insulin sensitivity (14, 16). More recently, the adiposity-insulin
sensitivity relationship has been further expanded to consider the
pathological role of adiposity in other anatomic locations, such as
skeletal muscle (18, 30) and the deep abdominal
subcutaneous compartment (22), in the development of
insulin resistance. These findings have sparked a considerable amount
of interest and debate regarding the relative importance of total and
regional adiposity in the regulation of insulin action. Presently,
however, there is no consensus regarding the role of these adiposity
measures in determining insulin sensitivity. Thus our first objective
was to examine the relationship of whole body and regional adiposity
measures to insulin-stimulated glucose disposal.
Physical activity modulates insulin sensitivity (23).
Physical fitness, as reflected by maximal oxygen consumption
(O2 max), is positively associated with
insulin sensitivity (34). Moreover, endurance exercise
training regimens that improve physical fitness increase
insulin-stimulated glucose disposal (31). One mechanism by
which physical fitness or activity may alter insulin sensitivity is
through the modulation of overall or regional body fat. For example,
endurance training has been shown to decrease total body fat and
abdominal adiposity (35). Despite the well known effect of
physical activity on body fat regulation, few studies have considered
simultaneously the relative importance of physical fitness and
adiposity in the regulation of insulin sensitivity. Those studies that
have attempted to address this question have yielded conflicting
results (5, 6, 9, 18, 29). Moreover, to our knowledge, no
study to date has examined the relationship of physical activity energy
expenditure to insulin-stimulated glucose disposal. Thus the importance
of physical fitness or the caloric expenditure of physical activity in
explaining variation in insulin sensitivity among individuals and their
role in mediating the relationship between adiposity and insulin
sensitivity has yet to be clearly defined. Our second objective,
therefore, was to examine the relationship of
O2 max and physical activity energy
expenditure (measured over 10 days by use of doubly labeled water) to
insulin-stimulated glucose disposal. These measurements permit us to
examine the relationship of insulin sensitivity to the physiological
capacity for aerobic activity and the caloric expenditure of physical activity.
To accomplish our objectives, we examined data from a cohort of
nonobese, nondiabetic, middle-aged women. Although this cohort was
nonobese by design (body mass index 30 kg/m2), there was
a wide range in total and regional adiposity. In addition, because we
did not restrict recruitment to sedentary women, there was significant
variability in both physical fitness and activity energy expenditure.
The considerable degree of variation in adiposity, fitness, and
activity in this cohort provided an ideal sample for us to examine the
relative importance of these factors in determining insulin
sensitivity. We limited our investigation to women to remove any
confounding effects of gender on glucose disposal or the relationship
of adiposity, physical fitness, or physical activity energy expenditure
to insulin sensitivity.
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METHODS |
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Materials. D-[6,6-2H2]glucose (98% 2H), L-[1-13C]leucine (99% 13C), and sodium [13C]bicarbonate (99% 13C) were obtained from Cambridge Isotope Laboratories (Andover, MA). Chemical and isotopic purity was determined by gas chromatography-mass spectrometry (GC-MS). Solutions of each isotope were prepared using aseptic technique. Each compound was dissolved in weighed volumes of sterile, pyrogen-free saline and filtered through a 0.22-µm Millipore filter before use. An aliquot of the sterile solution was initially verified to be pyrogen free before administration. 2H2O (99% 2H2O) and H218O (10% H218O) were obtained from Cambridge Isotope Laboratories. Isotopic purity was determined by isotope ratio-mass spectrometry (IRMS).
Subjects. Volunteers (n = 45) in the present study were recruited from Burlington, Vermont, and surrounding areas to participate in the Vermont Longitudinal Study of the Menopause. Details of the recruitment of these volunteers and the purpose of this study have been described previously (46), where data from the first-year evaluation are presented. Data from this cohort have been published previously examining menopause-related differences in body composition (48) and insulin sensitivity (43) and correlates of energy expenditure (46), protein metabolism (47), and cardiovascular disease risk (41). The nature, purpose, and possible risks were explained to each subject before written consent to participate was given. The experimental protocol was approved by the Committee on Human Research at the University of Vermont.
