Postprandial Glucagon-like Peptide-1 Concentrations Research Articles

Metabolic biomarkers of appetite control in Parkinson's disease patients with and without cognitive impairment

BackgroundAppetite dysregulation in Parkinson’s Disease (PD) appears to be linked to physical and cognitive deterioration. PD patients with and without cognitive impairment (CI) were compared to an age-matched control group to explore predictors of appetite control in fasting and post-prandial conditions. MethodsFifty-five patients were recruited and divided into three groups: twenty controls (age: 74y, BMI: 25.8kg/m2), nineteen PD patients without CI (72.5y, 25.1kg/m2) and sixteen PD patients with CI (74.3y, 24.0kg/m2). Self-reported appetite perception and circulating blood metabolic biomarkers were measured in fasting and over a three-hour post-prandial period. Biomarkers included glucose, insulin, tumour necrosis factor alpha (TNF-α), leptin, acyl-ghrelin, total ghrelin, peptide YY (PYY), glucagon like peptide 1 (GLP-1), insulin growth factor 1 (IGF-1), growth factor (GF) and triglycerides. Patients were then provided with a mixed meal to eat ad libitum with the aim to evaluate links between metabolic biomarkers and control of energy intake. ResultsPD patients with CI had a significant lower protein intake (7.4±2.5g, p=0.01) compared to controls (21.9±3.1g) and PD patients without CI (14.3±3.0g). Post-prandial plasma GLP-1 concentrations were associated with decreased hunger perception (B±SE, -5.3±2.4mm·hour-1, p=0.04). PYY concentrations were significantly associated with GLP-1 in fasting (r=0.40, p=0.005) and post-prandial (r=0.46, p<0.001) conditions. In a multivariate model, post-prandial PYY concentrations were a significant predictor of ad libitum energy intake in all subjects (B±SE, -87.5±34.9kcal, p=0.01) and in patients with PD (B±SE, -106.8±44.9kcal, p=0.04). ConclusionsPYY and GLP-1 appeared to influence appetite control in PD patients and their roles merit further investigation.

Effects of Breaking Up Sitting on Gut Hormone Responses and Subsequent Compensatory Behaviors in Physically Inactive Adults.

The effects of breaking up sitting on gut hormone responses and free-living energy compensatory behaviors are still unclear in people of Asian ethnicity. Twenty-six Asians including 13 lean individuals (Lean) and 13 individuals with centrally overweight/obesity (OW), aged between 20 and 45 yr, completed a randomized crossover study with either 5.5-h uninterrupted sitting (SIT) or 5.5-h sitting with 2-min walking at 6.4 km·h -1 every 20 min (ACTIVE) in the laboratory. Blood samples were collected at regular time points to examine postprandial glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) concentrations. Free-living physical activity and energy intake were recorded using wearable devices and weighed food diaries outside the laboratory until midnight. Paired t -tests were conducted to compare responses between trials. Postprandial GLP-1 and PYY incremental area under the curve values were higher in the ACTIVE trial versus SIT in both Lean and OW groups (all, P < 0.05), but there was no difference in GIP in either group (both, P > 0.05). There were no differences in free-living physical activity (volume and intensity) or energy intake (total and macronutrients) between trials in either group (all, P > 0.05), resulting in greater total physical activity over the 24-h monitoring period in ACTIVE trial versus SIT trial (both, P < 0.05). Breaking up sitting increases postprandial GLP-1 and PYY concentrations in Asians, but does not induce subsequent behavioral compensation, resulting in greater 24-h physical activity levels and lower relative energy intake, in inactive individuals irrespective of bodyweight status.

Effect of vegetable consumption with chewing on postprandial glucose metabolism in healthy young men: a randomised controlled study

Although thorough chewing lowers postprandial glucose concentrations, research on the effectiveness of chewing vegetables in different forms on postprandial glucose metabolism remains limited. This study examined the effects of vegetables consumed in solid versus puree forms on postprandial glucose metabolism. Nineteen healthy young men completed two 180-min trials on separate days in a random order: the chewing trial involved the consumption of shredded cabbage with chewing and the non-chewing trial involved the consumption of pureed cabbage without chewing. Energy jelly was consumed immediately after the consumption of shredded or puree cabbage. Blood samples were collected at 0, 30, 45, 60, 90, 120 and 180 min. Circulating concentrations of glucose, insulin, total glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) concentrations were measured from the plasma. Although plasma glucose concentrations did not differ between the trials, the plasma insulin and GIP incremental area under the curve values were higher in the chewing than in the non-chewing trial. Postprandial total GLP-1 concentrations were higher in the chewing than in the non-chewing trial at 45, 60 and 90 min. This study demonstrates that consuming shredded cabbage while chewing enhances postprandial incretin secretion but has no effect on postprandial glucose concentration.Trial registration: Clinical trial registration ID.: UMIN000052662, registered 31 October 2023.

