Diabetes: is high blood sugar the consequence instead of the cause of the disease?
Those suffering from type II diabetes also have high risks of heart attack and stroke, massive circulatory disorders in the legs and serious damage to the eyes, nerves and kidneys. Most of the time, doctors in this context do not “only” speak of risks, but late effects of “diabetes”. The cause is an increased blood sugar level, which arises when the body cells no longer respond to the blood-sugar-lowering hormone insulin. But new scientific work suggests that type II diabetes could have other molecular causes that are independent of insulin and sugar.
The level of blood sugar correlates with the extent of the diabetic symptoms. If a very high blood sugar level is reduced with medication, the rate of heart attacks and strokes decreases, and the blood circulation also improves.
"But that only applies to a certain point," says Peter Nawroth, medical director of the Clinic for Endocrinology, Metabolism and Clinical Chemistry at Heidelberg University Hospital. “Large clinical studies in recent years have shown that even though medication has been able to lower blood sugar below the diabetes threshold, many of the patients still developed typical diabetes damage to the nerves and kidneys. This suggests that Type 2 diabetes could actually have other molecular causes that are independent of insulin and sugar. ”
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Peter Nawroth and Aurelio Teleman, who heads the Cancer and Metabolism-Related Signaling department at the German Cancer Research Center (DKFZ), knew from the observation that Type 2 diabetics have a high level of the sugar breakdown product methylglyoxal (MG). So far, doctors thought this was a consequence of the increased blood sugar level. According to the teaching opinion, MG can damage proteins and is then jointly responsible for the damage typical for diabetes. However, the metabolism experts Teleman and Nawroth now question this sequence of events given their current results.
If rats are given MG through food, they develop many of the typical signs of diabetes, including insulin resistance. The Heidelberg researchers now wanted to examine how a permanently elevated MG level affects the organism. They chose fruit flies as a model for this. “Bow tie and human are not particularly closely related. But energy metabolism developed very early in evolution, so the results are very meaningful and can usually be transferred to mammals and humans, ”explains Teleman.
The researchers genetically switched off the MG-degrading enzyme in the flies. As a result, the MG sugar breakdown product accumulated in the animals. The flies developed insulin resistance early on. They later became obese and their sugar levels derailed as they grew older.
“Obviously, simply increasing the MG level is enough to trigger insulin resistance and diabetes-specific metabolic disorders,” summarizes Aurelio Teleman. "This is a clear indication that MG is not the result, but rather the cause of type 2 diabetes."
This observation in turn raises the question of the possible cause of an increased MG level. For example, obese people who are not diabetic also have an elevated MG level. “We don't know why. This is an important aspect of our future research, ”says Nawroth. Aurelio Teleman adds: “The production and the breakdown of MG are influenced by numerous metabolic processes that we do not yet know and need to understand better. In addition, we now urgently want to investigate in mice which clinical symptoms are caused by a permanently elevated MG level in the mammal. (sb)
Original publication: Alexandra Moraru, Janica Wiederstein, Daniel Pfaff, Thomas Fleming, Aubry K. Miller, Peter Nawroth and Aurelio A. Teleman: Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes-Cell Metabolism 2018, DOI: 10.1016 / j .cmet2018.02003
* A measured value for the level of blood sugar is the HbA1c value. This is the proportion of the blood pigment hemoglobin that has bound sugar. In healthy people it is less than six percent.