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Current time:0:00Total duration:9:17

Treating type II diabetes - Pharmacology

Video transcript

type 2 diabetes' receives a lot of attention in the lay press as a public health threat as it affects about 10 percent of the global population and is currently the eighth most common cause of death worldwide as such understanding how to treat type 2 diabetes is very important because if it's treated properly one can avoid nearly all of the complications of type 2 diabetes and live a happy and healthy life now before we dive into the specific treatments let's first discuss the glucose regulation pathway as it will help us to better understand the pharmacokinetics or the mechanisms of action for the different treatments of type 2 diabetes now in the center here is the blood glucose level and as blood glucose levels increase say after eating a meal this is sensed by the pancreas and the beta cells within the pancreas secrete insulin which acts on cells throughout the body to lower the blood glucose level then as blood glucose levels decrease this is also sensed by the pancreas and then the alpha cells secrete glucagon which acts to raise the blood glucose levels and one of the mechanisms by which it does so is by promoting the conversion of glycogen to glucose in the liver which is then released into the bloodstream now diabetes mellitus is a group of disorders that's caused by dysfunction of the insulin pathway resulting in an inability to lower blood glucose levels and as you can see by this diagram there are two main steps that must occur for this pathway to work properly first insulin must be secreted by the beta cells of the pancreas then second the cells throughout the body must respond to insulin for it to have an effect and this glucose regulation pathway can be thought of as similar to that of the temperature regulation in a building the thermostat is analogous to the pancreas and that it senses the changes in temperature and sends different signals accordingly if the temperature increases then it sends a signal to the air conditioner to turn on which then lowers the temperature conversely if the temperature decreases this is also sensed by the thermostat and it sends a signal to the boiler and radiator to turn on which then raises the temperature now once again there are two important steps the thermostat must sense the change in temperature and send a signal which is similar to the first step in the insulin pathway then second the air conditioner must be able to act upon this signal in order to have an effect so let's go back to our insulin pathway when we think of the types of diabetes in general we think of type 1 diabetes as dysfunction of the first step and type 2 diabetes as occurring due to dysfunction of the second step so it would make sense that the treatment of the different types of diabetes will be different as their underlying mechanisms are different in the treatment of type 2 diabetes some medications are given to increase insulin secretion to help overcome the resistance and others are given to directly decrease the insulin resistance in the second step so let's now discuss the specific treatments for type 2 diabetes and the mechanisms by which they work and we'll begin with lifestyle modifications the first lifestyle intervention is that of proper nutrition and weight loss regardless of one's initial weight proper nutrition and associated weight loss improves the body's ability to regulate blood glucose levels and proper nutrition for type 2 diabetes includes a well-balanced low-calorie and low carbohydrate diet admittedly this can be a very difficult change for many people with type 2 diabetes as it takes a great deal of dedication and self-control however it is extremely important because a proper diet and weight loss have been shown to both increase insulin secretion and decrease insulin resistance the other lifestyle modification is physical activity independent of weight loss increased physical activity has been shown to improve glycemic control through reducing insulin resistance and the benefits of exercise begin almost immediately however they can be short lived if physical activity is not maintained persisting only about three to six days after the cessation of routine exercise so the recommendations for routine exercise include 30 minutes a day five days a week of moderate-intensity aerobic activities such as walking jogging or biking and the great thing about these lifestyle modifications is they don't just treat type 2 diabetes a proper diet in routine physical activity will also improve one's cardiovascular function lipid profile as well as their general mental well-being in addition to lifestyle modifications there are many different medications available to treat type 2 diabetes however it can be confusing to keep them all straight instead of discussing each of the medications individually let's classify the different medications into groups based on their mechanism of action and how it relates to our diagram of glucose regulation and we'll start with a group of medications known as the big one IDEs and I know I just said we won't be discussing the individual medications however there is one exception and that is with metformin and this is because metformin is by far the most common big one i prescribed for type 2 diabetes and it's also the first-line medication for the disease now metformin has three mechanisms of action that improve glucose regulation most importantly metformin directly increases the peripheral insulin sensitivity it also acts by decreasing the action of glucagon in the liver so instead of just augmenting the insulin pathway metformin also inhibits the opposing glucagon pathway then lastly although not shown in this diagram metformin reduces intestinal absorption of glucose which then decreases the amount of glucose available to enter the bloodstream unfortunately metformin is also very effective on average metformin can reduce someone's hemoglobin a1c by about one percent however it is important to note that individuals with liver failure cannot take metformin and a small percentage of individuals who take the medication will need to stop taking it due to an adverse side effect known as lactic acidosis the next group of medications have a somewhat difficult name they are the thiazolidinediones or TZ DS for short similar to metformin TZD s also work to increase type-2 diabetes by acting on the second step to increase insulin sensitivity however the means by which they do so is different T C DS activate a receptor known as the peri axis on proliferator activated receptor gamma or peep are gamma for short and people are gamma is a transcription factor for multiple genes that increase insulin sensitivity in adipose muscle and liver cells as such by activating pbar gamma t zds indirectly increase insulin sensitive now the next group of medications is the sulfonylureas which are another common group of anti-diabetic medications so finding areas inhibit the potassium channels on the beta cells within the pancreas and by inhibiting these channels potassium builds up within the cell and this depolarizes the cell membrane which opens voltage-gated calcium channels this causes an influx of calcium into the beta cells which triggers the release of insulin into the bloodstream so instead of decreasing insulin resistance sulfonylureas treat type 2 diabetes by overcoming the insulin resistance through increased insulin secretion the last two groups of type 2 diabetes medications act upon the in cretan pathway and are therefore known as in cretins and they are the glucagon-like peptide one or glp-1 agonists and the dipeptidyl peptidase-4 or DPP for antagonists in cretins such as glp-1 or hormones that have two synergistic effects the result in the lowering of blood glucose levels first they directly stimulate the release of insulin from the beta cells in the pancreas and second they inhibit the release of glucagon DPP four on the other hand is an enzyme that inhibits the action of glp-1 therefore glp-1 agonist can be given to directly stimulate this increment pathway to augment the insulin pathway and treat type 2 diabetes similarly dpp-4 inhibitors can be given to indirectly augment the insulin pathway by inhibiting the inhibition of the accreting pathway so it's important to note that any of the treatments for type 2 diabetes that act upon this first step in the insulin pathway and therefore increase insulin secretion will therefore also carry a risk of inducing hypoglycemia or low blood sugar levels and the treatments that act upon this step and carry this risk include lifestyle modifications sulfone areas and the Inc reasons and one way to decrease this risk is to take the medications with a meal now this is just an overview of the pharmacokinetics of the different interventions used to treat type 2 diabetes and this is helpful for understanding how we can use medications to reverse and treat the underlying mechanisms that cause the disease however just understanding the mechanisms does not convey a very practical approach to treating this disease for most individuals treating type 2 diabetes requires a combination of lifestyle modifications potentially multiple medications and routine care by a primary care provider to achieve a happy and healthy life free of the complications of type 2 diabetes