Intra-pancreatic fat is associated with high circulating glucagon and GLP-1 concentrations following whey protein ingestion in overweight women with impaired fasting glucose: A randomised controlled trial

AimIntra-pancreatic fat deposition (IPFD) while hypothesised to impair beta-cell function, its impact on alpha-cells remains unclear. We evaluated the association between IPFD and markers of pancreatic cells function using whey protein. MethodsTwenty overweight women with impaired fasting glucose (IFG) and low or high IPFD (<4.66% vs ≥4.66%) consumed 3 beverage treatments: 0 g (water control), 12.5 g (low-dose) and 50.0 g (high-dose) whey protein, after an overnight fast, in randomised order. Blood glucose, insulin, C-peptide, glucagon, gastric-inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and amylin were analysed postprandially over 4 h. Incremental area-under-the-curve (iAUC), incremental maximum concentration (iCmax), and time to maximum concentration (Tmax) for these were compared between IPFD groups using repeated measures linear mixed models, also controlled for age (pcov). ResultsiAUC and iCmax glucose and insulin while similar between the two IPFD groups, high IPFD and ageing contributed to higher postprandial glucagon (iAUC: p = 0.012; pcov = 0.004; iCmax: p = 0.069; pcov = 0.021) and GLP-1 (iAUC: p = 0.006; pcov = 0.064; iCmax: p = 0.011; pcov = 0.122) concentrations. ConclusionIn our cohort, there was no evidence that IPFD impaired protein-induced insulin secretion. Conversely, IPFD may be associated with increased protein-induced glucagon secretion, a novel observation which warrants further investigation into its relevance in the pathogenesis of dysglycaemia and type-2 diabetes.

Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety

BackgroundPostprandial metabolic responses following dairy consumption have mostly been studied using stand-alone dairy products or milk-derived nutrients. ObjectiveAssessing the impact of ingesting dairy products as part of a common breakfast on postprandial aminoacidemia, glycemic control, markers of bone metabolism, and satiety. MethodsIn this randomized, crossover study, 20 healthy young males and females consumed on 3 separate occasions an iso-energetic breakfast containing no dairy (NO-D), 1 dairy (ONE-D), or 2 dairy (TWO-D) products. Postprandial concentrations of amino acids, glucose, insulin, glucagon-like peptide-1 (GLP-1), calcium, parathyroid hormone (PTH), and markers of bone formation (P1NP) and resorption (CTX-I) were measured before and up to 300 min after initiating the breakfast, along with VAS-scales to assess satiety. ResultsPlasma essential and branched-chained amino acids availability (expressed as total area under the curve (tAUC)) increased in a dose-dependent manner (P<0.05 for all comparisons). Plasma glucose tAUCs were lower in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons). Plasma GLP-1 tAUC increased in a dose-dependent manner (P<0.05 for all comparisons), whereas no differences were observed in plasma insulin tAUC between conditions (P>0.05 for all comparisons). Serum calcium tAUCs were higher in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons), along with lower PTH tAUCs in ONE-D and TWO-D compared with NO-D (P=0.001 for both comparisons). In accordance, serum CTX-I concentrations were lower in the late postprandial period in ONE-D and TWO-D compared with NO-D (P<0.01 for both comparisons). No differences were observed in P1NP tAUCs between conditions (P>0.05). The tAUC for satiety was higher in TWO-D compared with NO-D and ONE-D (P<0.05 for both comparisons). ConclusionsIso-energetic replacement of a carbohydrate-rich breakfast component with one serving of dairy improves postprandial amino acid availability, glycemic control, and bone metabolism. Adding a second serving of dairy in lieu of carbohydrates augments postprandial amino acid and GLP-1 concentrations while further promoting satiety.This study was registered at https://doi.org/10.1186/ISRCTN13531586 with Clinical Trial Registry number ISRCTN13531586.

