The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3–36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3–36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3–36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

The importance of achieving tight glycemic control, usually assessed by glycated hemoglobin (HbA1c), for both the prevention and delay in the progression of diabetes-related microvascular complications, is established, and the American Diabetes Association/European Association for the Study of Diabetes joint committee has recommended an HbA1c <7% as the goal in patients with type 2 diabetes (1). The relative contributions of pre- and postprandial glycemia to HbA1c have been clarified during the last decade following the seminal report by Monnier et al. (2) indicating that in type 2 diabetes, postprandial glycemic excursions account for about 70% of variability when HbA1c is <7.3%, while the contribution of “fasting” glycemia is greater in less well-controlled patients. Subsequent studies have confirmed the predominance of postprandial glycemia in determining overall glycemic control in “well-controlled” type 2 diabetic patients managed by oral hypoglycemic agents or basal insulin (3). The importance of postprandial glycemia to overall glycemic control is not surprising considering that 1 ) humans in modern societies spend only about 3 or 4 h before breakfast in a truly fasting state because in health, gastric emptying of meals occurs at an overall rate of 1–4 kcal/min (4), and 2 ) postprandial hyperglycemia occurs frequently in diabetes (1). The relevance of postprandial glycemia is further increased by the recognition that it may represent an independent risk factor for adverse cardiovascular outcomes in both diabetic and nondiabetic populations (5). The determinants of postprandial glycemia include preprandial glycemic levels, meal composition, gastric emptying, insulin secretion, small intestinal glucose absorption, and hepatic and peripheral glucose metabolism. Furthermore, the relative contribution of each of these factors may vary over time during the postprandial state. Nevertheless, both the rate of gastric emptying and the secretion and action of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide …

This article reviews the impact of ageing on the gastrointestinal tract, including effects on the absorption of nutrients and drugs and the gastrointestinal tract defence system against ingested pathogens. Recent publications support earlier observations of an age-related selective decline in gut function including changes in taste, oesophageal sphincter motility, gastric emptying, and neurons of the myenteric plexus related to gut transit which may impact the nutritional status. Ageing is also associated with structural and functional mucosal defence defects, diminished abilities to generate protective immunity, and increased incidence of inflammation and oxidative stress. A number of gastrointestinal disorders occur more frequently in the elderly population. Alterations in gut function with ageing have particular implications for oesophageal, gastric, and colonic motility. Older individuals are particularly susceptible to malnutrition, postprandial hypotension, dysphagia, constipation, and faecal incontinence. Decrease in the number of nerve cells of the myenteric plexus that impact digestive absorption and the surface area of the small intestine because of degeneration of villi may lead to blunted absorption of nutrients. Impairment of the intestinal immune system as a result of ageing, including the mucosal layer of the gastrointestinal tract, appears to be a significant contributor to the age-related increase in the incidence and severity of infections.