A.

SPECIFIC AIMS

Southeast Asian populations have high rates of type 2 diabetes (T2D) despite low rates of obesity. The World
Health Organization (WHO) and International Diabetes Federation have recognized T2D as a pressing
pandemic, especially in populations of Southeast Asia. The extremely high public health and economic burden
of this disease, along with the large population sizes in this part of the world, make the future implications for
global health and economics staggering. Within the massive region of Southeast Asia, India appears likely to
have the higher rates of T2D, although more and better population-based cohort studies and community
surveillance are needed to more definitively characterize the T2D burden in India. While WHO’s Asian-specific
lower thresholds for defining obesity underscore the particular susceptibility of these ethnic groups to T2D, the
specific underlying biological and environmental causes for the excess risk in India is unknown. We believe the
studies we aim to develop, as described in the current application, will move the field forward in understanding
the biological and environmental determinants of T2D risk in Asian Indians, and therefore improve risk
stratification so that those at greatest risk can be identified for early prevention and treatment efforts.
Given the lack of understanding of T2D etiology in Southeast Asian, the world’s hotbed for T2D,it is paramount
that a highly qualified team of transdisciplinary international collaborations begin tackling the many important
etiological, epidemiological, and public health problems that remain unanswered in this area. Therefore, the
overall aim of this proposal is to begin laying the groundwork for a large, state-of-the art cohort study on T2D
etiology and epidemiology in India that will span all major areas of scientific inquiry including genetic,
biological, lifestyle, cultural, and geographical components, as well as the interactions among these
components. We will use the currently requested resources to assemble a team of investigators from India
and the U.S. to develop the specific scientific aims and hypotheses for an ensuing cohort study, to conduct
infrastructure inventory with respect to the proposed aims, to collect preliminary data, and to prepare a robust
scientific proposal to request funding from the U.S. and Indian governments.

B. Background [Mark will modify and shorten this entire Background section for our current developmental
grant. You don’t have to read this yet, but any general or specific suggestions will be incorporated. I’d
suggest skimming this section B, and then focus more on what I am thinking about in sections C and D
below.]