Primary weight loss failure after Roux-en-Y gastric bypass is characterized by impaired gut-hormone mediated regulation of food intake

Background/ObjectivesAfter Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.Subjects/MethodsTwenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.ResultsOn placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (−1% [−13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).ConclusionsPrimary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.

The relative importance of Endogenously Secreted incretin hormones, GLP‐1 and GIP for Postprandial Glucose Tolerance and β‐Cell Function After Roux‐en‐Y Gastric Bypass and Sleeve Gastrectomy Surgery

Bariatric surgery procedures, namely Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) is increasingly used worldwide, have been shown to be the most effective strategy to induce and maintain weight loss as well as inducing long-term remission from type 2 diabetes among people with significant obesity. The mechanism for diabetes remission remains unclear and multi-factorial, although increased secretion of endogenous glucagon-like peptide 1 (GLP-1) hormones to improve postprandial β-cell function is widely considered to be the main mechanism for diabetes remission following RYGB. However, recent studies have shown that rate of remission between the two types of bariatric surgery procedures are similar but yet, the mechanism for remission above and beyond weight loss per se following SG is less clear. Beyond GLP-1, the role of the other major incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is relatively unexplored after bariatric surgery. A study published in Diabetes Care have therefore studied the effects of separate and combined GLP-1 receptor (GLP-1R) and GIP receptor (GIPR) blockade during mixed-meal tests in un-operated (CON), SG-operated, and RYGB-operated people with no history of diabetes. The investigator found that, as expected, postprandial GLP-1 concentrations were highest after RYGB but also higher after SG compared with CON. In contrast, postprandial GIP concentrations were lowest after RYGB. Interestingly, blockage of GLP-1R reduced β-cell glucose sensitivity and increased postprandial glucose responses in both surgical groups but had no effect in CON. Blockage of GIPR however reduced β-cell glucose sensitivity and increased postprandial glucose responses in the CON and SG groups but had no effect in the RYGB group. This study showed that while GLP-1 is the most important mediator of improved beta cell function after RYGB, both GLP-1 and GIP are equally important after SG. The combine benefits of GLP-1 and GIP following SG is interesting, given the recent emergence of the dual GLP-1 and GIP agonist for the treatment of diabetes and obesity. It would be interesting also to explore the relative role of Glucagon on beta cell function following both procedures.

The Importance of Endogenously Secreted GLP-1 and GIP for Postprandial Glucose Tolerance and β-Cell Function After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Surgery.

Enhanced secretion of glucagon-like peptide 1 (GLP-1) seems to be essential for improved postprandial β-cell function after Roux-en-Y gastric bypass (RYGB) but is less studied after sleeve gastrectomy (SG). Moreover, the role of the other major incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is relatively unexplored after bariatric surgery. We studied the effects of separate and combined GLP-1 receptor (GLP-1R) and GIP receptor (GIPR) blockade during mixed-meal tests in unoperated (CON), SG-operated, and RYGB-operated people with no history of diabetes. Postprandial GLP-1 concentrations were highest after RYGB but also higher after SG compared with CON. In contrast, postprandial GIP concentrations were lowest after RYGB. The effect of GLP-1R versus GIPR blockade differed between groups. GLP-1R blockade reduced β-cell glucose sensitivity and increased or tended to increase postprandial glucose responses in the surgical groups but had no effect in CON. GIPR blockade reduced β-cell glucose sensitivity and increased or tended to increase postprandial glucose responses in the CON and SG groups but had no effect in the RYGB group. Our results support that GIP is the most important incretin hormone in unoperated people, whereas GLP-1 and GIP are equally important after SG, and GLP-1 is the most important incretin hormone after RYGB.

Interrupting Prolonged Sitting with Intermittent Walking Increases Postprandial Gut Hormone Responses.

