Postprandial Glucagon-like Peptide-1 Response Research Articles

GLP-1 response during pregnancy: variations between trimesters and associations with appetite sensations and usual energy intake.

Further research is required to understand hormonal regulation of food intake during pregnancy and its association with energy intake. The objectives are to (i) compare postprandial responses of plasma glucagon-like peptide-1 (GLP-1) between trimesters, (ii) compare postprandial appetite sensations between trimesters, and (iii) examine trimester-specific associations between GLP-1 levels, appetite sensations, and usual energy intake. At each trimester, participants (n=26) consumed a standard test meal following a 12 h fast. Plasma GLP-1 levels were measured by enzyme-linked immunosorbent assay method at fasting and at 30, 60, 120, and 180 min postprandial. A visual analogue scale assessing appetite sensations was completed at fasting and at 15, 30, 45, 60, 90, 120, 150, and 180 min postprandial. Mean energy intake was assessed using three web-based 24 h dietary recalls at each trimester. Lower postprandial GLP-1 responses were observed in the 2nd (p=0.004) and 3rd trimesters (p<0.001) compared to the 1st trimester. Greater postprandial sensations of desire to eat, hunger, and prospective food consumption were noted in the 3rd trimester compared to the 1st trimester (p<0.04, for all). Fasting GLP-1 was negatively associated with fasting appetite sensations (except fullness) at the 2nd trimester (p<0.02, for all). Postprandially, significant associations were observed for incremental areas under the curve from 0 to 30 min between GLP-1 and fullness at the 2nd (p=0.01) and 3rd trimesters (p=0.03). No associations between fasting or postprandial GLP-1 and usual energy intake were observed. Overall, GLP-1 and appetite sensation responses significantly differ between trimesters, but few associations were observed between GLP-1, appetite sensations, and usual energy intake.

Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling

ABSTRACT The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients' insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.

609-P: Postprandial GLP-1 Response to Two Diabetes-Specific Formulas Compared with Instant Oatmeal in Adults With Type 2 Diabetes

Diabetes specific formulas (DSFs) are designed with an optimized macronutrient profile as a meal or snack replacement to meet the nutritional needs of people with diabetes while helping to manage blood glucose response. Macronutrients found in DSFs have been shown to promote glucagon-like peptide-1 (GLP-1) secretion, a key hormone involved in regulating incretin response to manage blood glucose levels during the postprandial period. We tested the postprandial GLP-1 response in two randomized, controlled crossover studies in adults with T2D with two DSFs (DSF-1; Study 1, DSF-2; Study 2) varying in macronutrient composition compared to isocaloric instant oatmeal (IOM). In each study, participants were randomly allocated to receive IOM or the study DSF on two test days separated by 4 - 14 days. Total GLP-1 concentration was measured at baseline, 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption. Outcome parameters included adjusted peak GLP-1 concentration, and positive area under the curve (pAUC) over 0 - 240 minutes for each participant. Respectively, Study 1 and Study 2 included 26 (n = 15 males, n = 11 females; mean age = 63.6 ± 1.4 years; mean BMI = 30.0 ± 0.9) and 22 (n = 14 males, n = 8 females; mean age = 64.6 ± 2.0 years; BMI = 32.8 ± 0.9) completed participants. Median (1st and 3rd quartile) adjusted peak GLP-1 concentration was significantly higher for DSF-1 (9.2 (6.4, 16.5) pmol/L vs. 3.7 (2.5, 9.0) pmol/L; p = 0.012) and DSF-2 (10.8 (7.5, 20.0) pmol/L vs. 6.3 (4.3, 9.4) pmol/L; p &amp;lt; 0.001) compared to IOM. DSFs significantly increased pAUC for GLP-1 response (DSF-1: 901 (410, 1091) vs. IOM: 177 (47, 421); p &amp;lt;0.001 and DSF-2: 1122 (682, 1820) vs. IOM: 403 (183, 778); p &amp;lt; 0.001) by 410% and 178%, respectively. As part of a diabetes management plan, DSFs can serve as a convenient tool to meet nutritional needs while improving GLP-1 response to help manage blood glucose. Disclosure S.Thomas: Employee; Abbott Nutrition. B.Besecker: Employee; Abbott Nutrition, Stock/Shareholder; Abbott Nutrition. Y.Choe: Employee; Abbott Nutrition.

The Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis

Background: There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Results: Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.

