Why you can prevent type 2 diabetes and your grandfather cannot.

Probably everyone has heard of it: Diabetes mellitus. Although people can live with this disease, the number of persons having diabetes is increasing. Around the world there are approximately 115 million patients suffering from diabetes. In 2010 approximately 25 million Americans were affected, whereas in 2012 already 29 million Americans were affected. This massive increase makes diabetes a serious health issue not only in America, but worldwide. There are now indications that in early stages of type 2 diabetes in some cases diabetes can be reversed.

Normally, when you eat carbohydrates, these are broken down into glucose. The cells of the small intestine absorb the glucose and transport it to the blood. This leads to an increase in blood glucose levels. To prevent too high blood glucose levels, the pancreas secretes insulin. Insulin tells the cells of the liver and muscles via the insulin receptor to take up glucose and burn it or store it in the form of glycogen. For example, glycogen functions as fuel storage in muscles when you need to take a sprint. In this way, the blood glucose levels decrease and fuel storage in the cell is made.

Diabetes consists of two subtypes, most commonly known as: juvenile diabetes (type 1 diabetes) and adult-onset diabetes (type 2 diabetes). In both types of diabetics, insulin does not properly tell the cells what to do, leading to a misbalance in blood glucose levels. This is called insulin resistance and can lead to damage to tissues, seizures, coma, and even death. However, the cause of these two types of diabetes leading to insulin resistance is different. In type 1 diabetes the pancreas cannot make insulin. In type 2 diabetes the insulin receptor does not function properly, which is needed to activate the uptake, burning, and storage of glucose (Figure 1).

Figure 1: The difference between normal regulation by insulin, type 1 diabetes, and type 2 diabetes 

(see text).

Type 2 diabetes is the most common form of diabetes and occurs in 95% of all diabetics. That is why we further focus here on type 2 diabetes. Type 2 diabetics cannot activate the receptor to stimulate lowering of the blood glucose levels. Insulin normally tells the cells to take up, burn, and store glucose by binding and activating the insulin receptor at the cell surface. The insulin receptor passes the signal to other proteins that activate these processes. When the insulin receptor does not function properly, at first, extra insulin is made by the pancreas to compensate. Over time, the pancreas cannot make large amounts of insulin anymore and becomes exhausted. The blood glucose levels are then high and stay high.

When you think of type 2 diabetes, people mostly think of obesitas and elderly. It indeed can roughly be said that these two groups form the majority of type 2 diabetes patients. Both groups differ in cause for the malfunctioning of the insulin receptor in type 2 diabetics.

Obese people are characteristic for their high percentage of body fat. This means that they have too much of different types of fats. Glycosphingolipids, a type of fat, is highly present in obese people. These glycosphingolipids lie next to receptors, like insulin receptors, at the cell surface. These molecules can indirectly block the insulin receptor, by physically blocking the receptor. This means that it is harder for insulin to bind and activate the insulin receptor to lower blood glucose levels (Figure 2).

Elderly, on the contrary, do not have a physical blocking of the receptor. They have accumulated mutations in the DNA, our genetic material. This means that some elderly could have accumulated mutations in the insulin receptor. These mutations in the insulin receptor result in malfunctioning of the insulin receptor, because the receptor is not or not properly activated (Figure 2).

Figure 2: The difference between normal regulation of insulin, type 2 diabetes with obesitas, and type 2 diabetes in elderly (see text).

Type 2 diabetes, due to wear and tear of age, cannot be cured or repaired. However, there are indications that in early stages of diabetes, due to obesity, can be reversed and thus worse can be prevented. This can either happen by losing weight or iminosugar treatment. With losing weight, you mostly lose fat tissue and lower the amount of multiple types of fat. Iminosugar is a molecule that inhibits the production of glycosphingolipids. So, both ways are based on reducing the amount of glycosphingolipids. Prevention is always better than treatment. The wear and tear of age cannot be prevented, while obesitas can. That is why you can prevent diabetes and your grandfather cannot.

By Larissa van Ek 07-10-2015