Chapter 46
Obesity and Diabetes — 5
Metabolic syndrome is present in about two-thirds of people with obesity and is a marker of increased risk of heart disease, cancer, and neurodegenerative disease. It consists of five features (diagnosis of metabolic syndrome requires at least three of these five features to be present): high fasting glucose (>110 mg/dl), high blood pressure (more than 130/85 mm Hg), high fasting triglycerides (more than 150 mg/dl), low high-density lipoprotein (HDL) cholesterol (below 40 mg/dl in men or <50 mg/dl in women), and central adiposity as defined by waist circumference more than forty inches in men or thirty-five plus inches in women. All are ameliorated in most people with obesity who take GLP-1 drugs. Because only three of the five features are needed to meet the diagnosis of metabolic syndrome, obesity is not a necessary component. We must flag that metabolic syndrome is prevalent in one-third of people who are not obese, thus further expanding the potential use of these drugs in the future.
GLP-1 drug reduces inflammation throughout the body and in the brain. Receptors to GLP-1 are plentiful in the brain, unlike other parts of the body. An elegant study that tested different GLP-1 drugs in mice whose GLP-1 receptors were erased from their brains showed that without these receptors, the anti-inflammatory effect was lost. Since there are no GLP-1 receptors in the cells of many organs, such as blood vessels and the liver, it questions how inflammation is suppressed by these drugs. Everything we know at this point implicates the GLP-1 impact on the brain as a key mediator for the body-wide reduction of inflammation. Recent work has shown that activation of GLP-1 receptors on T cells is another mechanism for the anti-inflammatory properties of these drugs.
ADIPOSE CELLS AND TISSUE
Before we leave obesity and switch over to diabetes and metabolic health, it’s worth looking closely at a few salient features of adipose tissue. It’s composed of two main types of cells—white and brown. The white fat cells layer around our organs to provide protection, insulate our body heat, and store energy. In adults who are lean, white fat deposits account for 30 to 40 percent of total body mass in women, and 15 to 25 percent in men. Shown in figure 4.1 is the remarkable disparity in estimated cell count and mass in a lean male of about 150 pounds.