Diabetes mellitus and serum carotenoids: findings of a
population-based study in Queensland, Australia1–3
Terry Coyne, Torukiri I Ibiebele, Peter D Baade, Annette Dobson, Christine McClintock, Sophie Dunn,
Dympna Leonard, and Jonathan Shaw
ABSTRACT
Background: Epidemiologic evidence suggests that serum carote-
noids are potent antioxidants and may play a protective role in the
development of chronic diseases including cancers, cardiovascular
disease, and inflammatory diseases. The role of these antioxidants in
the pathogenesis of diabetes mellitus remains unclear.
Objective: This study examined data from a cross-sectional survey
to investigate the association between serum carotenoids and type 2
diabetes.
Design: Study participants were adults aged 욷25 y (n ҃ 1597) from
6 randomly selected cities and towns in Queensland, Australia.
Study examinations conducted between October and December
2000 included fasting plasma glucose, an oral-glucose-tolerance
test, and measurement of the serum concentrations of 5 carotenoid
compounds.
Results: Mean 2-h postload plasma glucose and fasting insulin
concentrations decreased significantly with increasing quintiles of
the 5 serum carotenoids—␣-carotene, ␤-carotene, ␤-cryptoxanthin,
lutein/zeaxanthin, and lycopene. Geometric mean concentrations for
all serum carotenoids decreased (all decreases were significant ex-
cept that of lycopene) with declining glucose tolerance status.
␤-Carotene had the greatest decrease, to geometric means of 0.59,
0.50, and 0.42 ␮mol/L in persons with normal glucose tolerance,
impaired glucose metabolism, and type 2 diabetes, respectively (P 쏝
0.01 for linear trend), after control for potential confounders.
Conclusions: Serum carotenoids are inversely associated with type
2 diabetes and impaired glucose metabolism. Randomized trials of
diets high in carotenoid-rich vegetables and fruit are needed to con-
firm these results and those from other observational studies. Such
evidence would have very important implications for the prevention
of diabetes. Am J Clin Nutr 2005;82:685–93.
KEY WORDS Type 2 diabetes, diabetes mellitus, impaired
glucose tolerance, serum carotenoids, ␣-carotene, ␤-carotene,
␤-cryptoxanthin, lutein/zeaxanthin, lycopene, antioxidant vitamins,
diet, cross-sectional surveys, health surveys, nutrition
INTRODUCTION
Carotenoids are a wide range of compounds derived solely
from plants; the major ones found in serum are ␣-carotene,
␤-carotene, ␤-cryptoxanthin, lutein/zeaxanthin, and lycopene.
Considerable epidemiologic evidence exists that some carote-
noids are potent antioxidants and may play a protective role
Am J Clin Nutr 2005;82:685–93. Printed in USA. © 2005 American Society for Clinical Nutrition
Downloaded from https://academic.oup.com/ajcn/article/82/3/685/4863025 by guest on 22 November 2020
against the development of chronic diseases such as atheroscle-
rosis (1, 2), stroke (3), certain cancers (4), and inflammatory
diseases (5). Although obesity and physical inactivity are known
to be major risk factors for type 2 diabetes, evidence suggests that
oxidative stress also may contribute to the pathophysiology of
type 2 diabetes (6). Multiple factors have been associated with
increased oxidative stress in diabetes mellitus. These factors
include glucose autoxidation that results in the production of free
radicals, an increase in protein glycation (glucooxidation), and a
decrease in antioxidant defenses. Enhanced oxidative stress is
considered an underlying condition that is responsible for some
of the complications of diabetes (7).
Serum or dietary vitamin A, E, and C concentrations have been
hypothesized to be lower in persons with impaired glucose tol-
erance (IGT) or with type 2 diabetes than in those who have
normal glucose tolerance (8, 9); nevertheless, there is conflicting
evidence concerning these relations (10, 11). Several cross-
sectional epidemiologic studies have reported an inverse relation
between serum carotenoids and diabetes status (12–15), and yet
intervention studies providing supplements of antioxidant
vitamins have shown conflicting results (7, 16). In this study,
we investigated the relations between the major serum
carotenoids—␣-carotene, ␤-carotene, ␤-cryptoxanthin, lutein/
zeaxanthin, and lycopene—and type 2 diabetes status in a cross-
sectional population-based study in Queensland, Australia.
1
From the School of Population Health, University of Queensland, Bris-
bane, Australia (TC and AD); the Epidemiology Services Unit, Health In-
formation Branch, Queensland Health, Brisbane, Australia (TC, TII, and
CM); the Viertel Center for Research in Cancer Control, Queensland Cancer
Fund, Brisbane, Australia (PDB); Oxfam, Oxford (SD) Tropical Public
Health Unit, Queensland Health, Cairns, Australia (DL); and the Interna-
tional Diabetes Institute, Melbourne, Australia (JS).
2
Supported by the Australian Department of Health and Ageing, state and
territory governments, and pharmaceutical companies: Eli Lilly (Aust) Pty
Ltd, Janssen - Cilag (Aust) Pty Ltd, Knoll Australia Pty Ltd, Merck Lipha s.a.
Alphapharm Pty Ltd, Merck Sharp & Dohme (Aust), Pharmacia and Upjohn
Pty Ltd, Roche Diagnostics, Servier Laboratories (Aust) Pty Ltd, SmithKline
Beecham International, BioRad Laboratories Pty Ltd and HITECH Pathol-
ogy Pty Ltd; Qantas Airways Ltd and the Australian Kidney Foundation. The
Queensland phase of the study was partially funded by Queensland Health.
3
Reprints not available. Address correspondence to T Coyne, School of
Population Health, The University of Queensland, Public Health Building,
Herston 4029, Queensland, Australia. E-mail: t.coyne@sph.uq.edu.au.
Received December 8, 2004.
Accepted for publication June 3, 2005.
685
686 COYNE ET AL
SUBJECTS AND METHODS
Subjects
The study was conducted between October and December
2000 as part of a national study, the Australian Diabetes, Obesity
and Lifestyle Study (AusDiab), to determine the prevalence of
diabetes and associated cardiovascular disease risk factors
among adults aged 욷25 y (17). Six urban sites (cities and towns)
were randomly selected from census collector districts (CDs) in
Queensland. The CDs were selected and with probability pro-
portional to size. Noninstitutionalized adults aged 욷25 y who
were residing in private dwellings were included in the survey if