Rise in Postprandial GLP-1 Levels After Roux-en-Y Gastric Bypass: Involvement of the Vagus Nerve-Spleen Anti-inflammatory Axis in Type 2 Diabetic Rats.

The mechanism underlying postprandial glucagon-like peptide-1 (GLP-1) changes after metabolic surgery remains mostly unclarified. This investigation aimed to address whether the vagus nerve-spleen anti-inflammatory axis is involved in the rise in postprandial GLP-1 levels in type 2 diabetes mellitus (T2DM) rats following metabolic surgery. T2DM rat model was established with a high-fat diet and a low dose of streptozotocin and subjected to Roux-en-Y gastric bypass (RYGB) and splenic denervation. A mixed-meal tolerance test for postprandial GLP-1 response was performed. TNF-α in the plasma, spleen, and ileum was measured by ELISA, and alpha 7 nicotinic acetylcholine receptor (α7nAChR) expression in the spleen was analyzed by Western blot. Postprandial GLP-1 improvement by RYGB was accompanied by the reduction of TNF-α levels in spleen and ileum and up-regulation of splenic α7nAChR in T2DM rats. Splenic denervation abrogates a rise in postprandial GLP-1 levels in response to the mixed-meal challenge, along with higher TNF-α levels in spleen and ileum and down-regulation of splenicα7nAChR, compared with denervated sham rats. Our results reveal that the vagus nerve-spleen anti-inflammatory axis mediates the rise of postprandial GLP-1 response after RYGB through lowering TNF-α contents in the intestinal tissue in T2DM rats.

Differences in gastrointestinal hormones and appetite ratings among obesity classes

The aim of this study was to compare gastrointestinal (GI) hormones and subjective ratings of appetite among obesity classes, and between classes of obesity and controls. Ninety-eight adult individuals with obesity, divided into class I (n = 35), II (n = 44) and III (n = 19), together with 45 controls without obesity were included in this cross-sectional analysis. Body weight/composition, and basal and postprandial (after a 600 kcal fixed breakfast) plasma concentrations of acylated ghrelin, active glucagon-like peptide 1 (GLP-1), total peptide YY (PYY), cholecystokinin (CCK) and insulin, as well as subjective ratings of hunger, fullness, desire to eat (DTE) and prospective food consumption (PFC) were measured. There were no differences in the plasma concentration of GI hormones (either basal or postprandial) among obesity classes, except for insulin. In general, obesity was associated with impaired secretion of GI hormones. Ghrelin secretion did not decline postprandially in class-III obesity. GLP-1 peak for obesity class I and II was early and lower, while class III showed no postprandial GLP-1 response. Postprandial PYY response for obesity class II and III was absent, and class III showed a delayed and shortened postprandial CCK response. Obesity class II and III had greater basal insulin concentration compared to controls and postprandial insulin was greater in obesity class III versus class II, class I and controls. No differences were found for appetite ratings among obesity classes. In conclusion, obesity is characterized by impaired secretion of GI hormones, with reduced postprandial satiety, particularly in individuals with obesity class III. This abnormal pattern may lead to overeating.

Metabolic profiles, energy expenditures, and body compositions of the weight regain versus sustained weight loss patients who underwent Roux-en-Y gastric bypass.

Weight regain (WR) has been an emerging problem after Roux-en Y gastric bypass (RYGB) and little is known about the mechanisms of WR after RYGB. To evaluate the mechanisms of WR after RYGB through the postprandial gut hormones response, particularly glucagon-like peptide-1 (GLP-1), which regulates appetite control, energy expenditure, body composition, physical activities, dietary intake, and psychological factors. Duke University Medical Center, Durham, North Carolina. A cross sectional study of 34 patients who underwent RYGB at least 2 years and achieved ≥50% of excess weight loss at 1year was conducted. The subjects were categorized into WR group or sustained weight loss group, based upon whether their WR was ≥15% of postoperative lowest weight. The WR group had less augmented postprandial GLP-1 response but exaggerated hyperinsulinemia. Postprandial peptide YY, ghrelin, and glucose were not different between group. Patients who regained weight required less weight-adjusted energy expenditure and had more percentage body fat and less percentage lean mass. The caloric intake and diet composition were comparable between groups; however, the WR group had higher depression scores, binge eating scales, and hunger rating and spent significantly less time on vigorous exercise. The mechanisms of WR in patients who were initially successful after RYGB are complex and involved not only the role of postprandial gut hormone response but are also related to energy expenditure adaptation and body composition changes. Moreover, food preference and physical activity may play roles in weight control after bariatric surgery. Further prospective controlled trial is needed to explore the mechanisms of WR.

