Type-2 diabetes is a progressive disease in which the risks of serious complications are all strongly associated with hyperglycemia. The disease’s course is primarily characterized by a decline in β-cell function and/or worsening of insulin resistance (1).
The good news is that it can be prevented or even reversed. In this article, we’ll look at a revolutionary strategy, which many scientists believe could be the key to reversing Type-2 Diabetes (2).
Why Treatments Fail in Type-2 Diabetes?
Currently, all forms of diabetes treatment are focused on reducing blood sugar. While these treatments are essential, experts have found that they are insufficient. In fact, most patients have felt that their medications gradually lose their effectiveness, despite having worked fine for a few years. Once this happens, patients will need two or more medications to regulate their blood sugar levels.
Indeed, medications don’t lose their effectiveness. Every pill must pass strict quality control before it can be put on the market. The real reason behind this decreased effectiveness is that the β cells begin to fail and no longer keep pace with insulin needs.
Imagine a tug of war in which the insulin-producing pancreatic β cells team up with diabetic medications to fight insulin resistance in a nip and tuck situation. Although it indicates the blood sugar is being controlled at the moment, the combined force of β cells and medications will inevitably become weaker, and the blood sugar level elevates. The reason is that our β cells are constantly damaged by the Endoplasmic Reticulum (ER) Stress and Oxidative Stress – the two leading causes of β cells death (3, 4). As you may expect over time, the combined force of our β cells and medications diminishes, and to maintain the same level of blood sugar, the patient would need stronger medications as the number of β cells go down.
Maintaining Healthy beta Cell Function Is the Key
In most cases, pre-diabetes is caused by insulin resistance—a condition where our bodies do not respond well to the effect of insulin. This means it takes more insulin to maintain normal blood sugar levels, and so our pancreatic β cells are forced to make more insulin (a phenomena called hyperinsulinemia). As a result, even after insulin resistance has developed, hyperinsulinemia can help our postprandial and fasting blood sugar levels remain normal for up to five years before the onset of Type-2 diabetes (5). Hence, healthy β cell function can prevent hyperglycemia even if insulin resistance exists. However, the downside is that overworking results in ER and Oxidative stress, which consequently kill β cells (we will explain how below).
Indeed, the high blood sugar caused by insulin resistance appears only after 50% or more of β cells have lost. This means the surviving β cells have to double or even triple their work to compensate the loss. Surprisingly, after a diagnosis of Type-2 diabetes, insulin resistance no longer accounts for rising blood sugar levels, or at least it isn’t playing a major role (6). Instead, due to overworking, the β cells will continuously be damaged by ER and Oxidative stress at a faster pace. They will no longer be able to produce enough insulin, resulting in something called “beta burnout.” Again, the “combined force” will become weaker.
How Does Overworking Damage β Cells?
Eating too much sugar (and other carbohydrates) and insulin resistance are two main factors that cause β burnout. In the past, we did not know how overworking kills pancreatic β cells. Thanks to diligent scientists, now we understand that overworking induces ER stress and oxidative stress, which subsequently kill β cells (3, 4). Unfortunately, current medications have not been able to resolve these two issues.
ER is a factory in the β cells, which prepares newly synthesized insulin precursor (as proinsulin) to work. However, even under normal physiological conditions, approximately 20% of newly synthesized proinsulin aren’t able to finish this process, and they become misfolded or defective (7). The accumulation of misfolded (defective) proinsulin in the β cells is called “ER stress”. Just like a company shuts down a production line that produces too many defects, our bodies tell β cells to kill themselves (apoptosis) when there’s too much defective proinsulin. Consuming a high amount of carbohydrates makes the situation worse. As more insulin is made, more defective proinsulin is simultaneously produced. The consequent β cell death then called glucotoxicity.
Oxidative stress is caused by oxidative species (and partly by the ER stress) located within the β cells. These reactive oxygen species attack the β cells by oxidizing almost everything, including the DNA of the β cells. Once the DNA is damaged, β cells die. Unfortunately, β cells are extremely sensitive to oxidative stress.
Both the above factors combined induce apoptosis and rapidly speed up β cell mass destruction, resulting in lowered β cell function.
Endoplasmic Reticulum Associated Degradation
Endoplasmic Reticulum Associated Degradation (ERAD) is a cellular physiological process which specifically targets and removes harmful misfolded proinsulin from β cells. Since ERAD can prevent misfolded proinsulin from accumulating in the ER, it reduces ER stress and indirectly, the oxidative stress. Hence, enhancing ERAD has been considered a therapeutic target for many degenerative diseases (8).
Restoring β Cell Function
For those of you looking to prevent, or even reverse, Type-2 Diabetes, restoring beta cell homeostasis is essential. After all, the stronger your β cells are, the less medication you’ll need to maintain the same level of blood sugar. In addition to the regular medications, you’ll need useful methods such as enhancing your ERAD and removing free radicals and oxidative species from the β cells. By doing this, you are getting what you have been missing from currently available treatments. This means that your β cells death rates will slow down dramatically, while the body is generating new and healthy β cells (9).
Finally, we will talk to you about what you can do to better manage diabetes. These include:
Medications –They all directly help maintain your blood sugar level. As prolonged hyperglycemia causes serious complications, prescribed medications are essential.
Synergistic supplements that reduce ER and Oxidative Stress – As β cells homeostasis has not been addressed by regular diabetic medicines, taking supplements that help reduce the ER stress and oxidative stress should be another smart approach for people to manage their diabetes.
Healthy lifestyle – When it comes to treating diabetes, nothing is more important than leading a healthy lifestyle. Don’t eat or drink sugary foods, cut out excessive junk food, get plenty of exercise, drink water, and try to manage your weight and maintain it at a healthy level.