B.1. Characterization and Epidemiology of Type 2 Diabetes

Type 2 diabetes mellitus (T2D), characterized by chronic hyperglycemia resulting from insulin resistance and
relative insulin insufficiency,1 presents a modern day crisis for global health. 2, 3 T2D carries an enormous
burden and cost due its high prevalence and its many morbid complications and chronic conditions owing to
the fact that it is often inadequately treated.3, 4 The strongest risk factors for T2D are age, obesity, and family
history. Excess body fat, particularly in the intraabdominal or visceral region, has a pernicious impact on insulin
resistance and diabetes risk, likely due to its intimate relation to hepatic metabolism, with the liver being a
critical organ for glucose metabolism. 5-7 Lifestyle changes, particularly dietary and physical activity patterns,
may contribute in important ways to the diabetes risk imparted by aging, obesity, and other aspects of body
composition. Indeed, clinical mechanistic studies as well as large epidemiologic studies have consistently
demonstrated the important role of exercise and dietary patterns in modulating insulin sensitivity, possibly beta-
cell function as well, and diabetes risk. Several randomized trials to date have demonstrated the efficacy of
prudent dietary patterns and regular physical activity, and weight gain prevention in decreasing the incidence
of T2D.8-10 While such interventions have underscored the role of environment factors in T2D etiology, family
history and twin studies have demonstrated that there is a strong genetic component to this disease. The
tremendous heterogeneity in diabetes risk between ethnic groups and geographic regions speaks to the likely
complex interplay of polygenic and environmental factors driving T2D risk.
B.2. Global Burden of Type 2 Diabetes
The World Health Organization and International Diabetes Federation have recognized type 2 diabetes as a
pressing pandemic.11, 12 Based on projections from existing surveillance systems around the globe, the number
of people with diabetes is expected to increase from 194 million in the year 2003 to 333 million by the year
2025, with the crude prevalence rate expected to increase by 20%. 12 Unfortunately, rates and absolute
numbers of cases of T2D are expected to increase the most in many developing regions, particularly
throughout parts of Asia, that may be the least equipped to deal with such a public health crisis. 2 Due to the
increases in prevalence and the increasing size of the populations in these areas, T2D cases are expected to
increase in Southeast Asia from 39 million to 82 million between the years 2003 and 2025.2 In India the
prevalence of diabetes is expected to increase from __% in 2003 to __% in 2025, when it will rank as the __th
highest in the world behind.2
B.2.1. The Southeast Asian Paradox of Diabetes. It is paradoxical that T2D rates are so high in many of
the Asian populations that have relatively low rates of obesity, compared to Caucasian populations where rates
of diabetes tend to be somewhat lower despite high rates of obesity. While the Southeast Asian-specific lower
thresholds for defining overweight and obesity underscore the particular susceptibility of these ethnic groups,
the underlying biology for the excess risk in Asians is unclear. In most Southeast Asian countries, even using
the Asian-specific lower cutoff points for obesity on the BMI scale, prevalence of obesity is typically less than
15%, compared to 30% or higher in the U.S., while rates of diabetes are typically 2- to 4-fold higher in
Southeast Asia than in the U.S. 12 Southeast Asians not only have the highest documented rates of type 2
diabetes, but also have some of the highest rates of coronary disease and stroke worldwide.13-16
While these ecological correlations are indeed paradoxical in light of obesity being the second most important
risk factor for T2D, as well as a risk factor for cardiovascular disease, we must turn our attention to clinical and
epidemiological cohort studies in order to begin to understand how the causal pathological agents of T2D may
differ between ethnic groups. Scientific discovery from such observational and experimental work will be critical
towards the ultimate goal of improving our ability to screen, risk stratify, prevent, and treat T2D, especially in
parts of the developing world with high disease rates and compromised healthcare systems.
B.2.2. Body Composition / Anthropometric Factors. As a possible explanation for the paradox of low
general obesity yet high rates of diabetes in Southeast Asians, it has been hypothesized that Southeast Asians
have a propensity towards central (intra-abdominal or visceral) obesity and associated insulin resistance at
relatively low body weights.17-24 Indeed, clinical studies have suggested that associations between adiposity
and insulin sensitivity may differ between Southeast Asians and Caucasians, with Southeast Asians having
lower insulin sensitivity (more insulin resistance) at similar levels of overall adiposity.18-20 Clinical detailed
comparisons of body composition across ethnic groups has shed light on some of the underlying etiological
factors that may explain this Southeast Asian paradox. It has been observed that Asian Indians all have
higher body fat at any given BMI level compared to Caucasians. 25-27 There is ample support for the hypothesis
that Southeast Asians not only have higher relative body fat levels, but they tend to have relatively more fat
stored in the visceral cavity, inside the liver, and inside skeletal muscles, compare to Caucasians. 28 Therefore,
body composition differences between Southeast Asians and Caucasians are highly relevant to our
understanding of possible differences in genetic propensities for insulin resistance and type 2 diabetes
between Southeast Asians and other groups. For a variety of anatomical and physiological reasons, these fat
deposits are thought to be most pernicious, relative to subcutaneous fat stores, in promoting insulin resistance,
disturbances in glycemic control, dyslipidemia, and possibly hypertension.5-7
The the scientific basis for setting separate thresholds for disease risk across race-ethnicity, based on body
mass index and waist circumferences, continues to be a matter of scientific debate. 29-31 While there is general
agreement that excess adiposity, especially excess body fat stored in liver and muscle, promotes metabolic
disturbances that heighten risk for diabetes and cardiovascular disease, and that risk can be modified across
ethnic groups by improved dietary and exercise patterns, 8-10 there is clearly a strong and complex genetic
component to type 2 diabetes risk, as discussed below. Currently, we know very little about the specific genetic
lesions that carry risk for type 2 diabetes, how these lesions may vary by ethnic group, and how they interact
with other genes and environmental factors to modulate risk for type 2 diabetes. As will be discussed, the
technology is now in place by several research groups, including ours, to pursue comprehensive studies of the
human genome in relation to type 2 diabetes risk, the next frontier in enhancing our understanding of such
complex chronic diseases so that we may have better prevention and therapeutic strategies in the near future.
B.3. Genetic Factors in Diabetes
Extensive evidence supports the hypothesis that genetic factors are a major contributor toward the risk of type
2 diabetes in human populations. Numerous rare monogenic forms of diabetes, such as several forms of
MODY (Maturity-Onset Diabetes in the Young), have been identified and clearly have a proven genetic basis.
Albeit, these monogenic forms account for only a small fraction of the risk of diabetes. On the other hand, a
few less severe forms of monogenic disorders have been associated with a population-wide increased risk of
diabetes. These genetic variants have been summarized by O’Rahilly et al. 32 and include PPARG, KCNJ11
and HNF4A genes. The genetic variants of these genes account for a larger, but still small fraction of the risk
associated with diabetes. Nonetheless, these variants can be considered common susceptibility factors.
Evidence for more common genetic factors comes from a range of studies. Different ethnic groups, in a shared
environment, vary dramatically in their susceptibility to diabetes. For instance, in the UK, the prevalence of
diabetes is 2.4% in Caucasians, but 3-6 fold higher among Southeast Asians and African-Caribbeans. 17, 33, 34
Numerous family studies consistently have found an elevated risk of diabetes among 1st degree relatives of
diabetics, including Southeast Asian populations.35-37 Twin studies have shown a higher concordance for
diabetes among monozygotic twins as compared with dizygotic twins.38-42 Each of these studies suggests the