Plasma GLP-1 Response to Oral and Intraduodenal Nutrients in Health and Type 2 Diabetes-Impact on Gastric Emptying.

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. 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. We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D). 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). 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.

Blood Sampling From Rat Ileal Mesenteric Vein Revealed a Major Role of Dietary Protein in Meal-Induced GLP-1 Response.

The present study was conducted to examine region-dependent glucagon-like peptide-1 (GLP-1) responses to “meal ingestion” under physiological (conscious and unrestrained) conditions using rats with a catheter inserted into either the portal vein (PV) or the ileal mesenteric vein (ILMV). After recovery from the cannulation surgery, blood samples were collected from either PV or ILMV catheter before and after the voluntary ingestion of test diets. After an AIN-93G standard diet ingestion, GLP-1 concentration was higher in ILMV than in PV, and postprandial responses of peptide-YY (PYY) had similar trend, while that of glucose dependent-insulinotropic polypeptide showed an opposite trend to GLP-1/PYY responses. In a separated experiment, a protein-enriched diet containing casein at 25% wt/wt transiently increased GLP-1 concentration only in ILMV; however, a protein-free diet did not increase GLP-1 concentrations in PV or ILMV. These results indicate that postprandial GLP-1 is immediately released from the distal intestine under physiological conditions, and that dietary protein has a critical role in the enhancement of postprandial GLP-1 response.

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.

The role of GLP-1 in postprandial glucose metabolism after bariatric surgery: a narrative review of human GLP-1 receptor antagonist studies.

The Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) bariatric procedures lead to remission or improvement of type 2 diabetes. A weight loss-independent augmentation of postprandial insulin secretion contributes to the improvement in glycemic control after RYGB and is associated with a ∼10-fold increase in plasma concentrations of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the physiologic importance of the markedly increased postprandial GLP-1 secretion after RYGB has been much debated. The effect of GLP-1 receptor blockade after RYGB has been investigated in 12 studies. The studies indicate a shift toward a more prominent role for GLP-1 in postprandial β-cell function after RYGB. The effect of GLP-1 receptor antagonism on glucose tolerance after RYGB is more complex and is associated with important methodological challenges. The postprandial GLP-1 response is less enhanced after SG compared with RYGB. However, the effect of GLP-1 receptor blockade after SG has been examined in 1 study only and needs further investigation.

Exaggerated postprandial GLP-1 secretion following esophagectomy is not associated with gastric emptying and intestinal transit.

Esophagectomy causes postprandial symptoms associated with an exaggerated postprandial gut hormone response. This study aimed to compare the gastrointestinal transit time of patients 1year after esophagectomy with unoperated controls, including its relation to satiety gut hormone release. In this cross-sectional study, consecutive, disease-free patients after esophagectomy with pyloroplasty were compared with unoperated control subjects to assess gastric emptying (GE) and cecal arrival time (CAT). Serial plasma samples were collected before, and for 300minutes after, a mixed-meal challenge. Body composition was assessed, and symptom scores were calculated. Eleven patients 1year post-esophagectomy (age: 62.6 ± 9.8, male: 82%) did not show a significantly different GE pattern compared with 10 control subjects (P = 0.245). Rather, patients could be categorized bimodally as exhibiting either rapid or slow GE relative to controls. Those with rapid GE trended toward a higher postprandial symptom burden (P = 0.084) without higher postprandial glucagon-like peptide-1 (GLP-1) secretion (P = 0.931). CAT was significantly shorter after esophagectomy (P = 0.043) but was not significantly associated with GE, GLP-1 secretion, or symptom burden. Neither early nutrient delivery to the proximal small intestine nor to the colon explains the exaggerated postprandial GLP-1 response after esophagectomy. GE varies significantly in these patients despite consistent pyloric management.

1905-P: Downregulation of HMGCS2 Expression in Small Intestinal Mucosa Biopsies after Roux-en-Y Gastric Bypass Surgery: A Possible Contributor to GLP-1 Hypersecretion?

