obesity, metabolic syndrome and cardiovascular disease

Grundy, S.M., et al. 2004. Definition of metabolic syndrome: Report of the NIH/
AHA conference on scientific issues related to definition. Circulation, 109, 433–8.

Context. Scott Grundy, MD, PhD, director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas and an eminent researcher in nutrition, lipid disorders and metabolism has reviewed recent findings on the relationship between overaccumulation of fat and the metabolic syndrome. Most healthcare professionals consider Dr. Grundy the highest and most respected authority on cholesterol disorders and the metabolic syndrome in the United States. This brief segment of his full-text paper reflects the present understanding of the relationships among obesity, diabetes and cardiovascular disease (CVD). This synopsis is essential reading for all fitness professionals who specialize in weight management and/or diabetes and CVD risk reduction.

Obesity can be called an underlying risk factor for CVD because it raises the risk of CVD through other risk factors. These other factors include hypercholester-
olemia, hypertension, hyperglycemia, high triglyceride levels, insulin resistance, arterial inflammation and blood thrombosis tendency.

Obesity is also a risk factor for type 2 diabetes. Diabetes itself is a CVD risk factor. Despite the strong association between obesity and CVD, the mechanisms underlying this relationship are not well understood.

Our understanding of the connection between obesity and vascular disease is complicated by a plethora of possibilities. Obesity acts on so many metabolic pathways, producing so many potential risk factors, that it is virtually impossible to differentiate between those that are more important and those that are less important. The potential for confounding variables is enormous.

This complexity provides a great challenge for basic and clinical research. It also raises the possibility for new targets of therapy for the metabolic syndrome (described below). With this said, the fundamental challenge lies in how to intervene at the public-health level to reduce the high prevalence of obesity in the general population. This approach offers the greatest possibility for reducing the CVD risk that accompanies obesity.

Assessing Obesity

In clinical practice, the best way to measure obesity is to measure waist circumference. This is because an excess of abdominal fat is most tightly associated with the metabolic risk factors (triglycerides, insulin, glucose, etc.). In the U.S., abdominal obesity is defined as a waist circumference in men of 40 inches or more and in women of 35 inches or more. Body mass index (BMI) is also a marker of body fat content.

An optimal way to define body obesity would be in terms of percent total body fat, as measured by skinfold thickness, bioelectrical impedance or underwater weighing; however, these techniques are rarely used in clinical practice because of inconvenience and cost.

Abdominal Fat Compartments

Abdominal fat is located in two major compartments. Intraperitoneal, or visceral, fat consists of the fat surrounding the abdominal organs. The fatty acids released by visceral fat drain into the portal circulation, which feeds directly into the liver. Some investigators (Bosello & Zamboni 2000) believe that an excess of visceral fat (visceral obesity) is more strongly related to metabolic risk factors than any other fat compartment.

Subcutaneous (sc) adipose tissue (i.e., fat just beneath the skin) is nonetheless a much larger compartment than visceral fat. Sc fat is usually divided into gluteo-femoral and truncal sc adipose tissue. Truncal fat is more strongly related to metabolic risk factors than is gluteo-femoral fat (National Institutes of Health [NIH] 1998). Moreover, truncal sc fat—because of its greater mass—may have a greater impact on risk factors than visceral fat does (Abate 1995).

Several terms have been applied to excess fat in the trunk: abdominal obesity, truncal obesity and upper-body obesity. There is a strong correlation between waist circumference and upper-body fat content.