they had resided full-time at the address for 욷6 mo before the
survey. Persons with physical or intellectual disabilities that pre-
cluded participation in the study were not included.
Trained interviewers conducted house-to-house interviews,
and eligible participants were invited to attend a biomedical
examination that included collection of blood samples, blood
pressure measurements, and anthropometric measurements and
the administration of standardized questionnaires related to diet
as well as sociodemographic, lifestyle, and health-related char-
acteristics. Details of the sampling framework and overall study
design have been published elsewhere (18). A total of 1634
persons in Queensland completed the physical examination. Al-
though the overall response rate in the study was low (앒50% of
those invited and 30% of those estimated to be eligible), the
internal validity and quality control of the data collection were
high (18).
All respondents gave written informed consent to participate
in the survey on arrival at the testing site.The study was approved
by the International Diabetes Institute and The University of
Queensland ethics committees.
Methods
Study participants arrived for the examination after having
fasted for 욷12 h. Blood pressure measurements were taken by
using a Dinamap sphygmomanometer (Critikon, Tampa, FL).
Blood was drawn for fasting glucose and insulin determinations.
Participants not taking hypoglycemic medication completed a
2-h oral-glucose-tolerance test (OGTT) after consuming a 75-g
glucose drink. Fasting and 2-h glucose were measured enzymat-
ically (glucose oxidase) on an Olympus AU600 analyzer (Olym-
pus Optical Co, Tokyo, Japan). Insulin analysis was conducted
for all participants aged 쏜35 (n ҃ 1303) by using the Human
Insulin Specific RIA Kit (catalog #HI-14K; Linco Research Inc,
St Charles, MO).
The lipids total and HDL cholesterol and triacylglycerol were
measured enzymatically on an Olympus AU 600. LDL choles-
terol was calculated from the equation of Friedewald et al (19):
LDL ⫽ total cholesterol ⫺
[HDL ⫹ (triacylglycerol/5)] (1)
Glucose, insulin, and lipid determinations were carried out as
part of the AusDiab study.
Blood was drawn for the carotenoid determinations at the time
of the 2-h OGTT or, for those subjects who did not take the
OGTT, 2 h after the fasting sample. Serum samples were metic-
ulously handled and protected from light at each stage of pro-
cessing to prevent deterioration and degradation (20). The serum
TABLE 1
Classification of glucose tolerance status according to fasting plasma
glucose values and 2-h plasma glucose values obtained during a 75-g
oral-glucose-tolerance test1
Plasma glucose
Classification Fasting 2-h
mmol/L
Diabetes 욷 7.0 욷 11.1
Impaired glucose tolerance 쏝 7.0 7.8–11.0
Impaired fasting glucose 6.1–6.9 쏝 7.8
Normal glucose tolerance 쏝 6.1 쏝 7.8
1
Data taken from reference 22. Both the fasting and 2-h values are
needed for diagnosis in all cases except diabetes, which requires only 1 of the
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2 values.
was pipetted, frozen, packed in dry ice, shipped to the laboratory
in Brisbane, and analyzed within 3 wk of collection. The 5 serum
carotenoids were assayed simultaneously according to the HPLC
procedure described by Talwar et al (21). Reported intrabatch
CVs obtained by using this method were 6.5%, 7.6%, 7.3%,
6.9%, and 9.0%, and interbatch (analyzed after storage at Ҁ70 °C
for 8 wk) CVs were 13%, 9.6%, 8.7%, 8.5%, and 11%, respec-
tively, for ␣-carotene, ␤-carotene, ␤-cryptoxanthin, lutein/zeax-
anthin, and lycopene (21). Complete data for serum carotenoids
and plasma glucose were available for 1597 adults.
The diagnostic criteria for the presence of diabetes, IGT, and
impaired fasting glucose were based on values for venous plasma
glucose concentration (fasting and 2-h measurements) outlined
in the World Health Organization report on the diagnosis and
classification of diabetes mellitus (22) and are summarized in
Table 1. Participants were also classified as having diabetes if
they were receiving treatment for diabetes in the form of tablets
or insulin at the time of the study.
Of those diagnosed with diabetes, 2.5% were classified as
having type 1 diabetes and were excluded from the analysis.
Participants were defined as having type 1 diabetes if insulin
treatment had been started within 2 y of diagnosis and, for those
aged 욷40 y when diagnosed, if their current BMI was 쏝27. For
the purpose of this analysis, diabetes status was categorized as
normal glucose tolerance, impaired glucose metabolism
(IGM)— calculated as IGM ҃ IGT and impaired fasting glucose
combined—and type 2 diabetes.
Demographic and lifestyle variables were collected by using
standardized questionnaires and were categorized as follows.
Age was divided into 10-y age groups. Educational status was
categorized as secondary school or less, trade certificate or bach-
elor’s degree, and postgraduate qualification. Body mass index
(BMI; in kg/m2) was categorized as obese (BMI 욷 30), over-
weight (BMI 욷 25 to 쏝30), and normal-weight (BMI 쏝 25) (23).
Because only 18 participants were classified as underweight
(BMI 쏝 18.5), they were grouped with the normal-weight group.
Smoking status was categorized as current smoker (at least
daily), former smoker (less than daily for at least the last 3 mo, but
used to smoke daily), and nonsmoker (smoked 쏝 100 cigarettes
over lifetime) (24). Alcohol consumption was categorized as
none, 울60 standard drinks/mo, or 쏜60 standard drinks/mo (24).
Physical activity beneficial to health was categorized as suffi-
ciently active (쏜150 min physical activity time in the previous
 DIABETES AND SERUM CAROTENOIDS
week), insufficiently active but not sedentary (쏝150 min phys-
ical activity time in the previous week), and sedentary (no par-
ticipation in physical activity in the previous week). Physical
activity time was calculated as the sum of the time spent walking
or performing moderate activity plus double the time spent in
vigorous activity (to reflect its greater intensity) (25). Vitamin
supplement use during the previous 24 h was categorized as yes
for respondents who indicated that they took any vitamin or
mineral supplements on the previous day and no for respondents
who indicated they did not do so.
Plasma lipids were categorized by using the criteria for abnor-