Background and Aims: Roux-en-Y gastric bypass (RYGB) surgery significantly improves glucose metabolism independently of surgery-induced weight loss; partly due to the increased postprandial secretion of the insulinotropic gut hormone glucagon-like peptide 1 (GLP-1). Mouse studies have shown that intestinally derived ketone bodies inhibit GLP-1 secretion from enteroendocrine L cells, and it was recently suggested that RYGB-induced downregulation of intestinal ketogenesis contributes to the increased GLP-1 secretion after RYGB. We investigated the intestinal expression of genes involved in ketogenesis and postprandial plasma GLP-1 responses before and after RYGB. Materials and Methods: Twenty obese individuals underwent mixed meal tests and anterograde enteroscopy with gut mucosal biopsy retrieval before and 3 months after RYGB. A global gene expression analysis was performed on the mucosal biopsies. Here, we report the expression of genes involved in ketogenesis and postprandial plasma GLP-1 responses. Results: We observed a significant 7.6-fold downregulation of the gene encoding 3-hydroxy-3- methylglutaryl-CoA synthase 2 (HMGCS2) (the rate-determining enzyme in ketogenesis) in the alimentary limb after RYGB. The proglucagon gene encoding GLP-1 was significantly upregulated after surgery and postprandial plasma GLP-1 responses increased significantly after RYGB. Conclusions: RYGB-induced downregulation of intestinal HMGCS2 gene expression in obese individuals may indicate reduced intestinal ketogenesis; supporting the notion (originating from animal studies) that reduced ketone body-mediated inhibition of L cells constitute a contributor to postprandial hypersecretion of GLP-1 after RYGB. Disclosure C. Legart: None. T. Jorsal: None. C.A. Hagemann: Employee; Self; Gubra. D. Worm: None. C.B. Juhl: None. A.R. Andries: None. C. Zhang: Employee; Self; Gubra. N. Vrang: Board Member; Self; Gubra. Employee; Self; Gubra. Stock/Shareholder; Self; Gubra. K. Rigbolt: Employee; Self; Gubra. J. Jelsing: Board Member; Self; Gubra. Stock/Shareholder; Self; Gubra. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp &amp; Dohme Corp., Sanofi. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Norgine B.V., Novo Nordisk A/S.

Acute Effect of Pistachio Intake on Postprandial Glycemic and Gut Hormone Responses in Women With Gestational Diabetes or Gestational Impaired Glucose Tolerance: A Randomized, Controlled, Crossover Study.

Long-term consumption of pistachios could potentially improves glucose homeostasis. Impaired postprandial glucose, insulin, and glucagon-like peptide-1 (GLP-1) responses have been reported in gestational diabetes mellitus (GDM) patients. The objective of this study was to evaluate the acute effects of two isocaloric test meals, 42 g pistachios and 100 g whole-wheat bread (WWB) on postprandial glucose, insulin, and gut derived incretin levels in Chinese women with gestational impaired glucose tolerance (GIGT) or GDM. Expected glucose and insulin responses were observed after WWB consumption. Isocaloric pistachio intake had minimal effect on blood glucose or insulin. In both GIGT and GDM patients, significant higher GLP-1 levels were observed at 90 and 120 min after pistachio compared to WWB intake. Significant lower gastric inhibitory polypeptide (GIP) levels were observed at 30 and 60 min in GDM patients or 120 min in GIGT patients after pistachio compared to WWB intake. In summary, isocaloric pistachio intake induced significantly lower postprandial glucose, insulin and GIP but higher GLP-1 levels compared to WWB. Our data suggest pistachios are effective alternative to a low-fat, high-carbohydrate food to improve postprandial glucose, insulin, and GLP-1 response in women with GDM and GIGT.

1145-P: Acarbose-Induced Glucagon-Like Peptide-1 Secretion Contributes to the Glucose-Lowering Effect of Acarbose

