Consuming fat before carbohydrates reduces post-meal blood glucose

In treating diabetes, post-meal elevation of glucose levels is an important therapeutic target. Existing clinical studies indicate that eating vegetables, protein, or fat before carbohydrates can moderate a post-meal rise in blood glucose, pointing to the potential of meal-sequencing as a simple and sustainable dietary strategy.

Scientists have often attributed the benefits of this strategy to slower gastric emptying and greater secretion of incretin hormones, such as GLP-1, that decrease blood glucose levels. However, the roles that gut and pancreatic hormones, as well as neural pathways, play in this process have remained less understood. This motivated an international team of researchers to investigate how the timing of fat intake influences glucose levels, hormone secretion, and gastric emptying.

Our group has long been interested in practical dietary approaches that people can continue in everyday life. Meal-sequencing is appealing because it merely changes how a meal is eaten rather than requiring people to avoid entire food groups."

Daisuke Yabe, corresponding author, Kyoto University

The team used mice in their investigation, first having the subjects fast overnight. The mice were then divided into three groups, with one receiving water followed by glucose, another olive oil followed by glucose 15 minutes later, and the final group glucose followed by olive oil 15 minutes later. After feeding the mice accordingly, the researchers measured blood glucose, plasma insulin, glucagon, GIP, and GLP-1 levels. The team also gave the mice acetaminophen and estimated gastric emptying by measuring blood acetaminophen levels after oral administration.

The scientists then repeated this experiment in a few other groups of mice, including those with type 2 diabetes and those lacking the GLP-1 receptor. Additional experiments also included inhibiting glucagon or GLP-1 signaling, performing bilateral sub-diaphragmatic vagus nerve ligation, and testing other dietary fats to confirm that responses were not specific to olive oil.

These test results revealed that giving mice olive oil before rather than after glucose reduced an early rise in blood glucose levels and slowed gastric emptying. Consuming fats before glucose also increased early secretion of glucagon, GIP, and GLP-1, and all of these beneficial effects were retained in mice with type 2 diabetes and severe insulin deficiency.

The researchers observed that inhibiting either glucagon or GLP-1 signaling alone did not attenuate the glucose-lowering effect of the olive oil preload, whereas combined inhibition did, and that glucagon signaling, which is best known for raising blood glucose, also contributes to the glucose-lowering response of an olive oil preload in mice. The experiments involving vagus nerve ligation also suggested that vagal pathways contribute to these responses.

By providing a physiological explanation for the influence of nutrient order on post-meal glucose levels, this study strengthens the rationale for testing practical meal-sequencing strategies in people with and without diabetes.

"Our findings suggest that the order in which nutrients reach the gut can engage a coordinated hormone-nerve response that changes how quickly the stomach delivers glucose to the intestine," says Yabe.