Diabetes: Olive Oil Before Carbohydrates Reduced the Rise in Blood Glucose

It has long been known that eating vegetables, protein, or fat before carbohydrates can reduce the post-meal blood sugar spike. This makes the order in which foods are consumed a simple and sustainable dietary strategy. However, the roles of intestinal and pancreatic hormones, as well as neural pathways, in this process have not been fully understood.

The researchers used mice that had been fasted overnight. They divided the animals into three groups: one received water followed by glucose; the second received olive oil followed by glucose 15 minutes later; and the third received glucose followed by olive oil 15 minutes later.

After feeding, the scientists measured blood levels of glucose, insulin, glucagon, GIP, and GLP-1. To assess how quickly food left the stomach, they gave the mice acetaminophen, a common painkiller also known as paracetamol. The faster it appeared in the bloodstream, the faster the stomach was emptying.

The experiment was then repeated in mice with type 2 diabetes and in mice lacking the GLP-1 receptor. The researchers also blocked glucagon or GLP-1 signaling pathways, performed bilateral subdiaphragmatic vagotomy — cutting the vagus nerve below the diaphragm — and tested other dietary fats.

Olive oil consumed before glucose, rather than after it, reduced the early rise in blood glucose and slowed gastric emptying. Consuming fat before glucose also increased the early secretion of glucagon, GIP, and GLP-1. These effects persisted in mice with type 2 diabetes and severe insulin deficiency.

Blocking either glucagon or GLP-1 alone did not weaken olive oil's blood-glucose-lowering effect; only the combined inhibition did so. The researchers also found that glucagon signaling — despite glucagon being primarily known for raising blood glucose — contributed to the reduction in glucose levels following fat intake. Experiments involving vagotomy pointed to the involvement of vagal pathways, the nerve fibers connecting the brain with the digestive system.

The study provides a physiological explanation for how the order in which nutrients are consumed affects post-meal blood glucose levels. The findings strengthen the rationale for testing practical food-sequencing strategies in people with and without diabetes.

“Our results show that the order in which nutrients reach the intestine can trigger a coordinated hormonal and neural response that changes the rate at which glucose moves from the stomach into the intestine,” said study author Daisuke Yabe of Kyoto University.