Ethnic differences in pancreatic fat accumulation and its relationship with other fat depots and inflammatory markers.

Abstract

Visceral adipose tissue (VAT) and hepatic fat are associated with insulin resistance and vary by sex and ethnicity. Recently, pancreatic fat fraction (PFF) has also been linked with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relationship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and inflammation in obese adolescents and young adults.
We examined 138 (40 males, 98 females) obese Hispanics and African Americans (13-25 years). Subcutaneous adipose tissue and VAT volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging. Insulin sensitivity and β-cell function were assessed during an intravenous glucose tolerance test.
Hispanics had higher PFF than African Americans (7.3 ± 3.8 vs. 6.2 ± 2.6%, P = 0.03); this ethnic difference was higher in young adults compared with children and adolescents (ethnicity × age: P = 0.01). Males had higher PFF than females (P < 0.0001). PFF was positively correlated with VAT (r = 0.45, P < 0.0001), HFF (r = 0.29, P < 0.0001), and FFA (r = 0.32, P = 0.001). PFF positively correlated with inflammatory markers but lost significance when adjusted for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF (adjusted R(2) = 0.40). There were no significant correlations between PFF and markers of insulin sensitivity or β-cell function.
PFF is higher in Hispanics than African Americans, and this difference increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA, thus possibly contributing to their increased risk for type 2 diabetes and related metabolic disorders.

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Ethnic Differences in Pancreatic Fat
Accumulation and Its Relationship With
Other Fat Depots and Inflammatory
Markers
KIM-ANNE LÊ, PHD1
EMILY E. VENTURA, PHD1
JESSICA Q. FISHER, BSC1
JAIMIE N. DAVIS, PHD1
MARC J. WEIGENSBERG, MD2
MARK PUNYANITYA, PHD3
HOUCHUN H. HU, PHD4
KRISHNA S. NAYAK, PHD4
MICHAEL I. GORAN, PHD1
OBJECTIVE—Visceral adipose tissue (VAT) and hepatic fat are associated with insulin re-
sistanceandvarybysexandethnicity.Recently,pancreaticfatfraction(PFF)hasalsobeenlinked
with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relation-
ship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and
inflammation in obese adolescents and young adults.
RESEARCH DESIGN AND METHODS—We examined 138 (40 males, 98 females)
obese Hispanics and African Americans (13–25 years). Subcutaneous adipose tissue and VAT
volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging.
Insulinsensitivityandb-cellfunctionwereassessedduringanintravenousglucosetolerancetest.
RESULTS—Hispanics had higher PFF than African Americans (7.3 6 3.8 vs. 6.2 6 2.6%, P =
0.03); this ethnic difference was higher in young adults compared with children and adolescents
(ethnicity 3 age: P = 0.01). Males had higher PFF than females (P , 0.0001). PFF was positively
correlated with VAT (r = 0.45, P , 0.0001), HFF (r = 0.29, P , 0.0001), and FFA (r = 0.32, P =
0.001).PFFpositivelycorrelatedwithinflammatorymarkersbutlostsignificancewhenadjusted
for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF
(adjusted R2= 0.40). There were no significant correlations between PFF and markers of insulin
sensitivity or b-cell function.
CONCLUSIONS—PFF is higher in Hispanics than African Americans, and this difference
increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA,
thus possibly contributing to their increased risk for type 2 diabetes and related metabolic
disorders.
Diabetes Care 34:485–490, 2011
A
adipose tissue (VAT), skeletal muscle, or
liver,islinkedtoinsulinresistance,which
iscentraltothepathophysiologyoftype2
diabetes (1–3). The unifying mechanisms
are that in obese individuals, alteration
of adipose tissue lipolysis increases
ccumulation of lipids in tissues oth-
ers than subcutaneous adipose tis-
sue (SAT), such as in the visceral
circulating free fatty acids (FFA), which
may play a role in liver fat accumulation
(4) and inflammatory processes (5).
