Tiny Causes, Big Effects: Labs Help to Determine the Causes & Effects of Obesity

By Renee DiIulio

We have gotten fat. Everyone tells us so—physicians, statisticians, politicians. The causes and effects differ for each individual, but they ultimately result from an energy imbalance. Body weight, according to the Centers for Disease Control and Prevention (CDC of Atlanta), is the result of genes, metabolism, behavior, environment, culture, and socioeconomic status. Nonmedical factors, such as unhealthy eating and inactivity, are likely greater influences than medical causes, but laboratories can help to identify those instances when the reason is biological.

This information can direct treatment and inspire changes intended to decrease the negative effects of excessive weight and obesity. Except for osteoporosis (where it is protective), obesity speeds the onset, increases the prevalence, and intensifies the severity of all the major diseases of old age.¹ Laboratories help to identify these as well, creating opportunities for prevention and treatment.

How Fat Are We?
The CDC determines overweight and obesity status using the body mass index (BMI), a measure calculated with height and weight (see sidebar). Overweight people have a BMI between 25.0 and 29.9; obese people have a BMI greater than 30.0.

The American Obesity Association (AOA of Washington, DC) reports that approximately 127 million adults in the United States are overweight; 60 million (30.5%) are obese, and 9 million (4.7%) are severely obese.² These numbers, from the years 1999–2000, are higher than earlier studies. Research from 1988–1994 showed that 56% of the population was overweight, 23% was obese, and 2.9% was severely obese.2 From 1976–1980, only 46% of the population was found to be overweight and 14.4% were obese; no data exists for the severely obese during this period.²

This rise in the number of people who are either overweight or obese has had an impact on the prevalence of related conditions and diseases, such as diabetes. The CDC states that from 1980 through 2002, the number of Americans with diabetes more than doubled (from 5.8 million to 13.3 million). Though the increase is not entirely due to the rise in obesity, the two conditions have been linked. A BMI greater than or equal to 27 is a risk factor for diabetes,³ and Type 2 diabetes is a well-established consequence of obesity.¹ Recent data has suggested that the frequency of Type 1 diabetes is also increased by the presence of obesity.¹

Obesity’s Obscene Cost
As a result of these related conditions, obesity has costs—both for the individual, who may suffer from a variety of health conditions and/or discrimination, and society, which helps to bear the resulting economic impact. According to a study of national costs attributed to both excessive weight and obesity, medical expenses accounted for 9.1% of the total US expenditures in 1998 and may have reached as high as $78.5 billion.⁴ Approximately half of these costs were paid by Medicare and Medicaid.⁴

A more recent study conducted in California, The Economic Costs of Physical Inactivity, Obesity, and Overweight in California Adults, found that, in year 2000 dollars, physical inactivity, obesity, and excessive weight cost California an estimated $21.7 billion per year.⁵ The costs include direct and indirect medical care ($10.2 billion), workers’ compensation ($338 million), and lost productivity ($11.2 billion).⁵ If population trends and rising health care costs continue, these expenses are projected to reach $28 billion this year.⁵

The report breaks the costs down by status: obesity accounts for an estimated $6.4 billion; physical inactivity for $13.3 billion; and exessive weight for $2 billion.⁵ Public and private employers assume about three-fourths of these costs via health insurance and lost work productivity.⁵

The California study found that a 5% improvement in the rates of physical activity and healthy weight over 5 years could save more than $6 billion.⁵ A 10% improvement could save nearly $13 billion. If even one or two of every 20 sedentary and/or overweight Californians would reduce their BMI to a leaner category and become more physically active, the state could realize significant savings.⁵

Fat Factors
Losing weight successfully, however, takes work—literally. And some people have to work at it harder than others. How hard can be determined by biological factors. Classic studies have concluded that obesity has a strong but poorly defined genetic basis.¹

The discovery of new single-gene defects that cause obesity, although rare, continues. “Currently, less than five percent of all severe obesity is associated with a single gene,” says Jesse Roth, MD, FACP, professor of medicine, Albert Einstein College of Medicine (Bronx, NY), and geriatrician-in-chief for the North Shore—Long Island Jewish Health System (New Hyde Park, NY).

His report states that the most common monogenic obesity is the mutation of the melanocortin 4 receptor, which has recently been shown to be highly associated with binge eating.¹ Another defect associated with overeating results in leptin deficiency. The National Association of Biochemistry (Washington, DC) does not recommend routine testing of leptin values for the evaluation or management of patients with diabetes or obesity. But if such a patient is diagnosed, he or she can be easily treated with daily leptin injections—“if they can afford them,” adds Roth.

The report authored by Roth and colleagues identified four candidates for key roles in the causes and consequences of obesity:

1. Metabolic programming, where food acts as a developmental regulator;
2. The “metabolic syndrome,” which encompasses a constellation of defects;
3. Cortisol overproduction in adipose tissue; and
4. Insulin resistance.¹

Genetic testing related to obesity may be undertaken, but it is not regularly ordered. However, the results can be used to suggest appropriate preventive measures, diagnose related conditions, and develop treatment plans.