mal lipid concentrations that were based on recommendations
from the National Heart Foundation (26) and the Australian
Diabetes Society (27). The presence or absence of hypertension
was determined for each participant in accordance with World
Health Organization guidelines (28).
Intakes of vegetables and fruit were approximated by asking 2
questions. Participants were asked, “How many serves [ie, serv-
ings] of vegetables do you usually eat each day? Including fresh,
frozen or tinned vegetables (a serve ҃ 1⁄2 cup [ie, 75 g] cooked
vegetables or 1 cup [ie, 앒130 g] salad vegetables).” Usual con-
sumption of fruit was assessed by the question, “How many
serves of fruit do you usually eat each day? Including fresh,
frozen, or canned fruit (a serve ҃ 1 medium piece or 2 small
pieces of fruit or 1 cup [ie, 150 g] diced pieces of fruit.).” Par-
ticipants were categorized into 3 groups (ie, 울 1 serving, 2–3
servings, and 욷4 servings) according to their responses to both
questions.
Statistical analysis
Data were analyzed by using the survey commands in STATA
statistical software (version 8; Stata Corp, College Station, TX;
29). These commands take into account the complex survey
design in the calculation of estimates, variance, SEs, and CIs.
Pearson’s chi-square statistic was used to assess the relation
between diabetes status and selected categorical variables. Stu-
dent’s t test was used to compare differences in means between
2 groups; analysis of variance was used to assess overall differ-
ences in means between serum carotenoids and the variables with
쏜2 groups.
Mean fasting plasma glucose, 2-h postload glucose, and
plasma insulin concentrations were estimated for quintiles of
each serum carotenoid after adjustment for age, and P for trend
was calculated by using multiple linear regression. Distributions
of serum carotenoids were skewed and therefore were natural
logarithmically transformed to better approximate the normal
distribution for regression analyses. Associations between serum
carotenoids as dependent variables and diabetes status (as an
ordinal variable) were assessed by using multiple linear regres-
sion analysis, and P for trend was estimated. The adjust com-
mand in STATA was used to provide adjusted predictions of
mean serum carotenoid concentrations for each level of diabetes
status. Results are reported as back-transformed geometric
means. Analysis was performed separately for each serum ca-
rotenoid, after adjustment for the potential confounders age; sex;
BMI; physical activity; education; vitamin use; smoking status;
alcohol intake; systolic and diastolic blood pressures; total, HDL,
and LDL cholesterol; and triacylglycerol. The confounders were
put into the model simultaneously as categorical variables. Be-
cause of missing values, the sample size is not the same for all
analyses.
687
RESULTS
The prevalence of diabetes and IGM according to demo-
graphic and health-related characteristics is shown in Table 2.
There was no significant difference in diabetes status between
males and females. Significant differences in diabetes status
were evident for subjects by age, BMI, physical activity status,
total and HDL cholesterol, triacylglycerol, and systolic blood
pressure.
The relations between the 5 serum carotenoids and the various
sociodemographic, anthropometric, and health-related variables
are shown in Table 3. Although there were significant differ-
ences in mean serum carotenoids within many of these catego-
ries, age group, BMI, alcohol intake, and HDL and LDL choles-
terol had significant relations with all the serum carotenoids.
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Apart from educational status, all the other variables in Table 3
were related to some but not all carotenoids.
The mean fasting plasma glucose, 2-h postload glucose, and
fasting insulin by quintiles of each serum carotenoid are shown
in Table 4. The median of each of the carotenoids is provided for
each quintile. Mean 2-h postload glucose and fasting insulin
concentrations decreased significantly with increasing quintiles
of each serum carotenoid (P for trend 쏝 0.05). Fasting glucose
concentrations also decreased significantly with increasing quin-
tiles of ␣-carotene and ␤-carotene (P 쏝 0.01).
After adjustment for the potential confounders age; sex; BMI;
physical activity; educational status; smoking; alcohol intake;
vitamin use; total, HDL, and LDL cholesterol; triacylglycerol;
and systolic and diastolic blood pressures, significant linear
trends in serum carotenoid concentrations (except lycopene) by
diabetes status were evident (Table 5). ␤-Carotene showed the
most decline; its geometric means were 0.59, 0.50, and 0.42
␮mol/L in persons with normal glucose tolerance, IGM, and type
2 diabetes, respectively (P 쏝 0.01 for linear trend).
DISCUSSION
The data from the current population study suggest that serum
carotenoids are associated with diabetes status. Our study
showed an increasing trend in 2-h postload plasma glucose and
fasting insulin concentrations with decreasing quintiles of all of
the carotenoids tested. A decreasing trend in fasting plasma glu-
cose concentrations was observed with increasing quintiles of
␣-carotene and ␤-carotene. In addition, serum carotenoid con-
centrations showed a linear decrease with the degree of glucose
tolerance abnormality. This decrease was significant for all of the
carotenoids except lycopene. These findings are consistent with
data reported by Ford et al (12) from the third National Health and
Nutrition Examination Survey (NHANES III; 12). In NHANES
III, Ford et al reported a significant linear decrease in ␤-carotene
and lycopene in persons with IGT and in persons with newly
diagnosed diabetes compared with persons with normal glucose
concentrations, after adjustment for confounding factors similar
to those in our study. The association between serum carotenoid
concentrations and diabetes status observed in our study was also
consistent with associations reported in studies from several
other countries (13–15, 30, 31).
Because of the cross-sectional design of our study, however, it
is not possible to draw inferences as to whether the lower serum
carotenoid concentrations found in participants with diabetes are
the result of increased utilization of these antioxidants due to the
688 COYNE ET AL

