PRIOR INGESTION OF A KETONE MONOESTER SUPPLEMENT REDUCES POSTPRANDIAL GLYCEMIC RESPONSES IN YOUNG HEALTHY WEIGHT INDIVIDUALS

2020 ◽  
Author(s):  
Grant Greaves ◽  
Richard Xiang ◽  
Hossein Rafiei ◽  
Adeeb Malas ◽  
Jonathan P. Little
Keyword(s):  
Fatty Acid ◽  
Gastric Emptying ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
Healthy Weight ◽  
Mixed Meal ◽  
Double Blind ◽  
Acute Ingestion ◽  
Beta Hydroxybutyrate

The main objective of this study was to determine whether acute ingestion of a ketone monoester (KME) supplement impacted mixed meal tolerance test (MMTT) glucose area under the curve (AUC). Nineteen healthy young volunteers (10 males/9 females, 24.7 ± 4.9 years, BMI = 22.7 ± 2.4) participated in a double-blind, placebo-controlled crossover study. Following overnight fasting (≥10 h), participants consumed 0.45mL/kg of a KME supplement or taste-matched placebo followed by a MMTT 15 minutes later. Blood samples were collected every 15-30 minutes over 2.5 hours. KME supplementation acutely raised beta-hydroxybutyrate (β-OHB) AUC (590%, P < 0.0001, d = 2.4) and resulted in decreases in blood glucose AUC (-9.4%, P = 0.03, d = 0.56) and non-esterified fatty acid (NEFA) AUC (-27.3%, P = 0.023, d = 0.68) compared to placebo. No differences were found for plasma insulin AUC (P = 0.70) or gastric emptying estimated by co-ingested acetaminophen AUC (P = 0.96) between ketone and placebo. Overall, results indicate that KME supplementation attenuates postprandial glycemic and NEFA responses when taken 15 min prior to a mixed meal in young healthy individuals. Future studies are warranted to investigate whether KME supplementation may benefit individuals with impaired glycemic control. Novelty Bullets • Acute ketone monoester supplementation 15 min prior to a mixed meal decreased postprandial glucose and non-esterified fatty acid (NEFA) levels without significantly impacting postprandial insulin or estimates of gastric emptying. • Glucose and NEFA lowering effects of ketone monoester supplementation are apparently not mediated by changes in insulin release or gastric emptying.

scholarly journals Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance

2018 ◽  
Vol 104 (2) ◽  
pp. 359-368 ◽  
Author(s):  
Martin B Whyte ◽  
Fariba Shojaee-Moradie ◽  
Sharaf E Sharaf ◽  
Nicola C Jackson ◽  
Barbara Fielding ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glycosylated Hemoglobin ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
Glucose Production ◽  
Postprandial Glucose ◽  
Double Blind ◽  
Single Meal

Abstract Context Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. Objective To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. Design Randomized, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Patients Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. Interventions Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. Main Outcome Measures Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60–480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0–240min were reduced with lixisenatide (P = 0.0051; P &lt; 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0–360min (P = 0.006) were lower with lixisenatide than with placebo. Conclusions Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance.

Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist

2019 ◽  
Vol 105 (3) ◽  
pp. 803-820 ◽  
Author(s):  
Victoria E R Parker ◽  
Darren Robertson ◽  
Tao Wang ◽  
David C Hornigold ◽  
Marcella Petrone ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Double Blind ◽  
Glucose Lowering ◽  
End Of Treatment ◽  
Gastric Emptying Time ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms

Abstract Context Cotadutide is a dual receptor agonist with balanced glucagon-like peptide-1 and glucagon activity. Objective To evaluate different doses of cotadutide and investigate underlying mechanisms for its glucose-lowering effects. Design/setting Randomized, double-blind, phase 2a study conducted in 2 cohorts at 5 clinical trial sites. Patients Participants were 65 adult overweight/obese patients with type 2 diabetes mellitus; 63 completed the study; 2 were withdrawn due to AEs. Intervention Once-daily subcutaneous cotadutide or placebo for 49 days. Doses (50–300 µg) were uptitrated weekly (cohort 1) or biweekly (cohort 2). Main outcome measures Co-primary end points (cohort 1) were percentage changes from baseline to end of treatment in glucose (area under the curve from 0 to 4 hours [AUC0–4h]) post–mixed-meal tolerance test (MMTT) and weight. Exploratory measures included postprandial insulin and gastric emptying time (GET; cohort 2). Results Patients received cotadutide (cohort 1, n = 26; cohort 2, n = 20) or placebo (cohort 1, n = 13; cohort 2, n = 6). Significant reductions were observed with cotadutide vs placebo in glucose AUC0–4h post MMTT (least squares mean [90% CI], −21.52% [−25.68, −17.37] vs 6.32% [0.45, 12.20]; P &lt; 0.001) and body weight (−3.41% [−4.37, −2.44] vs −0.08% [−1.45, 1.28]; P = 0.002). A significant increase in insulin AUC0–4h post MMTT was observed with cotadutide (19.3 mU.h/L [5.9, 32.6]; P = 0.008) and GET was prolonged on day 43 with cotadutide vs placebo (t½: 117.2 minutes vs −42.9 minutes; P = 0.0392). Conclusion These results suggest that the glucose-lowering effects of cotadutide are mediated by enhanced insulin secretion and delayed gastric emptying. Trial Registration ClinicalTrials.gov, NCT03244800.