The glucose-lowering alpha-glucosidase inhibitor acarbose, is believed to act by delaying digestion and absorption of dietary carbohydrates. It has been shown that acarbose 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 (T2D). In a double-blinded, placebo-controlled, randomized, cross-over study, 15 participants with metformin-treated T2D (age 57-85 years, BMI 23.6-34.6 kg/m2, HbA1c 40-74 mmol/mol (5.8-8.9%)) were subjected to two 14-day treatment periods with acarbose (uptitrated to 100 mg TID) and placebo treatment, respectively, with an interposed 6-week wash-out period. At the end of each treatment period, we performed two randomized 4-hour mixed meal tests (including acetaminophen for evaluation of gastric emptying) with concomitant infusion of exendin(9-39)NH2 (1000 pmol/kg/min for 20 min followed by 450 pmol/kg/min for 240 min) and saline, respectively. Acarbose treatment lowered fasting plasma glucose (P&amp;lt;0.0001) and postprandial plasma glucose excursions (P&amp;lt;0.0001) compared to placebo. Furthermore, acarbose almost doubled the postprandial GLP-1 response (P=0.0032), reduced postprandial glucose-dependent insulinotropic polypeptide (P&amp;lt;0.0001) and delayed gastric emptying (P=0.0395). No absolute difference was seen in exendin(9-39)NH2-induced postprandial plasma glucose changes between treatment periods (P=0.54), but relative to postprandial glucose tolerance during exendin(9-39)NH2 infusions, the change (i.e., contribution of GLP-1) was significantly higher during acarbose (56±26%) compared to placebo treatment (37±15%) (P=0.042). We conclude that acarbose treatment robustly stimulates GLP-1 secretion in patients with T2D and that acarbose-induced GLP-1 secretion contributes to the glucose-lowering effect of acarbose. Disclosure N.B. Dalsgaard: None. L.S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. L.S. Hansen: None. N.L. Hansen: None. S. Stensen: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsbøll: None. 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.

Continuous feeding of a combined high-fat and high-sucrose diet, rather than an individual high-fat or high-sucrose diet, rapidly enhances the glucagon-like peptide-1 secretory response to meal ingestion in diet-induced obese rats.

Glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L-cells in response to nutrient ingestion. To date, GLP-1 secretion in diet-induced obesity is not well characterized. We aimed to examine GLP-1 secretion in response to meal ingestion during the progression of diet-induced obesity and determinewhether a combined high-fat and high-sucrose (HFS) diet, an individual high-fat (HiFat), or a high-sucrose (HiSuc) diet affect adaptive changes in the postprandial GLP-1 response. Rats were fed a control, HiFat diet (30% weight), HiSuc diet (40% weight), or HFS (30% fat and 40% sucrose) diet for 5 wk. Meal tolerance tests were conducted to determine postprandial glucose, insulin, and GLP-1 responses to standard (control) diet ingestion every 2 wk. After 5 wk, body weight gain of the HiFat (232.3 ± 7.8 g; P = 0.021) and HFS groups (228.0 ± 7.8; P = 0.039), but not the HiSuc group (220.3 ± 7.9; P = 0.244), were significantly higher than that of the control group (200.7 ± 5.4 g). In meal tolerance tests after 2 wk, GLP-1 concentration was significantly elevated in the HFS group only (17.2 ± 2.6 pM; P < 0.001) in response to meal ingestions, but the HiFat group (16.6 ± 3.7 pM; P = 0.156) had a similar response as the HFS group. After 4 wk, GLP-1 concentrations were similarly elevated at 15min in the HFS (14.1 ± 4.4; P = 0.010), HiFat (13.2 ± 2.0; P < 0.001), and HiSuc (13.0 ± 3.3; P = 0.016) groups, but the HFS (9.8 ± 1.0; P = 0.019) and HiFat (8.3 ± 1.5; P = 0.010) groups also had significant elevation at 30min. These results demonstrate that the continuous ingestion of excessive fat and sucrose rapidly enhances the GLP-1 secretory response to luminal nutrients, and the HiFat diet may have a potent effect compared with the HiSuc diet on GLP-1 secretory responses. The increment of postprandial GLP-1 and insulinsecretion may have a role in normalizing postprandial glycaemia and slowing the establishment of glucose intolerance.

A high carbohydrate, but not fat or protein meal attenuates postprandial ghrelin, PYY and GLP-1 responses in Chinese men.

It is known that the macronutrient content of a meal has different impacts on the postprandial satiety and appetite hormonal responses. Whether obesity interacts with such nutrient-dependent responses is not well characterized. We examined the postprandial appetite and satiety hormonal responses after a high-protein (HP), high-carbohydrate (HC), or high-fat (HF) mixed meal. This was a randomized cross-over study of 9 lean insulin-sensitive (mean±SEM HOMA-IR 0.83±0.10) and 9 obese insulin-resistant (HOMA-IR 4.34±0.41) young (age 21–40 years), normoglycaemic Chinese men. We measured fasting and postprandial plasma concentration of glucose, insulin, active glucagon-like peptide-1 (GLP-1), total peptide-YY (PYY), and acyl-ghrelin in response to HP, HF, or HC meals. Overall postprandial plasma insulin response was more robust in the lean compared to obese subjects. The postprandial GLP-1 response after HF or HP meal was higher than HC meal in both lean and obese subjects. In obese subjects, HF meal induced higher response in postprandial PYY compared to HC meal. HP and HF meals also suppressed ghrelin greater compared to HC meal in the obese than lean subjects. In conclusion, a high-protein or high-fat meal induces a more favorable postprandial satiety and appetite hormonal response than a high-carbohydrate meal in obese insulin-resistant subjects.

