The most typical alterations in people with type 2 diabetes are insufficient secretion of insulin and reduced sensitivity to insulin in different organs. To examine what happens in these organs when type 2 diabetes develops, the researchers in the current study have looked at proteins both in the cell islets in the pancreas where insulin is produced, and in the main tissues that insulin acts on, namely the liver, skeletal muscle, fat and blood.

The researchers compared proteins in samples from people with type 2 diabetes, prediabetes, i.e. a stage before fully developed type 2 diabetes, and without any diabetes. The results showed far more disturbances in metabolic pathways than previously known. There was also a correlation between the alterations and the different stages of the disease.

“We detected many protein levels that were either higher or lower than normal in tissues from people at different stages of disease. People with prediabetes displayed major alterations that are associated with inflammation, coagulation and the immune system in the pancreatic islets. In fully developed type 2 diabetes there were more widespread abnormalities, for example in lipid and glucose metabolism and in energy production in the liver, muscle and fat,” says the senior study author.

The study builds on tissue samples collected from donors at different stages of disease and healthy individuals.

Using novel techniques, the researchers could quantify thousands of proteins from each organ and therefore obtain a view of the metabolism that has not been possible before.

In summary, the findings show a highly disturbed metabolism in different pathways in examined organs and at different stages of disease. The data points to new potentially causal mechanisms of the disease, which can be further investigated in the search for new ways of preventing or treating type 2 diabetes.

“Our results may also support the development of simple tests that can identify people at high risk of diabetes and its complications, and also guide which type of intervention is best for the individual,” says another author.

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00318-4

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