TABLE 2
The prevalence of type 2 diabetes and impaired glucose metabolism by demographic and health-related characteristics for adults aged 욷25 y in the 2000
Queensland AusDiab study1

Categorical variables Normal glucose tolerance2 Impaired glucose metabolism Type 2 diabetes p3

n (%)
Sociodemographic variables
Sex
Males 484 (77.2) 132 (15.9) 63 (6.9) 0.63
Females 661 (75.3) 188 (17.9) 69 (6.8)
Age group
25–34 y 170 (94.5) 12 (54.8) 0 (0.0) 쏝 0.01
35–44 y 286 (86.7) 39 (11.6) 7 (1.7)
45–54 y 298 (76.4) 68 (16.6) 29 (6.9)
55–64 y 220 (64.9) 83 (24.7) 31 (10.4)
65–74 y 125 (50.4) 81 (33.0) 39 (16.5)
욷75 y 46 (39.6) 37 (33.8) 26 (26.6)

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Educational status
Secondary school or less 418 (71.4) 145 (20.1) 63 (8.5) 0.05
Trade certificate or bachelor’s degree 631 (78.3) 155 (15.1) 66 (6.5)
Postgraduate qualification 92 (81.1) 20 (16.1) 3 (1.9)
BMI (kg/m2)
Obese (BMI 쏜 30) 206 (55.9) 110 (27.5) 67 (16.6) 쏝 0.01
Overweight (BMI 욷 25 to 쏝 30) 417 (77.7) 124 (17.0) 40 (5.2)
Normal (BMI 쏝 25) 519 (85.6) 84 (11.0) 24 (3.0)
Health-related behaviors
Smoking status
Current smoker 168 (84.4) 27 (9.6) 20 (5.9) 0.11
Former smoker 306 (71.7) 104 (20.2) 44 (8.1)
Never smoker 655 (76.4) 185 (17.3) 65 (6.3)
Alcohol intake
None 233 (70.1) 84 (19.7) 41 (10.2) 쏝 0.05
울 60 standard drinks/mo 789 (78.8) 195 (15.5) 74 (5.7)
쏜 60 standard drinks/mo 123 (72.4) 41 (20.1) 17 (7.5)
Physical activity beneficial to health
Sufficiently active 560 (79.8) 135 (14.8) 51 (5.4) 0.03
Insufficiently active 374 (74.7) 112 (17.9) 46 (7.5)
Sedentary 206 (69.1) 73 (21.2) 35 (9.7)
Vitamin use in previous 24 h
Yes 350 (75.7) 90 (17.0) 38 (7.3) 0.79
No 719 (77.0) 206 (16.5) 81 (6.5)
Plasma lipids
Total cholesterol
쏝 5.5 mmol/L 555 (81.1) 130 (14.3) 44 (4.6) 0.01
욷 5.5 mmol/L 590 (71.3) 190 (19.5) 88 (9.1)
HDL cholesterol
쏝 1.0 mmol/L 104 (67.4) 45 (19.8) 32 (12.8) 0.01
욷 1.1 mmol/L 1041 (77.5) 275 (16.5) 100 (6.0)
LDL cholesterol
쏝 3.5 mmol/L 566 (79.6) 144 (15.2) 48 (5.4) 0.06
욷 3.5 mmol/L 553 (74.6) 159 (18.0) 67 (7.5)
Triacylglycerol
쏝 2.0 mmol/L 955 (82.1) 208 (14.0) 59 (3.9) 쏝0.01
욷 2.0 mmol/L 190 (54.2) 112 (27.7) 73 (18.0)
Blood pressure
Systolic blood pressure
쏝 140 mm Hg 962 (81.6) 206 (13.6) 74 (4.8) 쏝 0.01
욷 140 mm Hg 175 (53.3) 110 (31.2) 56 (15.6)
Diastolic blood pressure
쏝 90 mm Hg 1110 (77.0) 300 (16.2) 124 (6.7) 0.10
욷 90 mm Hg 29 (57.7) 15 (31.0) 7 (11.3)
Dietary intake of vegetables and fruit4
Servings of vegetables
울1 180 (75.6) 51 (18.2) 21 (6.2) 0.34
2–3 598 (76.4) 163 (15.5) 82 (8.1)
욷4 344 (75.8) 101 (19.2) 26 (5.0)
Servings of fruit
울1 459 (79.0) 112 (15.6) 42 (5.4) 0.17
2–3 519 (73.4) 165 (18.2) 73 (8.5)
욷4 139 (76.5) 38 (17.9) 13 (5.6)
1
Because of missing values, the total n is not the same for all variables. AusDiab, Australian Diabetes, Obesity, and Lifestyle.
2
Percentages weighted for age and sex to the Queensland population aged 쏜 25 y for the survey year.
3
Chi-square test of association with adjustment for cluster design.
4
A serving of cooked vegetables was 75 g (1/2 cup), of salad vegetables was 앒130 g (1 cup), and of diced or canned fruit was 150 g (1 cup).
 DIABETES AND SERUM CAROTENOIDS 689
TABLE 3
Geometric mean (and 95% CI) concentrations of serum carotenoids by selected variables for adults aged 욷25 y in the 2000 Queensland AusDiab study1