Continuous exercise can increase postprandial gut hormone such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) responses, but it is unknown whether interrupting prolonged sitting with intermittent walking elicits this effect. Ten participants with central overweight/obesity (7 men and 3 postmenopausal women, 51 ± 5 yr; mean ± SD) completed a randomized crossover study in which they consumed breakfast and lunch in the laboratory while either sitting continuously for the entire 5.5-h period (SIT) or the prolonged sitting interrupted every 20 min by walking briskly (6.4 km·h-1) for 2 min (BREAKS). Blood samples were collected at regular intervals to examine postprandial plasma GLP-1, PYY, and glucose-dependent insulinotropic polypeptide concentrations. Adipose tissue samples were collected at baseline and at the end of the trials to examine changes in net dipeptidyl peptidase 4 secretion from primary explants. Mean (95% confidence interval) postprandial GLP-1 and PYY incremental area under curve values were elevated by 26% and 31% in the BREAKS trial versus SIT (8.4 [0.7, 16.1] vs 6.7 [-0.8, 14.2], P = 0.001, and 26.9 [8.1, 45.6] vs 20.4 [5.1, 35.8] nmol·330 min·L-1, P = 0.024, respectively) but without any such effect on glucose-dependent insulinotropic polypeptide (P = 0.076) or net adipose tissue dipeptidyl peptidase 4 secretion (P > 0.05). Interrupting prolonged sitting with regular short bouts of brisk walking increases postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.

Plasma concentrations of glucagon and glucagon-like peptide-1 are reduced in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome versus healthy dogs: a preliminary study.

To compare plasma concentrations of glucagon and glucagon-like peptide-1 (GLP-1) between healthy dogs and dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) dogs. Privately owned healthy (n = 5) control (CON) and ACHES (8; including 3 with diabetes mellitus) dogs enrolled between October 2, 2019, and March 4, 2020. This was a prospective case-control study. Fasting and 15-minute postprandial plasma glucagon total GLP-1 concentrations were measured with commercial immunoassays. Dogs with ACHES had lower fasting (median, 0.5; mean difference, 3.8; 95% CI, 0.52 to 7.0 pmol/L; P = .021) and postprandial (median, 0.35; mean difference, 5.0; 95% CI, 1.8 to 8.3 pmol/L; P = .002) plasma glucagon concentrations than CON (fasting and postprandial medians, 3.5 and 4.6 pmol/L, respectively). ACHES dogs had significantly (median, 4.15; mean difference, 12.65; 95% CI, 2.0 to 16.3 pg/ml; P = .011) lower postprandial plasma GLP-1 concentrations than CON (median, 16.8 pg/ml). There was no significant difference between fasting GLP-1 levels between the 2 groups. Lower postprandial plasma GLP-1 concentrations may contribute to the propensity of diabetes mellitus in ACHES. Lower glucagon concentrations may reflect an appropriate physiologic response to hypoaminoacidemia.

The relation between postprandial glucagon-like peptide-1 release and insulin sensitivity before and after bariatric surgery in humans with class II/III obesity.

Glucagon-like peptide-1 (GLP-1) receptor agonist treatment is beneficial for the human glucose metabolism, and GLP-1 secretion is greatly enhanced following Roux-en-Y gastric bypass (RYGB). To elucidate the relationship between GLP-1 concentrations and insulin sensitivity in subjects with class II/III obesity without diabetes and to assess the relation between GLP-1 and the improvements in glucose metabolism following RYGB. Clinical research facility in a university hospital. We recruited 35 patients scheduled for RYGB and assessed their plasma GLP-1, insulin, and glucose responses to a high-fat mixed meal. Basal and insulin-mediated glucose fluxes were determined during a 2-step hyperinsulinemic-euglycemic clamp with stable isotope-labeled tracers. Out of 35 subjects, 10 were studied both before surgery and at 1 year of follow-up. Plasma GLP-1 increased following the high-fat mixed meal. Postprandial GLP-1 excursions correlated positively with hepatic and peripheral insulin sensitivity, but not with body mass index. At 1 year after RYGB, participants had lost 24% ± 6% of their body weight. Plasma GLP-1, insulin, and glucose levels peaked earlier and higher after the mixed meal. The positive association between the postprandial GLP-1 response and peripheral insulin sensitivity persisted. Postprandial GLP-1 concentrations correlate with insulin sensitivity in subjects with class II/III obesity without diabetes before and 1 year after RYGB. Increased GLP-1 signaling in postbariatric patients may, directly or indirectly, contribute to the observed improvements in insulin sensitivity and metabolic health.

