The GI quantifies the widely variable increases in blood glucose after ingestion of different carbohydrates, with the concept that larger increases cause the development of cardiometabolic diseases.

The metabolic effects of sugars depend primarily on the intestinal hormones GIP and GLP-1, which release insulin and regulate metabolic responses such as insulin resistance, adipose tissue subclinical inflammation, hepatic fat accumulation, and postprandial vascular responses.

The GIP-releasing K cells are located in the proximal small intestine, while GLP-1 is released by more distally located L cells. Their responses to sugars depend on the site of resorption.

GIP has mostly unfavorable, while GLP-1 has beneficial, metabolic and cardiovascular properties. The release of GIP therefore appears to be a primary mediator of the deleterious effects of sugars with a high glycemic index in metabolism.