Diabetes type II High blood sugar does not cause but the consequence?

Diabetes: High blood sugar is the consequence of the disease?

Those suffering from type II diabetes also have high risks of heart attack and stroke, massive circulatory disorders of the legs and severe damage to the eyes, nerves and kidneys. In most cases, physicians do not speak "only" of risks in this context, but the long-term consequences of "diabetes". The cause is an elevated blood sugar level, which develops when the body cells no longer respond to the blood sugar-lowering hormone insulin. However, recent scientific work indicates that type II diabetes may have other molecular causes that are independent of insulin and sugar.

The level of blood sugar correlates with the extent of diabetic symptoms. If a very high blood sugar level is lowered with medication, the rate of infarctions and strokes goes back, and the blood circulation also improves.

The energy metabolism can be well researched on flies. Here the fly's body fat is made visible by the fluorescent protein GFP ("green fluorescent protein"). Source: Teleman / DKFZ

"But that only applies to a certain point," says Peter Nawroth, medical director of the Department of Endocrinology, Metabolism and Clinical Chemistry at Heidelberg University Hospital. "Large clinical trials in recent years have shown that although blood sugar with medications could be lowered below the diabetes threshold, many of the patients still developed typical diabetes damage to the nerves and kidneys. This suggests that type 2 diabetes may actually have other molecular causes that are independent of insulin and sugar. "

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Peter Nawroth and Aurelio Teleman, who heads the Department of Cancer and Metabolism-associated Signal Transduction at the German Cancer Research Center (DKFZ), were aware of the observation that Type 2 diabetics have a high level of the sugar-degrading product methylglyoxal (MG). So far, physicians have considered this to be a consequence of the high blood sugar level. MG, according to the doctrine, can damage proteins and is then jointly responsible for the diabetic damages. This sequence of events doubt the metabolism experts Teleman and Nawroth now, however, given their current results.

Obtaining rats via the feed MG, they develop many of the typical diabetes signs, including insulin resistance. The Heidelberg researchers now wanted to examine how a permanently elevated MG level affects the organism. As a model, they chose fruit flies. "Fly and man are not very closely related. But the energy metabolism has evolved very early in evolution, so the results are quite meaningful and can usually be applied to mammals and humans, "explains Teleman.

The researchers genetically switched off the MG-degrading enzyme in the flies. As a result, the sugar degradation product MG accumulated in the animals. The flies developed early insulin resistance. Later they became obese, then in older age derail their sugar levels.

"It is obviously enough simply to raise the MG level to trigger insulin resistance and diabetes-typical metabolic lapses," says Aurelio Teleman. "This is a clear indication that MG is not the result, but rather the cause of type 2 diabetes."

This observation again raises the question of the possible cause of an increased MG level. For example, even obese people who are not diabetic have an elevated MG level. "We do not know why. That's an important aspect of our future research, "says Nawroth. Aurelio Teleman adds: "The production as well as the degradation 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 cause a permanently increased 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 measure of the level of blood sugar is the HbA1c value. That is the proportion of the blood pigment hemoglobin that has bound sugar. He lies in the healthy at less than six percent.