Hi, everyone. This is Dr. Sandy Basson. In this presentation, we'll review the foundations of obesity medicine, including the prevalence, pathophysiology, and diagnosis. The learning objectives for this presentation are as follows. To understand the prevalence and ethnic disparities of obesity, to review the pathophysiology of obesity, to understand the regulation and energy balance and metabolic adaptation to weight loss, to review the rationale for treating obesity as a chronic disease and its associated disease complications, to review the diagnostic criteria for obesity, and to identify clinically significant weight loss. Worldwide, obesity has nearly tripled since 1975. In the table, we can see the prevalence of obesity worldwide in the past, present, and projections for the future. In 2020, the prevalence of obesity was 15%, of which 5% was defined as severe obesity, and projections are only expected to rise, where in 2030, it is expected to be 18%, or 1 billion people. In fact, most of the world's population lives in countries where overweight and obesity kills more people than underweight. Within the United States, the prevalence of obesity is even more staggering, where 42% of the population meets criteria for obesity and 70% meets criteria for overweight or obesity, making obesity the most common chronic disease in the United States. This table and graph shows the prevalence of obesity based on ethnicity. There is an increased prevalence amongst Hispanic men at 45%, and even more notable is amongst black women, who have a prevalence of obesity at 57%, compared to other ethnicities, such as white and Hispanic, which are closer to around 40%. Additionally, the prevalence of obesity is almost 50% in both black men and women. The pathophysiology of obesity is complex and not fully understood. It can be caused by genetic factors, such as mutations and deficiencies of molecules, and can be due to secondary causes, such as hypothalamic or endocrine conditions, medication side effects, as well as be impacted by the environment and psychological factors. The image on the right shows the many hormones which regulate appetite and are released from the GI tract, adipose tissue, and the brain. The well-known but erroneous calories-in, calories-out model of treating obesity is the concept that eating fewer calories and extending more calories as activity will result in weight loss. This implies that weight management is a static process, only impacted by the food we consume. This model does not consider the numerous metabolic changes which the body undergoes with weight loss, many of which promote weight regain. Rather, body weight is the result of a dynamic process of food intake and energy expenditure regulation. Hormones released from the gastrointestinal tract, pancreas, and adipose tissue, such as luctin, ghrelin, cholecystokinin, peptide YY, insulin, and glucagon-like peptide 1, all play a role in modulating appetite. Additionally, the development of obesity involves increased pre-adipocyte proliferation, allowing for increased fat storage capacity compared to those who are non-obese. Neurophysiologically, changes to the dopaminergic reward pathway from chronic overconsumption of hyperpalatable foods can lead to perceived reward deficits when consumption is reduced. Due to these modulators, calorie restriction leads to the body becoming more efficient at conserving energy, requiring fewer calories to complete the same tasks, and increased levels of these appetite-regulating hormones. This makes obesity more challenging to manage after it's established. Studies show a biochemical set point that is often higher than the weight loss attempting to be achieved. In fact, this daily energy expenditure conservation is noted even one year after people have maintained a reduced body weight. As briefly mentioned in the previous slide, the set point theory is based around the idea that the body will work to maintain weight at a certain level. Based on various factors, including biological, genetic, environmental, and behavioral, this set point is determined. Of note, this set point can change throughout the lifespan. For example, women after menopause, unfortunately, are more predisposed to gain weight. As will be further described in upcoming slides, lifestyle interventions are often successful in short-term weight loss, if not actively maintained, and current obesity medications help with weight loss during their use, but weight often returns after discontinuation. This suggests that appetite-inducing and suppressing hormone release is altered to promote a positive energy balance and cause weight gain when efforts to lose weight reach below a certain individualized threshold. As mentioned in the prior slide, obesity becomes more difficult to manage the longer it's established, with multiple hormonal pathways attempting to reverse weight loss even years after weight reduction. Obesity is now defined as an adiposity-based chronic disease, or ABCD, to further emphasize the lifelong need for lifestyle and medical management. Multiple large lifestyle intervention trials, like the Look Ahead for Health in Diabetes and the Swedish Obesity Subject Study, have shown that despite weight loss after intensive lifestyle management, weight often relapses. This is graphically shown on the image on the right, which shows despite significant weight loss in the first year, patients often regained weight to reach a higher equilibrium. Given that this image shows follow-up over 10 years, it very clearly depicts the chronicity of living with obesity, where short-term interventions don't help the underlying biological reset. While these studies show that despite lifestyle intervention, weight often returns to a possible set point, it is important to discuss lifestyle changes with patients, as healthy habits can avoid further weight gain and help prevent or treat other chronic conditions like diabetes, hypertension, and hyperlipidemia. Obesity, or adiposity-based chronic disease, is associated with over 236 different complications, from more well-known ones such as cardiovascular, metabolic, musculoskeletal, and pulmonary complications like hypertension, type 2 diabetes, fatty liver, sleep apnea, and osteoarthritis, to less well-known complications including increased risk of cancer and coagulability such as thrombosis and lung embolism, as well as skin conditions like psoriasis, reproductive conditions like infertility and PCOS, as well as urogenital like incontinence, and mental health conditions including depression and anxiety. Globally, 44% of diabetes, 23% of ischemic heart disease, and between 7 and 41% of certain cancer burdens are attributable to overweight and obesity. It is the fifth leading cause of death internationally, taking over 5 million lives. Shown here are the diagnostic criteria for obesity. BMI, or body mass index, is noted to be a normal weight from 18.5 to 24.9, overweight from 25 to 29.9, and obesity from greater than 30, with the various classes noted here. Keep in mind that some ethnicities have lower cutoffs. Waist circumference can also be used as greater than 40 inches for men and greater than 35 inches of abdominal obesity for women. Percent fat classification can also be used for greater than 25% body fat in men and greater than 32% body fat in women. The methods of calculation can be done by a DEXA bone scan, BIA or bioelectrical impedance analysis, as well as hydrometry. As mentioned previously, diagnostic criteria for obesity vary by ethnicity, and oftentimes these cutoffs are lower than the BMI cutoffs noted in Caucasians. For example, Indians and Singaporeans are identified as overweight with a BMI greater than 22 or 23, and obesity is identified at a BMI greater than 27, rather than 30. Additionally, ethnic South and Central Americans have similar BMI cutoffs to Indians and Singaporeans. Adiposity-based chronic disease is associated with 236 complications. Additionally, it impacts the quality of life, increasing depression and fatigue and decreasing the quality of sleep. Based on several large trials, the U.S. Food and Drug Administration defines clinically significant weight loss as weight loss greater than 5%. Additionally, this is the FDA standard of weight loss that all approved anti-obesity medications must meet. As seen on the graph, improvements in multiple comorbidities, including hypertension, cholesterol, triglycerides, and cardiovascular disease, occur at this 5% weight loss marker. Of note, some complications and comorbidities require further weight loss to have significant improvements, such as remission of type 2 diabetes and improvement in sleep apnea, fatty liver, or heartburn. Hyperglycemia, on the other hand, can have improvement in as little as 3-5% sustained weight loss. The light purple bars indicate even further improvement in symptoms or conditions with additional weight loss.

obesity medicine

prevalence

pathophysiology

diagnosis

complications