Study: Insulin Levels Rise Before Cells Develop Resistance


Study findings contradict a long-standing hypothesis that held the pancreas increases insulin production because the cells have already become insulin-resistant and blood sugar rises as a result.

New diabetes research suggests that free fatty acids (FFAs) in the blood trigger insulin release even at normal blood-sugar levels. This finding could have implications for diabetes treatments and is linked to obesity, because the amount of FFAs is largely dependent on excess adipose tissue.

Researchers from the University of Gothenburg are working to clarify exactly what happens in the body as type 2 diabetes progresses and why obesity is such a major risk factor for the disease. The investigators described it as a “chicken-or-egg question” between insulin resistance or elevated insulin levels. The dominant hypothesis has been that the pancreas increases insulin production because the cells have already become insulin-resistant, causing blood sugar to rise as a result.

The new study findings oppose that idea, suggesting that insulin increases first. Investigators compared metabolism in adipose tissue among 27 research subjects, 9 of whom had normal weight, 9 who were obese but had normal blood sugar, and 9 with both obesity and progressed type 2 diabetes. For several days, the participants underwent extensive examinations and researchers analyzed metabolism and gene expression in the participants’ subcutaneous fat, and the levels of blood sugar, insulin, and FFAs in their blood.

According to their findings, the participants with obesity but not diabetes had the same, normal blood-sugar levels as the healthy individuals of normal weight.

“Interestingly, the non-diabetes with obesity had elevated levels of both free fatty acids and insulin in their blood, and those levels were similar to or higher than the levels we were able to measure in blood from the participants with both obesity and type 2 diabetes,” said first author Emanuel Fryk, a doctoral student at Sahlgrenska Academy, University of Gothenburg, in the press release.

Furthermore, Fryk and his colleagues found that high FFA levels in the blood after overnight fasting raised insulin production in the morning. This could suggest that FFAs have a role in the progression of type 2 diabetes, according to the study authors.

“The fact that we saw a link between free fatty acids and insulin there, too, suggests that the fatty acids are connected with the insulin release, and contribute to increased insulin production on an empty stomach, when blood sugar hasn’t risen,” Fryk said in the press release.

As one of the most common diseases and with many undetected cases, the study authors noted that diabetics are at a significantly increased risk for serious conditions such as cardiovascular disease. Lifestyle changes such as a healthier diet and increased physical activity are essential to minimizing these risks or even preventing the development of diabetes altogether.

“There are many factors that contribute to the progression of type 2 diabetes, but it’s our lifestyle that has, in absolute terms, the largest impact for most people,” Fryk said in the press release. “Our study provides another argument that the most important thing you can do to slow diabetes progression is to change your lifestyle early in the progression of the disease, before blood glucose is elevated.”


Insulin rises before cells develop resistance, new diabetes research implies [news release]. University of Gothenburg; March 9, 2021. Accessed March 18, 2021.

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