Plasma GLP-1 response to oral and intraduodenal nutrients in health and type 2 diabetes – impact on gastric emptying

2021 ◽  
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Linda E Watson ◽  
Stijn Soenen ◽  
Richard L Young ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Breath Test ◽  
Oral Glucose ◽  
Gastric Emptying Rate ◽  
Postprandial Glycemia ◽  
Glucagon Like Peptide 1 ◽  
The Relationship ◽  
Potato Meal

Abstract Context Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. Objective To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. Design We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 T2D subjects; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4kcal/min) during euglycemia and hyperglycemia in 11 healthy, and 12 T2D, subjects, (b) intraduodenal fat (2kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75g oral glucose and the GLP-1 response to intraduodenal glucose (4kcal/min) in 21 subjects (9 healthy, 12 T2D). Results The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r=0.65, P=0.002). Conclusions In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.

scholarly journals Effects of a D-Xylose Preload With or Without Sitagliptin on Gastric Emptying, Glucagon-Like Peptide-1, and Postprandial Glycemia in Type 2 Diabetes

Diabetes Care ◽  
2013 ◽  
Vol 36 (7) ◽  
pp. 1913-1918 ◽  
Author(s):  
T. Wu ◽  
M. J. Bound ◽  
B. R. Zhao ◽  
S. D. Standfield ◽  
M. Bellon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Postprandial Glycemia ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Effects of sustained treatment with lixisenatide on gastric emptying and postprandial glucose metabolism in type 2 diabetes: a randomized controlled trial

2020 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Continuous Exposure ◽  
Short Acting ◽  
Postprandial Glycemia ◽  
Gastric Emptying Scintigraphy

<i>Objective</i> <p>Slowing of gastric emptying by GLP-1 exhibits tachyphylaxis with continuous exposure. We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist (GLP-1RA), lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. </p> <p> </p> <p><i>Research design and methods</i></p> <p>30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20µg subcutaneously daily) or placebo, in a double-blind randomized parallel design.</p> <p> </p> <p><i>Results</i></p> <p>Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under curve (AUC) over 240 min of 2.19 (95% CI 1.82, 2.64; P<0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P<0.001) and incremental AUC for blood glucose (P<0.001). Lixisenatide suppressed both glucagon (P=0.003) and insulin (P=0.032), but not endogenous glucose production, over 120 min after oral glucose. Postprandial glucose-lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048), but unrelated to ß-cell function (assessed by ß-cell glucose sensitivity).</p> <p> </p> <p><i>Conclusions</i></p> <p>8 weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1RAs therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.</p>

scholarly journals Effects of sustained treatment with lixisenatide on gastric emptying and postprandial glucose metabolism in type 2 diabetes: a randomized controlled trial

2020 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Continuous Exposure ◽  
Short Acting ◽  
Postprandial Glycemia ◽  
Gastric Emptying Scintigraphy

<i>Objective</i> <p>Slowing of gastric emptying by GLP-1 exhibits tachyphylaxis with continuous exposure. We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist (GLP-1RA), lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. </p> <p> </p> <p><i>Research design and methods</i></p> <p>30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20µg subcutaneously daily) or placebo, in a double-blind randomized parallel design.</p> <p> </p> <p><i>Results</i></p> <p>Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under curve (AUC) over 240 min of 2.19 (95% CI 1.82, 2.64; P<0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P<0.001) and incremental AUC for blood glucose (P<0.001). Lixisenatide suppressed both glucagon (P=0.003) and insulin (P=0.032), but not endogenous glucose production, over 120 min after oral glucose. Postprandial glucose-lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048), but unrelated to ß-cell function (assessed by ß-cell glucose sensitivity).</p> <p> </p> <p><i>Conclusions</i></p> <p>8 weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1RAs therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.</p>

scholarly journals Cigarette Smoking Is Negatively Associated with the Prevalence of Type 2 Diabetes in Middle-Aged Men with Normal Weight but Positively Associated with Stroke in Men

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Su Wang ◽  
Jie Chen ◽  
Yuzhong Wang ◽  
Yu Yang ◽  
Danyu Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cigarette Smoking ◽  
Normal Weight ◽  
Anthropometric Measurement ◽  
Oral Glucose ◽  
Model Assessment ◽  
Family History Of Diabetes ◽  
Negatively Associated ◽  
The Relationship

