Ethnic variation in adiponectin and leptin levels and their association with adiposity and insulin resistance.

Abstract

To investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high-glycemic index diet account for ethnic variation in insulin resistance.
In 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment-insulin resistance (HOMA-IR).
Adiponectin concentrations were significantly higher in Europeans (adjusted mean 12.94 [95% CI 2.27-13.64]) and Aboriginal people (11.87 [11.19-12.59]) than in South Asians (9.35 [8.82-9.92]) and Chinese (8.52 [8.03-9.03]) (overall P < 0.001). Serum leptin was significantly higher in South Asians (11.82 [10.72-13.04]) and Aboriginal people (11.13 [10.13-12.23]) than in Europeans (9.21 [8.38-10.12]) and Chinese (8.25 [7.48-9.10]). BMI and waist circumference were inversely associated with adiponectin in every group except the South Asians (P < 0.001 for interaction). Adiponectin was inversely and leptin was positively associated with HOMA-IR (P < 0.001). The increase in HOMA-IR for each given decrease in adiponectin was larger among South Asians (P = 0.01) and Aboriginal people (P < 0.001) than among Europeans. A high glycemic index was associated with a larger decrease in adiponectin among South Asians (P = 0.03) and Aboriginal people (P < 0.001) and a larger increase in HOMA-IR among South Asians (P < 0.05) relative to that in other groups.
South Asians have the least favorable adipokine profile and, like the Aboriginal people, display a greater increase in insulin resistance with decreasing levels of adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic differences in insulin resistance.

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Ethnic Variation in Adiponectin and Leptin
Levels and Their Association With
Adiposity and Insulin Resistance
ANDREW MENTE, PHD1,2
FAHAD RAZAK, BENG, MSC1
STEFAN BLANKENBERG, MD3
VLAD VUKSAN, PHD4
A. DARLENE DAVIS, RN5
RUBY MILLER, RN5
KOON TEO, MBBCH, PHD1,2
HERTZEL GERSTEIN, MD, MSC1,2
ARYA M. SHARMA, MD, PHD1,2
SALIM YUSUF, MBBS, DPHIL1,2
SONIA S. ANAND, MD, PHD1,2
FOR THE STUDY OF HEALTH ASSESSMENT
AND RISK EVALUATION (SHARE) AND
SHARE IN ABORIGINAL PEOPLES
(SHARE-AP) INVESTIGATORS
OBJECTIVE — Toinvestigateethnicdifferencesinadiponectinandleptinconcentrationand
to determine whether these adipokines and a high–glycemic index diet account for ethnic
variation in insulin resistance.
RESEARCH DESIGN AND METHODS — In 1,176 South Asian, Chinese, Aboriginal,
and European Canadians, fasting blood samples were drawn, and clinical history and dietary
habits including glycemic index/glycemic load were recorded using standardized question-
naires. Insulin resistance was defined using homeostasis model assessment–insulin resistance
(HOMA-IR).
RESULTS — Adiponectin concentrations were significantly higher in Europeans (adjusted
mean 12.94 [95% CI 2.27–13.64]) and Aboriginal people (11.87 [11.19–12.59]) than in South
Asians(9.35[8.82–9.92])andChinese(8.52[8.03–9.03])(overallP?0.001).Serumleptinwas
significantly higher in South Asians (11.82 [10.72–13.04]) and Aboriginal people (11.13
[10.13–12.23]) than in Europeans (9.21 [8.38–10.12]) and Chinese (8.25 [7.48–9.10]). BMI
and waist circumference were inversely associated with adiponectin in every group except the
South Asians (P ? 0.001 for interaction). Adiponectin was inversely and leptin was positively
associated with HOMA-IR (P ? 0.001). The increase in HOMA-IR for each given decrease in
adiponectin was larger among South Asians (P ? 0.01) and Aboriginal people (P ? 0.001) than
among Europeans. A high glycemic index was associated with a larger decrease in adiponectin
among South Asians (P ? 0.03) and Aboriginal people (P ? 0.001) and a larger increase in
HOMA-IR among South Asians (P ? 0.05) relative to that in other groups.
CONCLUSIONS — South Asians have the least favorable adipokine profile and, like the
Aboriginal people, display a greater increase in insulin resistance with decreasing levels of
adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic
differences in insulin resistance.
