# 28 - SECTION 3 Obesity, Diabetes Mellitus, and Metabolic Syndrome

## SECTION 3 Obesity, Diabetes Mellitus, and Metabolic Syndrome

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identity data in electronic health records: Workshop summary. 2013. 
Available at https://www.nap.edu/catalog/18260/collecting-sexualorientation-and-gender-identity-data-in-electronic-health-records.
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competence, patient- and family-centered care for the lesbian, gay, 
bisexual, and transgender community: A field guide. 2011. Available 
at www.jointcommission.org/lgbt.
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2015 U.S. Transgender Survey. 2015. Available at https://transequality.
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Section 3	 Obesity, Diabetes Mellitus, 
and Metabolic Syndrome
Stephen O’Rahilly, I. Sadaf Farooqi

Pathobiology of Obesity
Adipose tissue evolved as a solution to the challenge of the intermittent 
availability of food. At times when food is plentiful, excess calories are 
converted to triglycerides and efficiently stored in the unilocular lipid 
droplets that occupy most of the volume of fat cells. When needed, 
the triglyceride is rapidly broken down to free fatty acids and glycerol, 
which provide an energy source to other sites throughout the body. 
However, in environments where food is abundant and when indi­
viduals tend to be sedentary, the chronic excess of energy intake over 
expenditure leads to obesity. The risks of developing obesity under 
those circumstances and of developing the illnesses associated with 
obesity vary greatly between individuals, with that variation having a 
strong genetic basis.
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■DEFINITION OF OBESITY AND OVERWEIGHT
Obesity is defined as a state of excess adipose tissue mass that adversely 
affects health. The direct measurement of fat mass is not something 
that is readily undertaken in routine clinical practice, so a proxy mea­
sure, the body mass index (BMI), is generally used. This is calculated 
as weight/height2 (in kg/m2) (Fig. 413-1). BMI-based definitions of 
obesity and overweight have been established based on associations 
with certain morbidities and excess mortality. These definitions have 
been based largely on studies of predominantly white, Western popula­
tions, and there is growing evidence that the relationship between BMI 
and adverse outcomes is different in people from other ethnic groups, 
usually in the direction of worse health outcomes being seen at lower 
levels of BMI. The World Health Organization (WHO) defines a BMI 
of 30 kg/m2 as the cutoff point for obesity, while individuals with values 
between 25 and 30 kg/m2 are classified as overweight. For individuals 
with a very muscular body habitus, the BMI may overestimate the 

Body Mass Index
(weight in kg/height in meters squared)
Pathobiology of Obesity
CHAPTER 413
Underweight
<18.5
Normal weight
18.5–24.9
Overweight
25–29.9
Obese
>30.0
FIGURE 413-1  Definitions of overweight and obesity. The World Health Organization 
defines obesity based on body mass index (BMI), which is calculated as weight in 
kilograms divided by the height in meters squared.
amount of body fat. For any given BMI, women will generally have a 
higher percentage of body fat than men.
The extent to which different adipose depots expand in response 
to chronic overnutrition varies markedly between people. In general, 
females store more fat in subcutaneous tissues, especially on buttocks, 
thighs, and upper arms, whereas men are more prone to store fat in 
intraabdominal and truncal subcutaneous sites. A simple measure of 
fat distribution is provided by a measurement of the waist-to-hip ratio. 
Independent of the degree of obesity, a waist-to-hip ratio >0.9 in women 
and >1.0 in men is associated with adverse health outcomes such as 
type 2 diabetes and dyslipidemia.
■
■EPIDEMIOLOGY
The annual National Health and Nutrition Examination Survey 
(NHANES) provides an ongoing record of the prevalence of obesity in 
the United States. In 2017–2018, 42.4% of U.S. adults aged ≥20 years old 
had obesity with no significant differences in prevalence by age group. 
Non-Hispanic black people had the highest prevalence of obesity at 
49.6%, followed by Hispanic (44.8%), non-Hispanic white (42.2%), and 
non-Hispanic Asian (17.4%) people. In the United States, Asians repre­
sent a highly heterogeneous group encompassing both East and South 
Asia as well as a substantial Filipino community. The risks of obesity 
and its complications may differ greatly between people from different 
parts of Asia; in general, the prevalence of obesity is somewhat higher 
in women than in men, with black women having the highest preva­
lence at 56.9%. There has been a marked increase in the prevalence of 
obesity over time. For example, between 1976 and 1980, the NHANES 
survey reported a prevalence of 14.5%, indicating a near threefold 
increase over the past 40 years.
This trend is seen globally. According to the WHO, obesity has 
nearly tripled worldwide since 1975. In 2016, >1.9 billion adults aged 
≥18 years old were overweight. Of these, >650 million were obese; 39% 
of adults aged ≥18 years old were overweight in 2016, and 13% were 
obese. Most of the world’s population lives in countries where over­
weight and obesity kills more people than underweight.
During this time, one of the most striking changes has been in the 
prevalence of obesity in children. In children, the relationship between 
BMI and body fat varies considerably with age and with pubertal 
maturation; however, when adjusted for age and sex, BMI is a reason­
able proxy for fat mass. Using age- and sex-specific BMI cutoffs (over­
weight ≥91st percentile; obesity ≥99th percentile), in 2019, the WHO 
estimated that 38 million children under the age of 5 were overweight 
or obese, and in 2016, they reported that 340 million children and 
adolescents aged 5–19 were overweight or obese.
■
■PHYSIOLOGIC REGULATION OF ENERGY 
BALANCE
Discussions about obesity so frequently focus on the issues of personal 
choice or the obesogenic environment that it can be easy to forget that