Most prior work in the area of ectopic
fat has focused on muscle and liver, but
there is also evidence that pancreatic fat
deposition is related to obesity (6). Early
autopsy studies from the 1930s demon-
strated an association between body
weight and pancreas weight in humans
and a higher fat content in the pancreas
ofobeseversusleancadavers.Morerecent
studies using imaging techniques con-
firmed that the pancreatic fat content in-
creased with BMI and age (6–9).
Hispanics and African Americans are
twoethnicgroupswithhighprevalenceof
obesity and type 2 diabetes (10). How-
ever,regionalfatdistributionsignificantly
differs between these two ethnicities: His-
panics tend to accumulate more VAT and
have higher hepatic fat fraction (HFF),
whereas African Americans have lower
levels of VAT and HFF but higher levels
of SAT (11). Whether pancreatic fat dif-
fers between these two at-risk minorities
remains unknown.
The primary focus of the current
study was to determine ethnic differences
in pancreatic fat fraction (PFF) in obese
Hispanic and African American adoles-
cents and young adults. The secondary
aims were to assess the associations be-
tween pancreatic fat and other fat com-
partments including liver, VAT, and SAT,
as well as circulating FFA and insulin
sensitivity, b-cell function, and circulat-
ing markers of inflammation.
RESEARCH DESIGN AND
METHODS
Study subjects
This cross-sectional analysis includes 138
overweight (age- and sex-specific BMI
$85th percentile based on Centers for
Disease Control and Prevention charts
or BMI $30 kg/m2in adults), African
American or Hispanic ethnicity (self-
report and based on all four grandparents
beingofthesameethnicgroup),aged13–
25yearsold.Participantswereexcludedif
they had taken medications known to ef-
fect body composition, been diagnosed
with any major illness since birth, or
had any diagnostic criteria for diabetes.
Written informed consent and assent
was received from both parents and chil-
dren. This study was approved by the In-
stitutional Review Board.
c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c c
From the1Department of Preventive Medicine, Childhood Obesity Research Center, University of Southern
California, Los Angeles, California; the2Department of Pediatrics, Keck School of Medicine, University of
Southern California, Los Angeles, California; the3Obesity Research Center, Columbia University, New
York, New York; and the4Magnetic Resonance Engineering Laboratory, Ming Hsieh Department of Elec-
tricalEngineering,ViterbiSchoolofEngineering,UniversityofSouthernCalifornia,LosAngeles,California.
Corresponding author: Michael I. Goran, goran@usc.edu.
Received 26 April 2010 and accepted 6 November 2010.
DOI: 10.2337/dc10-0760. Clinical trial reg. no. NCT00697580, clinicaltrials.gov
© 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited,theuseiseducationalandnotforprofit,andtheworkisnotaltered.Seehttp://creativecommons.org/
licenses/by-nc-nd/3.0/ for details.
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Anthropometry and fat
quantification
Weight and height were measured to the
nearest 0.1 kg and 0.1 cm, respectively,
using a beam medical scale and wall-
mounted stadiometer, and BMI was cal-
culated(12).Wholebodyfatandsoftlean
tissuewasmeasuredbydual-energyX-ray
absorptiometry (DEXA) using a Hologic
QDR 4500 W (Hologic, Bedford, MA).
Abdominal magnetic resonance imag-
ing data were obtained by the Dixon
method,withasensitivethree-pointchem-
ical-shift fat-water separation method
using a 1.5 Tesla Siemens Symphony
Maestro whole-body scanner (Siemens
AG, Erlangen, Germany) with Numaris 4
software. A two-dimensional multislice
breath-hold protocol previously reported
by Hussain et al. (13) was adopted to ob-
tain 19 axial images across the abdomen
from the dome of the liver to the L2-L3
vertebrae. The standard body transmit
and receive coil was used, along with a
rectangular field-of-view of 420 mm
(right/left) by 315 mm (anterior/poste-
rior). The slice thickness was 10 mm
withnointerslicegaps.Thefat-onlydata-
set was used in the subsequent quantifi-
cation of SAT and VAT volume, whereas
the fat fraction dataset was used to assess
percent hepatic and pancreatic fat con-
tent (HFF, PFF). The computations for
SAT, VAT, HFF, and PFF were performed
by a trained operator (M.P.) at the Image
Analysis Laboratory of St. Lukes-Roosevelt
Hospital Center in New York. A com-
mercially available image segmentation
and quantification software (SliceOmatic,
Tomovision) was used. SAT and VAT
volumeswerecomputedacrossall19im-
age slices in each subject. HFF and PFF
were computed as the mean fat fraction
of all imaging slices within which the
liver and the pancreas was present,
respectively.