Diabetes Care 33:1629–1634, 2010
E
ple of European origin have a relatively
low prevalence of insulin resistance and
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●
Fromthe1PopulationHealthResearchInstitute,HamiltonHealthSciences,McMasterUniversity,Hamilton,
Ontario, Canada; the2Departments of Medicine and Clinical Epidemiology and Biostatistics, McMaster
University, Hamilton, Ontario, Canada; the3Department of Medicine, University of Mainz, Mainz, Ger-
many; the4Departments of Nutritional Sciences and Endocrinology, University of Toronto, Toronto,
Ontario, Canada; and5Six Nations Health Services, Ohsweken, Ontario, Canada.
Corresponding author: Sonia S. Anand, anands@mcmaster.ca.
Received28July2009andaccepted29March2010.Publishedaheadofprintathttp://care.diabetesjournals.
org on 22 April 2010. DOI: 10.2337/dc09-1932.
© 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly
cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.
org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby
marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
pidemiologic studies have consis-
tently shown that compared with
nonwhite ethnic populations, peo-
type 2 diabetes despite having compara-
ble or greater body weight (1,2). Al-
though there is controversy regarding the
definition and use of the term “metabolic
syndrome,” which is often applied to the
clustering of risk factors such as abdomi-
nal obesity, elevated glucose, abnormal
lipids, and elevated blood pressure, in-
sights into the pathophysiology of adi-
pose tissue and the presence of these
insulin resistance–related factors may be
gained from studies of high- and low-risk
populations.
Insulinresistanceiscloselyassociated
with abdominal adiposity, a surrogate
measure of visceral adiposity (3). Adipo-
cytes secrete a variety of bioactive sub-
stances known as adipokines, including
twoproteins,adiponectinandleptin.Adi-
ponectin, a plasma protein secreted from
visceral adipose tissue, increases insulin
sensitivity and tissue fat oxidation, result-
ing in reduced circulating fatty acid levels
(4). Leptin, a protein that circulates in
proportion with body fat mass, provides
information about nutritional status and
subcutaneous fat mass to neural centers
that regulate feeding behavior, appetite,
andenergyexpenditure(5).Itistherefore
plausible that differences in adiponectin
and leptin levels correlate with ethnic
variations in insulin resistance and meta-
bolic syndrome–related factors.
Dietary factors may also potentially
influence adipokine levels and insulin
sensitivity. There is a growing body of lit-
eratureshowingthathigherconsumption
of foods with high glycemic index/
glycemic load values is associated with
lower adiponectin levels in both healthy
and diabetic individuals (6) and higher
leptin levels (7). Glycemic foods are
knowntoinducebothhyperglycemiaand
hyperinsulinemia (8,9). Conversely, high
intake of fiber may attenuate the glycemic
effectofafullmeal,andcerealfiberintake
is positively associated with adiponectin
(6).Previousstudieshaveshownthateth-
nic populations at higher risk for meta-
bolic syndrome–related conditions
largely consume a diet consisting of foods
with a high glycemic index (10). It is not
known whether a higher consumption of
glycemic foods influences adipokine lev-
els and insulin resistance in these
populations.
Using a multiethnic population–
based sample in which adiposity, adipo-
kines, and insulin resistance–related
C a r d i o v a s c u l a r a n d M e t a b o l i c R i s k
O R I G I N A LA R T I C L E
care.diabetesjournals.orgDIABETES CARE, VOLUME 33, NUMBER 7, JULY 2010
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Page 2

factors were measured in a standardized
manner, we investigated 1) ethnic varia-
tion in levels of adipokines, 2) whether
higher intake of glycemic foods differen-
tiallyaffectsadipokinelevelsacrossethnic
populations, and 3) whether levels of adi-
pokines and high glycemic index/
glycemicloadaccountforethnicvariation
in insulin resistance.
RESEARCH DESIGN AND
METHODS— The study population
comprised Canadians of South Asian,
Chinese, Aboriginal, or European origin
who participated in the Study of Health
Assessment and Risk in Ethnic Groups
(SHARE), a cross-sectional prevalence
study of cardiovascular disease risk fac-
tors conducted between 1996 and 1998
(2). Individuals were randomly selected
from three cities (Toronto, Hamilton, and
Edmonton)andfromtheSixNationsRes-
ervation (Ohsweken, ON) as described
previously (1,2). Subjects’ ages were
35–75 years, and they had lived in Can-
adafor?5years.Individualswithtreated
diabetes or chronic debilitating illnesses
such as terminal cancer and renal failure
were excluded. Ethics approval was ob-
tained from the McMaster University Re-
search Ethics Board and all participating
institutions. Informed consent was ob-
tained from each subject. The investiga-
tion conforms with the principles
outlined in the Declaration of Helsinki.
