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The body mass index (BMI) is a ratio of weight to height and is one tool for measuring body size in health care and research. Epidemiological research indicates that individuals with a healthy BMI (between 20 and 25) have the lowest risk of cardiovascular disease and death compared to individuals with underweight (BMI less than 18.5), overweight (BMI between 25 and 30), and obesity (BMI greater than 30); however, some people with a healthy BMI experience metabolic dysfunction and an increased risk of death. Authors of the following report explore the condition lipodystrophy, its physiological causes, and its prevalence in the general population.

Lipodystrophy is a condition in which the amount and/or distribution of fat tissue in the body is abnormal. Visceral fat is fat stored in the abdomen and is associated with insulin resistance, elevated triglycerides, and fatty liver. This is in contrast to fat stored in the lower body, called subcutaneous fat, which is not associated with metabolic dysfunction. In short-term studies, people with a healthy BMI and an increased waist-to-hip ratio (i.e., ratio of visceral to subcutaneous fat) are at a three times greater risk of death than people with obesity and no metabolic dysfunction, a condition referred to as metabolically healthy obesity. However, long-term studies (those with greater than 10 years' follow-up) show that people with metabolically healthy obesity have a 24 percent increased risk of death, suggesting metabolically healthy obesity is a transient stage between metabolic health and metabolic disease.

The authors recruited almost 1,000 Caucasian/white participants of varying weight status who were at an increased risk of cardiometabolic disease based on weight, family and personal history of diabetes, and elevated glucose levels. The researchers used magnetic resonance imaging (MRI) to precisely measure body fat amount and distribution. They also measured blood pressure, fasting triglyceride levels, fasting glucose, the inflammatory marker C-reactive protein, insulin resistance, and carotid intima thickness (a measure of atherosclerosis). They defined good metabolic health as having two or fewer of the following criteria: blood pressure greater than 130/85 millimeters of mercury or the use of blood pressure medication; fasting triglycerides greater than 150 milligrams per deciliter; fasting HDL cholesterol (i.e., good cholesterol) less than 40 milligrams per deciliter in males or less than 50 milligrams per deciliter for females; fasting glucose greater than 100 milligrams per deciliter or the use of diabetic medication; C-reactive protein level in the 90th percentile or above; or insulin resistance in the 90th percentile or above.

Compared to people with a healthy BMI and good metabolic health, those with a healthy BMI and more than two metabolic risk factors had more insulin resistance, nonalcoholic fatty liver disease, visceral obesity, less lower body subcutaneous fat, and increased atherosclerosis. However, they did not have an increased prevalence of high blood pressure, high triglycerides, low good cholesterol, or increased inflammation. Compared to people with a healthy BMI and metabolic dysfunction, people with overweight or obesity and metabolic dysfunction had a gradual increase in the prevalence of visceral adiposity, fatty liver, insulin resistance, atherosclerosis, and low subcutaneous fat volume in the lower body as BMI increased. This means that metabolic dysfunction in people with a healthy BMI is most characterized by insulin resistance and atherosclerosis and is most strongly associated with lower subcutaneous fat in the lower body than visceral adiposity in the abdomen. The authors used this to support the existence of a lipodystrophy phenotype in people with a healthy BMI.

The authors conclude that some people with a healthy BMI may still have lipodystrophy that puts them at an increased disease risk compared to individuals with a healthy BMI and normal fat distribution. They recommend early testing of insulin sensitivity and use of medications that increase insulin sensitivity in people with lipodystrophy to lower disease risk.

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