Frequently sampled intravenous
glucose tolerance test
An insulin-modified frequently sampled
intravenous glucose tolerance test
(IVGTT) (14,15) was performed after an
overnight fast. Upon arrival, a topical
anesthetic (EMLA cream; Aztrozeneca,
Wilmington, DE) was appliedtotheante-
cubital area of both arms and an hour
later a flexible intravenous catheter was
inserted into both of the arms. At time
0 min, glucose (25% dextrose, 0.3 g/kg
body wt) was administered intrave-
nously. Insulin (0.02 units/kg body wt,
Humulin R [regular insulin for human
injection]; Eli Lilly, Indianapolis, IN)
was injected intravenously at 20 min.
Blood samples of glucose and insulin
were collected at time points 215, 25,
2, 4, 8, 19, 22, 30, 40, 50, 70, 100, and
180 min and of FFA at time 215.
Blood analysis
Blood samples from all time points taken
during the IVGTT were centrifuged im-
mediately for 10 min at 860 g and 8–10°C,
and plasma was collected and frozen at
270°Cuntilassayed.Glucosewasassayed
in duplicate on a Yellow Springs Instru-
ment 2700 Analyzer (Yellow Springs In-
strument, Yellow Springs, OH) using the
glucose oxidase method. Insulin was as-
sayed in duplicate using a specific human
insulin ELISA kit from Linco (St. Charles,
MO) and FFA using a colorimetric kit
(NEFA-HR[2],WakoDiagnostics).Circu-
lating inflammatory mediators including
plasminogen activator inhibitor 1 (PAI-1),
monocyte chemoattractant protein-1
(MCP-1), interleukin-8 (IL-8), tumor ne-
crosis factor-a (TNF-a), and hepatocyte
growth factor (HGF) were measured in
batch using multiplex Luminex assays
(Linco Research) (16). High-sensitivity
C-reactive protein (hs-CRP) was mea-
sured chemically using ADVIA 1800
Chemistry System (Siemens Healthcare
Diagnostics, Deerfield, IL). Because of
missing samples, cytokines were obtained
only in a subgroup of 108 participants.
Calculations
Plasma collected during the IVGTT was
analyzed for glucose and insulin, and
values were entered into the MINMOD
Millenium 2003 computer program (ver-
sion 5.16, Bergman) to determine insulin
sensitivity index (ISI), glucose effective-
ness (Sg), acute insulin response (AIR),
and disposition index (DI) (17). ISI was
defined as the net capacity for insulin to
promote the disposal of glucose and to
inhibit the endogenous production of
glucose,whereasSgindicatedthecapacity
of glucose to mediate its own disposal.
AIR was defined as the area under the
plasma insulin curve between 0 and
10 min, and DI, an index of b-cell func-
tion, was calculated as the product of AIR
and ISI.
Statistical methods
ANOVA was used to compare unadjusted
insulin sensitivity, fat distribution, and
body composition variables by sex and
ethnicity. Post hoc comparisons were
done using Tukey-Kramer test. Because
HFF, PFF, PAI-1, and hs-CRP were not
normally distributed, they were log-
transformed before all statistical analyses.
Adjustments of comparisons for potential
confoundersincludingage,sex,ethnicity,
BMI, total fat, visceral fat, and lean body
mass were performed using ANCOVA
when appropriate. Pearson correlation
tests were used to assess the relationships
between PFF and the other parameters.