Assessment of adipokines and
insulin resistance–related factors
Participants completed lifestyle question-
naires, which recorded information on
physical activity, smoking patterns, and
dietary intake as described previously
(1,2). Physical measurements included
height,weight,andwaistandhipcircum-
ference using a standardized protocol.
Thephysicalactivityindexinvolvedsum-
ming ordinal categories of intensity of
physicalexertionestimatedfromreported
type of work, time spent playing sports,
and type of leisure-time activities. Occu-
pation, sports, and leisure-time activities
were classified according to exertion as
1 ? low, 2 ? moderate, and 3 ? high
based on the published literature (10).
Fasting blood samples were collected
in the morning from all participants.
Blood samples were collected and pro-
cessed according to a standard protocol
andwereshippedtothecorelaboratoryin
Hamilton for analysis. All subjects under-
went a 12-h fast before blood was drawn,
and nondiabetic participants underwent
an oral glucose tolerance test with mea-
surement of glucose, insulin, triglyceride,
and free fatty acid levels at baseline and at
2 h after the glucose load. Glucose was
measured using enzymatic methods, and
insulin was determined by manual radio-
immunoassay assay (Diagnostic Products
Corporation, Los Angeles, CA). Analysis of
adiponectin and leptin was performed in
the laboratory of Dr. Stephan Blankenberg
at the University of Mainz (Mainz, Ger-
many) using a commercially available hu-
man adiponectin ELISA (RD195023100)
and human leptin ELISA (RD191001100),
producedbyBiovendorResearchProducts.
For adiponectin, the intra-assay impreci-
sion is 6.4–7.0% and the interassay impre-
cision is 7.3–8.2%. For leptin, the intra-
assay imprecision is 3.0–7.5% and the
interassay imprecision is 3.2–9.2%. Basal
insulin resistance was calculated using the
previouslyvalidatedhomeostasismodelas-
sessment of insulin resistance (HOMA-IR).
Dietary assessment
On the food-frequency questionnaire,
participants reported how often, on aver-
age, they consumed selected foods in the
previous year. We calculated nutrient in-
takes by multiplying the average nutrient
contentofaparticularfoodportionbythe
number of times it was consumed. Glyce-
mic index and glycemic load were esti-
mated based on the International Table of
GlycemicIndexforspecificfoods.Briefly,
weassignedglycemicindexvaluestoeach
of the individual food frequency ques-
tionnaire food items by manual review of
the glycemic index table. We then com-
puted sex- and serving size–specific gly-
cemic loads for each of the food items
using the weighted mean methods as
described by Subar et al. (11). Each unit
of glycemic load represents both the
quality and the quantity of carbohy-
drate intake (or the equivalent of 1 g of
carbohydrate from white bread). The
overall glycemic index for each partici-
pant was calculated by dividing the par-
ticipant’s glycemic load by the total
grams of carbohydrate consumed,
which represents the overall quality of
carbohydrate intake.
Statistical analysis
All analyses were computed using SAS
(version 9.1; SAS Institute, Cary, NC).
Distributions of adiponectin, leptin, and
HOMA-IR were highly skewed, so geo-
metric means and natural logs are pre-
sented, adjusting for age, sex, and
adiposity measures where appropriate.
Post hoc pairwise comparisons were per-
formed using Tukey tests to adjust for
multiple comparisons. Pearson correla-
tion coefficients and linear regression
wereusedtoassesstheassociationamong
continuous variables, with age, sex, and
markers of adiposity used as covariates
where indicated. The independent pre-
dictive value of logarithmically trans-
formed adiponectin and leptin on insulin
resistance was examined in a linear re-
gression model with log-transformed
HOMA-IR as the dependent variable
along with other known determinants of
insulin resistance as independent vari-
ables (age, ethnicity, smoking, BMI,
waist-to-hip ratio [WHR], glycemic load,
energy intake, C-reactive protein, and
physical activity). Linear regression mod-
eling was also used to assess effects of gly-
cemic index or load on adipokine
concentration and insulin resistance by
ethnic origin. Differences with P ? 0.05
were considered statistically significant.
