New research into diabetes – Insulin increases before cells develop resistance
Researchers at the University of Gothenburg, Sweden, recently presented results that could change our basic view of how type-2 diabetes occurs. Their study indicates that the free fatty acids (AGL) in the blood trigger the release of insulin even at a normal level of blood sugar, without obvious uncompensated insulin resistance in fat cells. Moreover, researchers demonstrate the connection with obesity: the amount of AGL depends largely on how many extra pounds of adipose tissue a person has, but also on how the body adapts to increased adiposity.
On a global scale, extensive research is underway to clarify exactly what happens in the body as type 2 diabetes progresses and why obesity is such a high risk factor for the disease. For nearly 50 years, diabetes researchers have been discussing which of the two first appears – insulin resistance or high insulin levels? The dominant hypothesis has long been that the pancreas intensifies its insulin production because the cells have already become resistant to insulin and their blood sugar rises. However, the results now published in the journal EBioMedicine support the opposite idea: that insulin is the one that grows first.
The study indicates that high levels of AGL in the blood after fasting overnight increase insulin production in the morning. Free fatty acids have long been part of the main research equation for type 2 diabetes, but now we are offered another role, in the progression of the disease.
For the study, the researchers compared fat metabolism (fat storage) for 27 carefully selected subjects (9 with normal weight, 9 with obesity and normal blood sugar, and 9 with both obesity and advanced type 2 diabetes). For several days, they were subjected to extensive examinations in which samples were taken under different conditions. The researchers analyzed the metabolism and expression of genes in the participants’ subcutaneous fat and the levels of blood sugar, insulin and AGL in their blood. AGLs appear to trigger insulin production.
People who were obese, but without diabetes, have been shown to have the same normal blood sugar levels as healthy people with normal weight.
“Interestingly, obese non-diabetic subjects had high levels of both free fatty acids and insulin in their blood, and these levels were similar to, or higher than the levels we were able to measure in the blood of obese participants and type 2 diabetes, ”says Emanuel Fryk, a general practitioner and doctoral student at the Sahlgrenska Academy, University of Gothenburg, who is one of the first authors of the study.
In collaboration with researchers at Uppsala University, he observed the same pattern in a population study based on blood samples taken from 500 people after an overnight fast.
“The fact that we have also identified a link between free fatty acids and insulin suggests that fatty acids are connected to the release of insulin and contribute to increased insulin production on an empty stomach, when blood sugar has not risen,” says Fryk, who points out that this finding must be confirmed with more research.
Free fatty acids are found naturally in the bloodstream and, like glycerol, are a product of fat metabolism in the body. In the study subjects, the amount of glycerol released was found to be generally the same per kilogram of body fat, regardless of their normal weight, or if they had type 2 diabetes or obesity.
“Our hypothesis is that free fatty acids increase in the blood, because adipose tissue can no longer store excess energy. We believe, in this case, that it could be an early sign of type 2 diabetes. If our results are confirmed when using other research methods, there may be a chance that certain fatty acids may be converted to biomarkers. But it’s still there, “says Fryk.
Although diabetes is one of the most common diseases, there are an extremely large number of undetected cases because many people with type 2 diabetes do not yet know that they are ill. Diabetics are at increased risk for a number of serious conditions, such as cardiovascular disease (which can lead to heart attacks and strokes).
“There are many factors that contribute to the progression of type 2 diabetes, but our lifestyle is the one that has, in absolute terms, the greatest impact for most people. Our study provides another argument that the most important thing you can do to slow the progression of diabetes is to change your lifestyle early in the progression of the disease, before your blood sugar rises,” says Fryk.
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