Afterpotential ethnicand sexinteractions
were tested, these calculations were per-
formed in the entire sample when inter-
actions were found not significant. To
examine the main predictor of pancreatic
fat, we performed a stepwise multiple
regression analysis including ethnicity,
sex, age, total fat, visceral fat, hepatic fat,
FFA, and DI as independent variables. All
data are means 6 SD, and statistical anal-
yses were performed using STATA ver-
sion 11.0 (Stata Corp, College Station,
TX), with a significance level of P , 0.05.
RESULTS
Ethnic, sex, and age differences
in fat depots
Characteristics of subjects by ethnicity
and sex subgroups are shown in Table 1.
All subgroups were of similar age and
BMI. Hispanics had higher levels of total
body fat (40.2 6 6.0 vs. 37.5 6 6.5%, P =
0.007), VAT (2.6 6 1.3 vs. 1.5 6 0.9 L,
P , 0.0001), and HFF (7.3 6 5.3 vs.
4.5 6 3.2%, P , 0.0001) than African
Americans as well as a trend for lower
subcutaneous fat (13.9 6 5.1 vs. 15.4 6
5.9 L, P = 0.056) (Fig. 1). PFF was higher
in males compared with females (8.3 6
3.8 vs. 6.4 6 3.2%, P = 0.006). These
results remained significant when ad-
justed for sex, BMI, and age. In both eth-
nicities, there was a significant (P , 0.05)
effect of age on all fat compartments. Par-
ticipants aged 18–25 years compared with
the13–17yearsgrouphadhigherlevelsof
SAT (16.1 6 13.9 vs. 13.9 6 5.8 L), VAT
(2.9 6 1.6 vs. 1.8 6 1.1 L), HFF (7.5 6
6.0 vs. 5.7 6 4.3%), and PFF (8.7 6 4.5
vs. 6.4 6 2.9%). These differences re-
mained significant after adjusting for eth-
nicity, sex, BMI, and lean body mass.
Hispanics over age 18–25 years have
higher PFF than younger Hispanics aged
13–17 years or African Americans of sim-
ilar age: in ANCOVA analysis of PFF in-
cluding ethnicity,age, and the ethnicity3
age interaction, all factors were significant
(ethnicity: P = 0.02; age: P = 0.001; eth-
nicity 3 age: P = 0.01) (Fig. 1).
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Relationships with other fat depots
and indexes of obesity
In univariate analysis, there was a signifi-
cant relationship between PFF and several
body composition variables, including
BMI, SAT, VAT, and HFF, as well as
circulatingFFA(Table2).Afteradjustment
forethnicity,sex,age,BMI,andoveralltotal
fat, PFF remained correlated with BMI (r =
0.28, P = 0.01), SAT (r = 0.21, P = 0.06),
and VAT (r = 0.35, P = 0.002). HFF and
PFF were positively correlated with each
other (r = 0.34, P , 0.0001), but this cor-
relation was no longer significant after ad-
justing for VAT (Fig. 2).
TherelationshipbetweenPFFandVAT
was significantly influenced by ethnicity
(P = 0.03 for interaction), with a stronger
relationship between PFF and VAT in His-
panics than African Americans (Hispanics:
r=0.58,P,0.0001;AfricanAmericans:r=
0.32, P = 0.01). Multiple stepwise regres-
sion analysis using PFF as the dependant
variable and ethnicity, sex, age, total fat,
SAT, VAT, HFF, FFA, and DI as indepen-
dent variables showed that only VAT and
FFA were significant predictors of PFF
(VAT:P , 0.001;FFA: P ,0.05),together
explaining 40% of the variance in PFF.
Relationships between PFF and
insulin sensitivity, b-cell function,
and markers of inflammation
PFF was not correlated with any outcome
relatedtoglucoseorinsulin,includingISI
andDI(P.0.05),evenafteradjustingfor
ethnicity, sex, BMI, and age. Relation-
ships between PFF and AIR or DI were
further adjusted for ISI, which did not
modify the results. Among inflammatory
markers, PFF was positively correlated
with PAI-1 (r = 0.26, P = 0.009), MCP-1
(r = 0.23, P = 0.02), IL-8 (r = 0.28, P =
0.006), and HGF (r = 0.20, P = 0.04),
and a trend was observed for TNF-a (r =
0.18, P = 0.07). These correlations, how-
ever, were no longer significant when ad-
justed for VAT. There was no significant
relationship between PFF and hs-CRP
(P . 0.05).