Influences of Dietary Added Sugar Consumption on Striatal Food-Cue Reactivity and Postprandial GLP-1 Response.

Sugar consumption in the United States exceeds recommendations from the American Heart Association. Overconsumption of sugar is linked to risk for obesity and metabolic disease. Animal studies suggest that high-sugar diets alter functions in brain regions associated with reward processing, including the dorsal and ventral striatum. Human neuroimaging studies have shown that these regions are responsive to food cues, and that the gut-derived satiety hormones, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY), suppress striatal food-cue responsivity. We aimed to determine the associations between dietary added sugar intake, striatal responsivity to food cues, and postprandial GLP-1 and PYY levels. Twenty-two lean volunteers underwent a functional magnetic resonance imaging (fMRI) scan during which they viewed pictures of food and non-food items after a 12-h fast. Before scanning, participants consumed a glucose drink. A subset of 19 participants underwent an additional fMRI session in which they consumed water as a control condition. Blood was sampled for GLP-1, and PYY levels and hunger ratings were assessed before and ~75 min after drink consumption. In-person 24-h dietary recalls were collected from each participant on three to six separate occasions over a 2-month period. Average percent calories from added sugar were calculated using information from 24-h dietary recalls. A region-of-interest analysis was performed to compare the blood oxygen level-dependent (BOLD) response to food vs. non-food cues in the bilateral dorsal striatum (caudate/putamen) and ventral striatum (nucleus accumbens). The relationships between added sugar, striatal responses, and hormone changes after drink consumption were assessed using Spearman’s correlations. We observed a positive correlation between added sugar intake and BOLD response to food cues in the dorsal striatum and a similar trend in the nucleus accumbens after glucose, but not water, consumption. Added sugar intake was negatively associated with GLP-1 response to glucose. Post hoc analysis revealed a negative correlation between GLP-1 response to glucose and BOLD response to food cues in the dorsal striatum. Our findings suggest that habitual added sugar intake is related to increased striatal response to food cues and decreased GLP-1 release following glucose intake, which could contribute to susceptibility to overeating.

GLP-1 response to sequential mixed meals: influence of insulin resistance.

Previous work has shown that potentiation of insulin release is impaired in non-diabetic insulin resistance; we tested the hypothesis that this defect may be related to altered glucagon-like peptide-1 (GLP-1) release. On consecutive days, 82 non-diabetic individuals, classified as insulin sensitive (IS, n=41) or insulin resistant (IR, n=41) by the euglycaemic clamp, were given two sequential mixed meals with standard (75 g, LCD) or double (150 g, HCD) carbohydrate content. Plasma glucose, insulin, C-peptide, non-esterified fatty acids (NEFA) and GLP-1 concentrations were measured; β-cell function (glucose sensitivity and potentiation) was resolved by mathematical modelling. Fasting GLP-1 levels were higher in IR than IS (by 15%, P=0.006), and reciprocally related to insulin sensitivity after adjustment for sex, age, fat mass, fasting glucose or insulin concentrations. Mean postprandial GLP-1 responses were tightly correlated with fasting GLP-1, were higher for the second than the first meal, and higher in IR than IS subjects but only with LCD. In contrast, incremental GLP-1 responses were higher during (i) the second than the first meal, (ii) on HCD than LCD, and (iii) significantly smaller in IR than IS independently of meal and load. Potentiation of insulin release was markedly reduced in IR vs IS across meal and carbohydrate loading. In the whole dataset, incremental GLP-1 was directly related to potentiation, and both were inversely related to mean NEFA concentrations. We conclude that (a) raised GLP-1 tone may be inherently linked with a reduced GLP-1 response and (b) defective post-meal GLP-1 response may be one mechanism for impaired potentiation of insulin release in insulin resistance.