II. STATEMENT OF GROUNDS
A. SCIENTIFIC REPORTS FROM THE PAST DECADE CONFIRM THAT THE CONDITION OF
OVERWEIGHT IS A SIGNIFICANT RISK FACTOR FOR SERIOUS CHRONIC DISEASES
Recent estimates indicate that at least one third of American adults are overweight and
the numbers are growing each year. s At the same time, the number of children and adolescents
who are overweight has risen dramatically in the past several years. 6 This trend is quite
troubling because, as the number of Americans who are overweight increases each year, so does
the number of individuals who are at increased risk of developing serious chronic diseases.
Indeed, a substantial body of scientific evidence published during the past decade confirms that
being “overweight” – as opposed to being obese – is an independent and significant risk factor
for such diseases and other medical conditions. In light of these studies, which are summarized
below, both the National Institutes of Health (“NIH”) and the Centers for Disease Control and
Prevention (“CDC”) have expressly recognized and highlighted these risks. 7
The health risks of being overweight are often discussed in conjunction with obesity and,
as a result, until relatively recently they have been overshadowed by that disease. In the past
several years, however, there has been new and significant research conducted into the
independent health risks associated with overweight regardless of whether an individual
eventually proceeds from the overweight category to the obese category. One of the first major
government documents to focus on these risks was a report issued by NIH in September 1998.8
5 Centers for Disease Control and Prevention, National Center for Health Statistics. Prevalence of overweight and
obesity among adults: United States, 2003-2004. (Accessed January 3, 2008, at
http://www.cdc.gov/nchs/products/pubs/pubd/hestats/overweight/overwght adult 03.htm) (reporting that 66.3% are
overweight or obese and 32.2% are obese). Although there has been no significant change in obesity prevalence
since 2003-2004, obesity rates have increased substantially since the 1980s. See Ogden C, et al. Obesity among
adults in the United States: no change since 2003-2004. Washington, DC: Centers for Disease Control and
Prevention, November 2007. (Accessed January 3, 2008, at http://www.cdc.gov/nchs/data/databriefs/dbOl .pdt).
6 Ogden CL, et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295:1549-55
(reporting that in 2003-2004, 17.1% of U.S. children and adolescents were overweight). (Exh. 1).
7 See National Institute of Diabetes and Digestive and Kidney Diseases. Do you know the health risks of being
overweight? (Accessed January 3, 2008, at http://win.niddk.nih.gov/publications/health risks.htm); Centers for
Disease Control and Prevention. Overweight and obesity. (Accessed January 3, 2008, at
http://www.cdc.gov/nccdphp/dnpa/obesity/).
g Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the
Evidence Report. Washington, DC: National Institutes of Health, September 1998. (NIH Publication No. 98-4083).
(Exh. 2).
Since publication of that report, a wealth of scientific and epidemiological studies has been
published establishing that overweight is a risk factor for several serious diseases, including type
2 diabetes, cardiovascular disease, certain types of cancer, and obesity.9 These studies are briefly
summarized below for each of these diseases. 10
Moreover, petitioners are attaching an expert report from five top scientists in the field.”
To ensure that the scientific bases underlying this petition are principled and sound, GSK
convened a panel of these researchers and clinicians in May 2006 to evaluate the relationship
between being overweight and the risk of developing serious chronic diseases. Specifically, the
expert panel examined the available epidemiological evidence in the scientific literature on the
health risks of being overweight, with a specific focus on the relationship between BMI and type
2 diabetes, cardiovascular disease, cancer, and morbidity. Their report was limited to an
examination of these relationships. The individuals serving on this panel included: George
Blackburn, M.D., Ph.D., Harvard Medical School; Madelyn Fernstrom, Ph.D., University of
Pittsburgh Medical Center; John Foreyt, Ph.D., Baylor College of Medicine; Arthur Frank, M.D.,
George Washington University; and Anne Wolf, M.S., R.D., University of Virginia School of
Medicine. As can be seen from their report included in the addendum to this petition, these
scientists confirmed that there is strong relationship between the state of being overweight and an
increased risk of disease.