CONCLUSIONS—This study shows
that obese Hispanic young adults have
higher pancreatic fat accumulation than
obese African Americans and that this
ethnic difference becomes greater with
increasing age. Pancreatic fat was posi-
tively associated with VAT volume and
liver fat deposition, as well as increased
concentrations of plasma FFA.
Previous studies have consistently
reported that Hispanics accumulate
more VAT and HFF than African Amer-
icans,whereasthelatterhavehigherlevels
of SAT (11). VAT is known to be more
deleterious than SAT, because of its high
rate of lipolysis and delivery of portal in-
flammatorycytokines(18).Thismaycon-
tribute to higher liver fat deposition, a
strong predictor of insulin resistance
(18).Our resultssupportthese ethnicdif-
ferencesinfatpartitioningandfurtherun-
derlinethefactthattheyaredetectedearly
in life. Furthermore, we show that pan-
creatic fat deposition is higher in Hispan-
ics than African Americans. Pancreatic fat
has recently been identified as a novel
obesity-related fat depot (6–9). It is
higher in males than females and linearly
increases with age and BMI (6,7), consis-
tent with our results. In this study, we
further show that ethnic differences in
PFF are exacerbated with increased age
even in young populations, with a two-
fold higher PFF in Hispanics versus Afri-
can Americans from the 19–25 year
group. This suggests that in Hispanic
populations, PFF may cluster with high
amounts of VAT and liver fat, thus possi-
blycontributing totheirincreasedrisk for
type 2 diabetes and related metabolic dis-
orders as they grow up.
We therefore addressed the relation-
ships between these various fat depots.
HFF increases with obesity, and more
specifically VAT (19–21). VAT has a high
rate of lipolysis, which allows direct de-
livery of fatty acids into the portal vein,
leading to hepatic lipid accumulation
(18,22). Similar relationships exist in re-
gard to pancreatic fat: recent imaging
studies showed that both pancreatic vol-
ume and fat content increased with BMI
(6,7), waist:hip ratio (6), and VAT depo-
sition (9,23). We further extend this
Table 1—Anthropometric and metabolic parameters of subjects
HispanicAfrican American
P value
ethnicity
P value
sex
Males
(n = 20)
Females
(n = 54)
Males
(n = 20)
Females
(n = 44)
Anthropometric parameters
Age (years)
BMI (kg/m2)
Fat depots
Total fat (%) (n = 99)
SAT (L)
VAT (L)
HFF (%)
PFF (%)
Plasma FFA (mmol/L)
Glucose and insulin homeostasis
Fasting glucose (mmol/L)
Fasting insulin (pmol/L)
AIR (pmol/L 3 10 min)
Sg(% per min)
ISI (31024min21/mU/mL)
DI (31024min21)
Data are means 6 SD. Fasting glucose and fasting insulin values for both Hispanics and African Americans were tested using a two-way ANOVA, followed by Tukey-
Kramer tests.