The inclusion criteria were that subjects had to 1) be between 40 and 52 yr of age, 2) be premenopausal as defined by the occurrence of two menses in the 3 mo preceding testing, with no increase in cycle irregularity for 12 mo preceding testing and a follicle-stimulating hormone level <30 IU/l, 3) be nonsmoking, 4) have a normal electrocardiogram at rest and during an exercise test, 5) be weight stable (± 2 kg) during the 6 mo before testing, and 6) have a body mass indexExperimental protocol.
Each prospective volunteer underwent an outpatient screening visit, at
which time medical history, physical examination, biochemical laboratory tests, treadmill test, and an oral glucose tolerance test
were performed. Volunteers who met the eligibility criteria after
screening and consented to participate were studied during two
inpatient visits to the General Clinical Research Center (GCRC). The
first inpatient visit occurred during the follicular phase and the
second inpatient visit during the luteal phase of each woman's
menstrual cycle. For 3 days before each admission, subjects consumed a
standardized weight maintenance diet provided by the Metabolic Kitchen
of the GCRC (1,988 ± 193 kcal/day: 60% carbohydrate, 25% fat,
15% protein) that provided 250 g of carbohydrate/day. Volunteers
refrained from exercise for 24 h before each inpatient visit.
Body composition. Body mass was measured on a metabolic scale (Scale-Tronix, Wheaton, IL) with the volunteer clothed in a hospital gown. Whole body fat mass, FFM, and bone mineral mass were measured by dual-energy X-ray absorptiometry using a Lunar DPX-L densitometer (Lunar, Madison, WI). All scans were analyzed using the Lunar Version 1.3y DPX-L extended analysis program for body composition. In our laboratory, the coefficient of variation (CV) for repeat determinations in seven older women was 1% for fat mass and 2% for FFM.
CT.
Abdominal adipose tissue areas and thigh muscle composition were
measured by CT with a GE High Speed Advantage CT scanner (General
Electric Medical Systems, Milwaukee, WI). Subjects were examined in the
supine position with both arms stretched above the head. By use of a
scout image to establish the correct position, scans were performed
between the L4 and L5 vertebrae and
approximately midway between the patella and the anterior superior
iliac crest (ASIC) (average distance from ASIC to thigh slice: 295 ± 83 mm). Adipose tissue was highlighted and computed using an
attenuation range from 190 to
30 Hounsfield units (HU) with
commercially available software (GE Medical Systems). Intra-abdominal
adipose tissue area was quantified by delineating the intra-abdominal cavity at the innermost aspect of the abdominal and oblique muscle walls surrounding the cavity and the posterior aspect of the vertebral body. Subcutaneous adipose tissue area was quantified by highlighting of adipose tissue located between the skin and the outermost aspect of
the abdominal muscle wall. Abdominal subcutaneous adipose tissue was
further divided into deep and superficial depots along the subcutaneous
fascial plane, as described (20). Deep subcutaneous adipose tissue was defined as the area between the subcutaneous fascia
and the abdominal muscle wall, and the superficial subcutaneous adipose
tissue was defined as the area between the subcutaneous fascia and the
skin. CT was also used to measure midthigh muscle fat content
(17). Tissue areas were delineated using attenuation values of
190 to
30 HU for adipose tissue, 0-100 HU for
muscle, and >200 HU for bone. The average attenuation value of
skeletal muscle from the right and left thighs was used as an indicator of thigh skeletal muscle density.
O2 max.
O2 max was assessed by a progressive
and continuous test to exhaustion on a treadmill, as previously
described (44). A comfortable initial walking or jogging
speed was determined for each individual and was maintained throughout
the test. After the first 2 min, the incline was increased by 2.5%
every 2 min until volitional fatigue. Heart rate was monitored
throughout the test with a 12-lead electrocardiogram.