Body Fat and the Metabolic Syndrome

The metabolic syndrome is a constellation of several metabolic risk factors:

• atherogenic dyslipidemia (elevated serum triglycerides; elevated apolipoprotein B; and small LDL cholesterol particles, along with low HDL
  cholesterol)

• elevated blood pressure

• elevated glucose

• prothrombotic state (tendency for blood to clot)

• proinflammatory state (tendency for inflammation in specific arteries)

In 2001, the NIH published the National Cholesterol Education Program Adult Treatment Panel III Report (with Grundy as principal author). The paper proposed a simple scheme for the routine diagnosis of the metabolic syndrome. According to this scheme, a diagnosis of metabolic syndrome can be made if a person has any three of the following five features:

• increased waist circumference (≥ 35 inches in women, ≥ 40 inches in men)

• elevated triglycerides (≥ 150 milligrams per deciliter [mg/dl])

• reduced HDL cholesterol (< 40 mg/dl in men, < 50 mg/dl in women)

• elevated blood pressure (≥ 130/85 or on treatment for hypertension)

• elevated fasting glucose (≥ 100 mg/dl)

The cut points of 35 and 40 inches for defining abdominal obesity are arbitrary. For susceptible individuals, lesser accumulations of abdominal fat can precipitate or aggravate metabolic risk factors. This is particularly so in certain populations; for example, in Asian populations lower waist-circumference cut points have been identified to define abdominal obesity.

Our understanding of the relation between obesity and metabolic risk factors is growing rapidly. This understanding is based on the discovery of multiple products released from adipocytes, or fat cells. In the presence of obesity, these products are released in abnormal amounts. Each of these products has been implicated in the causation of one or other of the metabolic risk factors. The following is a list of the factors most implicated in the development of metabolic syndrome:

• non-esterified fatty acids (excess leads to insulin resistance)

• inflammatory factors (e.g., C-reactive protein)

• PAI-1 (plasminogen activator inhibitor-1, which can increase blood clotting tendency)

• adiponectin (has anti-inflammatory and anti-atherogenic properties)

• leptin (appetite suppressant derived from adipose tissue)

• resistin (hormone that opposes the
  action of insulin)

The Bottom Line

Several recent reports (Isomaa et al. 2001; Alexander et al. 2003; Lakka et al. 2002) indicate that the presence of the metabolic syndrome is associated with increased risk of CVD and type 2 diabetes. Persons with the metabolic syndrome have at least a twofold increase in risk for CVD compared with those without, and a fivefold increase in risk for type 2 diabetes. The risk for diabetes is highest in those with impaired fasting glucose (i.e., fasting glucose of 100–125 mg/dl).

Comments

This paper is important. Dr. Grundy is highly respected, and his paper elucidates the latest research and consensus opinion on the relationships among obesity, diabetes and CVD. Fitness professionals should look at the metabolic syndrome as an opportunity to integrate a range of healthy behaviors (diet, physical activity, weight loss) for a multi-risk-factor package. To be sure, many higher-risk clients with the metabolic syndrome will also require pharmacologic therapy to optimally manage their atherogenic dyslipidemia.

Regarding the assessment of body fat, caution should be used with specific ethnic groups when predicting body fat percent from body density conversion formulas (these are “built in” in bioimpedance and skinfold evaluations). Most body fat conversion formulas use generalized population body density equations that are not specific to particular ethnic groups. Unless you are using a population-specific formula that matches the ethnic group being tested, there can be significant error. Reliable body density equations for ethnic groups are currently scarce. For this reason, the careful and skilled measurement of waist circumference and BMI is recommended. Absolute skinfold measures (in millimeters) can be helpful for assessing adiposity changes between visits or during follow-up. I recommend measuring specific skinfolds (triceps and/or subscapular) throughout the course of dietary and exercise therapy for the metabolic syndrome—particularly within formal metabolic-syndrome management programs.

Those seeking a deeper understanding of the relationship between obesity and metabolic syndrome should refer to Dr. Grundy’s recent review of the NIH/AHA metabolic syndrome conference (Grundy 2004). Finally, for qualified health professionals using the NIH’s three-out-of-five criteria to diagnose the metabolic syndrome, it is recommended that two of the three risk factors be impaired fasting glucose (i.e., 100–125 mg/dL) and increased waist circumference (or BMI > 30). These risk factors will more specifically target diabetes risk. n

According to the National Institutes of Health, a diagnosis of metabolic syndrome can be made if a person has any three of the following five features: