Yup, it's yet another post about diabetes. (See here, here, here and here for my previous posts on diabetes.) Most of the content in this lecture was covered in the earlier posts, so I'm just going to cut straight to the bits that I haven't spoken about before.
Glucose Regulating Hormones
Firstly, a quick note on glucose regulating hormones. Insulin responds to increased blood glucose, causing blood glucose to go back down. There are four hormones that do the opposite (i.e. make blood glucose go up when it is low): glucagon, adrenaline, glucocorticoids and growth hormone.
Type 1 Diabetes Treatment
Obviously, people with type 1 diabetes need to take exogenous insulin. In the "basal-bolus regimen," patients take long-acting insulin at bedtime to maintain basal levels of insulin, and rapid-acting insulin (kicks in after around 5-15min) before they eat. This intensive regimen requires at least four injections a day, but it gives decent control over glucose levels.
Just like any other treatment, insulin therapy is not without its risks. If you give too much insulin, hypoglycaemia may result (see here for notes on insulin shock). Weight gain is also a potential side effect, as insulin is important in storage of various macronutrients. Finally, if the injection site is not rotated, scarring and lipohypertrophy or lipoatrophy may occur at the injection site.
There are several new treatments that are being developed in order to eliminate the need for needles. The bionic pancreas is a "closed-loop system" that continuously monitors glucose levels and delivers insulin or glucagon as necessary. Microneedle patches are small patches that have nanoparticles with a glucose sensor and insulin.
Type 2 Diabetes Treatment
The main treatments for type 2 diabetes are weight loss (which works for <10% of patients), oral hypoglycaemic agents, insulin, and treatment of associated conditions. In this post, I will go into a little bit more detail into some of the hypoglycaemic agents.
Metformin
Metformin is a biguanide that helps to decrease gluconeogenesis in the liver, but the exact mechanism is unknown. It is the drug of first choice as it does not cause hypoglycaemia or weight gain, and may even cause a decrease in colorectal cancer risk. Side-effects include gastrointestinal problems (which are usually transient) and lactic acidosis (though this is extremely rare).
Sulfonylureas
Sulfonylureas bind to the SUR1 receptor on β-cells, blocking the potassium channels, which in turn stimulates insulin release (see here for an explanation as to why). As sulfonylureas' mechanism of action relies on stimulation of insulin release, patients taking this drug must still have some functional β-cells.
Sulfonylureas are not the drug of first choice (they are the drug of second choice) due to drug-drug interactions (DDIs) and side effects. Sulfonylureas bind albumin in the blood and are metabolised in the liver, similar to many other drugs. DDIs tend to cause hypoglycaemia. Unlike metformin, hypoglycaemia is a possible side-effect of sulfonylureas, as well as weight gain. Nevertheless, sulfonylureas are often co-adminstered with metformin or are given to patients that cannot tolerate metformin.
Thiazolidinediones (TZDs/Glitazones)
See here. Effects can take weeks to develop.
α-Glucosidase Inhibitors
These drugs inhibit α-glucosidase in the intestines, thus inhibiting the breakdown of maltose into glucose and slowing absorption of glucose. Side-effects include bloating, flatulence and diarrhoea.
SGLT2 Inhibitors
These drugs block reabsorption of glucose in the proximal tubule so that more of it will be excreted in the urine.
Incretin-Based Therapies
Incretins, such as GLP-1, are gut peptides that increase insulin release after food (which is why insulin levels rise more after oral glucose, rather than IV glucose). Incretins are usually broken down by enzymes such as DPP-4. Incretin-based therapies include GLP1 mimetics such as exenatide and DPP-4 inhibitors such as sitagliptin. These drugs work to stimulate insulin release, and may also increase β-cell function and mass.
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