O2 and
CO2 were monitored continuously using an
open-circuit gas analysis system (Ametek, Pittsburgh, PA). A volunteer
was judged to have reached
O2 max if
she reached a respiratory quotient > 1.1 and her age-predicted maximal
heart rate was ±10 beats/min. All volunteers met this criteria.
O2 max was defined as the highest 30-s
average
O2 reached during the final 2 min of the test. Test-retest conditions (
1 wk) for
O2 max in a previous group of 18 female
volunteers had yielded an intraclass correlation of 0.98 and a CV of
3.4%
Energy metabolism.
Daily energy expenditure (DEE) was measured on 29 volunteers by means
of the doubly labeled water technique, as previously described
(45). DEE was calculated from
CO2 data obtained from isotope
decay curves by use of the equations outlined by Tchernof et al.
(40). Resting (REE) and postprandial energy expenditure
were determined using indirect calorimetry, as previously described
(46). The thermic effect of the liquid meal (TEM; 10 kcal/kg FFM of Ensure Plus, Ross Laboratories, Columbus, OH: 53.3%
carbohydrate, 32% fat, 14.7% protein) was calculated by measuring the
area under the curve (AUC) with the trapezoid method and was expressed
as a fraction of the energy content of the liquid meal by dividing the
AUC by the caloric content of the liquid meal. Physical activity energy
expenditure (PAEE) was calculated as
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(1) |
Analytical methods.
Serum insulin was determined with a double antibody radioimmunoassay
(Diagnostic Products, Los Angeles, CA). The intra- and interassay CVs
for insulin were 4% and 10%, respectively. Plasma glucose
concentrations were measured by a glucose analyzer (Yellow Springs
Instrument, Yellow Springs, OH). Plasma glucose enrichment was measured
by electron impact ionization GC-MS, as previously described
(15). Before measurement by GC-MS, glucose was derivatized to the butane boronate acetyl derivative, as described
(4). Injections of butane boronate-glucose were made
isothermally into the GC-MS (model 5971A, Hewlett-Packard, Palo Alto,
CA) while the [M 57]+ ions
were monitored at a mass-to-charge ratio (m/z) of 297 and 299 for unlabeled and [2H2]glucose,
respectively. Plasma
-ketoisocaproate (KIC) enrichment was measured
by electron impact ionization GC-MS, as previously described
(47). Before measurement by GC-MS, keto acids were isolated from plasma and derivatized to
tert-butyldimethylsilyl (t-BDMS)-quinoxalinol
derivatives (26). The t-BDMS derivative of the
keto acids was also measured by GC-MS with selected monitoring of the
[M
57]+ ion at m/z = 259 and 260 for unlabeled and [13C]KIC, respectively. The
enrichment of expired 13CO2 [molar percent
excess (MPE) × 1,000] was measured by IRMS (VG Sira II,
Middlewich, Cheshire, UK). Urine samples were analyzed for
18O enrichment by the CO2 equilibration
technique (10) and for 2H enrichment by the
zinc catalyst method of Wong et al. (51) by IRMS.
Calculations.
During hyperinsulinemia, steady state was achieved for plasma glucose
concentrations and enrichment. Thus the rate of insulin-stimulated glucose disposal corresponded to the removal of glucose from two sources: the dextrose infusion used to maintain euglycemia and residual
endogenous glucose production [rate of appearance (Ra)]. To calculate the residual endogenous glucose production, we had to
consider the input of [2H2]glucose into the
plasma pool from two sources: 1) the
[2H2]glucose infusion and 2) the
dextrose infusion. Thus Ra was calculated as
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(2) |
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(3) |
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(4) |
Statistics.
