The new test will help detect pre-diabetes

Assessing the level of one of the enzymes in red blood cells can help detect pre-diabetes and thus help prevent type 2 diabetes and its complications, according to a study in the Diabetes journal.

Pre-diabetes, which is a high-risk state of developing type 2 diabetes, is characterized by a decreased ability of the body to metabolize glucose. Currently, it is assessed on the basis of one of two tests – either by measuring the level of fasting glucose or by performing the oral glucose load test, in which the patient is given 75 g of glucose dissolved in 300 ml of water, on an empty stomach. In the first case, pre-diabetes is diagnosed when fasting glucose is elevated – i.e. 100-125 mg per 100 ml of blood – but not sufficient for a diagnosis of diabetes. In the second test, patients with pre-diabetes reach levels of 140 to 199 mg of glucose per 100 ml of blood two hours after taking this sugar.

Early detection of pre-diabetes allows for quick lifestyle changes – such as a lower-calorie diet richer in vegetables and fruits, or increased exercise – that can prevent the development of type 2 diabetes and its serious complications without the need for medication. The most serious complications of diabetes include cardiovascular disease, kidney failure, eye damage, and diabetic foot.

The latest research by scientists from the Johns Hopkins School of Medicine may help develop a simple, routine test that will further identify people at risk of type 2 diabetes.

Researchers have observed that in both people with diabetes and those with prediabetes, there is a 2,3-fold increase in the levels of an enzyme called beta-N-acetylglucosaminidase in red blood cells (erythrocytes).

The role of this enzyme is to detach sugar residues in the form of N-acetyl-glucosamine from protein molecules. The joining of these residues by another enzyme (O-GlcNAc transferase) in the so-called the O-glycosylation process is a common process of protein modification that changes their function. Glycosylation depends on many environmental factors, such as stress and diet. It is known, for example, that large amounts of glucose and fats in food intensify this process.

When the number of sugar residues attached to proteins exceeds a certain level, as is the case, for example, in patients with poorly controlled diabetes (who have persistently high blood glucose levels), this phenomenon becomes harmful to cells. Then the activity of beta-N-acetylglucosaminidase, which cuts off sugar residues, increases significantly.

To find out whether the same applies to people at risk of type 2 diabetes, researchers took blood from 36 people with normal glucose metabolism, from 13 people with pre-diabetes and 53 people with diabetes, as assessed by their fasting glucose levels.

Then, they assessed the level of glycosylation of proteins present in their red blood cells and measured the content of beta-N-acetylglucosaminidase.

It turned out that the level of protein glycosylation in these cells was very high in both people with poorly controlled diabetes and prediabetes. Researchers also found high levels of beta-N-acetylglucosaminidase in both groups.

When I checked the level of this enzyme and discovered how dramatically its concentration differs in the blood cells of healthy people and those of people with pre-diabetes, I thought that I made a mistake. Then I repeated the test five times as long as I could trust myself – comments Kyoungsook Park participating in the research.

As research co-author Dr. Gerald Hart speculates, since attaching too many sugar residues to proteins is not beneficial, the blood cells of diabetic patients as well as people with pre-diabetes respond to the rise in sugar levels by increasing the production of an enzyme that cuts these residues off.

According to the researchers, their work may in the future result in an easy test for the early identification of people with pre-diabetes. However, before that happens, the latest results in large clinical trials must be verified, emphasize the authors of the study. (PAP)

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