RESULTS— Complete data were
available for 1,258 people from the
SHARE population. From this sample, 18
individuals who had implausible levels of
adiponectin (?100 ?g/ml) or leptin
(?180 ng/ml) and 64 with treated diabe-
tes were excluded, leaving a final sample
of 1,176 participants.
The characteristics of participants are
displayed in Table 1. The mean age of the
overall population was 50.3 years, and
men and women were equally repre-
sented. Significant differences in age and
lifestyle factors including current smok-
ing, physical activity, measures of adipos-
ity, plasma lipids, diastolic blood
pressure, and insulin resistance were
present among ethnic groups (Table 1).
For example, Aboriginal people had sub-
stantially higher BMI and abdominal obe-
sity relative to those of other ethnic
groups.Conversely,peopleofChineseor-
igin had the lowest BMI and abdominal
adiposity. Europeans have a higher BMI,
yetlessabdominalobesitycomparedwith
South Asians. Despite these differences,
South Asians and Aboriginal people were
moreinsulinresistantthantheEuropeans
(all P ? 0.05).
Adipokines and ethnicity
Adiponectin levels were significantly
higher in Europeans and Aboriginal peo-
ple than in those of the other ethnic
groups (age- and waist-adjusted mean
[95% CI] in Europeans 12.96 ?g/ml
[12.27–13.64] and Aboriginal people
Adipokines, ethnicity, and insulin resistance
1630
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Page 3

11.87 ?g/ml [11.19–12.59] vs. South
Asians 9.35 ?g/ml [8.82–9.92] and Chi-
nese 8.52 ?g/ml [8.03–9.03]; overall P ?
0.001)(Table1).Serumleptinlevelswere
significantly higher in South Asians
(11.82 [10.72–13.04]) and Aboriginal
people(11.13[10.13–12.23])thaninEu-
ropeans (9.21 [8.38–10.12]) and Chi-
nese (8.25 [7.48–9.10]) (Table 1).
SouthAsianwomenandmenhadsig-
nificantly higher leptin concentrations
than all other groups (Table 1). A signifi-
cant sex by ethnic origin interaction with
serum leptin was present (P ? 0.01), as
Aboriginal women had significantly
higher leptin concentrations than Euro-
pean women for the same BMI, whereas
no significant differences were observed
among men. No significant sex by ethnic
origin interaction was observed for
adiponectin.
Adipokines and ethnicity by
adiposity
Adiponectin was strongly and inversely
associated with all adiposity measures,
whereas leptin was positively associated
with the adiposity measures (all P values
?0.001). As shown in Table 1 (available
in an online appendix at http://care.
diabetesjournals.org/cgi/content/full/dc09-
1392/DC1), adiponectin was negatively
associatedwithBMI,waistcircumference,
waist adjusted for hip circumference, and
WHRinEuropeans,Chinese,andAborig-
inal people, but not in South Asians. Lep-
tin was significantly associated with BMI
and central adiposity measures across all
ethnic groups.
Adipokines and insulin resistance
To determine whether adiponectin and
leptin were independently associated
with insulin resistance over and above
factors known to be associated with insu-
lin resistance (i.e., adiposity, glycemic
diet, smoking, and physical activity), a
multivariatelinearregressionanalysiswas
performed.AsshowninTable2(available
in the online appendix), factors that were
positively associated with insulin resis-
tance included South Asian (P ? 0.001),
Chinese(P?0.001),andAboriginal(P?
0.001) ancestry, serum leptin (P ?
0.001), age (P ? 0.01), BMI (P ? 0.001),
and WHR (P ? 0.001). Factors that were
negatively associated with insulin resis-
tance included serum adiponectin (P ?
