Gastric emptying is abnormally delayed in ~40% of patients with longstanding type 1 or type 2 diabetes and may occasionally be accelerated – perhaps particularly in ‘early’ type 2 diabetes1. Gastric emptying should ideally be measured using scintigraphy, or alternatively, with a stable isotope breath test and exhibits a large inter-, but much smaller intra-individual, variation. The pathogenesis of diabetic gastroparesis is complex and multifactorial with abnormalities in multiple, interacting cell types, including decreased numbers of interstitial cells of Cajal, which underlie gastrointestinal contractile activity, deficiencies in inhibitory neurotransmission, reduced extrinsic autonomic neurons, muscle fibrosis and abnormalities in the function of immune cells. Gastric emptying is slower during acute hyperglycaemia when compared to euglycaemia, and accelerated during insulin-induced hypoglycaemia. Gastrointestinal symptoms occur frequently in type 1 and 2 diabetes and impact negatively on quality of life, but the relationship between symptoms and disordered gastric emptying is weak.
Gastric emptying is a major determinant of postprandial glycaemia in health and diabetes; the relationship of glycaemia (and GLP-1 secretion) with small intestinal glucose delivery is non-linear. Exogenous GLP-1 slows gastric emptying and, thereby, glucose absorption. Moreover, inhibition of gastric emptying by acute administration of exogenous GLP-1 appears to outweigh its direct insulinotropic effects, so that the reduction in postprandial glycaemia is related to the magnitude of slowing of gastric emptying and greater when gastric emptying is relatively more rapid. There may be tachyphylaxis to the slowing of gastric emptying by exogenous GLP-1. The reduction in postprandial glycaemia and impact on postprandial insulin induced by GLP-1 analogues are also related to slowing of gastric emptying. The slowing of gastric emptying by liraglutide and exenatide LAR (and presumably other ‘long-acting’ GLP-1 analogues), but not exenatide bd or lixisenatide (‘short-acting’), appears to diminish with time. Baseline gastric emptying is likely to be relevant to the choice of GLP-1 agonist in type 2 patients; ‘short-acting’ drugs may be optimally combined with ‘long-acting’ insulin to target postprandial glucose preferentially.