␣-Carotene ␤-Carotene ␤-Cryptoxanthin Lutein/zeaxanthin Lycopene

␮mol/L
Sociodemographic variables
Sex2
P 쏝 0.01 쏝 0.01 쏝 0.01 0.07 0.30
Male (n ҃ 674) 0.10 (0.07, 0.14) 0.42 (0.31, 0.58) 0.18 (0.14, 0.23) 0.39 (0.32, 0.46) 0.43 (0.37, 0.49)
Female (n ҃ 923) 0.14 (0.09, 0.20) 0.61 (0.44, 0.85) 0.22 (0.17, 0.28) 0.42 (0.37, 0.47) 0.41 (0.36, 0.45)
Age group3
P 쏝 0.01 쏝 0.01 쏝 0.01 쏝 0.01 쏝 0.01
25–34 y (n ҃ 190) 0.10 (0.08, 0.14) 0.42 (0.31, 0.56) 0.14 (0.11, 0.17) 0.33 (0.27, 0.40) 0.55 (0.45, 0.67)
35–44 y (n ҃ 335) 0.11 (0.07, 0.18) 0.45 (0.31, 0.65) 0.17 (0.14, 0.20) 0.36 (0.31, 0.43) 0.51 (0.42, 0.62)
45–54 y (n ҃ 393) 0.13 (0.08, 0.19) 0.53 (0.38, 0.73) 0.19 (0.15, 0.24) 0.40 (0.34, 0.47) 0.44 (0.37, 0.53)
55–64 y (n ҃ 329) 0.12 (0.09, 0.17) 0.58 (0.43, 0.78) 0.24 (0.18, 0.33) 0.45 (0.39, 0.52) 0.39 (0.33, 0.47)

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65–74 y (n ҃ 240) 0.12 (0.08, 0.19) 0.57 (0.40, 0.81) 0.24 (0.18, 0.32) 0.47 (0.40, 0.55) 0.31 (0.25, 0.38)
욷75 y (n ҃ 111) 0.15 (0.11, 0.19) 0.71 (0.57, 0.88) 0.31 (0.26, 0.39) 0.46 (0.37, 0.58) 0.25 (0.21, 0.29)
Educational status3
P 0.54 0.47 0.15 0.22 0.09
Postgraduate (n ҃ 117) 0.11 (0.07, 0.19) 0.59 (0.52, 0.67) 0.25 (0.21, 0.29) 0.40 (0.31, 0.50) 0.49 (0.43, 0.57)
Trade certificate or bachelor’s degree 0.12 (0.09, 0.17) 0.52 (0.38, 0.69) 0.19 (0.15, 0.25) 0.40 (0.34, 0.47) 0.44 (0.40, 0.48)
(n ҃ 848)
Secondary school or less (n ҃ 627) 0.14 (0.12, 0.16) 0.52 (0.35, 0.78) 0.20 (0.16, 0.26) 0.42 (0.37, 0.76) 0.37 (0.32, 0.43)
Anthropometric measures
BMI (kg/m2)3
P 쏝 0.01 쏝 0.01 0.01 0.01 0.02
Normal (n ҃ 624) 0.14 (0.10, 0.22) 0.64 (0.45, 0.92) 0.23 (0.17, 0.31) 0.43 (0.38, 0.48) 0.42 (0.38, 0.47)
Overweight (n ҃ 576) 0.12 (0.09, 0.17) 0.52 (0.39, 0.67) 0.20 (0.16, 0.27) 0.41 (0.34, 0.51) 0.45 (0.40, 0.50)
Obese (n ҃ 381) 0.09 (0.06, 0.12) 0.38 (0.29, 0.51) 0.16 (0.13, 0.19) 0.37 (0.31, 0.43) 0.36 (0.31, 0.43)
Health-related behaviors
Smoking status3
P 0.01 0.03 쏝 0.01 0.01 0.45
Never (n ҃ 907) 0.14 (0.10, 0.19) 0.59 (0.45, 0.77) 0.23 (0.19, 0.28) 0.43 (0.37, 0.51) 0.42 (0.40, 0.44)
Former (n ҃ 450) 0.12 (0.09, 0.18) 0.52 (0.39, 0.71) 0.21 (0.17, 0.25) 0.40 (0.34, 0.46) 0.43 (0.38, 0.49)
Current (n ҃ 217) 0.07 (0.05, 0.10) 0.32 (0.21, 0.49) 0.11 (0.08, 0.15) 0.32 (0.26, 0.38) 0.37 (0.26, 0.52)
Alcohol intake3
P 0.01 0.01 0.01 쏝 0.01 0.01
None (n ҃ 359) 0.13 (0.08, 0.21) 0.54 (0.36, 0.83) 0.22 (0.18, 0.26) 0.42 (0.38, 0.47) 0.34 (0.29, 0.39)
울60 drinks/mo (n ҃ 1060) 0.13 (0.09, 0.18) 0.57 (0.45, 0.73) 0.21 (0.17, 0.27) 0.42 (0.36, 0.48) 0.45 (0.43, 0.48)
쏜60 drinks/mo (n ҃ 177) 0.07 (0.05, 0.11) 0.27 (0.17, 0.44) 0.11 (0.07, 0.18) 0.34 (0.26, 0.43) 0.37 (0.25, 0.56)
Physical activity3
P 0.02 0.01 쏝 0.01 0.20 0.01
Sufficiently active (n ҃ 742) 0.13 (0.09, 0.19) 0.56 (0.40, 0.78) 0.21 (0.16, 0.27) 0.41 (0.35, 0.49) 0.44 (0.39, 0.49)
Insufficiently active (n ҃ 535) 0.12 (0.08, 0.18) 0.51 (0.35, 0.74) 0.20 (0.15, 0.26) 0.41 (0.35, 0.47) 0.40 (0.34, 0.47)
Sedentary (n ҃ 314) 0.11 (0.08, 0.14) 0.46 (0.38, 0.56) 0.17 (0.14, 0.21) 0.39 (0.33, 0.45) 0.39 (0.36, 0.41)
Vitamin use during previous 24 h2
P 0.02 쏝 0.01 0.04 0.01 0.45
Yes (n ҃ 479) 0.14 (0.09, 0.22) 0.67 (0.46, 0.96) 0.22 (0.16, 0.24) 0.43 (0.37, 0.50) 0.40 (0.34, 0.48)
No (n ҃ 1006) 0.11 (0.08, 0.16) 0.47 (0.36, 0.63) 0.20 (0.16, 0.30) 0.40 (0.34, 0.46) 0.42 (0.39, 0.46)
Plasma lipids2
P 0.14 0.01 쏝 0.01 쏝 0.01 0.02
Cholesterol 쏝 5.5 mmol/L (n ҃ 728) 0.11 (0.08, 0.17) 0.48 (0.34, 0.66) 0.17 (0.14, 0.22) 0.36 (0.31, 0.42) 0.39 (0.34, 0.44)
Cholesterol 욷 5.5 mmol/L (n ҃ 869) 0.12 (0.09, 0.18) 0.56 (0.41, 0.78) 0.23 (0.18, 0.28) 0.45 (0.39, 0.51) 0.44 (0.39, 0.49)
P 쏝 0.01 쏝 0.01 쏝 0.01 0.02 0.04
HDL 쏝 1.0 mmol/L (n ҃ 181) 0.08 (0.06, 0.10) 0.34 (0.26, 0.44) 0.15 (0.13, 0.18) 0.35 (0.30, 0.40) 0.34 (0.27, 0.43)
HDL 욷 1.0 mmol/L (n ҃ 1416) 0.13 (0.09, 0.18) 0.55 (0.40, 0.76) 0.21 (0.16, 0.76) 0.41 (0.35, 0.49) 0.43 (0.38, 0.47)
P 0.02 쏝 0.01 쏝 0.01 쏝 0.01 0.03
LDL 쏝 3.5 mmol/L (n ҃ 758) 0.12 (0.08, 0.17) 0.48 (0.35, 0.66) 0.18 (0.14, 0.24) 0.37 (0.32, 0.44) 0.38 (0.33, 0.44)
LDL 욷 3.5 mmol/L (n ҃ 779) 0.13 (0.09, 0.19) 0.61 (0.44, 0.83) 0.23 (0.18, 0.29) 0.44 (0.39, 0.50) 0.46 (0.40, 0.51)
P 쏝 0.01 쏝 0.01 0.01 0.97 0.05
Triacylglycerol 쏝 2.0 (n ҃ 1221) 0.13 (0.09, 0.19) 0.58 (0.42, 0.78) 0.21 (0.16, 0.27) 0.41 (0.35, 0.48) 0.43 (0.38, 0.47)
Triacylglycerol 욷 2.0 (n ҃ 376) 0.09 (0.07, 0.12) 0.38 (0.27, 0.52) 0.18 (0.14, 0.22) 0.41 (0.35, 0.47) 0.38 (0.33, 0.44)
Blood pressure2
P 0.10 쏝 0.01 0.42 0.77 0.02
Systolic 쏝 140 mm Hg (n ҃ 1240) 0.13 (0.08, 0.19) 0.54 (0.39, 0.75) 0.20 (0.16, 0.25) 0.41 (0.35, 0.46) 0.44 (0.39, 0.49)
(Continued)
690 COYNE ET AL

