Type 2 diabetes is much different than type 1 diabetes. Type 1 is caused by the lack of insulin, and therefore it is a must to replace it (in both long acting and short acting forms). Patients with type 1 diabetes are usually insulin sensitive and thus do not usually require large doses. In its simplest form, type 2 diabetes is caused by insulin resistance, meaning insulin does not work well, and higher insulin amounts (either naturally produced or injections) are needed to control blood sugars. However, it is not necessarily that simple. Type 2 diabetes actually contains 8 different defects in sugar metabolism that lead to high blood sugars. This has been referred to as the “Ominous Octet”. The 8 defects are shown in the figure below.
So what does all of this mean?
Let’s break down each one:
1. Decreased Insulin Secretion
Although insulin resistance typically causes increased amounts of insulin initially, these amounts are not enough to overcome the amount of glucose in the blood. The inability to correct blood sugars to normal levels is called impaired glucose tolerance (IGT). It has been found that once IGT is present, about 80% of pancreatic beta cell function has been lost. Further, over time, the remaining pancreas beta cells get “tired” and stop producing insulin altogether. This is why some type 2 diabetes patients are considered “insulin-dependent”.
2. Decreased Incretin Effect
Another set of important hormones for glucose regulation are referred to as incretins. These are hormones that come from the intestine, and they have direct beneficial effects on some of the other defects listed here (total of 6 out of 8).
3. Increased Lipolysis
This simply refers to increased fat breakdown. What is the problem with that, right? Well it’s not the same as breaking down fat with exercise. Fat cells release more free fatty acids, and the excess lipid accumulates in liver (fatty liver), muscle and pancreas. This worsens overall insulin resistance and decreases insulin secretion.
4. Increased Glucose Reabsorption
The kidney has a remarkable ability to hold on to the glucose it filters, which is critical to providing for the energy demands of the body’s tissues. However, in diabetes, it is problematic since it holds on to most of the glucose, even if the glucose levels are already high.
5. Decreased Glucose Uptake
Muscle cells have decreased ability to take up glucose and remove it from the blood stream. Tip: Exercise can improve this dysfunction.
6. Neurotransmitter Dysfunction
The brain plays an important role in glucose metabolism. Neurotransmitters are natural chemicals that stimulate the brain and nervous system. These signals are disrupted, and one of the major consequences is an increase in appetite. This is likely why obesity and type 2 diabetes are highly correlated.
7. Increased Hepatic Glucose Production (HGP)
In times of need, the liver produces blood sugar through processes called gluconeogenesis and glycogenolysis. This system goes unchecked in diabetes, where the liver continues to produce significant amounts of sugar, even when blood sugars are already high.
8. Increased Glucagon Secretion
The pancreas has beta cells that produce insulin and alpha cells that produce glucagon. Glucagon causes the liver to produce more glucose for energy demand. It is counteracted by insulin. So if insulin is impaired, this regulation is also unchecked and broken, leading to even higher glucose levels.
In conclusion, the identification of these 8 defects has significant implications for treating type 2 diabetes. Many patients come to me on a long-acting insulin and another medication that stimulates glucose production (usually glimepiride), and maybe metformin. Giving insulin and stimulating its production is only addressing 1 out of the 8 defects. Metformin is a great medication to be on, as long as it is tolerated, as it hits 2 of the 8 defects. However, I have had the most success when treating several or even all 8 defects, which hits the diabetes from multiple angles to get the best blood sugar control. Sometimes, this can even be done by avoiding insulin altogether. If you feel that your diabetes is not being addressed by a comprehensive approach, then please schedule a consult to discuss further.