Harrison’s Manual of Medicine



Associated Risks

Obesity is a state of excess adipose mass. It is a chronic disorder that is increasing in prevalence. Obesity should not be defined by body weight alone, as muscular individuals may be overweight by arbitrary standards without having increased adiposity. The most widely used method to gauge obesity is the body mass index (BMI), which is equal to weight/height2 in kg/m2. At a similar BMI, women have more body fat than men. A BMI between 20 and 25 kg/m2 is considered an appropriate weight for most individuals. Overweight is defined as a BMI > 25–27 kg/m2, and obesity is defined as a BMI > 30 kg/m2.
Excess accumulation of body fat is the consequence of environmental and genetic factors; social factors and economic conditions also represent important influences. The susceptibility to obesity is polygenic in nature, and 30–50% of the variability in total fat stores is believed to be genetically determined. Rare genetic syndromes associated with obesity include the Prader-Willi syndrome, Ahlstrom’s syndrome, Laurence-Moon-Biedl syndrome, Cohen’s syndrome, and Carpenter’s syndrome. Animal models also exist in which a single-gene mutation causes obesity, but defects in the corresponding genes in humans appear to be very rare. These include mutations in leptin, the leptin receptor, the melanocortin 4 receptor, and the pro-opiomelanocortin locus, among others. Animal models of obesity make clear the central role of the adipocyte in the pathogenesis. In addition to storing fat, these cells secrete lipoprotein lipase, tumor necrosis factor, angiotensinogen, and leptin. Leptin is an important satiety signal that acts directly in the hypothalamus to reduce food intake.
Weight gain or loss in individuals is determined by the balance between energy (food) intake and energy expenditure. The strong correlation between energy expenditure and fat-free body mass indicates that heavier people must on average ingest more food to provide the excess energy for weight gain. Obese individuals tend to underreport food intake by 50% or more. Physiologic variables that promote weight gain in the absence of significant increase in food intake include low metabolic rate, enhanced oxidation of carbohydrate relative to lipid, and insulin resistance. Secondary causes of obesity include hypothalamic injury, hypothyroidism, Cushing’s syndrome, hypogonadism, and certain drugs (Table 56-1). Insulin-secreting tumors can also cause overeating.

Table 56-1 Drugs That Enhance Appetite and Predispose to Obesity

Associated Risks
Increased mortality from obesity is primarily due to cardiovascular disease, hypertension, gall bladder disease, diabetes mellitus, and certain forms of cancer. The incidence of non-insulin-dependent diabetes is increased in individuals with a BMI > 22 kg/m2. Cardiovascular mortality is linked to increased risk of sudden death from arrhythmias and the complications of atherosclerosis that are due to an atherogenic lipid profile (increased LDL cholesterol, very low density lipoprotein, and triglyceride; decreased HDL cholesterol). Hypertension is also common and is related to hyperinsulinemia and insulin resistance. The incidence of endometrial cancer and postmenopausal breast cancer, prostate cancer, and colorectal cancer in both men and women is increased with obesity. Sleep apnea in severely obese individuals poses potentially serious health risks. Obesity is also associated with an increased incidence of symptomatic gallstones and osteoarthritis.
Regional fat distribution may also influence the risks associated with obesity. Central obesity (high ratio of the circumference of the waist to the circumference of the hips) is associated with high triglyceride levels, low HDL cholesterol levels, and insulin resistance.

Obesity is a chronic medical condition that requires ongoing treatment and lifestyle modifications. Palliation is the aim as cure is unlikely. Treatment is important because of the associated health risks but is made difficult by a limited repertoire of effective therapeutic options. Weight regain after weight loss is common with all forms of nonsurgical therapy. The urgency and selection of treatment modalities should be based on the BMI and a risk assessment. Associated risk factors such as age > 40, family history of coronary artery disease or diabetes mellitus, or presence of an obesity-related condition such as hypertension or osteoarthritis make treatment more urgent.
Low to Moderate Risk Behavior modification including group counseling, diet diaries, and changes in eating patterns should be initiated. Food-related behaviors should be monitored carefully (avoid cafeteria-style settings, eat small and frequent meals, eat breakfast). A deficit of 7500 kcal will produce a weight loss of approximately 1 kg. Therefore, eating 100 kcal/d less for a year should cause a 5-kg weight loss, and a deficit of 1000 kcal/d should cause a loss of approximately 1 kg per week. Physical activity should be increased. Exercise is not useful as a primary strategy to lose weight but helps to maintain weight loss and may reinforce efforts to reduce caloric intake.
High Risk Appetite-suppressing drugs such as fenfluramine and phentermine may result in greater weight loss than behavior modification alone; unfortunately, these drugs are associated with development of pulmonary hypertension and valvular heart disease and are no longer FDA approved in combination. Sibutramine is a central reuptake inhibitor of both norepinephrine and serotonin with efficacy in short-term trials, though it increases pulse and bp in some pts. Orlistat is an inhibitor of intestinal lipase that causes modest weight loss due to drug-induced fat malabsorption. Surgery is also an option in morbid obesity, which is defined as either 45 kg or 100% above ideal body weight. Weight regain and other medical problems are minimal with either a Roux-en-Y gastric bypass procedure or vertically banded gastroplasty (Fig. 77-8 in HPIM-15).


For a more detailed discussion, see Flier JS: Obesity, Chap. 77, p. 479, in HPIM-15.


2 comments on “56 OBESITY

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