(USMLE topics) Mechanisms by which obesity and physical inactivity can cause pre-diabetes and diabetes. This video is available for instant download licensing here: https://www.alilamedicalmedia.com/-/galleries/narrated-videos-by-topics/diabetes/-/medias/b42e945a-389f-41d0-b592-77aad378a24d-how-unhealthy-lifestyle-causes-prediabetes-and-diabetes-narrat
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Diabetes refers to a group of conditions characterized by high levels of blood glucose, commonly known as blood sugar. Glucose comes from digestion of carbohydrates in food, and is carried by the bloodstream to various body tissues. But glucose cannot cross the cell membrane to enter the cells on its own; to do so, it requires assistance from a hormone produced by the pancreas called insulin. Binding of insulin to its receptor on a target cell triggers a signaling cascade that brings glucose transporters to the cell membrane, creating passageways for glucose to enter the cells. In most tissues, muscles for example, glucose is used as an energy source, while in the liver and adipose tissue, it is also stored for later use, in the form of glycogen and fats. When the body is in the fasted state, the liver produces and secretes glucose into the blood, while adipose tissues release free fatty acids to the liver where they are converted into additional metabolic fuel.
Diabetes happens when insulin is either deficient or its action is compromised. Without insulin, glucose cannot enter the cells; it stays in the blood, causing high blood sugar levels.
There are 2 major types of diabetes. Type 1 is when the pancreas does not produce enough insulin; and type 2 is when the body’s cells do not respond well to insulin - they are insulin-resistant. Both types are caused by a combination of genetic and environmental factors but genetics plays a major role in type 1, while lifestyle is a predominant risk factor for type 2. For this reason, type 1 diabetes usually starts suddenly in childhood, while type 2 progresses gradually during adulthood, going through a so called pre-diabetic stage, which is defined as borderline blood sugar levels. Pre-diabetes is very common. Unhealthy lifestyle is the trigger of pre-diabetes and the main driving force behind its progression to diabetes type 2. The key factors are obesity and physical inactivity.
There are at least 2 ways by which obesity can cause insulin resistance and high blood glucose.
First, in obesity, fat cells have to process more nutrients than they can manage and become stressed. As a result, they release inflammatory mediators, known as cytokines. Cytokines interfere with the signaling cascade by insulin receptor, blocking the action of insulin.
Second, excess adipose tissue releases abnormally large amount of free fatty acids to the liver – an event that normally happens only when the body is fasting. This tricks the liver into producing and releasing more glucose into the blood. High blood glucose stimulates further insulin secretion. Constant high insulin levels de-sensitize body tissues, causing insulin insensitivity.
Intra-abdominal fat appears to produce more fatty acids and cytokines, and therefore has more severe effect on blood glucose, than subcutaneous, or peripheral fat. For this reason, large waist size is a greater risk factor than high body mass index.
Sedentary lifestyle, apart from having indirect effect by causing weight gain, has its own direct impact on insulin resistance. This is because physical activity is required to maintain healthy blood sugar levels. Physical activity increases energy demand by the muscles, which consume glucose from the blood, and subsequently from glucose storage in the liver and adipose tissue. High energy expenditure helps to clear up faster the spikes of blood glucose that follow every meal. High energy demand also promotes better cellular response to insulin, increasing insulin sensitivity. Physical inactivity, even for a short period of time, results in consistently higher spikes of blood sugar after meals, which can trigger pre-diabetic changes in healthy individuals, or speed up transition from pre-diabetes to diabetes. This happens not only to over-weight patients, but also to people with seemingly healthy weight.