17.1 6 2.7
34.2 6 4.3
16.8 6 3.2
35.1 6 5.5
17.7 6 4.4
36.0 6 5.3
17.2 6 2.9
34.8 6 6.7
NS
NS
NS
NS
31.8 6 3.6
13.7 6 4.7
3.4 6 1.5
8.9 6 6.6
8.0 6 4.0
0.80 6 0.13
42.5 6 4.4
14.0 6 5.3
2.2 6 1.1
6.7 6 4.8
7.0 6 3.8
0.78 6 0.18
31.5 6 7.3
15.2 6 5.2
2.1 6 1.2
6.0 6 4.0
7.9 6 3.6
0.76 6 0.15
39.0 6 5.2
15.9 6 6.2
1.2 6 0.08
3.8 6 1.8
5.5 6 1.6
0.69 6 0.18
,0.0001
NS
,0.0001
,0.001
,0.0001
0.04
0.01
NS
,0.0001
,0.0001
,0.005
NS
5.1 6 0.3
127 6 69
10,438 6 5,535
0.02 6 0.01
1.6 6 0.8
2,047 6 1,018
5.1 6 0.4
152 6 91
9,208 6 5,286
0.02 6 0.02
1.8 6 1.5
1,708 6 754
5.0 6 0.5
137 6 118
16,619 6 10,872
0.02 6 0.01
1.5 6 1.0
2,696 6 1,295
5.4 6 0.4
127 6 69
13,486 6 10,885
0.02 6 0.01
1.4 6 0.9
2,009 6 1,189
0.01
NS
0.001
NS
NS
0.02
NS
NS
NS
NS
NS
0.01
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finding and show that PFF positively cor-
relates with both VAT and HFF, indepen-
dently of BMI, total fat, and SAT content
in an at-risk minority population. A pre-
vious study also reported simultaneous
occurrence of fatty liver and fatty pancreas
in overweight individuals (23), suggesting
a common etiology to fat accumulation in
these two organs. These results contrast
with those from the Tushuizen study (8),
who did not report any relationship be-
tween PFF and HFF. These contradictory
results may possibly arise from method-
ology differences since Tushuizen et al.
used magnetic resonance spectropscopy
or from differences in population age
and ethnicity. Because Hispanics are
highly prone to visceral and liver fat ac-
cumulation, they may be genetically pre-
disposed to altered fat partitioning in
ectopic tissues as a whole.
We subsequently addressed whether
PFF was related to abnormal endocrine
function. PFF has been linked to low
insulin sensitivity, measured by 2-h post-
challenge glucose concentration (6,9) or
homeostasis model assessment of insulin
resistance(23),aswellasinsulinsecretion
(8). However, this last observation was
found in healthy individuals but not in
type 2 diabetic patients. In contrast,
Heni et al. reported an inverse relation-
ship between PFF and insulin secretion
in individuals with impaired fasting glu-
cose or impaired glucose tolerance but
not normoglycemic participants (9). The
authors postulated that PFF may have ad-
versemetaboliceffectswheninsulinresis-
tance is present. Our results support this
hypothesis: despite being overweight, all
study participants were normoglycemic.
Moreover, this study involved adoles-
cents and young adults, who may be at
more heterogeneous stages in the pro-
gression of b-cell failure, compared with
olderadults.Takentogether,theseresults
suggest that pancreatic fat is negatively
correlated with insulin secretion in indi-
viduals with impaired glucose tolerance
but not in normoglycemic individuals or
type 2 diabetic patients. Thus pancreatic
fat accumulation may play a pivotal role
during the intermediary step of the disease
and negatively affect insulin secretion only
by persistent insulin resistance, when
b-cells cannot anymore compensate for
the increased insulin demand.
To further identify metabolic pertur-
bations linked to PFF, we assessed the
relationship between PFF and FFA. FFA
are elevated in obese patients and are
strongpredictorsofhepaticfatdeposition
(4). We show that in a multiple stepwise
regression analysis, FFA and VAT were
the strongest predictors of PFF. Several
animal studies have assessed the effect of
lipotoxicity on b-cell function. In Zucker
diabetic fatty rats, plasma FFA were ele-
vated 3 to 4 weeks before they became
diabetic (22). The elevated FFA concen-
trations were followed within 2 weeks by
islet triglyceride accumulation and im-
paired insulin secretion. Interestingly,
these alterations were reversed by reduc-
ing plasma FFA, suggesting a causal role
ofhighplasmaFFAonalteredb-cellfunc-
tion. The authors proposed that high cir-
culating FFA may lead to b-cell lipid
Figure 1—SAT (A), VAT (B), HFF (C), and PFF (D) by age and ethnic groups. All data show
means 6 SE and were analyzed by using 2-factor ANOVA; the Tukey-Kramer test was used
during post hoc comparisons. AA, African American; Hisp, Hispanic. *Significant (P , 0.05)
effect of ethnicity; †significant (P , 0.05) effect of age.