0.001), female sex (P ? 0.02), and phys-
ical activity (P ? 0.003). C-reactive pro-
tein, glycemic index/glycemic load,
current smoking, and energy intake were
notindependentlyassociatedwithinsulin
resistance after accounting for the above
Table 1—Distribution of risk factors among Europeans, Chinese, South Asians, and Aboriginal people living in Canada
European ChineseSouth AsianAboriginal Overall P value*
n
Age (years)
Female sex
Current smoker
BMI (kg/m2)†
WHR†
LDL cholesterol (mmol/l)†
HDL cholesterol (mmol/l)†
Triglycerides (mmol/l)†
C-reactive protein (mg/l)†
Free fatty acids (mEq/ml)†
Fasting glucose (mmol/l)
2-h glucose (mmol/l)
A1C (%)
Impaired fasting glucose
Impaired glucose tolerance
Newly diagnosed type 2 diabetes‡
HOMA-IR†
Systolic blood pressure (mmHg)†
Diastolic blood pressure (mmHg)†
Energy intake (kcal)†
High physical activity
Physical activity (h/week)†
Adiponectin (?g/ml)§
Men
Women
Total
Leptin (ng/ml)?
Men
Women
Total
Dataaremeans?SEMorn(%).*Pvalues:1P?0.05,Europeanvs.Chinese;2P?0.05,Europeanvs.SouthAsian;3P?0.05,Europeanvs.Aboriginalpeople;4P?
0.05, Chinese vs. South Asian;5P ? 0.05, Chinese vs. Aboriginal people;6P ? 0.05, South Asian vs. Aboriginal people. †Means are adjusted for age and sex. ‡New
clinicallydiagnosedtype2diabetesasdeterminedby2-horalglucosetolerancetest.§Geometricmeansforadiponectinareadjustedforageandwaistcircumference
(because adiponectin is highly correlated with waist girth). ?Geometric means for leptin are adjusted for age and BMI (because leptin is highly correlated with BMI).
312303 317 244
51.3 ? 0.6
160 (51.3)
52 (16.7)
27.5 ? 0.3
0.87 ? 0.004
3.17 ? 0.05
1.19 ? 0.02
1.39 ? 0.07
1.25 ? 0.17
512 ? 13
5.10 ? 0.06
6.08 ? 0.17
5.32 ? 0.04
8 (2.6)
35 (11.2)
16 ? 5.1
2.12 ? 0.14
119 ? 0.9
73 ? 0.6
1,994 ? 41
90 ? 31.6
8.05 ? 0.09
47.8 ? 0.6
150 (49.5)
17 (5.6)
23.8 ? 0.3
0.86 ? 0.004
3.14 ? 0.05
1.19 ? 0.02
1.46 ? 0.08
0.70 ? 0.14
523 ? 13
5.18 ? 0.06
6.79 ? 0.17
5.59 ? 0.04
1 (0.3)
46 (15.2)
12 ? 4.0
2.23 ? 0.11
119 ? 0.9
75 ? 0.6
1,850 ? 44
44 ? 16.7
7.11 ? 0.09
49.4 ? 0.6
142 (44.8)
32 (10.1)
26.1 ? 0.3
0.88 ? 0.004
3.29 ? 0.04
1.05 ? 0.02
1.70 ? 0.07
1.79 ? 0.20
535 ? 13
5.45 ? 0.06
7.14 ? 0.16
5.76 ? 0.04
7 (2.2)
56 (17.7)
27 ? 8.5
3.03 ? 0.23
120 ? 0.9
76 ? 0.6
1,754 ? 42
43 ? 15.5
7.25 ? 0.09
52.9 ? 0.6
141 (57.8)
97 (39.8)
31.9 ? 0.3
0.93 ? 0.004
3.16 ? 0.05
1.07 ? 0.02
1.68 ? 0.07
3.32 ? 0.28
544 ? 14
5.56 ? 0.07
6.41 ? 0.19
5.95 ? 0.05
11 (4.5)
30 (12.3)
21 ? 8.7
4.85 ? 0.35
118 ? 1.0
67 ? 0.6
2,218 ? 49
41 ? 22.9
7.74 ? 0.10
?0.0011–6
0.169
?0.051–6
?0.0011–6
?0.0011–6
0.0854
?0.0012–5
?0.0012–5
?0.0011–6
0.35
?0.0012–5
?0.0011,2,6
?0.0011–6
0.16
0.11
0.02
?0.0012–6
0.625
?0.0011–3,5,6
?0.0011–3,5,6
?0.0011,2,5,6
?0.0011–3,5,6
10.89 ? 0.86
15.01 ? 1.13
12.96 ? 0.73
7.53 ? 0.88
10.28 ? 0.71
8.52 ? 0.57
8.26 ? 0.45
11.02 ? 0.76
9.35 ? 0.43
9.63 ? 0.39
13.15 ? 0.63
11.87 ? 0.41
?0.00011,2,5,6
?0.00011–3,5,6
?0.00011,2,4–6
5.93 ? 0.86
13.60 ? 1.36
9.21 ? 0.85
5.37 ? 0.88
14.01 ? 1.21
8.25 ? 0.77
7.24 ? 0.60
22.87 ? 1.54
11.82 ? 0.94
5.37 ? 1.39
16.95 ? 2.07
11.13 ? 1.21
?0.00012,4,6
?0.00012–6
?0.00012–5
Mente and Associates
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factors (Table 2). These factors accounted
for 0.3% (P ? 0.11) of the variance in
HOMA-IR scores beyond the contribu-
tionofotherfactors.Theindividualfactor
contributions to the model are shown in
Table3(availableintheonlineappendix).