TABLE 3 (Continued)

␣-Carotene ␤-Carotene ␤-Cryptoxanthin Lutein/zeaxanthin Lycopene

Systolic 욷 140 mm Hg (n ҃ 343) 0.11 (0.08, 0.15) 0.47 (0.34, 0.65) 0.21 (0.15, 0.30) 0.41 (0.34, 0.50) 0.35 (0.29, 0.42)
P 0.01 쏝 0.01 0.23 0.28 0.43
Diastolic 쏝 90 mm Hg (n ҃ 1533) 0.12 (0.08, 0.18) 0.53 (0.38, 0.73) 0.20 (0.16, 0.26) 0.41 (0.36, 0.47) 0.42 (0.37, 0.46)
Diastolic 욷 90 mm Hg (n ҃ 52) 0.08 (0.06, 0.11) 0.34 (0.24, 0.49) 0.17 (0.10, 0.28) 0.37 (0.27, 0.52) 0.39 (0.31, 0.48)
Dietary intake of vegetables and fruit4
Servings of vegetables3
P 0.01 0.02 0.01 0.02 0.18
울 1 (n ҃ 250) 0.08 (0.06, 0.09) 0.38 (0.34, 0.43) 0.15 (0.12, 0.19) 0.34 (0.27, 0.42) 0.40 (0.34, 0.48)
2–3 (n ҃ 847) 0.12 (0.09, 0.17) 0.52 (0.38, 0.70) 0.20 (0.16, 0.25) 0.39 (0.33, 0.46) 0.44 (0.40, 0.48)
욷 4 (n ҃ 469) 0.15 (0.10, 0.24) 0.64 (0.44, 0.94) 0.24 (0.18, 0.32) 0.48 (0.43, 0.53) 0.39 (0.31, 0.48)
Servings of fruit3
P 0.01 쏝 0.01 쏝 0.01 0.01 0.79
울 1 (n ҃ 619)

