Impact of gastric emptying and small intestinal carbohydrate absorption on glycemia in health and diabetes: therapeutic implications

Gastric emptying, which exhibits a substantial inter-, but much lesser intraindividual, variation in health and is frequently disordered (particularly delayed) in diabetes, is now appreciated to be a major determinant of postprandial glycemia. The incretin hormones glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are secreted in the proximal and distal small intestine respectively in response to nutrients. GLP-1, together with peptide tyrosine-tyrosine (PYY), stimulates potent negative feedback on gastric emptying. Modulation of gastric emptying, through dietary, pharmacologic and surgical therapies has been utilized in current clinical practice for the treatment of hyperglycemia, particularly relating to type 2 diabetes. We review the complex, interdependent, relationships between gastric emptying, small intestinal transit, glucose absorption, neurohormonal regulatory responses and postprandial glycemia. We discuss how this has informed fundamental advances in the understanding and rational management of obesity, stress hyperglycemia, type 1, 2 and gestational diabetes and provide recommendations for research priorities that have the potential to impact on practice. We also discuss the frequent complication of abnormally delayed gastric emptying (gastroparesis) in both type 1 and type 2 diabetes, the implications for management of diabetes and the impact of treatment on gastric emptying. With the increasing recognition of the importance of gastric emptying in the management of conditions associated with disordered glucose metabolism, and the advent and increasing use of GLP-1 receptor agonists, an improved definition of the interactions between gastrointestinal motility (gastric emptying and small intestinal transit) and enteropancreatic hormonal responses is essential.