Relationships between variables were determined by Pearson correlation
coefficients. Partial correlation analysis was performed to examine the
relationship between glucose disposal measures and predictor variables
after statistical control for covariates. Because intra-abdominal fat
was not normally distributed (Shapiro-Wilk test, P < 0.01), data were log10 transformed [Shapiro-Wilk test, not
significant (NS)]. For all correlation analysis, glucose disposal data
were expressed relative to FFM (mg · kg
FFM1 · min
1). The adequacy of this
mathematical adjustment of glucose disposal data rests on the
assumptions that the y-intercept of the relationship between
glucose disposal and FFM is not different from zero and that adjusted
glucose disposal data (mg · kg
FFM
1 · min
1) are not related to FFM
(kg). Although glucose disposal (mg/min) and FFM (kg) were related
(r = 0.42, P < 0.01), the
y-intercept of this relationship was not different from zero
(y =
181 ± 204 mg/min, P = 0.38). More importantly, no correlations between adjusted glucose
disposal data (mg · kg
FFM
1 · min
1) and FFM were found
(total glucose disposal: r = 0.12; nonoxidative: r = 0.14; oxidative: r = 0.12),
suggesting that this method of data expression removed the effect of
FFM on glucose disposal measures.
O2 max was expressed as liters per
minute, given that we (44) and others (21)
have shown that expression of
O2 max
per kilogram of body weight or per kilogram of FFM can lead to
erroneous results. However, to ensure that the relationship of
O2 max to glucose disposal was not due
to the effects of FFM, we examined this relationship by use of partial
correlation analysis, with FFM as a covariate, after adjusting
O2 max for FFM with regression
techniques, as previously described (44), and after
dividing
O2 max by FFM. To control for
the effects of body size, physical activity energy expenditure was
adjusted for body mass by means of partial correlation analysis and was
divided by body mass0.5, as described (32).
Correlation coefficients from bivariate and partial correlation
analysis are expressed as r values. Stepwise regression
analysis was used to determine which variables predicted glucose
disposal measures. Possible predictor variables were entered into the
stepwise model if a physiological basis for explaining variation in
glucose disposal was supported by previous studies and if a significant
bivariate relationship was observed between the glucose disposal
measure and the predictor variable. The cumulative variation in glucose
disposal data accounted for by the stepwise model is expressed as an
r2 value. All data are expressed as means ± SD unless otherwise specified.
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RESULTS |
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Physical characteristics are shown in Table
1 and energy metabolism data in Table
2. These data show that the cohort is relatively homogeneous with respect to age, body mass, and FFM. In
contrast, the cohort showed a considerable degree of variability in
total and regional body fat, O2 max,
and physical activity energy expenditure, as indicated by CVs >20%.
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Total glucose disposal averaged 10.74 ± 2.92 mg · kg
FFM1 · min
1. Oxidative glucose
disposal accounted for 37 ± 2% (3.63 ± 0.88 mg · kg FFM
1 · min
1) of
total glucose disposal, with nonoxidative glucose disposal comprising
the remaining 63 ± 2% (7.11 ± 3.11 mg · kg
FFM
1 · min
1). Fat oxidation during
the final 30 min of the clamp averaged 0.89 ± 0.41 mg · kg FFM
1 · min
1.
Insulin levels averaged 598 ± 163 pmol/l, and glucose levels averaged 4.76 ± 0.27 mmol/l during the last 30 min of the clamp.
Correlation coefficients for the relationships between total,
nonoxidative, and oxidative glucose disposal and selected physiological variables are shown in Table 3. Of
particular note are the strong correlations of
O2 max (l/min) to total and
nonoxidative glucose disposal. These correlations were similar when
O2 max was adjusted for FFM with a
regression-based approach (44) (total: r = 0.64, P < 0.01; nonoxidative: r = 0.54, P < 0.01) or expressed per kilogram of FFM
(total: r = 0.65, P < 0.01;
nonoxidative: r = 0.56, P < 0.01).
Moreover, the relationship between
O2 max and both total and nonoxidative
glucose disposal persisted after statistical adjustment for FFM
(r = 0.64, P < 0.01 and
r = 0.54, P < 0.01, respectively) and
FFM and percent fat (r = 0.58, P < 0.01 and r = 0.49, P < 0.01, respectively). After statistical control for FFM, percent fat,
and intra-abdominal fat, the relationship between
O2 max and total glucose disposal
remained significant (r = 0.40, P < 0.01). No variable correlated with oxidative glucose disposal. However,
as expected, fat oxidation during euglycemic hyperinsulinemia showed a
strong inverse association with oxidative glucose disposal
(r =
0.89, P < 0.01; data not shown
in Table 3).