Background. The prevalence of diabetes and potentially related complications, including stroke, is rapidly increasing in China. The long-term effects of lifestyle may affect glucose metabolism in the general population. Although some studies have shown an association between smoking and the risk of type 2 diabetes mellitus (T2DM), the relationship remains unclear. Furthermore, the relationship between smoking and stroke in patients with T2DM has not been fully elucidated. Objective. We investigated the influence of cigarette smoking on T2DM and stroke in China. Detailed questionnaires about smoking status and anthropometric measurement were completed by participants, and oral glucose tolerance testing (OGTT), hemoglobin A1c (HbA1c), homeostasis model assessment of IR (HOMA-IR), and blood lipids were measured. Results. In total, 8196 adults aged 40 years or older were included. We found a reduced risk of impaired glucose regulation (IGR) and T2DM in male smokers with normal weight (body mass index BMI<25 kg/m2 or waist circumference WC<90 cm) compared with nonsmokers after adjusting for age, alcohol intake, physical activity, educational level, family history of diabetes, SBP, DBP, TG, TC, HDL-C, and LDL-C. However, no significant association was detected in male current smokers with overweight/obesity or female smokers. In addition, compared with nonsmokers without T2DM, current smokers with T2DM had a significantly higher risk of stroke (odds ratio: 2.64, 95% confidence interval: 1.25–5.57; P=0.011) after adjusting for confounders. Conclusions. Smoking was negatively associated with T2DM in Chinese men of normal body weight, but no significant association was found for men with overweight/obesity or women. In addition, smoking was positively associated with nonfatal stroke, especially in patients with T2DM. Further prospective studies are needed to examine the association between smoking, diabetes, and stroke in different ethnic groups.

scholarly journals Nutrient intakes and dysglycaemia in populations of West African origin

2011 ◽  
Vol 105 (2) ◽  
pp. 297-306 ◽  
Author(s):  
Simon G. Anderson ◽  
Novie Younger ◽  
Adrian H. Heald ◽  
Marshall K. Tulloch-Reid ◽  
Wiyumile P. Simukonda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dietary Intake ◽  
Tolerance Test ◽  
Cross Sectional Study ◽  
Dietary Factors ◽  
Oral Glucose ◽  
African Origin ◽  
Cross Sectional ◽  
The Relationship

Examining the relationship between glucose intolerance and dietary intake in genetically similar populations with different dietary patterns and rates of type 2 diabetes may provide important insights into the role of diet in the pathogenesis of this disease. The objective of the present study was to assess the relationship between dietary variables and dysglycaemia/type 2 diabetes among three populations of African origin. The study design consists of a cross-sectional study of men and women of African descent aged 24–74 years from Cameroon (n 1790), Jamaica (n 857) and Manchester, UK (n 258) who were not known to have diabetes. Each participant had anthropometric measurements and underwent a 2 h 75 g oral glucose tolerance test. Habitual dietary intake was estimated with quantitative FFQ, developed specifically for each country. The age-adjusted prevalence of undiagnosed type 2 diabetes in Cameroon was low (1·1 %), but it was higher in Jamaica (11·6 %) and the UK (12·6 %). Adjusted generalised linear and latent mixed models used to obtain OR indicated that each 1·0 % increment in energy from protein, total fat and saturated fats significantly increased the odds of type 2 diabetes by 9 (95 % CI 1·02, 1·16) %, 5 (95 % CI, 1·01, 1·08) % and 16 (95 % CI 1·08, 1·25) %, respectively. A 1 % increase in energy from carbohydrates and a 0·1 unit increment in the PUFA:SFA ratio were associated with significantly reduced odds of type 2 diabetes. The results show independent effects of dietary factors on hyperglycaemia in African origin populations. Whether modifying intake of specific macronutrients helps diabetes prevention needs testing in randomised trials.

scholarly journals Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

2014 ◽  
Vol 306 (4) ◽  
pp. G301-G309 ◽  
Author(s):  
Sara Chowdhury ◽  
Dominic N. Reeds ◽  
Dan L. Crimmins ◽  
Bruce W. Patterson ◽  
Erin Laciny ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Postprandial Glucose ◽  
Nerve Fibers ◽  
Intense Staining ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Glucagon Like Peptide 1

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

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