presence of additional genetic variants, which can increase susceptibility to diabetes.
The identification of common genetic factors influencing the risk of type 2 diabetes has been a challenging
area. Few candidate gene and even linkage studies have shown clear and reproducible evidence of a
relationship between common genetic variants and the risk of diabetes. There are many possible reasons for a
lack of consistent associations, including small sample sizes and a limited range of genetic analysis.
Nonetheless, considerable progress has been made recently through a new approach, whole genome scans.
This approach has identified genetic variants on several chromosomes including 1q, 2q, 3q, 9q, 10q and 11q. 43
More importantly, association with some of the SNPs has been replicated in several populations, providing
validation. A major locus associated with diabetes is the transcription factor 7-like 2 gene, TCF7L2. TCF7L2 is
a transcription factor that acts in the regulation of proglucagon gene expression and control of blood glucose
levels. Several SNPs and a marker of microsatellite DNA (intron 3) in the gene have been associated with type
2 diabetes.44 Relative risks for heterozygotes and homozygotes of the main at-risk allele were 1.45 and 2.41,
respectively. Other associated SNPs had similar odds ratios. Regarding the microsatellite locus, the
association had a p value of 2.1 x 10 -9.44 The population attributable risk was 21%. These findings have been
replicated in two additional populations in Denmark and the US. Also, a two-stage genome-wide association
study was performed in a French population. 45 It confirmed the association with TCF7L2 and identified 7
associated SNPs from or near 4 genes that may be involved in beta cell development or function. These genes
were SLC30AB, EXT2, LOC387761, and HHEX. All p values were less than 2.9 x 10 -5. An association study of
6,736 UK subjects also replicated the TCF7L2 results.46 It used four TCF7L2 SNPs in a case-control study (p
value = 1.3 x 10-11 for rs7903146) and a family-based study of 388 parent-offspring trios (62% transmission, p
value = 7.0 x 10-5). The effect size for allele-wise risk was 1.36, CI 1.24-1.48. The Diabetes Prevention
Program found an association between TCF7L2 SNPs and the progression of diabetes from impaired fasting
glucose to diabetes (hazard ratio = 1.55, CI =1.20-2.01 for rs7903146). 47 Together, these studies have
established the validity of genome-wide association studies and clearly identified TCF7L2 as a risk factor for
T2D.
In another recent set of genome-wide association studies, three new loci were associated with T2D. These
include loci in the non-coding region near CDKN2A and CDKNB, in the non-coding region of IGF2BP2, and an
intron of CDKAL1.48 This study also replicated associations with the TCF7L2 loci and loci near HHEX and
SLC30A8, which had been reported in a previous study. 48 It also confirmed associations with variants of
PPARgamma and KCNJ11. The population attributable risks for these 8 loci ranged between 5% and 27%.
These associations were confirmed in two additional studies.49, 50 One of these studies also identified an
intragenic region on 11p12 in a Finnish population.50
Together, the genome-wide association studies identify and validate several susceptibility loci for diabetes, all
in populations of European ancestry. These loci are significant contributors toward the risk of diabetes with
population attributable risks > 5% per locus. The results provide strong evidence for the existence and
identification of common genetic risk factors for diabetes.
B.3.1. Genetic Studies of Type 2 Diabetes in Southeast Asians. The relevance of the loci just described
in other ethnic groups is unknown. Of particular interest is their role in Southeast Asians, populations with a
high susceptibility to diabetes. It is likely that some of the genetic variants described above contribute toward
genetic susceptibility in these populations. However, an analysis of their possible contribution suggest that
additional variants must exist, which define the unique susceptibility to diabetes of the Southeast Asians and
their unique phenotype.
A phenotype associated with increased risk of type 2 diabetes is the “Asian Indian Phenotype.” 51 It was first
described for the Indian population, but similar forms of it are prevalent throughout Southeast Asia. It is
characterized by an enhanced accumulation of abdominal adiposity (higher abdominal fat per unit of BMI) and
insulin resistance (higher resistance per unit of BMI). Our preliminary studies indicate that the Singapore
Chinese have a similar or identical phenotype. Several studies indicate that their may be a genetic basis for
this heightened insulin resistance and impaired glucose tolerance in the Southeast Asians. A higher
percentage of Asian Indians have 1st degree relatives with diabetes than Europeans.52 The prevalence of type
2 diabetes cases among offspring in which both parents have diabetes is 10% in Asian Indians and only 1% in
Europeans.52 Among Asian Indian families wherein both parents have diabetes, sixty percent of their offspring
have diabetes or impaired glucose intolerance, which is much higher than occurs in European and American
families with two diabetic parents.35, 37, 53, 54 A positive family history is associated with a higher prevalence of
diabetes (18.2%) compared to those without a family history (10.6%) in the Indian population.55
Few candidate genes have been associated with T2D in the Southeast Indians. These include the Gly972Arg
variant of the IRS (Insulin receptor substrate) gene and the GLUT1 gene. 56, 57 Glucokinase may have a minor
role in susceptibility to T2D.57 Variants of the insulin receptor substrate-2,58 PPAR-co-activator -1 alpha (PCG-
1)/ENPP1gene have been associated with an increased risk of T2D. 59 Only the IRS variant has been confirmed
in several population studies. Associations with GLUT1 and glucokinase have been shown in only a small
population and require further confirmation. Many other candidate genes did not show an association with T2D.
These include the glucagon receptor, insulin receptor substrate 1, beta 3 adrenergic receptor, glycogen-
associated regulatory subunit of protein phosphatase-1, sulphonylurea receptor, uncoupling protein-2,
mitochondrial tRNA, fatty acid binding protein-2 and the insulin receptor.60
Overall, these observations support the hypothesis that genetic variants influence the risk of diabetes in
Southeast Asia populations. These variants can be identified with whole genome association studies and will
include the identification of variants which are unique to the Southeast Asian populations. The high
susceptibility and prevalence of diabetes in Southeast Asian population provides an opportunity for the
discovery of genetic variants which have not been previously associated with diabetes as well as confirmation
of SNPs associated with diabetes in this population.
B.4. Role of Lifestyle in Diabetes Relevant to Asian Indians [to be completed]
C. Overview of the Investigative Team and Potential Collaborators from India
C.1. U.S. Investigators
Mark A. Pereira, Ph.D., Principal Investigator. Dr. Pereira is an Associate Professor in the Division of
Epidemiology & Community Health, School of Public Health, University of Minnesota. He has a Ph.D. in
epidemiology and an M.S. in exercise science. Dr. Pereira’s research focuses on the etiology and primary
prevention of obesity and type 2 diabetes. His original published work in this area has involved a number of
populations from around the world for the past 15 years. 61-71 He has broad experience in chronic disease
epidemiology, including interventional61, 72-75 and prospective observational studies.62, 63, 65, 66, 70, 71, 76-82 An
example of Dr. Pereira’s leadership skills is his key role on the NHLBI-funded Pooling Project on Diet and
Coronary Disease, in which he led the scientific and logistical aspects of a state-of-the art meta-analyses in
collaboration with numerous senior investigators around the world. 77, 79 Dr. Pereira recognizes the unique value
of the Singapore Chinese Health Study Cohort and is committed, on a long-term basis, to using this ongoing
cohort study as the centerpiece of his research program. His commitment is evidenced by his efforts to date in
characterizing the major exposure-T2D associations within this high-risk cohort of subjects (see Sections C.2
and C.3 below for details). Dr. Pereira has been meeting regularly with Dr. Mimi Yu, PI of the Singapore
Chinese Health Study, since she relocated from the University of Southern California in Los Angeles to the
University of Minnesota nearly three ago. He also has traveled to Singapore to confer with the investigative
team members from the Genome Institute of Singapore and the National University of Singapore.