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Indicators of whole body and abdominal adiposity correlated negatively
with both total and nonoxidative glucose disposal. After statistical
control for percent body fat, intra-abdominal fat was the only regional
adiposity measure that remained significantly related to total glucose
disposal (r = 0.39, P < 0.05). In
addition, total abdominal adipose tissue area was negatively correlated to total (r =
0.41, P < 0.01) and
nonoxidative glucose disposal (r =
0.34,
P < 0.05). When expressed as a relative percentage of
total abdominal fat area or statistically adjusted for total abdominal
fat area by use of partial correlation analysis, none of the
subcompartments of abdominal fat were related to glucose disposal
variables. All correlations between subcompartments of abdominal
adiposity and glucose disposal became nonsignificant after statistical
control for
O2 max. No correlation was
found between glucose disposal data and physical activity energy
expenditure (n = 29) after adjustment for body mass
using partial correlation analysis (r = 0.30) or by
dividing by body mass0.5 (r = 0.27).
Neither age (r = 0.05) nor FFM (r = 0.12) was related to insulin-stimulated glucose disposal.
The relationships of O2 max (l/min) to
total, nonoxidative, and oxidative glucose disposal are shown in Fig.
1. The regression equation for the
relationship of
O2 max to total glucose
disposal was glucose disposal (mg · kg
FFM
1 · min
1) = 3.811 × [
O2 max (l/min)] + 3.596. The
regression equation for the relationship of
O2 max to nonoxidative glucose disposal
was glucose disposal (mg · kg
FFM
1 · min
1) = 3.771 × [
O2 max (l/min)] + 0.011. The slopes
for these relationships were indistinguishable [3.811 ± 0.761 vs. 3.771 ± 0.895 (mg · kg
FFM
1 · min
1)/(l/min).
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Using stepwise regression analysis, we found that
O2 max was the only significant
predictor of total (r2 = 0.40, P < 0.01) and nonoxidative glucose disposal
(r2 = 0.32, P < 0.01).
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DISCUSSION |
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This study examined the relationship of insulin sensitivity to
adiposity, physical fitness, and physical activity energy expenditure in a cohort of nonobese, nondiabetic, middle-aged, premenopausal women.
Our principal finding is that O2 max
was a stronger correlate of glucose disposal than total or regional
adiposity measurements. This finding is supported by several lines of
evidence. 1) The positive relationship between
O2 max and insulin sensitivity
persisted after adjustment for FFM, percent body fat, and
intra-abdominal fat; 2)
O2 max was the only variable to enter
stepwise regression models as a significant predictor of glucose
disposal; and 3) correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for
O2 max.
Insulin sensitivity and
O2 max.
Our results agree with several studies that have shown a strong,
positive relationship between aerobic capacity and insulin sensitivity
(5, 6, 29, 34). Bogardus et al. (5, 6) and
Nyholm et al. (29) showed that
O2 max was a stronger predictor of
insulin sensitivity than overall adiposity. These early studies did
not, however, measure abdominal or thigh muscle fat content. Recent
studies that have combined aerobic capacity measurements with imaging
techniques have shown that intra-abdominal, subcutaneous abdominal, and
thigh muscle fat are more closely associated with insulin sensitivity
than
O2 max (9, 18).
Although these results appear to disagree with the present study and
previous work (5, 6, 29), some important differences among
studies should be considered. Specifically, divergent results have been
derived from studies examining sedentary (18) and/or obese
(9, 18) individuals. Limiting the range of
O2 max by recruiting sedentary subjects
may reduce the correlation between
O2 max and glucose disposal by
restricting the range of the independent variable (37).
Additionally, the relationship between
O2 max and insulin sensitivity may be
less apparent in obese individuals (9, 18) as the effect
of adiposity on glucose disposal becomes predominant. Differences in
subject selection, therefore, may explain variable results among studies.