In a linear regression analysis of
HOMA-IR scores as a function of log adi-
ponectin by ethnic categories, the associ-
ation between adiponectin and insulin
resistance varied significantly across eth-
nic groups (P ? 0.009 for interaction), as
the increase in HOMA-IR for each given
decreaseinadiponectinwaslargeramong
South Asians (P ? 0.024) and Aboriginal
people (P ? 0.010) than among Europe-
ans. No significant effect modification by
ethnicity was found for leptin. There was
no significant three-way effect modifica-
tion among ethnicity, adiponectin and
leptin, and BMI and WHR.
Adipokines, insulin resistance, and
glycemic index/glycemic load
No significant association of glycemic in-
dex or glycemic load with adipokine con-
centration was observed overall. In an
assessment of effect modification by BMI
and ethnicity, there was a significant
three-way effect modification among eth-
nicity, glycemic index, and BMI in pre-
dicting adiponectin (P ? 0.006). Among
study participants with BMI ?30 kg/m2,
there was a larger decrease in adiponectin
levels for each given increase in glycemic
index in South Asians (P ? 0.03) and Ab-
original people (P ? 0.001) than in Euro-
peans. However, among nonobese
participants, the degree of change in adi-
ponectin with greater glycemic index was
similar across ethnic groups. No signifi-
cant two-way or three-way effect modifi-
cation among ethnicity, glycemic index/
glycemic load, and BMI was found for
leptin.
In a linear regression analysis for
HOMA-IR scores as a function of glyce-
mic index by ethnic categories, the asso-
ciation between glycemic index and
insulin resistance varied significantly
across ethnic groups (P ? 0.01 for inter-
action), as a positive association was
found only among South Asians (P ?
0.001). The increase in HOMA-IR for
eachgivenincreaseinglycemicindexwas
significantly larger among South Asians
than among Europeans (P ? 0.03), Chi-
nese (P ? 0.008), and Aboriginal people
(P ? 0.006). No significant effect modifi-
cation by ethnicity was found for glyce-
mic load (P ? 0.31). There was no
significant three-way effect modification
among ethnicity, glycemic index/
glycemic load, and adiponectin or leptin.
CONCLUSIONS— To our knowl-
edge, this investigation is the first to com-
pare adiponectin, leptin, and other
insulin resistance–related factors in a
large randomly assembled multiethnic
population. Our study demonstrates that
South Asians have an unfavorable adipo-
kine profile, which is characterized by
lower adiponectin and higher leptin for
the same degree of adiposity as Europe-
ans. Furthermore, we have shown that a
greater consumption of foods with a high
glycemic index is associated with a signif-
icantly larger decrease in adiponectin
among South Asians and Aboriginal peo-
ple compared with Chinese and Europe-
ans. In addition, these groups display a
greater increase in insulin resistance with
decreasing levels of adiponectin, and a
high glycemic diet predicts higher insulin
resistance predominantly in South
Asians. To date, few studies have assessed
dietary effects on adipokine concentra-
tions, and we know of no previous study
to assess dietary glycemic index in rela-
tion to adipokine profile and insulin re-
sistance in multiple ethnic groups
including populations at high risk. Our
findings suggest that modifying intake of
glycemic foods could especially improve
adipokine concentrations and insulin
sensitivity in South Asians and Aboriginal
people, two populations at increased risk
for insulin resistance.