Gundu Rao, M.D., Co-Principal Investigator. Dr. Rao….

Myron D. Gross, Ph.D., Co-Investigator. Dr. Gross is a Professor in the Department of Laboratory Medicine
and Pathology at the University of Minnesota School of Medicine, which oversees the clinical laboratories of
the main teaching hospital for the medical school (Fairview-University Medical Center) and supports numerous
nationally-funded research projects. He also is the Director of the Molecular Epidemiology and Biomarker
Research Laboratory and is an adjunct Professor in the Division of Epidemiology & Community Health in the
School of Public Health. Dr. Gross has worked closely with Dr. Pereira on past and present studies. 61, 83, 84 He
also has experience with international efforts85-87 in medical research, and importantly with the high prevalence
of diabetes in Southeast Asians. Specifically, he is a member of a Fogarity-funded training grant and has been
actively engaged in the design, implementation and training of health professionals in India during the past 5
years, including annual trips to India for on site training and project implementation. His role in this effort has
been extended recently for another 5 years. Dr. Gross brings an extensive background in the development and
implementation of a wide range of biochemical and genetic measurements in human and epidemiologic studies
to this effort. He has overseen a wide range of genetic analysis in epidemiologic studies and serves on the NCI
Steering Committee for PanScan, which is heading an effort for the identification of genetic variants associated
with the risk of pancreatic cancer through the use of genome-wide association studies in a consortium of 12
cohorts. Dr. Gross represents and is an investigator in the national screening study, PLCO, which is a cohort
of the consortium. His laboratory, the Molecular Epidemiology and Biomarker Research Laboratory (MEBRL),
has engaged in genetic and biomarker measurements for the last 20 years, serving as a core laboratory for
numerous NIH-funded studies including CARDIA, WAVE, MHS, ARIC, CPRU,
Andrew O. Odegaard, Ph.D., Co-Investigator. [Andy, we can start with what is in your AHA grant
investigator section…]
.

Noel T. Mueller, M.P.H, Graduate Research Assistant. Mr. Mueller….

C.2. India and other non-U.S. Investigators

Gundu Rao, M.D., Co-Principal Investigator. [Note that it may make sense to include Gundu here as
well as above, as he is on “both teams” for reasons that we need to make clear.] Dr. Rao….

Caroline HD Fall, MBChB DM FRCP FRCPCH, Professor of International Paediatric Epidemiology.

Honorary Consultant in Child Health
MRC Epidemiology Resource Centre
University of Southampton
Southampton General Hospital
Tremona Road
Southampton SO16 6YD

Dr Veena, MRC Epidemiology Resource Centre

Dr Krshnaveni, MRC Epidemiology Resource Centre

Dr. B.G.Ranganath, Head, Community Medicine. Sri Devaraja Urs Medical College, KOLAR.

Professor Krishnaswamy

Dr Asna Urooj. Dr Asna Urooj has been studying the role of diet in diabetics. She has published number of
articles on this subject.

Dr. Anura Kurpa, Dean of Research at St. Johns Medical Academy. Expertise in diet and disease in
Asian Indians.

C.3. Study Sites.

Kolar, Dev Raja Urs Academy of Medical Sciences and Research, Community Health Department

New Gemome Center for sample processing and PCR in Kolar

Mission Hospital MRC Epi unit.

The pioneering work on Low Birth Weight children brings great strength to our proposed studies.

University of Mysore, Division of Nutrition.

With collaboration from Dr Asna Urooj we can collaborate on the diet-related studies. It may also be possible to
establish a nutrition data base similar to NCC at the University of Minnesota.

Central Food Technological Research Institute, Mysore.

This center has been involved in food research for over 60 years. The Director is also the President of the
Nutrition Society of India. (There is another Institute in Hyderabad which also can help us at some point.
National Institute of Nutrition.)

Triesta Genome Center, Bangalore.

St John's Medical Academy, Bangalore.

D. RESEARCH DESIGN AND METHODS

D.1. Overview
Our overall approach is to foster collaborations across several study sites in India and the U.S. to coordinate
the personnel and infrastructure necessary to carry out a major cohort study, as well as future ancillary studies
in the area of diabetes etiology and epidemiology in India. Our ultimate goal moving into the future will be to
set up a transdisciplinary platform across multiple sites that is highly coordinated to capture, prospectively, an
array of multilevel data from the intrauterine environment and forward throughout life.

[If we have room, I’d like to include a theoretical model of how all the components/study centers fit together in
complimentary and overlapping ways.]

D.2. Feasibility Evaluation for Data Collection Across Multiple Sites

D.2.1. Population-Based Epidemiological Cohort Study.

The main site that will evaluated as the central data collection and processing center for a prospective
population-based cohort study will be Kolar, Dev Raja Urs Academy of Medical Sciences and Research,
Department of Community Health. At this site a new genomic center is also currently being established that
can potentially serve for blood sample processing for biomarker and genetic studies.

D.2.2. Genetic Studies.

Genetic studies, including potentially genome-wide association studies, will be considered to be performed
at the Triesta institute in Bangalore.

D.2.3. Studies of the intrauterine environment.

We will explore collaborations with the MRC unit, Mission Hospital, Mysore, on data that could be collected
to examine important yet-to-be answered questions on the impact of the intrauterine environment on the
transgenerational transmission of risk for type 2 diabetes in Asian Indians.

D.2.4. Lifestyle and Gene x Environment Interactions.

In collaboration with Mysore University and also the Population Research Center at St John's, Bangalore
we will develop systems to take advantage of the wealth of data on the Indian diet as it may relate to diabetes
risk. This will help to inform us on the best approaches towards developing a valid dietary assessment tool in
our cohort studies, as well as in connection with the genetic components of the proposed research to examine
diet x gene interactions for diabetes risk. Similar avenues will be explore for physical activity.