Table 2—Pearson correlation coefficients between PFF and other metabolic parameters
Pearson coefficient
P value
Body composition
BMI (kg/m2)
Total fat (%)
SAT (L)
VAT (L)
HFF (%)
Glucose and insulin homeostasis
AIR (mU/mL 3 10 min)
ISI (31024min21/mU/mL)
DI (31024min21)
Lipid metabolism
FFA (mmol/L)
Inflammation
MCP-1 (pg/mL)
IL-8 (pg/mL)
TNF-a (pg/mL)
HGF (pg/mL)
PAI-1 (pg/mL)
hs-CRP
0.24
—
0.21
0.45
0.29
0.02
NS
0.001
,0.0001
0.006
—
—
—
NS
NS
NS
0.32 0.0008
0.23
0.29
0.18
0.20
0.26
—
0.003
0.003
0.06
0.04
0.01
NS
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accumulation, which may subsequently
impair b-cell function, possibly by stim-
ulation of ceramide production, similarly
to what has been described in the skeletal
muscle (2) and liver (3).
Finally, markers of chronic inflam-
mation have been associated with type 2
diabetes, b-cell dysfunction (24), and he-
patic fat accumulation. We found that
PFFwasassociatedwithproinflammatory
cytokinesMCP-1,IL-8,TNF-a,HGF,and
thrombogenic factor PAI-1. These mark-
ers are usually elevated in obese patients
and are linked to insulin resistance and
liver fat. However, when adjusted for
VAT, these relationships were no longer
significant. This suggests that in our pop-
ulation, inflammatory markers merely re-
flect VAT-related inflammation rather
than cytokine production by the pan-
creas.Wethereforecannotstatethatthere
is a direct relationship between PFF and
inflammation either as a cause or conse-
quence.
A limitation of our study includes the
assessmentofinsulinsecretionbyIVGTT.
Although IVGTT is the gold-standard
method to evaluate glucose-mediated in-
sulin secretion, it does not allow mea-
surement of incretin-stimulated insulin
secretion that physiologically occurs after
meal consumption, which potentiates in-
sulin secretion (25). It remains therefore
possiblethatpancreaticfatmayaffectspe-
cifically meal-induced insulin secretion.
Collectively, these results raise con-
cern about the effects of pancreatic fat
accumulation in humans. Hispanics ac-
cumulatemorepancreaticfatthanAfrican
Americans.Pancreaticfatiscloselyrelated
to other deleterious fat depots, such as
VAT and liver fat, which are elevated in
Hispanics, a population at high risk for
metabolic disease. Pancreatic fat is also
positively related to circulating FFA,
which may trigger lipotoxicity and affect
pancreatic function in the long run.
Acknowledgments—This work was sup-
ported by the National Cancer Institute,
University of Southern California Center for
Transdisciplinary Research on Energetics and
Cancer(U54CA116848);theNationalInstitute
ofChildHealthandHumanDevelopment(R01-
HD/HL-33064); theDr.RobertC. and Veronica
Atkins Foundation; the National Cancer In-
stitute (Cancer Control and Epidemiology
Research Training Grant T32-CA-09492);
and the National Center for Research Re-
sources/National Institutes of Health (M01-
RR-00043). K.-A.L. is supported by a grant
from the Swiss National Science Foundation
(PBLA33-122719).
No potential conflicts of interest relevant to
this article were reported.
K.-A.L. collected and analyzed data, con-
tributed to discussion, wrote the article, and
read and reviewed the article. E.E.V. collected
data, contributed to discussion, and read and
reviewed the article. J.Q.F., J.N.D., M.J.W.,
and M.P. read and reviewed the article. H.H.H.,
K.S.N., and M.I.G. contributed to discussion
and read and reviewed the article.
The authors thank the teams from the Child-
hood Obesity Research Center who were in-
volved in the studies, as well as the nursing staff
at the General Clinical Research Center. In ad-
dition, the authors are grateful for study partic-
ipants and their families for their involvement.
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Pancreatic fat in minority populations