Effect of cacao polyphenol-rich chocolate on postprandial glycemia, insulin, and incretin secretion in healthy participants

ObjectivesThere is substantial interest in using dark chocolate to prevent postprandial hyperglycemia. We investigated the effects of cacao polyphenol-rich chocolate on postprandial glycemic and insulinemic responses and whether cacao polyphenol-rich chocolate increases glucagon-like peptide-1 (GLP-1) secretion. MethodsIn a stratified, randomized, crossover study, 48 healthy participants ingested either water (W) or cacao polyphenol-rich chocolate plus water (C) 15 min before a 50 g oral glucose tolerance test (OGTT). Pre- and postprandial concentrations of blood glucose, insulin, free fatty acid, glucagon, and GLP-1 were evaluated. ResultsPeak plasma glucose concentrations did not differ significantly between groups W and C; however, plasma glucose concentrations at 120 min in group C were significantly lower than those in group W (P < .01). Postprandial serum insulin and plasma GLP-1 concentrations and incremental serum insulin and plasma GLP-1 area under the curve (AUC)–15–180 min for group C were significantly higher than those for group W (P < .05). When comparing the changes after the OGTT, the incremental plasma glucose AUC0–180 min for group C was significantly lower than that for group W (P < .05), but the incremental serum insulin and plasma GLP-1 AUC0–180 min did not differ significantly between groups W and C. ConclusionsThis study indicated that the intake of cacao polyphenol-rich chocolate before a 50 g OGTT could enhance early insulin and GLP-1 secretion in healthy participants, and illustrates the potential of cacao polyphenol-rich chocolate in managing postprandial glucose excursions.

The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes.

The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes. In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed. Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163). We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.

The effect of diet change and insulin dysregulation on the faecal microbiome of ponies.

The equine microbiome can change in response to dietary alteration and may play a role in insulin dysregulation. The aim of this study was to determine the effect of adding pasture to a hay diet on the faecal bacterial microbiome of both healthy and insulin-dysregulated ponies. Faecal samples were collected from 16 ponies before and after dietary change to enable bacterial 16S rRNA sequencing of the V3-V4 region. The dominant phyla in all samples were the Firmicutes and Bacteroidetes. The evenness of the bacterial populations decreased after grazing pasture, and when a pony was moderately insulin dysregulated (P=0.001). Evenness scores negatively correlated with post-prandial glucagon-like peptide-1 concentration after a hay-only diet (r²=-0.7, P=0.001). A change in diet explained 3% of faecal microbiome variability. We conclude that metabolically healthy ponies have greater microbial stability when challenged with a subtle dietary change, compared with moderately insulin-dysregulated ponies.

Effect of high-protein breakfast meal on within-day appetite hormones: Peptide YY, glucagon like peptide-1 in adults

Summary Background This study was carried out to investigate the effect of a single high protein breakfast on appetite related hormones (Peptide YY (PYY), and Glucagon-like Peptide-1 (GLP-1)) and perceived appetite sensation among adults. Many studies showed that dietary protein is the most satiating macronutrient, since protein may affect appetite by its involvement with appetite regulating hormones. Methods Within-subject crossover design was used, where participants received one of two assigned breakfasts on two different mornings: the first breakfast were a high protein (HP) breakfast that contained (51% protein, 13% CHO, 36% fat), while the second one had a high carbohydrates (HC) breakfast (10% protein, 60% CHO, 30% fat). Results The findings showed that PYY levels were significantly higher at (P = 0.05) significance level after the HP breakfast than the HC breakfast at 120 min. It also showed that there was an increase in postprandial GLP-1 concentration tended to be greater at significance level (P Conclusion A single HP breakfast of 51% had a greater effect on satiety rather than 10% of energy from protein, meanwhile this effect does not apply to all satiety hormones.

Effect of Meal Acceptability on Postprandial Appetite Scores and Hormones of Male Participants with Varied Adiposity.