The large size and ethnic variation of
our cohort allowed us to examine adi-
ponectin and leptin over a wide range of
body weights and abdominal fat distribu-
tion. Overall, adiponectin decreased and
leptin increased with higher adiposity,
which is consistent with recent evidence
showing that the amount of intra-
abdominal fat modulates serum adipo-
kine levels (12). Cultured adipocytes
derived from visceral fat are known to se-
crete an increased amount of adiponectin
in response to insulin or rosiglitazone
treatment, whereas adipocytes derived
from subcutaneous fat are unaffected
(13).Insubgroupanalyses,wefoundthat
there is no association between adiponec-
tin and BMI, waist circumference, waist
adjusted for hip circumference, or WHR
in South Asians. Similar results have been
observed in a recent study of healthy
South Asians (14), yet another investiga-
tion showed an inverse association be-
tween adiponectin and BMI in South
Asian women with gestational diabetes
(15). Our findings may reflect the lack of
specificity of measuring adiposity using
BMI and waist circumference or may
reflect different pathogenic pathways
including the type, amount, and distribu-
tion of adipose tissue accumulation as
well as dietary and genetic influences that
may exist among South Asians.
Few previous studies have assessed
adipokine levels in South Asians com-
pared with those in individuals of Euro-
pean origin. Several reports showed that
adiponectinissignificantlylowerinSouth
Asians than in Europeans (16,17). These
studies, however, were generally small
and often did not include a comparison
group(15,18).Inourstudy,SouthAsians
displayed the least favorable adipokine
profile(loweradiponectinandhigherlep-
tin) of all ethnic groups, despite having
BMI comparable to that of Europeans.
The metabolic disturbance behind these
differences is not known but may be
related to differences in adipocyte prop-
erties (e.g., hypertrophic versus hyper-
plastic adipocytes) or distribution of
adipose tissue between the groups (19).
We also found strikingly high levels of
leptin among South Asian women com-
pared with those among European
women, a finding that was noted previ-
ously in young adults (20). Higher leptin
in women than in men is attributed to
theirgreatersubcutaneousfatmass.How-
ever, prior studies did not assess whether
these relationships vary by ethnic origin.
Our subgroup analysis showed a signifi-
cantly stronger correlation between se-
rum insulin and leptin among European
women than among South Asian women,
whereas WHR and leptin levels showed
similar correlation values across groups.
Therefore, distribution of fat (i.e., truncal
obesity) and hyperinsulinism do not ap-
pear to explain the higher leptin levels
among South Asian women. There is,
however, evidence that hypertrophic adi-
pocytes secret more leptin than do hyper-
plastic adipocytes (21), and subcutaneous
adipocyte hypertrophy could account for
thehigherleptinlevelsinSouthAsians(19).
Our study showed that Aboriginal
people have higher leptin levels than Eu-
ropeans but similar adiponectin levels.
The findings of previous studies compar-
ing adiponectin levels in Aboriginal peo-
ple with those in Europeans have been
inconclusive,withsomestudiesreporting
lowerlevelsinAboriginalpeople(22)and
other recent studies showing no signifi-
cant differences (12). These discrepant
Adipokines, ethnicity, and insulin resistance
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Page 5

findings may also be attributable to the
smaller sample of participants and differ-
ent sample selection. Our finding that
Chinese have lower adiponectin levels
than do Europeans is consistent with pre-
vious results in East Asian populations
(23) and with our past observations
showing that, despite having relatively
lowBMI,theChineseareatincreasedrisk
of developing impaired fasting glucose,
impairedglucosetolerance,andtype2di-
abetes with central fat accumulation (2).
Our finding that lower adiponectin
andelevatedleptinlevelsareindependent
determinants of increased insulin resis-
tance over and above lifestyle factors, an-
thropometric indexes, and inflammatory
markers is consistent with previous co-
hort studies (24). In addition, when we
assessedtheeffectofserumadipokineson
insulin resistance by ethnic group, South
Asians and Aboriginal people showed a
significantlygreaterincreaseininsulinre-
sistance per unit decrease in adiponectin
than Chinese and Europeans. Several
smaller studies (18), but not all (16,17),
have also related low adiponectin to
HOMA-IR values in young healthy South
Asians. In Alaskan and Canadian Native
populations, adiponectin was also in-
versely associated with HOMA-IR scores
(12,25). Our findings suggest that phar-
macologic agents that work by altering
adiponectin levels may be more effective
in these groups. Adiponectin levels in-
crease with reduction in fat mass, admin-
istration of peroxisome proliferator–
activated receptor-? agonists such as the
thiazolidinediones, and renin-angioten-
sinsystemblockade,andindividualswith
the lowest baseline levels may benefit the
mostfromthesetherapeuticstrategies(4).
