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>

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 Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial

Diabetes Care ◽  
2020 ◽  
Vol 43 (8) ◽  
pp. 1813-1821 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Controlled Trial ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Controlled Trial ◽  
Postprandial Glucose ◽  
Randomized Controlled

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 efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study

2021 ◽  
Vol 9 (1) ◽  
pp. e002208
Author(s):  
Marcus Hompesch ◽  
Jahoon Kang ◽  
OakPil Han ◽  
Michael E Trautmann ◽  
Christopher H Sorli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Phase Ib ◽  
Link Type ◽  
Drug Concentrations

IntroductionTo evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.Research design and methodsThis phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure.ResultsTreatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up.ConclusionsThe glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide.Trial registration numberNCT02059564.

scholarly journals Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Elevated Concentration ◽  
Endogenous Melatonin

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

Pre-diabetes and Type 2 Diabetes Status in Overweight and Obese Children in a Tertiary Care Hospital of Bangladesh

2021 ◽  
Vol 44 (3) ◽  
pp. 143-147
Author(s):  
Monira Hossain ◽  
Suraiya Begum ◽  
Shahana A Rahman
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Tertiary Care ◽  
Oral Glucose ◽  
Care Hospital ◽  
Obese Children ◽  
Diabetes Status

Introduction: Obesity in childhood is associated with many co-morbid conditions; one of them is alteration of glucose metabolism. Materials and Methods:This cross-sectional study was conducted among 100 overweight and obese children aged 5-16 years to determine the status of pre-diabetes (IFG and IGT) and type 2 diabetes mellitus (T2DM), attending the OPD, BSMMU, Dhaka. All overweight/obese children were included according to BMI for age and sex using CDC growth chart. Children taking steroid for any cause or having any endocrine disorder or syndrome was excluded from the study. Anthropometry and blood pressure measurement were done and skin manifestations of insulin resistance were looked for. Fasting lipid profile and oral glucose tolerance test (OGTT) was done for each child. Result: Among the studied children 62% were male and 38% female, 77% were obese and 23% were over weight. Evidence of insulin resistance were found among most of the children and most common evidence was dyslipidemia (80%) followed by acanthosis nigricans(76%). Skin manifestation of polycystic ovary syndrome (PCOS) was found in 3% of children. Impaired fasting glucose (IFG) was found in 4% and Impaired Glucose Tolerance (IGT) was found in 7% of children among them 4% had both IGT and IFT. No child was found diabetic in this study. Conclusion:Altered glucose metabolism was present in overweight and obese children of our children, so screening is recommended. Bangladesh J Child Health 2020; VOL 44 (3) :143-147

scholarly journals The SLC16A11 Risk Haplotype for Type 2 Diabetes (T2D) Is Associated to Differentiated Responses in Weight Loss, and Glucose Metabolism After Treatments to Prevent T2D

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1275-1275
Author(s):  
Magdalena Sevilla ◽  
Donaji Gomez-Velasco ◽  
Ivette Cruz-Bautista ◽  
Laura Lazaro-Carrera ◽  
Paloma Almeda-Valdes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Prolonged Release ◽  
Risk Haplotype ◽  
The Impact

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (&gt;150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve &gt;3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.

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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