More often, the causes of obesity are not solely biological. “For most patients, obesity is a complex disorder resulting from the interaction of multiple susceptibility genes with environmental factors over time.”¹

Viral Obesity
In some cases, environmental factors can play a greater role than biology—but not just the evident ones, such as what is on the lunch menu at school. RL Atkinson, MD, president, Obetech Obesity Research Center (Richmond, VA), is investigating the effect of adenovirus-36 (Ad-36) on humans and obesity. A recently published study by Atkinson and colleagues found that Ad-36 is associated with increased body weight and lower serum lipids in humans.⁶

Roughly 500 subjects were tested, and they underwent serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37, serum cholesterol, and triglycerides assays.6 The study found that approximately 30% of the obese patients had antibodies to Ad-36, while only 10% of nonobese people tested positive for Ad-36 antibodies.⁶ No association was found with other antibodies. In addition, subjects with the Ad-36 antibodies present were, on average, 50 pounds heavier than those without them.

The results produced in twins showed further evidence of the effect of Ad-36. The study presented 26 pairs of twins—one who tested positive for the antibodies, and one who did not. Despite genetic and environmental similarities, the Ad-36-infected twins weighed more and had a higher percentage of body fat than the non-infected twins.⁶

Further studies in humans are needed, but the information has a number of implications, which, Atkinson is careful to stress, does not mean that one can “catch” obesity from a fat person. “In reality, you want to be more cautious of the skinny person with a cold,” suggests Atkinson.

Ad-36 is similar to the common cold and can be caught at any time. “We have seen the antibodies in both children and the elderly,” says Atkinson. The virus can be diagnosed, and Obetech offers test kits online for $125.

However, the labor-intensive method of testing—a tissue culture assay—currently has a long turnaround time. The antibodies require an 8-day growth period, and the results typically are delivered within 14 days. Atkinson expects that a more user-friendly test can be produced if development is supported.

Diagnosis can benefit both the thin and fat infected patient. The lean person can change his or her habits to avoid gaining weight, which will mean eating less and exercising more. “In the animal studies, the infected and noninfected ate the same, but only the infected gained weight,” says Atkinson.

The body will eventually fight off the virus. “If a lean person with Ad-36 doesn’t gain 50 pounds, he or she can avoid obesity,” says Atkinson. Those who do become obese typically have an easier time losing the weight (though more studies are needed to repeat the data) and are psychologically boosted by knowing that the weight gain was due to a virus and not their behavior.

The research found that when infected, undifferentiated cells turned into fat cells; once they reached a certain size, they produced factors that caused the creation of new fat cells. Some of these factors contribute to the development of common obesity-related conditions, such as Type 2 diabetes.

Negative Effects
“The concept of fat as a secretory tissue dates mostly from the discovery of leptin roughly 10 years ago … Three of the most important peptide products are leptin (which regulates satiety and appetite, among other processes), adiponectin (which heightens sensitivity of target cells to insulin), and resistin (which heightens resistance to insulin). All three are produced only in fat tissue, whereas many of the other adipose-derived signaling molecules are also produced in other tissues.”¹

“Fat not only resides in fat cells, but is also deposited elsewhere in the body,” says Roth, referring to metastatic fat. In the liver, it can create the fatty liver condition that can lead to cirrhosis; in the pancreatic islets, it disrupts their function. The ability to measure these markers can be helpful. “Fat now is a secreting organ, and that is where labs play a role,” says Roth.

Labs can run the tests that determine the presence of related medical conditions that may cause poor health and premature death, 30 of which have been identified. These include coronary heart disease, stroke, hypertension, dyslipidemia (for example, high total cholesterol or high levels of triglycerides), Type 2 diabetes and possibly Type 1, gallbladder disease, hepatic steatosis (fatty liver), osteoarthritis, pulmonary disorders (such as sleep apnea and asthma), and some cancers, such as endometrial, breast, and colon. Obesity may also cause complications during and after surgery as well as with fertility, pregnancy, and delivery. Cardiovascular and cerebrovascular disease both significantly predispose toward dementia, and obesity has been associated with increases in depression and suicide.¹ “Social acceptance, quality of life, and career trajectories are all compromised, largely because of society’s discrimination against the disease.”¹

Society generally makes that call based on appearance alone. Diagnostics can help to determine the best way to treat the condition, though for many the best method is to consume less and exercise more. “Even without weight loss, the obese person who participates in a weight-loss program can experience the benefits,” says Roth. A loss of about 10% of body weight for persons with excessive weight or obesity can improve some obesity-related medical conditions, including diabetes and hypertension, suggests the AOA. That’s another tiny cause with big effect.

Renee DiIulio is a contributing writer for Clinical Lab Products.

References
1. Roth J, Qiang X, Marbán SL, Redelt H, and Lowell BC. The obesity pandemic: Where have we been and where are we going? Obes Res. 2004:12:88S-101S.
2. American Obesity Society. AOA Fact Sheet: Obesity in the US. Available at http://www.obesity.org/subs/fastfacts/obesity_US.shtml. Accessed May 7, 2005.
3. Obetech, LLC. Diabetes diagnosis. Available at http://www.obesityvirus.com/article.asp?id=31. Accessed May 7, 2005.
4. Centers of Disease Control and Prevention. Overweight and Obesity: Economic Consequences. Available at http://www.cdc.gov/needphp/dnpa/obesity/economic_consequencs.htm. Accessed May 7, 2005.
5. Sugarman SB, Foerster SB, Adkins SE, Carman JS, and Hooker SP. The Economic Costs of Physical Inactivity, Obesity, and Overweight in California Adults: Health Care, Workers’ Compensation, and Lost Productivity. Chenoweth & Associates Inc: April 2005.
6. Atkinson RL, Dhurandhar NV, Allison DB, Bowen RL, Israel BA, Albu JB, and Augustus AS. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes Relat Metab Disord. 2005:29(3):281–286.