Our finding that glycemic index pre-
dicts greater increases in insulin resis-
tance in South Asians compared with that
in other ethnic groups has not been re-
ported previously. There is some evi-
dence that carbohydrate intake is
associated with poorer glycemic control
inSouthAsians(8)andAboriginalpeople
(9), but total glycemic index/glycemic
load or long-term intake were not evalu-
ated. In this study, we did not find evi-
dence that glycemic index is associated
with insulin resistance. Nevertheless, our
findings show that South Asians and Ab-
original people display a greater decrease
in adiponectin with increasing glycemic
index, particularly at higher BMI. We are
not aware of any previous study that as-
sessed dietary effects on adipokine con-
centrations in ethnic populations. Our
findings suggest that modifying intake of
glycemic foods could improve adipokine
concentrations and insulin sensitivity
most profoundly in South Asians and Ab-
original people.
Although the underlying mechanism
linkingglycemicindextoadipokinelevels
is not clear, the findings are compatible
with the overall poor adipokine profile
observed in these groups. Glycemic foods
are known to induce both hyperglycemia
and hyperinsulinemia. There is evidence
that adipose tissue expression of adi-
ponectin is inversely correlated with fast-
ing glucose concentration and that a
glucose-rich diet reduces adiponectin ex-
pression in adipose tissue (26). South
Asian and Aboriginal populations largely
consume a diet consisting of foods with a
high glycemic index (10). It has been rec-
ognized that glycemic foods influence
body fat (27), which suggests that the ef-
fects could be at least partly mediated by
adipose tissue–related pathways. Con-
versely, fiber intake is positively associ-
ated with adiponectin (6) and may
promote the clearance of lipids and thus
reducefreefattyacidsavailableforstorage
in adipose tissue (28).
Our study has some limitations. We
used surrogate measures of adiposity
(e.g., BMI and waist circumference),
which are merely proxy indicators of vis-
ceral fat, a stronger predictor of insulin
resistance. Although these measures
show considerable variation among dif-
ferent ethnic groups (1,2), the findings
relating central fat with adiponectin in
our study should be viewed with caution.
Our study used total adiponectin as op-
posed to the active high–molecular-
weight multimer, which may be the
critical determinant of insulin sensitivity.
Nevertheless, total adiponectin was sig-
nificantly associated with insulin resis-
tance, and ethnic comparisons in our
study probably reflect similar relative dif-
ferences in high–molecular-weight adi-
ponectin.Drugtreatmentfordiabetescan
alter adipokine concentration, and thus,
weexcludedthesepatientsfromouranal-
yses. In a sensitivity analysis that further
excluded patients with new clinically di-
agnosed diabetes (n ? 76), the ethnic
differences in adipokine levels and
accompanying associations between adi-
pokines and insulin resistance were unal-
tered. Exclusion of individuals with
impaired fasting glucose (n ? 27), im-
paired glucose tolerance (n ? 167), and
newly diagnosed diabetes preserved the
trendsthatweobserved,althoughthesig-
nificancewasdiminishedbecauseofaloss
of statistical power.
In summary, South Asians have an
unfavorable adipokine profile compared
with that of other ethnic groups and, like
the Aboriginal people, display a greater
increase in insulin resistance with de-
creasinglevelsofadiponectin.Differences
in adipokines and responses to glycemic
foods parallel the increased propensity of
certain ethnic groups to develop insulin
resistance.
Acknowledgments— This study was sup-
ported by the Canadian Institutes of Health
Research (grant MT-12790), the Heart and
Stroke Foundation of Canada, and Merck
Frosst Canada. A.M. holds a Heart and Stroke
Foundation of Canada Postdoctoral Research
Fellowship. S.Y. holds a Heart and Stroke
Foundation of Ontario Chair in Cardiovascu-
larResearch.S.S.A.holdstheEliLillyMayCo-
hen endowed chair in Women’s Health
Research and the Michael G. DeGroote Heart
and Stroke Foundation of Ontario Research
Chair in Population Health Research.
No potential conflicts of interest relevant to
this article were reported.
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