scholarly journals Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2928
Author(s):  
Amelia K. Fotheringham ◽  
Jonatan I. Bagger ◽  
Danielle J. Borg ◽  
Domenica A. McCarthy ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Soluble Receptor ◽  
Incretin Hormone ◽  
Glycation End Products ◽  
Glucose Tolerance Tests ◽  
Glucagon Like Peptide 1

Postprandial glucose excursions are postulated to increase the risk for diabetes complications via the production of advanced glycation end products (AGEs). The soluble receptor of AGEs (sRAGE) likely acts as a decoy receptor, mopping up AGEs, diminishing their capacity for pro-inflammatory and pro-apoptotic signaling. Recent evidence suggests that AGEs and soluble receptor for AGEs (sRAGE) may be altered under postprandial and fasting conditions. Here, we investigated the effects of increasing oral glucose loads during oral glucose tolerance tests (OGTT) and matched isoglycaemic intravenous (i.v.) glucose infusions (IIGI) on circulating concentrations of sRAGE. Samples from eight individuals with type 2 diabetes and eight age-, gender-, and body mass index (BMI)-matched controls, all of whom underwent three differently dosed OGTTs (25 g, 75 g, and 125 g), and three matched IIGIs were utilised (NCT00529048). Serum concentrations of sRAGE were measured over 240 min during each test. For individuals with diabetes, sRAGE area under the curve (AUC0–240min) declined with increasing i.v. glucose dosages (p < 0.0001 for trend) and was lower during IIGI compared to OGTT at the 125 g dosage (p = 0.004). In control subjects, sRAGE AUC0–240min was only lower during IIGI compared to OGTT at the 25 g dose (p = 0.0015). sRAGE AUC0–240min was negatively correlated to AUC0–240min for the incretin hormone glucagon-like peptide −1 (GLP-1) during the 75 g OGTT and matched IIGI, but only in individuals with type 2 diabetes. These data suggest that gastrointestinal factors may play a role in regulating sRAGE concentrations during postprandial glucose excursions, thus warranting further investigation.

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>

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 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>

scholarly journals Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

2013 ◽  
Vol 169 (4) ◽  
pp. 421-430 ◽  
Author(s):  
Marjan Alssema ◽  
Josina M Rijkelijkhuizen ◽  
Jens J Holst ◽  
Tom Teerlink ◽  
Peter G Scheffer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Area Under The Curve ◽  
Population Based ◽  
Liver Fat ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Mixed Meal ◽  
Postprandial Triglyceride ◽  
Glucagon Like Peptide 1

ObjectiveTo i) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and ii) to investigate whether incretin responses are associated with hypertriglyceridaemia and alanine aminotransferase (ALT) as liver fat marker.DesignA population-based study.MethodsA total of 163 persons with normal glucose metabolism (NGM), 20 with intermediate hyperglycaemia and 20 with type 2 diabetes aged 40–65 years participated. Participants received a mixed meal and oral glucose load on separate occasions. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total area under the curve (tAUC) and incremental area under the curve.ResultsIn diabetic patients compared with persons with NGM, we found increased GLP-1 secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17.7–28.7) vs 18.0 (95% CI 16.9–19.1), P<0.05) but not after the mixed meal. GIP secretion among diabetic patients was increased on both occasions (82.9 pmol/l (55.9–109.8) vs 47.1 (43.8–50.4) for oral glucose and 130.6 (92.5–168.7) vs 83.2 (77.5–88.9) for mixed meal, both P<0.05). After oral glucose, GLP-1 (tAUC per hour) was inversely related to fasting triglycerides. GIP (tAUC per hour) was positively related to fasting and postprandial triglycerides. Higher fasting GIP levels were related to higher fasting and postprandial triglyceride levels and ALT.ConclusionThis study confirms that in type 2 diabetes, GLP-1 secretion is generally preserved and that GIP secretion is exaggerated. The mechanism underlying the divergent associations of GLP-1 and GIP metabolism with fat metabolism and liver fat accumulation warrants further study.

iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes

2017 ◽  
Vol 51 (11) ◽  
pp. 990-999 ◽  
Author(s):  
Jennifer Goldman ◽  
Jennifer M. Trujillo
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
English Language ◽  
Data Extraction ◽  
Safety Data ◽  
Fixed Ratio ◽  
Postprandial Glucose ◽  
The United States ◽  
Glucagon Like Peptide 1

Objective: To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. Data Sources: A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. Study Selection and Data Extraction: All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. Data Synthesis: iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. Conclusions: iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

scholarly journals Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes?

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Matthias Ploug Larsen ◽  
Signe Sørensen Torekov
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fasting Glucose ◽  
Incretin Effect ◽  
Nonesterified Fatty Acids ◽  
Incretin Hormone ◽  
Pubmed Database ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes.

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 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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