The spectrum of obesity-related diseases ranges from type 2 diabetes mellitus (DM) and cardiovascular disease to osteoarthritis and gallbladder disease. The relative risk of a number of these health problems associated with obesity is shown in Table 7 and Fig. 1.
Must et al. (54) used data from NHANES III to show that the prevalence of DM increased with increasing weight category (Fig. 1A), a relationship that was evident across racial, ethnic, and gender lines. Analysis of another U.S. study
Relative Risk of Health Problems Associated with Obesity
Greatly increased (relative Moderately increased Slightly increased risk much greater than 3) (relative risk 2-3) (relative risk 1-2)
Type 2 diabetes Gallbladder disease Dyslipidemia Insulin resistance Dyspnea/Hypoventilation Sleep apnea
Certain cancers Reproductive hormone
Hypertension Osteoarthritis abnormalities Polycystic ovarian
Hyperuricemia and gout syndrome Impaired fertility Low back pain Increased anesthetic risk Fetal defects
CHD, coronary heart disease. Adapted from ref. 4.
(BRFSS) revealed that every 1-kg increase in self-reported weight was associated with a 9% increase in the prevalence of DM for the 1991-1998 period (36). Remarkably, from 1999 to 2000, the average weight of U.S. adults increased by 0.5%, whereas the prevalence of DM increased by about 6% (36). Similar increases in diabetes risk in the obese population have been reported in studies conducted in Asia, Europe, and the Middle East. As previously noted, fat distribution (i.e., visceral obesity) is an important contributor and in many instances a strong predictor of the risk for developing DM.
Several studies, including the Atherosclerosis Risk in Communities (ARIC) Study, the Framingham Heart Study, the Nurses' Health Study, and NHANES, have shown that weight gain is clearly associated with increases in blood pressure, an association that has been observed in both developed and developing countries (55,56). In fact, in the analysis by Must et al. (54), hypertension was the most common obesity-related comorbidity and its prevalence showed a strong increase with increasing BMI class (Fig. 1B).
Fig. 1. (opposite page) The prevalence of type 2 diabetes mellitus (A) and Hypertension (B) by BMI class. BMI is expressed in kg/m2. [Adapted from an analysis of the NHANES III data by Must et al. (54).]
The lipid abnormality most commonly associated with obesity is low high-density lipoprotein (HDL) cholesterol with hypertriglyceridemia, a finding that is more profound in visceral obesity (57,58). The small dense (atherogenic) low-density lipoprotein (LDL) particles associated with this abnormality contribute to the increased cardiovascular risk that is associated with obesity. Not surprisingly, more stringent criteria for the recognition of low HDL (<40 mg/dL for men and <50 mg/dL for women) and high triglycerides (>150 mg/dL) were proposed in the recent guidelines issued by the National Cholesterol Education Program (59).
Cardiovascular disease, which includes coronary heart disease (CHD), cere-brovascular disease (stroke), and peripheral vascular disease, is the most significant problem associated with obesity. This is reflected in the recent "call to action" issued by the American Heart Association in response to the obesity epidemic (60). Although the increased cardiovascular disease risk results partly from the impact of obesity on dyslipidemia, hypertension, insulin resistance, and impaired glucose tolerance or frank DM (61,62), longer term studies have shown that obesity is also important as an independent risk factor for CHD (63,64).
Data from the Nurses' Health Study suggest that the risk for gallstones increases with higher body weight (65), which is also reflected in the analysis done by Must et al. (54). The same picture has been seen elsewhere (66), although it should be noted that transnational comparisons are complicated because the demographics of the study populations tend to be different as well as nonrepre-sentative. It is worth mentioning that rapid weight loss is also associated with an increased risk for the development of gallstones (4).
The association of osteoarthritis with increasing BMI was also evident in the study by Must et al. (54). From a purely mechanical viewpoint, it is logical that obesity would be associated with an increased risk of joint dysfunction. However, there is also an inflammatory component involved in this process, presumably owing to the release of cytokines; this would explain the observed increase in osteoarthritis of the hands with obesity, even though the joints are not weight-bearing (67).
Several studies have found an association between obesity and an increased risk for various cancers, particularly those that are gastrointestinal or hormone-dependent. Examples include cancer of the colon, stomach, gallbladder, prostate, breast, endometrium, ovary, cervix, and kidney (68-70). In a recent meta-analysis,
Bengstrom et al. (71) estimated that excess body mass accounts for 5% of all cancers in the European Union, or 72,000 cases of cancer annually. Along the same lines, a panel of experts who recently reviewed over 4000 studies on this subject concluded that 30-40% of all cases of cancer (3-4 million cases of cancer per year worldwide) could be prevented by better diets together with maintenance of physical activity and appropriate body weight (72).
Obesity, especially of the upper body, is a risk factor for pulmonary diseases such as obstructive sleep apnea and Pickwickian syndrome (obesity-hypoventilation). If left unchecked, the pulmonary dysfunction can over time cause right-sided heart failure or lead to sudden death secondary to an arrhythmia during sleep (73).
Hormonal abnormalities associated with obesity include hyperinsulinemia and insulin resistance, hypogonadism (in males), hyperandrogenism and ovula-tory dysfunction (in females), decreased growth hormone levels, and dysregulation of cortisol metabolism (74). These findings are particularly present in visceral obesity and, as discussed above, are believed to underlie many of the metabolic abnormalities associated with obesity.
Psychological problems associated with obesity include depression, low self-esteem, and distorted body image; societal issues include unemployment, discrimination, isolation, and marital stress (75). Women, especially those with physical ailments, are usually the most affected. In addition, there are interesting cultural differences; for example, although African-American women are two to three times more likely to be obese than white women in the United States, they (African-American women) face less social pressure regarding their body weight.
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