1. Numerous Epidemiological Studies from the Past Decade Establish
the Condition of Overweight as a Significant Risk Factor
for Diabetes, Cardiovascular Disease, Cancer, and Obesity
a. Diabetes
In the United States, 18.2 million people (6.3% of the population) have diabetes and, each
year, 1.3 million new cases are diagnosed in people 20 years of age or older. Complications of
diabetes can include, among other things, heart disease, stroke, high blood pressure, blindness,
and kidney disease. 12 The link between type 2 diabetes and weight gain is well established;
almost 90% of those with type 2 diabetes are overweight or obese. The association between the
risk for diabetes and weight gain in women was documented in the 1990 publication of the
9 The risk of increased morbidity from being overweight is distinguishable from the risk of increased mortality,
which is more difficult to determine. Compare Adams KF, Schatzkin A, Haris TB, Kipnis V, Mouw T, Ballard-
Barbash R, Hollenbeck A, Leitzmann MF. Overweight, obesity, and mortality in a large prospective cohort of
persons 50 to 71 years old. N Engl J Med 2006;355:763-78 and Jee SH, Sull JW, Park J, Lee S, Ohrr H, Guallar E,
Samet JM. Body-mass index and mortality in Korean men and women. N Engl J Med 2006;355:779-87 with Flegal
KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity.
JAMA 2005;293:1861-7.
to
Being overweight increases the risk of other diseases, including gallbladder disease, osteoarthritis, sleep apnea
and respiratory problems, fatty liver disease, and psoriasis. See National Institute of Diabetes and Digestive and
Kidney Diseases. Do you know the health risks of being overweight? (Accessed January 3, 2008, at
http://win.niddk.nih.gov/publications/health_risks.htm). These are not reviewed here.
I
1 Blackburn G, Fernstrom M, Foreyt J, Frank A, Wolf A. Impact of overweight on morbidity and mortality: report
submitted to G1axoSmithKline Consumer Healthcare. November l, 2007. (Exh. 3).
12
American Diabetes Association. (Accessed January 3, 2008, at www.diabetes.org).
Nurses’ Health Study. 13 A later study using data from the Nurses’ Health Study reported similar
results: the risk of diabetes increased with BMIs greater than 22.14 For those with a BMI in the
overweight range, the risk of diabetes was up to ten times greater relative to those with a BMI of
22 or less.
Since January 2000, several studies have been published that further establish and
highlight the risk that individuals who are overweight have of developing type 2 diabetes. For
example, in a study published in the New England Journal of Medicine in 2001, Hu et al.
examined 16 years of follow-up data from the Nurses’ Health Study and found that the relative
risk (“RR”) of developing the disease was 7.59.15 That same year, Field et al. also published a
report assessing the risk of developing diabetes in overweight individuals. 16 That study was
based on an analysis of data from two prospective cohort studies – the Nurses’ Health Study with
women and the Health Professionals Follow-up Study involving men. In both cohorts, these
investigators found that the risk of developing diabetes increased progressively with increasing
levels of BMI. Among both women and men, those who were overweight were significantly
more likely to develop diabetes (RR, 4.6 for women; RR, 3.5 for men) than their same-sex,
normal weight peers.
Two additional studies published in the last three years further demonstrate that the risk
of diabetes increases progressively with increasing weight. One of these reports – the San
Antonio Heart Study – involved a prospective, population-based study of Mexican Americans
and non-Hispanic whites.’ 7 Among Mexican Americans, those who were overweight had a risk
of diabetes that was 2.7 times greater than those of normal weight; for overweight, non-Hispanic
whites, the risk of diabetes was four times greater than for those of normal weight. That study
was followed up by a report published in 2004 by St-Onge et al. examining the association
between BMI and risk of the metabolic syndrome (a constellation of diabetes, hypertension, and
dyslipidemia risk factors) among individuals in the normal weight and slightly overweight
range. 18 On the basis of a review of NHANES III data, the authors corroborated the link
between increasing BMI and the risk of metabolic syndrome.
b. Cardiovascular Disease
With over one million new cases in the United States each year, cardiovascular disease
currently plagues more than 80 million Americans who suffer from stroke, atherosclerosis,
13
Colditz GA, Willett WC, Stampfer MJ, et al. Weight as a risk factor for clinical diabetes in women. Am J
Epidemiol 1990;132:501-13. (Exh. 4).
14
Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in
women. Ann Intern Med 1995;122:481-6. (Exh. 5).
15
Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC. Diet, lifestyle, and the risk of type
2 diabetes in women. N Engl J Med 2001;345:790-7. (Exh. 6).
16
Field AE, Coakley EH, Must A, et al. Impact of overweight on the risk of developing common chronic diseases
during a 10-year period. Arch Intem Med 2001;161:1581-6. (Exh. 7).
17 Burke JP, Williams K, Venkat Narayan KM, Leibson C, Haffner SM, Stern MP. A population perspective on
diabetes prevention: whom should we target for preventing weight gain? Diabetes Care 2003;26:1999-2004. (Exh.
8).
1g St-Onge MP, Janssen I, Heymsfield SB. Metabolic syndrome in normal-weight Americans: new definition of the
metabolically obese, normal-weight individual. Diabetes Care 2004;27:2222-8. (Exh. 9).
coronary heart disease, hypertension, congestive heart failure, and other forms of the disease. 19
The association between weight gain and the risk for cardiovascular heart disease was reported in
the mid-1990s by Willett et al .20 They found that the risk of coronary heart disease in women
increased consistently with increasing BMI, and that women with BMIs within the overweight
range had twice the risk of coronary heart disease as those in the normal weight range (RR, 2.06).
Even women with BMIs on the higher end of normal weight range (23-24.9) were found to be at
increased risk compared to those with a BMI of less than 21 (RR, 1.46). In a separate paper, the
same findings of risk were reported for men – overweight men had a relative risk of coronary
heart disease of 1.49 compared to men with a BMI of less than 23.21
Additional studies have fully established overweight as a significant risk factor for
cardiovascular disease. 22 For example, in 2001, Field et al. reported that individuals who are
overweight are significantly more likely than their normal weight peers to develop hypertension,
hypercholesterolemia, and heart disease (women: RR, 1.7, 1.1, and 1.4, respectively; men: RR,
1.7, 1.3, and 1.5, respectively).23 A year later, Wilson et al. also demonstrated that the risk of
hypertension, hypercholesterolemia, and cardiovascular disease increased among overweight
men and women.
24
In comparison to those of normal weight, the risk of hypertension,
hypercholesterolemia, and cardiovascular disease in overweight individuals was consistently
higher than for those of normal weight (women: RR, 1.75, 1.35 and 1.20, respectively; men: RR,
1.46, 1.19 and 1.21, respectively). These findings were further confirmed in 2004 on the basis of
a review of NHANES III data. 25 The odds of developing hypertension and hypercholesterolemia
once again were shown to be significantly greater for overweight individuals (women: OR, 1.92
and 2.26; men: OR, 1.75 and 1.57).26 Most recently, a study demonstrated that higher BMI
during childhood is associated with an increased risk of coronary heart disease in adulthood.27
19
American Heart Association; American Stroke Association. Heart disease and stroke statistics: 2008 update at-a-
glance. Dallas, TX: American Heart Association, 2008. (Exh. 10).
20
Willett WC, Manson JE, Stampfer MJ, Colditz GA, Rosner B, Speizer FE, Hennekens CH. Weight, weight
change, and coronary heart disease in women. JAMA 1995;273:461-5. (Exh. 11).
21 Rimm EB, Stampfer JM, Giovannucci E, Ascherio A, Spiegelman D, Colditz GA, Willett WC. Body size and fat
distribution as predictors of coronary heart disease among middle-aged and older U.S. men. Am J Epidemiol
1995;141:1117-27. (Exh. 12).
22 Anderson JW, Konz EC. Obesity and disease management: effects of weight loss on comorbid conditions. Obes
Res 2001;9(Supp14):326S-34S. (Exh. 13); Eckel RH, Krauss RM. American Heart Association call to action:
obesity as a major risk factor for coronary heart disease. Circulation 1998;97:2099-100. (Exh. 14); Krauss RM,
Winston M, Fletcher BJ, Grundy SM. Obesity: impact on cardiovascular disease. Circulation 1998;98:1472-6. (Exh.
15).
23
Field AE, Coakley EH, Must A, et al. Impact of overweight on the risk of developing common chronic diseases
during a 10-year period. Arch Intern Med 2001;161:1581-6. (Exh. 7).
24
Wilson PWF, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of
cardiovascular risk: the Framingham experience. Arch Intern Med 2002;162:1867-72. (Exh. 16).
ZS
Janssen 1, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health
risk. Am J Clin Nutr 2004;79:379-84. (Exh. 17).
26
Moreover, in a more recent paper evaluating the association of bodyweight with coronary artery disease, the
authors found that the better outcomes for those who were overweight and mildly obese could be explained by the
lack of discriminatory power of BMI to differentiate between body fat and lean mass. That suggests that a different
measure might further demonstrate that those who are overweight (like those who are obese) run an increased risk of
a cardiovascular event. Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG,

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