D.2.4. Surveillance Component

[I am going to talk to Jay Desai, one of our PhD students and a Diabetes Surveillance expert with
the Minn. Dep of Health, as well as Ed Gregg, Director of Diabetes Translation at the CDC, for advice on
how we can propose to conduct developmental projects around surveillance on diabetes in different
parts of the urban and rural Indian Communities. Then, we can take these ideas to our Indian
colleagues with Gundu’s involvement.]

D.3 Development of Quality Control Assurances.

D.4. Power Calculations for Eventual Cohort Study and Genetic Studies.

D.5 Data Management and Data Sharing Plans

D.6. Timeline of Proposed Study

D.7. Overall Summary, Strengths and Limitations of the Proposed Study

E. HUMAN SUBJECTS

E.1 Protection of Human Subjects

E.2 Inclusion of Women

E.3 Inclusion of Minorities

E.4 Inclusion of Children

This study involves only adults over the age of 45 years, since type 2 diabetes primarily occurs in older adults.

F. VERTEBRATE ANIMALS

None
H. LITERATURE CITED

1. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. Jul 2004;88(4):787-835, ix. (PMID:
15308380).
2. Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, Zimmet P, Son HY. Epidemic obesity and type 2 diabetes in
Asia. Lancet. 2006;368(9548):1681-1688. (PMID: 17098087).
3. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world--a growing challenge. N Engl J
Med. Jan 18 2007;356(3):213-215. (PMID: 17229948).
4. Economic consequences of diabetes mellitus in the U.S. in 1997. American Diabetes Association. Diabetes Care.
Feb 1998;21(2):296-309. (PMID: 9539999).
5. Matsuzawa Y, Shimomura I, Nakamura T, Keno Y, Kotani K, Tokunaga K. Pathophysiology and pathogenesis of
visceral fat obesity. Obes Res. Sep 1995;3 Suppl 2:187S-194S. (PMID: 8581775).
6. Despres JP. Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. J
Endocrinol Invest. 2006;29(3 Suppl):77-82. (PMID: 16751711).
7. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. Dec 14 2006;444(7121):881-887.
(PMID: 17167477).
8. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the
incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Feb 7 2002;346(6):393-403.
(PMID: 11832527).
9. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S,
Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in
lifestyle among subjects with impaired glucose tolerance. N Engl J Med. May 3 2001;344(18):1343-1350. (PMID:
11333990).
10. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP,
Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with
impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. Apr 1997;20(4):537-544. (PMID:
9096977).
11. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.
Lancet. Jan 10 2004;363(9403):157-163. (PMID: 14726171).
12. Federation ID. Diabetes Atlas Summary. 2nd ed. Brussels, Belgium: International Diabetes Federation; 2003:58.
13. Hughes K. Mortality from cardiovascular diseases in Chinese, Malays and Indians in Singapore, in comparison
with England and Wales, USA and Japan. Ann Acad Med Singapore. Nov 1989;18(6):642-645. (PMID: 2624412).
14. McKeigue PM, Miller GJ, Marmot MG. Coronary heart disease in south Asians overseas: a review. J Clin
Epidemiol. 1989;42(7):597-609. (PMID: 2668448).
15. Anand SS, Yusuf S, Vuksan V, Devanesen S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H, Hegele RA,
McQueen M. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in
Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet. Jul 22 2000;356(9226):279-
284. (PMID: 11071182).
16. Lee J, Heng D, Chia KS, Chew SK, Tan BY, Hughes K. Risk factors and incident coronary heart disease in Chinese,
Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study. Int J Epidemiol. Oct 2001;30(5):983-
988. (PMID: 11689508).
17. Mather HM, Keen H. The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans. Br
Med J (Clin Res Ed). Oct 19 1985;291(6502):1081-1084. (PMID: 3931804).
18. McKeigue PM, Pierpoint T, Ferrie JE, Marmot MG. Relationship of glucose intolerance and hyperinsulinaemia to
body fat pattern in south Asians and Europeans. Diabetologia. Aug 1992;35(8):785-791. (PMID: 1511807).
19. Forouhi NG, Jenkinson G, Thomas EL, Mullick S, Mierisova S, Bhonsle U, McKeigue PM, Bell JD. Relation of
triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian
men. Diabetologia. Aug 1999;42(8):932-935. (PMID: 10491752).
20. Dickinson S, Colagiuri S, Faramus E, Petocz P, Brand-Miller JC. Postprandial hyperglycemia and insulin sensitivity
differ among lean young adults of different ethnicities. J Nutr. Sep 2002;132(9):2574-2579. (PMID: 12221211).
21. Laws A, Jeppesen JL, Maheux PC, Schaaf P, Chen YD, Reaven GM. Resistance to insulin-stimulated glucose uptake
and dyslipidemia in Asian Indians. Arterioscler Thromb. Jun 1994;14(6):917-922. (PMID: 8199182).
22. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE. Body composition, visceral fat, leptin, and insulin
resistance in Asian Indian men. J Clin Endocrinol Metab. Jan 1999;84(1):137-144. (PMID: 9920074).
23. Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and
Caucasian. J Clin Endocrinol Metab. Nov 2001;86(11):5366-5371. (PMID:
24. Dhawan J, Bray CL, Warburton R, Ghambhir DS, Morris J. Insulin resistance, high prevalence of diabetes, and
