Relationships Between Gastric Emptying, Postprandial Glycemia, and Incretin Hormones
TL;DR: 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.
Abstract: 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 …
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Journal Article•
TL;DR: The position statement emphasizes that all patients should accept diabetes education aimed at hyperglycemia control and sets up the target of control of hyper glycemia flexibly according to natural course of disease, pathological condition,accompanied diseases, age, and life expectancy of the patients.
Abstract: " Management of Hyperglycemia in Type 2Diabetes : A Patient-Centered Approach — Position Statement of the American Diabetes Association(ADA) and the European Association for the Study of Diabetes(EASD)" was published in Diabetes Care and Diabetology in April this year.It,first,emphasizes the control of hyperglycemia in the treatment of T2DM;second,sets up the target of control of hyperglycemia flexibly according to natural course of disease,pathological condition,accompanied diseases,age,and life expectancy of the patients;third,once again emphasizes metformin for first-line use;fourth,more specifically discusses the applications,therapeutic effects,and advantages and disadvantages of various insulin preparations,GLP-1,DPP-4inhibitors and GLP-1receptor agonists;fifth,states the individualization treatment;and sixth,underlines that all patients should accept diabetes education aimed at hyperglycemia control.
405 citations
TL;DR: 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).
Abstract: 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.
387 citations
TL;DR: The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina, which plays a major role in many metabolic functions.
Abstract: The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.
244 citations
TL;DR: Gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia, so clinical implementation of incretin-based therapies for the management of T2DM, in part by slowing gastric empties, is widespread.
Abstract: The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia--gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.
210 citations
TL;DR: The intestine adapts differently to RYGB vs VSG, which increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observed improvements in glycemia.
165 citations
References
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TL;DR: Properties of currently available glucose-lowering agents that may guide treatment choice in individual patients with type 2 diabetes mellitus are explored.
Abstract: Erratum to: DiabetologiaDOI 10.1007/s00125-012-2534-0In the text box ‘Properties of currently available glucose-lowering agents that may guide treatment choice in individualpatients with type 2 diabetes mellitus ’ vildagliptin was incor-rectly assigned footnote ‘a’ (Limited use in the USA/Europe)instead of footnote ‘b’ (Not licensed in the USA).
4,126 citations
TL;DR: Clinical trials with the incretin mimetic exenatide and liraglutide show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) associated with weight loss, but long-term clinical studies are needed to determine the benefits of targeting the inc retin axis for the treatment of type 2 diabetes.
3,497 citations
"Relationships Between Gastric Empty..." refers background in this paper
...with type 2 diabetes, the magnitude of GLP-1 response is likely to be crucial given the reduced insulinotropic effect ofGIP (7)....
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...like peptide-1(7-36)amide on antro-pyloro-...
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...It is also recognized that they vary in the magnitude of their effects on pre- versus postprandial glycemia (7), although differences in effects on HbA1c hitherto appear subtle (1)....
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...They account for the “incretin effect”dan augmentation of insulin secretion following oral or enteral glucose exposure when compared with an isoglycemic intravenous glucose infusiondwhich is diminished in type 2 diabetes (7)....
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TL;DR: This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
3,103 citations
"Relationships Between Gastric Empty..." refers background in this paper
...like peptide-1(7-36)amide on antro-pyloro-...
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...While GIP may be the most important incretin hormone in health, its capacity to stimulate insulin is markedly diminished in type 2 diabetes (8)....
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...Carbohydrates, for example, stimulate incretin secretion through a number of interrelated mechanisms that are likely to include the sodium-glucose cotransporter-1 (SGLT-1) and intestinal “sweet taste” receptors (8)....
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...Each macronutrient has the capacity to stimulate GLP-1 and GIP release, although the mechanisms underlying secretion differ, and fat and carbohydrate may be more potent stimuli than protein (8)....
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TL;DR: This statement has been written incorporating the best available evidence and, where solid support does not exist, using the experience and insight of the writing group, incorporating an extensive review by additional experts (acknowledged below).
Abstract: Glycemic management in type 2 diabetes mellitus has become increasingly complex and, to some extent, controversial, with a widening array of pharmacological agents now available (1–5), mounting concerns about their potential adverse effects and new uncertainties regarding the benefits of intensive glycemic control on macrovascular complications (6–9). Many clinicians are therefore perplexed as to the optimal strategies for their patients. As a consequence, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a joint task force to examine the evidence and develop recommendations for antihyperglycemic therapy in nonpregnant adults with type 2 diabetes. Several guideline documents have been developed by members of these two organizations (10) and by other societies and federations (2,11–15). However, an update was deemed necessary because of contemporary information on the benefits/risks of glycemic control, recent evidence concerning efficacy and safety of several new drug classes (16,17), the withdrawal/restriction of others, and increasing calls for a move toward more patient-centered care (18,19).
This statement has been written incorporating the best available evidence and, where solid support does not exist, using the experience and insight of the writing group, incorporating an extensive review by additional experts (acknowledged below). The document refers to glycemic control; yet this clearly needs to be pursued within a multifactorial risk reduction framework. This stems from the fact that patients with type 2 diabetes are at increased risk of cardiovascular morbidity and mortality; the aggressive management of cardiovascular …
3,001 citations
TL;DR: The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening, providing a unifying explanation for the discrepancies as observed in previous studies.
Abstract: OBJECTIVE —The exact contributions of postprandial and fasting glucose increments to overall hyperglycemia remain controversial. The discrepancies between the data published previously might be caused by the interference of several factors. To test the effect of overall glycemic control itself, we analyzed the diurnal glycemic profiles of type 2 diabetic patients investigated at different levels of HbA 1c . RESEARCH DESIGN AND METHODS —In 290 non–insulin- and non–acarbose-using patients with type 2 diabetes, plasma glucose (PG) concentrations were determined at fasting (8:00 a.m.) and during postprandial and postabsorptive periods (at 11:00 a.m., 2:00 p.m., and 5:00 p.m.). The areas under the curve above fasting PG concentrations (AUC 1 ) and >6.1 mmol/l (AUC 2 ) were calculated for further evaluation of the relative contributions of postprandial (AUC 1 /AUC 2 , %) and fasting [(AUC 2 − AUC 1 )/AUC 2 , %] PG increments to the overall diurnal hyperglycemia. The data were compared over quintiles of HbA 1c . RESULTS —The relative contribution of postprandial glucose decreased progressively from the lowest (69.7%) to the highest quintile of HbA 1c (30.5%, P 1c : 30.3% in the lowest vs. 69.5% in the highest quintile ( P CONCLUSIONS —The relative contribution of postprandial glucose excursions is predominant in fairly controlled patients, whereas the contribution of fasting hyperglycemia increases gradually with diabetes worsening. These results could therefore provide a unifying explanation for the discrepancies as observed in previous studies.
1,417 citations
"Relationships Between Gastric Empty..." refers background in this paper
...(2) indicating that in type 2 diabetes, postprandial glycemic excursions account for about 70% of variability when HbA1c is ,7....
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