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0.09 (0.06, 0.13) 0.40 (0.28, 0.56) 0.12 (0.10, 0.16) 0.35 (0.30, 0.42) 0.41 (0.37, 0.69)
2–3 (n ҃ 751) 0.14 (0.11, 0.19) 0.60 (0.47, 0.75) 0.26 (0.22, 0.30) 0.43 (0.37, 0.51) 0.41 (0.37, 0.46)
욷 4 (n ҃ 190) 0.19 (0.113, 0.27) 0.79 (0.62, 1.01) 0.36 (0.29, 0.44) 0.47 (0.41, 0.54) 0.43 (0.36, 0.51)
1
n ҃ 1597; because of missing values, total n is not the same for all variables AusDiab, Australian Diabetes, Obesity, and Lifestyle.
2
t Test (test of association with adjustment for cluster design).
3
ANOVA (test of overall association with adjustment for cluster design).
4
A serving of cooked vegetables was 75 g (1/2 cup), of salad vegetables was 앒130 g (1 cup), and of diced or canned fruit was 150 g (1 cup).

oxidative stress effects of the disease or whether the low con-
centrations are involved in the pathogenesis of the disease and
reflect low intakes of carotenoid-rich vegetables and fruit. It has
been postulated that the lower serum carotenoid concentrations
found in this study may be due to the oxidative stress effects of
IGM. Research has shown that oxidative stress, an imbalance in
which the production of free radicals overwhelms the body’s
antioxidant defenses, is involved in the causation and progres-
sion of type 2 diabetes (32). There currently is considerable
evidence that hyperglycemia, hyperinsulinemia, and insulin re-
sistance result in greater reactive oxygen species production that
contributes to oxidative stress in diabetes (33), and that this
greater reactive oxygen species production may be beyond the
capacity of the antioxidant defense mechanisms (34). Oxidative
stress and free radical activity have been reported to be involved
in the pathogenesis of type 1 diabetes (35), as well as in the
development of complications associated with type 2 diabetes
(36, 37). It is postulated that the oxidative stress associated with
diabetes is responsible for the reduced carotenoid concentrations
found in this study, which suggests that glucose intolerance is
influencing the carotenoid concentrations, rather than the low ca-
rotenoid concentrations being causally related to diabetes status.
It has also been suggested that the oxidative stress observed in
persons with glucose impairment is due to lower antioxidant
concentrations. Facchini et al (38) suggested that insulin-
mediated glucose disposal in healthy persons is significantly
related to lipid hydroperoxide concentrations and fat-soluble
antioxidant vitamins. Their work showed that nondiabetic sub-
jects with insulin resistance had high plasma lipid peroxidation
values well before the development of IGT or type 2 diabetes.
They observed significant inverse associations between steady
state plasma glucose values and ␣-carotene, ␤-carotene, lutein,
␣-tocopherol, and ␦-tocopherol in 36 healthy nondiabetic vol-
unteers. Facchini et al also observed that the higher the steady
state plasma glucose, the more insulin resistant the person. They
hypothesized that insulin resistance can result in greater lipid
peroxidation, which is accompanied by a decrease in plasma
antioxidant concentrations. Conversely, lipid peroxidation is ac-
celerated by low antioxidant activity, which could impair insulin
action and result in diabetes (38). Thus it is possible that oxida-
tive stress is a result of low antioxidant concentrations in persons
who already have IGM and type 2 diabetes.
Several studies have shown a relation between vegetable or
carotenoid intake and diabetes status (9, 14, 31). Suzuki et al (15)
found a significantly lower odds ratio for high glycated hemo-
globin (Hb A1c) among those with the highest intakes of carrots
and pumpkin than among those with low intakes. The large
EPIC-Norfolk study found that persons with higher intakes of
vegetables and fruit have higher serum carotenoid concentra-
tions and lower risk of type 2 diabetes than do those with lower
intakes (39). Montonen et al (9) reported that, in older adults,
␤-cryptoxanthin intake was inversely associated with reduced
risk of type 2 diabetes. Ylönen et al (13) reported advantageous
associations with both dietary and plasma carotenoids and glu-
cose status among males but not among females in the Botnia
Dietary Study.
Serum carotenoids are considered reliable markers of vegetable
and fruit intake, and our study did find significant associations be-
tween the approximated vegetable and fruit intakes and serum con-
centrations of ␣-carotene, ␤-carotene, ␤-cryptoxanthin, and lutein/
zeaxanthin (40). We did not, however, find a significant association
between glucose intolerance and self-reported vegetable and fruit
intake or dietary ␤-carotene intake (not shown). This lack of asso-
ciation may have been due to the crudeness of our methods for
estimating vegetable and fruit intakes.
We recognize that residual confounding may have occurred in
our study because of suboptimal measurements of several fac-
tors. For instance, concentrations of carotenoids (except lyco-
pene) in our study were significantly lower among smokers,
which is consistent with other studies (12). However, there may
be residual confounding because of our simple categorization of
smoking. This could have enhanced the magnitude of the asso-
ciation between serum carotenoids and glucose status, but it is not
likely to explain most of the association.
 DIABETES AND SERUM CAROTENOIDS 691
TABLE 4
Age-adjusted mean fasting plasma glucose, 2-h postload plasma glucose, and fasting insulin by quintile (Q) of serum carotenoids for adults in the 2000
Queensland AusDiab study1

Fasting plasma glucose2 2-H postload plasma glucose2 Fasting insulin3

Serum carotenoids in
quintiles (median) Value P for trend4 Value P for trend4 Value P for trend4

mmol/L mmol/L mmol/L

␣-Carotene 쏝 0.01 쏝 0.01 쏝 0.01
Q1 (0.04) 5.60 앐 0.24 7.34 앐 0.78 16.90 앐 0.12
Q2 (0.08) 5.44 앐 0.23 7.01 앐 0.75 15.88 앐 0.11
Q3 (0.13) 5.32 앐 0.24 6.75 앐 0.78 14.60 앐 0.12
Q4 (0.21) 5.25 앐 0.25 6.52 앐 0.81 13.50 앐 0.12
Q5 (0.39) 5.19 앐 0.23 6.29 앐 0.76 11.33 앐 0.12
␤-Carotene 쏝0.01 쏝0.01 쏝0.01
Q1 (0.17) 5.61 앐 0.25 7.24 앐 0.82 17.01 앐 0.31
5.40 앐 0.24 6.98 앐 0.79 16.17 앐 0.31