This study portrays the effect of hedonic manipulation (high acceptability [HA] vs. low acceptability [LA]) on postprandial hormones and appetite scores in healthy males. Thirty participants (15 with normal weight and 15 with obesity) were recruited for a randomized, crossover design. They were randomly assigned to the HA or LA (with acesulfame-K) custard. Blood samples were drawn beforethe meals and for 4 hours after the meals and wereanalyzed for glucose, insulin, ghrelin, andglucagonlike peptide 1 (GLP-1). Appetite scores and subsequent energy intake were recorded. Postprandial glucose, insulin, and ghrelin were different according to adiposity, whereas meal acceptabilitydid not correspond to any significant difference in postprandial glucose, insulin, ghrelin, and GLP-1 concentrations. Appetite scores showed lower hunger, higher satiety, and fullness after the HA meal without a significant difference between the meals. Subsequent energy intake, expressed as a percentage of the resting energy expenditure, was higher in participants with obesity but did not reflect postprandial hormones and appetite scores; there was no significant difference between meals. Hedonic properties and palatability do not affect gut hormones, mainly ghrelin and GLP-1. Moreover, their postprandial concentrations were not paralleled by similar changes in appetite scores, and both were not found to affect subsequent intake.

Differential effects of a 40-hour fast and bile acid supplementation on human GLP-1 and FGF19 responses.

Bile acids, glucagon-like peptide-1 (GLP-1), and fibroblast growth factor 19 (FGF19) play an important role in postprandial metabolism. In this study, we investigated the postprandial bile acid response in plasma and its relation to insulin, GLP-1, and FGF19. First, we investigated the postprandial response to 40-h fast. Then we administered glycine-conjugated deoxycholic acid (gDCA) with the meal. We performed two separate observational randomized crossover studies on healthy, lean men. In experiment 1: we tested 4-h mixed meal after an overnight fast and a 40-h fast. In experiment 2, we tested a 4-h mixed meal test with and without gDCA supplementation. Both studies measured postprandial glucose, insulin, bile acids, GLP-1, and FGF19. In experiment 1, 40 h of fasting induced insulin resistance and increased postprandial GLP-1 and FGF19 concentrations. After an overnight fast, we observed strong correlations between postprandial insulin and gDCA levels at specific time points. In experiment 2, administration of gDCA increased GLP-1 levels and lowered late postprandial glucose without effect on FGF19. Energy expenditure was not affected by gDCA administration. Unexpectedly, 40 h of fasting increased both GLP-1 and FGF19, where the former appeared bile acid independent and the latter bile acid dependent. Second, a single dose of gDCA increased postprandial GLP-1. Therefore, our data add complexity to the physiological regulation of the enterokines GLP-1 and FGF19 by bile acids.

1980-P: A Characterization of Postprandial Glucose Metabolism and Incretin Hormone Responses in Patients with Bile Acid Malabsorption

Bile acid malabsorption (BAM) is characterized by an excessive spill-over of bile acids to the colon leading to bile acid-induced diarrhea; the condition is usually treated with bile acid sequestrants. Bile acids have been demonstrated to modulate the secretion of the incretin hormone glucagon-like peptide 1 (GLP-1) and the aim of this study was to characterize postprandial glucose metabolism and incretin hormone responses in patients with BAM. Twelve patients with BAM (6 women; mean age 39.1 (SD 13.2); mean BMI 28.4 kg/m2 (SD 1.2); HbA1c 31.4 (SD 3.7)) and 12 healthy gender, age, BMI and HbA1c-matched controls (6 women; mean age 39.3 (SD 15.6); mean BMI 29,1 kg/m2 (SD 1.1); HbA1c 31.0 (SD 2.8)) were subjected to two 4-hour standardized liquid meal tests with double-blinded single-dose administration of the bile acid sequestrant colesevelam (3.75 g) and placebo, respectively, performed on separate days, and in randomized order. Fasting and postprandial plasma GIP and GLP-1 concentrations were comparable among patients with BAM and control subjects and unaffected by colesevelam administration. Peak plasma glucose concentrations were higher in BAM patients vs. control subjects, but area under curve for plasma glucose did not differ between the two groups. Patients with BAM exhibited significantly higher postprandial serum C-peptide concentrations and hyperglucagonemia compared to controls. Single-dose colesevelam had no effect on postprandial glucose or glucagon excursions in any of the groups but decreased the postprandial C-peptide response in BAM patients. Patients with BAM are characterized by elevated serum C-peptide concentrations and hyperglucagonemia whereas postprandial glucose tolerance and GLP-1 and GIP responses are similar to healthy controls. Disclosure M.L. Kårhus: None. D.P. Sonne: None. M.L. Thomasen: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsbøll: None. A. Brønden: Other Relationship; Self; AstraZeneca. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp &amp; Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp &amp; Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S. Funding Novo Nordisk Foundation