scholarly journals Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kamal Albarazanji ◽  
Andrea R. Nawrocki ◽  
Bin Gao ◽  
Xiaoli Wang ◽  
Yixin Wang ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Glucose Homeostasis ◽  
Plasma Glucose ◽  
Nonhuman Primates ◽  
Surrogate Marker ◽  
Tolerance Test ◽  
Mixed Meal ◽  
C Peptide ◽  
Meal Tolerance Test ◽  
Mixed Meal Tolerance Test

AbstractMeal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

Five batches representative of Ontario-grown American ginseng root produce comparable reductions of postprandial glycemia in healthy individualsThis article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (9) ◽  
pp. 856-864 ◽  
Author(s):  
Anamaria Dascalu ◽  
John L. Sievenpiper ◽  
Alexandra L. Jenkins ◽  
Mark P. Stavro ◽  
Lawrence A. Leiter ◽  
...  
Keyword(s):  
Fasting Blood Glucose ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
American Ginseng ◽  
Tolerance Test ◽  
Ginseng Root ◽  
Oral Glucose ◽  
Natural Health Products ◽  
Water Control ◽  
Postprandial Glycemia

Evidence indicates that the glycemia-lowering effect of American ginseng root may be batch dependent. We therefore evaluated the effect of 5 root batches, representative of Ontario-grown American ginseng, on postprandial glucose and insulin indices. Twelve healthy subjects (5 male, 7 female), mean ± SE age 26.5 ± 2 years, body mass index 23.96 ± 3.41 kg/m2, fasting blood glucose 4.77 ± 0.04 mmol/L, were assigned to consume 9 g of American ginseng from 5 farms (A–E), administered in randomized sequence on 5 separate visits, and a water-control during the 6th and last visit. Treatments were consumed 40 min before a 2-hour 75-gram oral glucose tolerance test. Plasma glucose and insulin were measured at baseline, before, and during the test. Compared with control, batches A and C reduced glucose incremental area under the curve (IAUC) by 35.2% (156 vs. 240 mmol·min/L) and 32.6% (162 vs. 240 mmol·min/L), respectively. Batches A, C, and E reduced incremental peak glucose by 1.3, 1.2, and 1.1 mmol/L, respectively. Batch C reduced the insulin IAUC by 27.7% (15.8 vs. 21.8 nmol·min/L). Effects on glucose and insulin parameters were not different across ginseng treatments. The mean of the 5 ginseng treatments reduced peak postprandial glucose by 1.0 mmol/L, glucose IAUC by 27.7% (173 vs. 240 mmol·min/L), and insulin IAUC by 23.8% (16.6 vs. 21.8 nmol·min/L) relative to control. (All results statistically significant at p < 0.05.) American ginseng decreased postprandial glycemia and insulinemia; however, 40% of the batches did not reduce glycemia with the anticipated magnitude, irrespective of their saponin composition.

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 Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

scholarly journals Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Giulio R Romeo ◽  
Junhee Lee ◽  
Christopher M Mulla ◽  
Youngmin Noh ◽  
Casey Holden ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Cost Effective ◽  
Tolerance Test ◽  
Controlled Clinical Trial ◽  
Oral Glucose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Favorable Safety

Abstract Context The identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes. Objective The objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes. Design, Setting, Participants, and Intervention This double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks. Main Outcome Measures Primary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT. Results From a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P &lt; .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P &lt; .001) and of the 2-hour PG of the OGTT (P &lt; .05). There were no serious adverse events in either study group. Conclusions In individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

2001 ◽  
Vol 281 (3) ◽  
pp. G752-G763 ◽  
Author(s):  
Feruze Y. Enç ◽  
Neşe I˙meryüz ◽  
Levent Akin ◽  
Turgut Turoğlu ◽  
Fuat Dede ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Area Under The Curve ◽  
Gut Hormones ◽  
Random Order ◽  
Mixed Meal ◽  
Carbohydrate Absorption ◽  
Plasma Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We investigated the effect of acarbose, an α-glucosidase and pancreatic α-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 ( r = 0.68 , P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

2004 ◽  
Vol 287 (2) ◽  
pp. G363-G369 ◽  
Author(s):  
Emma Janet Castillo ◽  
Silvia Delgado-Aros ◽  
Michael Camilleri ◽  
Duane Burton ◽  
Debra Stephens ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Adverse Effects ◽  
Single Photon ◽  
Photon Emission ◽  
Area Under The Curve ◽  
Gastric Volume ◽  
Oral Solution ◽  
Gallbladder Emptying ◽  
Double Blind ◽  
Computed Tomographic

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by 99mTc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying ( P < 0.01) and fasting and postprandial volumes ( P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids ( P < 0.01) and increased fasting ( P = 0.035) gastric volumes without altering postprandial ( P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance ( P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.

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