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Q2 (0.36)
Q3 (0.55) 5.35 앐 0.26 7.00 앐 0.84 14.92 앐 0.31
Q4 (0.83) 5.26 앐 0.26 6.42 앐 0.85 12.97 앐 0.33
Q5 (1.50) 5.23 앐 0.24 6.36 앐 0.78 11.45 앐 0.32
␤-Cryptoxanthin 0.08 쏝0.01 쏝0.01
Q1 (0.07) 5.42 앐 0.24 6.94 앐 0.79 16.70 앐 0.27
Q2 (0.13) 5.34 앐 0.23 6.78 앐 0.76 15.28 앐 0.26
Q3 (0.21) 5.38 앐 0.25 6.86 앐 0.80 13.61 앐 0.28
Q4 (0.33) 5.43 앐 0.26 6.71 앐 0.83 14.22 앐 0.30
Q5 (0.66) 5.26 앐 0.23 6.67 앐 0.75 12.46 앐 0.27
Lutein/zeaxanthin 0.07 0.03 쏝0.01
Q1 (0.20) 5.45 앐 0.25 7.00 앐 0.82 14.81 앐 0.07
Q2 (0.32) 5.30 앐 0.24 6.55 앐 0.79 14.52 앐 0.07
Q3 (0.42) 5.44 앐 0.22 7.02 앐 0.72 15.24 앐 0.07
Q4 (0.56) 5.36 앐 0.24 6.73 앐 0.77 14.56 앐 0.07
Q5 (0.82) 5.28 앐 0.24 6.66 앐 0.78 13.35 앐 0.07
Lycopene 0.40 0.04 쏝0.01
Q1 (0.17) 5.47 앐 0.22 7.43 앐 0.67 14.54 앐 0.18
Q2 (0.33) 5.46 앐 0.21 7.14 앐 0.66 15.71 앐 0.17
Q3 (0.46) 5.39 앐 0.21 6.55 앐 0.65 15.28 앐 0.17
Q4 (0.65) 5.22 앐 0.20 6.33 앐 0.61 13.48 앐 0.15
Q5 (0.98) 5.29 앐 0.20 6.45 앐 0.61 13.44 앐 0.15
1
AusDiab, Australian Diabetes, Obesity, and Lifestyle.
2
Adults aged 욷 25 y (n ҃ 1597).
3
Adults aged 욷 35 y (n ҃ 1303).
4
Across categories of serum carotenoids by using a regression model adjusted for age and cluster design.

Whereas our findings and data from other studies suggest a male health professionals, Liu et al (16) found no difference in
probable association between several carotenoids and diabetes, the incidence of diabetes between the group receiving ␤-carotene
they do not establish a causal relation. In a clinical trial among US supplements and the control group. Liu et al concluded, however,

TABLE 5
Adjusted geometric mean (and 95% CI) concentrations of serum carotenoids by diabetes status for adults aged 욷25 y who participated in the 2000
Queensland AusDiab study1

Diabetes status2

Normal glucose Impaired glucose Type 2 diabetes

tolerance (n ҃ 1145) metabolism (n ҃ 320) (n ҃ 132) P for trend

Serum carotenoids (␮mol/L) 3

␣-Carotene 0.13 (0.10, 0.18) 0.12 (0.09, 0.16) 0.10 (0.08, 0.14) 0.011
␤-Carotene 0.59 (0.47, 0.73) 0.50 (0.38, 0.64) 0.42 (0.30, 0.58) 0.01
␤-Cryptoxanthin 0.22 (0.19, 0.25) 0.20 (0.17, 0.23) 0.19 (0.16, 0.22) 0.041
Lutein/zeaxanthin 0.42 (0.35, 0.50) 0.39 (0.35, 0.43) 0.35 (0.33, 0.38) 0.026
Lycopene 0.44 (0.40, 0.49) 0.39 (0.34, 0.45) 0.35 (0.27, 0.44) 0.053
1
n ҃ 1597. AusDiab, Australian Diabetes, Obesity, and Lifestyle. Multiple linear regression model after adjustment for potential confounders including
sex; age in 10-y age grouping; BMI (in kg/m2); physical activity; education; vitamin use; smoking status; alcohol consumption; total, LDL, and HDL cholesterol;
triacylglycerol; systolic blood pressure; and diastolic blood pressure and for cluster design (potential confounders included in the model as categorical variables).
Values were estimated from the regression model with all other variables set to average sample values. Geometric means were back transformed.
2
Included in the regression model as a continuous variable.
3
Serum carotenoids were log transformed for regression analyses.
692 COYNE ET AL
that the results of their trial of ␤-carotene supplementation
“should not be interpreted as refuting the findings of observa-
tional studies that suggest that increased intake of vegetables rich
in carotenoids and other antioxidants may decrease the risk of
type 2 diabetes” (16).
Diabetes is increasing in most countries of the world today and
will continue to increase (41). As populations continue to age and
as overweight and obesity continue to escalate, especially among
children, diabetes will become an increasing burden on the health
system. Lifestyle interventions have shown a dramatic reduction
in risk of diabetes among those with IGT (42, 43). However,
strategies for both primary and secondary prevention will be
necessary to reduce the burden of diabetes in future years and
generations in both developed and developing countries. Clinical
trials based on diets high in carotenoid-rich vegetables and fruit
may provide important insight in relation not only to the preven-
tion of complications of diabetes, but also to reducing the risk of
developing the disease, especially among those with IGT.
TC was responsible for the concept and conduct of the study and preparing
the manuscript. TII performed the statistical analysis and writing the results
section. PDB and AD provided technical assistance on the data analysis. JS,
SD, and CM provided details regarding the study methods. DL gave technical
assistance on writing and interpretation. None of the authors had a personal
or financial conflict of interest.
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