OR05-6 The Effect of the GLP1R Variant rs6923761 on Post-Prandial Glucose Levels during Treatment with Sitagliptin

BACKGROUND: Glucagon-like peptide-1 (GLP-1) functions to increase insulin production in a glucose-dependent manner. Endogenous GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase 4 (DPP4), and GLP-1 receptor agonists and DPP4 inhibitors (DPP4Is) are now used in the treatment of diabetes. The GLP-1 receptor (GLP-1R) is a G-protein coupled receptor that is expressed widely, encoded for by GLP1R. The GLP1R variant rs6923761 (Gly168Ser) has been associated with increased weight loss in response to GLP-1 agonist therapy in some studies. This study tested the hypothesis that this variant would be associated with responsiveness to endogenous GLP-1 during DPP4I therapy. METHODS: Forty-seven subjects with hypertension and type 2 diabetes mellitus were assigned to one-week crossover therapy with placebo and the DPP4I sitagliptin (100 mg/d), and underwent a mixed meal study. Subjects were excluded for type 1 diabetes, poorly controlled diabetes with Hgb A1c ≥8.7%, use of an anti-diabetic medication other than metformin for last 12 months, or presence of secondary hypertension. RESULTS: Post-prandial GLP-1 levels were increased during sitagliptin (AUC 11413, 95% CI [7113, 15712]) as compared with placebo treatment (AUC 5101, 95% CI [2254, 7949], p<0.05), and did not significantly differ by genotype. Peak post-prandial glucose was significantly higher in placebo as compared with sitagliptin treatment (146.6 +/- 35.8 mg/dL versus 133.0 +/- 26.5 mg/dL, respectively; t=90 minutes, p<0.01). Subjects with one or two copies of the wild-type allele (Gly/Gly or Gly/Ser) had increased post-prandial glucose excursion as compared with Ser/Ser subjects, in both the placebo and sitagliptin treatments (plasma glucose at 90 minutes: placebo Gly/- 150.1 +/- 38.0 mg/dL vs Ser/Ser 132.6 +/- 13.7 mg/dL, p<0.05; sitagliptin Gly/- 135.8 +/- 27.3 mg/dL vs Ser/Ser 117.4 +/- 14.7 mg/dL, p<0.05). Post-prandial insulin levels were not different in the placebo versus sitagliptin treatments (AUC 13264, 95% CI [9296,17232] vs 11996, 95% CI [8278, 15714], respectively), but there was a genotype by drug treatment interaction (p<0.05) such that Ser/Ser subjects had higher post-prandial insulin in the placebo treatment as compared with other genotypes. This difference was eliminated with sitagliptin therapy. CONCLUSIONS: Homozygosity for the Ser variant of GLP1R is associated with decreased glucose after a mixed meal without altering the effect of sitagliptin on post prandial GLP-1 concentrations. Further studies are needed to assess whether this variant confers increased sensitivity at the GLP-1R and whether it affects the long-term response to DPP4I.

Polyphenol-rich curry made with mixed spices and vegetables increases postprandial plasma GLP-1 concentration in a dose-dependent manner.

Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis. Evidence is emerging that dietary bioactive phytochemicals such as polyphenols can increase GLP-1 concentration in vivo. Spices are rich in polyphenols and have oro-sensory properties, both of which can increase GLP-1 secretion. We therefore investigated the effects of mixed spices intake on postprandial GLP-1 concentration. Using a randomised, controlled, dose-response crossover trial in 20 young, healthy, Chinese men, volunteers were served white rice with 3 doses of curry made with mixed spices and vegetables. These test meals were isocaloric and macronutrient matched. Plasma total GLP-1 concentrations were measured before (baseline) and for up to 3 h after the consumption of test meals. We found a significant dose dependent increase in total AUC of plasma GLP-1 concentrations, adjusted for baseline, with increasing mixed spice doses [adjusted mean (±SEM) of 10568.3 ± 1267.9, 12391.8 ± 1333.94, and 13905.1 ± 1267.6 pg ml-1.min for Dose 0 Control, Dose 1 Curry and Dose 2 Curry respectively (p = 0.019)]. Consumption of polyphenol rich mixed spices and vegetables can therefore increase in vivo GLP-1 concentration.