Insulin sensitivity and physical activity energy expenditure.
To our knowledge, this is the first study to examine the relationship
between physical activity energy expenditure measured by doubly labeled
water and insulin-stimulated glucose uptake in humans. Physical
activity energy expenditure was not related to insulin-stimulated
glucose disposal or its components. The extent to which our measurement
of physical activity energy expenditure reflects the "amount" of
physical activity is not known, because differences in body size among
individuals can alter the energetic cost of a given amount of physical
activity. No correlation was found, however, between glucose disposal
data and physical activity energy expenditure after statistical
adjustment for body mass with partial correlation analysis or when
physical activity energy expenditure was divided by body
mass0.5. Thus, we conclude from these findings that insulin
sensitivity was more closely related to the physiological capacity for
aerobic activity, as reflected by
O2 max, than the caloric expenditure of
physical activity, as measured by doubly labeled water over a 10-day period.
Insulin sensitivity and adiposity. Measures of total and regional adiposity were negatively related to insulin sensitivity. Total adiposity, expressed on an absolute (kg) or relative basis (%body mass), was a stronger correlate of glucose disposal measures than regional body fat measurements. Our results agree with Bonoro et al. (8), who showed that total adiposity was a stronger correlate of glucose disposal than either abdominal subcutaneous or intra-abdominal fat in nonobese, premenopausal women. Our findings differ, however, from recent studies showing stronger relationships of intra-abdominal, deep subcutaneous abdominal, and thigh muscle fat to insulin sensitivity compared with total adiposity (9, 18, 22). One explanation for differences among studies is subject selection. Previous studies that have found relatively strong correlations between regional adiposity measures and insulin sensitivity have included obese subjects (9, 18, 22). Regional adiposity measures have been shown to be stronger determinants of glucose disposal in obese compared with nonobese individuals (8, 18). Thus the absence of an association between insulin sensitivity and regional adiposity measurements in the current study may relate to the fact that nonobese women were studied.
Reasons for the differing relationship of insulin sensitivity to total and regional adiposity in the nonobese and obese states are not clear (8). This observation could reflect differences in the effect of overall and regional adiposity on pathways of insulin-stimulated glucose disposal throughout the adiposity spectrum. For example, as demonstrated by Bogardus et al. (5) in Pima Indian men, total adiposity may antagonize insulin sensitivity up to some threshold level and then lose its effect at higher levels of body fat (>28% body fat). This threshold may mark the point at which fat accumulates in specific anatomic depots (i.e., intra-abdominal, deep subcutaneous abdominal, thigh muscle) to a level where it affects glucose disposal. At this point, the distribution of fat would become a more important modulator of insulin sensitivity than overall adiposity. This threshold level of adiposity, however, may vary among individuals, depending on age, gender, and ethnic admixture. An equally tenable explanation, however, is that differences in the predictors of insulin sensitivity between lean and obese individuals are a function of the variation in total and regional adiposity measures in these two populations. In studies that have examined obese individuals (9) or combined obese and lean volunteers (18, 22), the CV for total adiposity measures is less than that for regional adiposity markers. In contrast, in nonobese populations, the CVs for total adiposity measures are nearly equivalent to regional adiposity measures (Table 1). Considering that, mathematically, the correlation coefficient is a function of the standard deviations of the dependent and independent variable, the reduced variability in overall adiposity in obese individuals could limit the strength of its association to insulin sensitivity (37). In conclusion, our findings suggest that ![]() |
ACKNOWLEDGEMENTS |
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The authors thank all the participants who volunteered their time for this study. We are grateful to Chris Potter for skilled assistance.
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FOOTNOTES |
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This work was supported by grants from National Institutes of Health (AR-02125, AG-13978, M01 RR-1093252, and AG-151121), the US Department of Agriculture (96-35200-3488), and the General Clinical Research Center (RR-00109).
Address for reprint requests and other correspondence: E. T. Poehlman, Given Bldg. C-247, Univ. of Vermont, Burlington, VT 05405.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 2 October 2000; accepted in final form 28 February 2001.
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