Obesity: Pathophysiology and Management

Gadde KM, Martin CK, Berthoud HR, Heymsfield SB.
Obesity: Pathophysiology and Management. J Am Coll Cardiol 2017;71:69-84.

The following are key points to remember from this review article about the pathophysiology and management of obesity:

  1. As of 2015, an estimated 600 million adults are obese, and elevated body mass index (BMI) accounts for 4 million deaths globally. The pathogenesis of obesity is complex with environmental, sociocultural, physiological, medical, behavioral, genetic, and epigenetic factors contributing to the cause.
  2. More than 140 genetic chromosomal regions have been identified as related to obesity. However, only a few genes with a large effect size on BMI have yet been identified. It is highly likely that obesity genes act within the hypothalamic homeostatic regulator of energy balance, but also within neural circuits which influence reward-based decision making, learning and memory, delayed discounting, and spatial orientation.
  3. BMI ranges for Americans and Europeans for underweight, normal weight, overweight, and obese are <18.5, 18.5-24.9, 25-29.9, and >30 kg/m2, respectively. Obesity by BMI can be further stratified into class I (30-34.9), class II (35-39.9), class III (≥40), class IV (≥50), and class V (≥60). Recommended cut points for overweight and obesity are lower in some Asian nations.
  4. Weight loss is recommended for all patients who are overweight or obese. An initial goal of 5-10% weight loss over 6 months is recommended. A multimodal lifestyle intervention with dietary modification and increased physical activity, which includes behavioral modification delivered by a multidisciplinary team, is recommended as well.
  5. Weight loss achieved with diet and exercise improves cardiometabolic risk factors; however, data for reduction of cardiovascular events are lacking among those patients with type 2 diabetes after 10 years, as noted in the Look AHEAD trial. Blood pressure can be improved markedly, even without large weight loss, by eating a diet that is high in fruits, vegetables, and low-fat dairy, and low in saturated fat and total fat; however, the long-term effects of such a diet on morbidity and mortality have not been examined. For prevention of major adverse cardiac events in patients at high risk, the evidence to date supports Mediterranean diets supplemented with olive oil or nuts.
  6. Five medications are currently approved in the United States for long-term management of obesity with placebo-subtracted weight loss ranging from ~9% for phentermine/topiramate to ~3% for lorcaserin and orlistat. Pharmacotherapy should be a consideration for patients with a BMI of ≥30 and BMI of ≥27 with weight-related comorbidities such as type 2 diabetes, or for those who failed lifestyle modification or maintenance of weight loss. With the exception of orlistat, all currently approved anti-obesity medications help patients limit their caloric intake via enhancement of satiety and reduction in hunger and food cravings.
  7. Seven medical devices are FDA approved for the treatment of obesity. These include laparoscopic adjustable gastric band devices. Three intragastric balloons are approved for up to 6 months of use among patients with BMI 30-40 kg/m2. One device blocks the vagal nerve, thereby suppressing neural communication between the stomach and the brain, leading to increased satiety and decreased caloric intake. Another device consists of a gastrostomy tube connected to a skin-port outside of the abdomen, which allows the user to flush out food 20-30 minutes after each meal.
  8. Bariatric surgical procedures are indicated for patients with BMI ≥40 and ≥35 kg/m2 in the presence of weight-related comorbidities such as type 2 diabetes, with lower BMI cut-offs for laparoscopic adjustable gastric band. Such procedures include the sleeve gastrectomy, the Roux-en-Y gastric bypass, the laparoscopic adjustable gastric banding, and biliopancreatic diversion with duodenal switch. The Roux-en-Y gastric bypass is associated with the most weight loss in long-term follow-up studies.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Prevention, Genetic Arrhythmic Conditions, Diet, Exercise

Keywords: Blood Pressure, Body Mass Index, Comorbidity, Diabetes Mellitus, Diet, Diet, Mediterranean, Energy Intake, Exercise, Fruit, Gastrectomy, Gastric Balloon, Gastric Bypass, Gastroplasty, Gastrostomy, Genetics, Behavioral, Life Style, Metabolic Syndrome X, Nuts, Obesity, Overweight, Patient Care Team, Primary Prevention, Risk Factors, Vegetables, Weight Loss

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