cardiovascular risk in immigrant Asians. Genetic or environmental effect? Br Heart J. Nov 1994;72(5):413-421.
(PMID: 7818957).
25. Deurenberg P, Deurenberg-Yap M, Guricci S. Asians are different from Caucasians and from each other in their
body mass index/body fat per cent relationship. Obes Rev. Aug 2002;3(3):141-146. (PMID: 12164465).
26. Deurenberg P, Yap M, van Staveren WA. Body mass index and percent body fat: a meta analysis among different
ethnic groups. Int J Obes Relat Metab Disord. Dec 1998;22(12):1164-1171. (PMID: 9877251).
27. Deurenberg-Yap M, Chew SK, Deurenberg P. Elevated body fat percentage and cardiovascular risks at low body
mass index levels among Singaporean Chinese, Malays and Indians. Obes Rev. Aug 2002;3(3):209-215. (PMID:
12164474).
28. Gallagher D, Kuznia P, Heshka S, Albu J, Heymsfield SB, Goodpaster B, Visser M, Harris TB. Adipose tissue in
muscle: a novel depot similar in size to visceral adipose tissue. Am J Clin Nutr. Apr 2005;81(4):903-910. (PMID:
15817870).
29. Ramachandran A, Snehalatha C, Vijay V. Temporal changes in prevalence of type 2 diabetes and impaired
glucose tolerance in urban southern India. Diabetes Res Clin Pract. Oct 2002;58(1):55-60. (PMID: 12161057).
30. Razak F, Anand S, Vuksan V, Davis B, Jacobs R, Teo KK, Yusuf S. Ethnic differences in the relationships between
obesity and glucose-metabolic abnormalities: a cross-sectional population-based study. Int J Obes (Lond). Jun
2005;29(6):656-667. (PMID: 15782225).
31. Anjana M, Sandeep S, Deepa R, Vimaleswaran KS, Farooq S, Mohan V. Visceral and central abdominal fat and
anthropometry in relation to diabetes in Asian Indians. Diabetes Care. Dec 2004;27(12):2948-2953. (PMID:
15562212).
32. O'Rahilly S, Barroso I, Wareham NJ. Genetic factors in type 2 diabetes: the end of the beginning? Science. Jan 21
2005;307(5708):370-373. (PMID: 15662000).
33. Chaturvedi N, McKeigue PM, Marmot MG. Resting and ambulatory blood pressure differences in Afro-
Caribbeans and Europeans. Hypertension. Jul 1993;22(1):90-96. (PMID: 8319998).
34. Greenhalgh PM. Diabetes in British south Asians: nature, nurture, and culture. Diabet Med. Jan 1997;14(1):10-
18. (PMID: 9017348).
35. Meigs JB, Cupples LA, Wilson PW. Parental transmission of type 2 diabetes: the Framingham Offspring Study.
Diabetes. Dec 2000;49(12):2201-2207. (PMID: 11118026).
36. Groop LC, Tuomi T. Non-insulin-dependent diabetes mellitus--a collision between thrifty genes and an affluent
society. Ann Med. Feb 1997;29(1):37-53. (PMID: 9073323).
37. Viswanathan M, Mohan V, Snehalatha C, Ramachandran A. High prevalence of type 2 (non-insulin-dependent)
diabetes among the offspring of conjugal type 2 diabetic parents in India. Diabetologia. Dec 1985;28(12):907-
910. (PMID: 4092859).
38. Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD. Concordance for type 2 (non-insulin-
dependent) diabetes mellitus in male twins. Diabetologia. Oct 1987;30(10):763-768. (PMID: 3428496).
39. Kaprio J, Tuomilehto J, Koskenvuo M, Romanov K, Reunanen A, Eriksson J, Stengard J, Kesaniemi YA.
Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a
population-based cohort of twins in Finland. Diabetologia. Nov 1992;35(11):1060-1067. (PMID: 1473616).
40. Matsuda A, Kuzuya T. Diabetic twins in Japan. Diabetes Res Clin Pract. Oct 1994;24 Suppl:S63-67. (PMID:
7859635).
41. Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H. Heritability of type II (non-insulin-dependent) diabetes mellitus and
abnormal glucose tolerance--a population-based twin study. Diabetologia. Feb 1999;42(2):139-145. (PMID:
10064092).
42. Medici F, Hawa M, Ianari A, Pyke DA, Leslie RD. Concordance rate for type II diabetes mellitus in monozygotic
twins: actuarial analysis. Diabetologia. Feb 1999;42(2):146-150. (PMID: 10064093).
43. Stern MP. The search for type 2 diabetes susceptibility genes using whole-genome scans: an epidemiologist's
perspective. Diabetes Metab Res Rev. Mar-Apr 2002;18(2):106-113. (PMID: 11994901).
44. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H,
Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T,
Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C,
Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K. Variant of transcription factor
7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. Jan 15 2006;38(3):320-323. (PMID: 16415884).
45. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude
B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D,
Polychronakos C, Froguel P. A genome-wide association study identifies novel risk loci for type 2 diabetes.
Nature. Feb 22 2007;445(7130):881-885. (PMID: 17293876).
46. Groves CJ, Zeggini E, Minton J, Frayling TM, Weedon MN, Rayner NW, Hitman GA, Walker M, Wiltshire S,
Hattersley AT, McCarthy MI. Association analysis of 6,736 U.K. subjects provides replication and confirms TCF7L2
as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. Diabetes. Sep
2006;55(9):2640-2644. (PMID: 16936215).
47. Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, Knowler WC, Nathan DM, Altshuler D.
TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. Jul 20
2006;355(3):241-250. (PMID: 16855264).
48. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ,
Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson K, Isomaa B, Lettre G,
Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK,
Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E,
Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R,
Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D,
Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S. Genome-Wide Association
Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels. Science. Apr 26 2007. (PMID: 17463246).
49. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy
RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR,
Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT. Replication of Genome-Wide
Association Signals in U.K. Samples Reveals Risk Loci for Type 2 Diabetes. Science. Apr 26 2007. (PMID:
17463249).
50. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU,
Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG,
Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan
TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins
FS, Boehnke M. A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility
Variants. Science. Apr 26 2007. (PMID: 17463248).
51. Joshi SR. Metabolic syndrome--emerging clusters of the Indian phenotype. J Assoc Physicians India. May
2003;51:445-446. (PMID: 12974423).
52. Mohan V, Sharp PS, Aber VR, Mather HM, Kohner EM. Family histories of Asian Indian and European non-insulin-
dependent diabetic patients. Practical Diabetes. 1986;3:254-256. (PMID:
53. Mohan V, Shanthirani CS, Deepa R. Glucose intolerance (diabetes and IGT) in a selected South Indian population
with special reference to family history, obesity and lifestyle factors--the Chennai Urban Population Study (CUPS
14). J Assoc Physicians India. Aug 2003;51:771-777. (PMID: 14651136).
54. Sargeant LA, Wareham NJ, Khaw KT. Family history of diabetes identifies a group at increased risk for the
metabolic consequences of obesity and physical inactivity in EPIC-Norfolk: a population-based study. The
European Prospective Investigation into Cancer. Int J Obes Relat Metab Disord. Oct 2000;24(10):1333-1339.
(PMID: 11093296).
55. Radha V, Mohan V. Genetics of type 2 diabetes in Asian Indians. In: Mohan V, Rao GHR, eds. Type 2 diabetes in
South Asians: Epidemiology, risk factors and prevention. New Delhi: Under the Aegis of SASAT. Jaypee Brothers
Medical Publishers; 2006:182.
56. Hitman GA, Hawrami K, McCarthy MI, Viswanathan M, Snehalatha C, Ramachandran A, Tuomilehto J,
Tuomilehto-Wolf E, Nissinen A, Pedersen O. Insulin receptor substrate-1 gene mutations in NIDDM; implications
for the study of polygenic disease. Diabetologia. Apr 1995;38(4):481-486. (PMID: 7796990).
57. Pontiroli AE, Capra F, Veglia F, Ferrari M, Xiang KS, Bell GI, Baroni MG, Galton DJ, Weaver JU, Hitman GA,
Kopelman PG, Mohan V, Viswanathan M. Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes
to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations. Acta Diabetol.
Sep 1996;33(3):193-197. (PMID: 8904924).
58. Bodhini D, Radha V, Deepa R, Ghosh S, Majumder PP, Rao MR, Mohan V. The G1057D polymorphism of IRS-2
gene and its relationship with obesity in conferring susceptibility to type 2 diabetes in Asian Indians. Int J Obes
(Lond). Jan 2007;31(1):97-102. (PMID: 16652127).
59. Vimaleswaran KS, Radha V, Anjana M, Deepa R, Ghosh S, Majumder PP, Rao MR, Mohan V. Effect of
polymorphisms in the PPARGC1A gene on body fat in Asian Indians. Int J Obes (Lond). Jun 2006;30(6):884-891.
(PMID: 16446747).
60. Lepretre F, Vionnet N, Budhan S, Dina C, Powell KL, Genin E, Das AK, Nallam V, Passa P, Froguel P. Genetic
studies of polymorphisms in ten non-insulin-dependent diabetes mellitus candidate genes in Tamil Indians from
Pondichery. Diabetes Metab. Jun 1998;24(3):244-250. (PMID: 9690058).
61. Pereira MA, Jacobs DR, Jr., Pins JJ, Raatz SK, Gross MD, Slavin JL, Seaquist ER. Effect of whole grains on insulin
sensitivity in overweight hyperinsulinemic adults. Am J Clin Nutr. May 2002;75(5):848-855. (PMID: 11976158).
62. Pereira MA, Jacobs DR, Jr., Slattery M, Hilner J, Kushi LH. The association between whole grain intake and fasting
insulin in a bi-racial cohort of young adults: The Cardia Study. CVD Prevention. 1998;1:231-242. (PMID:
63. Pereira MA, Jacobs DR, Jr., Van Horn L, Slattery ML, Kartashov AI, Ludwig DS. Dairy consumption, obesity, and
the insulin resistance syndrome in young adults: the CARDIA Study. Jama. Apr 24 2002;287(16):2081-2089.
(PMID: 11966382).
64. Pereira MA, Kartashov AI, Ebbeling CB, Van Horn L, Slattery ML, Jacobs DR, Jr., Ludwig DS. Fast-food habits,
weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet. Jan 1
2005;365(9453):36-42. (PMID: 15639678).
65. Pereira MA, Kriska AM, Collins VR, Dowse GK, Tuomilehto J, Alberti KG, Gareeboo H, Hemraj F, Purran A, Fareed
D, Brissonnette G, Zimmet PZ. Occupational status and cardiovascular disease risk factors in the rapidly
developing, high-risk population of Mauritius. Am J Epidemiol. Jul 15 1998;148(2):148-159. (PMID: 9676696).
66. Pereira MA, Kriska AM, Joswiak ML, Dowse GK, Collins VR, Zimmet PZ, Gareeboo H, Chitson P, Hemraj F, Purran
A, et al. Physical inactivity and glucose intolerance in the multiethnic island of Mauritius. Med Sci Sports Exerc.
Dec 1995;27(12):1626-1634. (PMID: 8614318).
67. Pereira MA, Ludwig DS. Surveillance of insulin resistance in children. Clin Chem. Apr 2003;49(4):540-541. (PMID:
12651804).
68. Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year
prospective study of 28 812 postmenopausal women. Arch Intern Med. Jun 26 2006;166(12):1311-1316. (PMID:
16801515).
69. Kriska AM, Blair SN, Pereira MA. The potential role of physical activity in the prevention of non-insulin-
dependent diabetes mellitus: the epidemiological evidence. Exerc Sport Sci Rev. 1994;22:121-143. (PMID:
7925541).
70. Kriska AM, Pereira MA, Hanson RL, de Courten MP, Zimmet PZ, Alberti KG, Chitson P, Bennett PH, Narayan KM,
Knowler WC. Association of physical activity and serum insulin concentrations in two populations at high risk for
type 2 diabetes but differing by BMI. Diabetes Care. Jul 2001;24(7):1175-1180. (PMID: 11423498).
71. Fung TT, Hu FB, Pereira MA, Liu S, Stampfer MJ, Colditz GA, Willett WC. Whole-grain intake and the risk of type 2
diabetes: a prospective study in men. Am J Clin Nutr. Sep 2002;76(3):535-540. (PMID: 12197996).
72. Pereira MA, Swain J, Goldfine AB, Rifai N, Ludwig DS. Effects of a low-glycemic load diet on resting energy
expenditure and heart disease risk factors during weight loss. Jama. Nov 24 2004;292(20):2482-2490. (PMID:
15562127).
73. Pereira MA, Weggemans RM, Jacobs DR, Jr., Hanan PJ, Zock PL, Ordovas JM, Katan MB. Within-person variation
in serum lipids: implications for clinical trials. Int J Epidemiol. Mar 11 2004. (PMID: 15020568).
74. Pereira MA, Kriska AM, Day RD, Cauley JA, LaPorte RE, Kuller LH. A randomized walking trial in postmenopausal
women: effects on physical activity and health 10 years later. Arch Intern Med. Aug 10-24 1998;158(15):1695-
1701. (PMID: 9701104).
75. Jacobs DR, Jr., Pereira MA, Stumpf K, Pins JJ, Adlercreutz H. Whole grain food intake elevates serum
enterolactone. Br J Nutr. Aug 2002;88(2):111-116. (PMID: 12144714).
76. Jacobs DR, Pereira MA, Meyer KA, Kushi LH. Fiber from whole grains, but not refined grains, is inversely
associated with all-cause mortality in older women: the Iowa women's health study. J Am Coll Nutr. Jun
2000;19(3 Suppl):326S-330S. (PMID: 10875605).
77. Pereira MA, O'Reilly E, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL, Hallmans G, Knekt P, Liu S, Pietinen
P, Spiegelman D, Stevens J, Virtamo J, Willett WC, Ascherio A. Dietary fiber and risk of coronary heart disease: a
pooled analysis of cohort studies. Arch Intern Med. Feb 23 2004;164(4):370-376. (PMID: 14980987).
78. Ludwig DS, Pereira MA, Kroenke CH, Hilner JE, Van Horn L, Slattery ML, Jacobs DR, Jr. Dietary fiber, weight gain,
and cardiovascular disease risk factors in young adults. Jama. Oct 27 1999;282(16):1539-1546. (PMID:
10546693).
79. Knekt P, Ritz J, Pereira MA, O'Reilly EJ, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL, Hallmans G, Liu S,
Pietinen P, Spiegelman D, Stevens J, Virtamo J, Willett WC, Rimm EB, Ascherio A. Antioxidant vitamins and
coronary heart disease risk: a pooled analysis of 9 cohorts. Am J Clin Nutr. Dec 2004;80(6):1508-1520. (PMID:
15585762).
80. Kronenberg F, Pereira MA, Schmitz MK, Arnett DK, Evenson KR, Crapo RO, Jensen RL, Burke GL, Sholinsky P,
Ellison RC, Hunt SC. Influence of leisure time physical activity and television watching on atherosclerosis risk
factors in the NHLBI Family Heart Study. Atherosclerosis. Dec 2000;153(2):433-443. (PMID: 11164433).
81. Pereira MA, Folsom AR, McGovern PG, Carpenter M, Arnett DK, Liao D, Szklo M, Hutchinson RG. Physical activity
and incident hypertension in black and white adults: the Atherosclerosis Risk in Communities Study. Prev Med.
Mar 1999;28(3):304-312. (PMID: 10072750).
82. Evenson KR, Rosamond WD, Cai J, Pereira MA, Ainsworth BE. Occupational physical activity in the
atherosclerosis risk in communities study. Ann Epidemiol. May 2003;13(5):351-357. (PMID: 12821274).
83. Steffes MW, Gross MD, Schreiner PJ, Yu X, Hilner JE, Gingerich R, Jacobs DR, Jr. Serum adiponectin in young
adults--interactions with central adiposity, circulating levels of glucose, and insulin resistance: the CARDIA study.
Ann Epidemiol. Aug 2004;14(7):492-498. (PMID: 15301786).
84. Simon JA, Murtaugh MA, Gross MD, Loria CM, Hulley SB, Jacobs DR, Jr. Relation of ascorbic acid to coronary
artery calcium: the Coronary Artery Risk Development in Young Adults Study. Am J Epidemiol. Mar 15
2004;159(6):581-588. (PMID: 15003962).
85. Gokulakrishnan K, Deepa R, Mohan V, Gross MD. Soluble P-selectin and CD40L levels in subjects with
prediabetes, diabetes mellitus, and metabolic syndrome--the Chennai Urban Rural Epidemiology Study.
Metabolism. Feb 2006;55(2):237-242. (PMID: 16423632).
86. Guettier JM, Georgopoulos A, Tsai MY, Radha V, Shanthirani S, Deepa R, Gross M, Rao G, Mohan V.
Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the
metabolic syndrome and dyslipidemia in a South Indian population. J Clin Endocrinol Metab. Mar
2005;90(3):1705-1711. (PMID: 15598690).
87. Forman MR, Zhang J, Gunter E, Yao SX, Gross M, Qiao YL, Graubard BI, Taylor PR, Keith S, Maher M. Season-
specific correlation between dietary intake of fruits and vegetables and levels of serum biomarkers among
Chinese tin miners at high risk for lung cancer. Ann N Y Acad Sci. 1999;889:230-239. (PMID: 10668498).