Postprandial Glucose Concentrations Research Articles

Supplementing a carbohydrate-rich diet from late lactation to insemination increased glucose and insulin levels in weaned sows, leading to improved subsequent piglet birth weight.

Premating maternal nutrition is crucial for postweaning follicle growth, thereby influencing piglet birth weight in subsequent litters. The present study investigated the impact of supplementing a carbohydrate-rich premating diet in sows on metabolic hormones, subsequent piglet birth weight and reproductive performance. Sows were distributed into three groups, control (n=42) received standard diets; treatment I (n=41) received the same diets supplemented with 500 g of a carbohydrate-rich premating diet from weaning until insemination; treatment II (n=42) received the same diets supplemented with 500 g of a carbohydrate-rich premating diet from 7 days before weaning until insemination. Blood samples were taken from sows around weaning to measure serum insulin-like growth factor-1 and insulin, and blood glucose after feeding. The study found that sows on a carbohydrate-rich diet (treatment II) had higher postprandial glucose (P<0.05) and insulin levels (P=0.06) than others. This diet did not affect overall reproductive performance, but it did increase piglet birth weight and reduce the number of low-birth weight piglets compared to the control (P<0.001) and treatment I groups (P<0.05). Supplementing a carbohydrate-rich premating diet for 7 days before weaning until insemination enhanced postprandial glucose and insulin concentrations in weaned sows. This dietary intervention led to improved subsequent piglet birth weight and reduced the proportion of low-birth weight piglets.

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.

Dysglycaemia prediction using readily available clinical, anthropometric, and biochemical measurements

Background & aimsA 2-hour postprandial glucose (2-h PG) concentration greater than 140 mg/dL is associated with a greater risk of type-2 diabetes (TD2) and cardiovascular disease. An oral glucose tolerance test (OGTT) is the method most used for detecting either prediabetes or T2D; however, its use in clinical practice is limited due to the 2-h testing period. Therefore, the aim of the study was to assess dysglycaemia, through a prognostic assessment of body composition, biochemical and clinical parameters as predictors of an abnormal 2-h PG. MethodsParticipants underwent a physical examination in which their anthropometric measurements were obtained, and a blood sample was taken for biochemical and hormonal analysis. All patients underwent a 75-g OGTT after 8 h of fasting, and the levels of glucose and insulin were measured. The results were compared statistically by dividing the participants’ 2-h postprandial glucose (2-h PG) into the following groups: normoglycaemia (NGT), < 140 mg/dL; prediabetes, 140 to 199 md/dL; and T2D, ≥ 200 mg/dL. ResultsAmong 381 participants 220 belonged to the NGT group, 131 to the prediabetes group, and 30 to the diabetes group. As expected, fasting glucose, 1-h PG, 2-h PG, haemoglobin glycosylated (A1c) and QUICKI index were significantly higher as the stages of glycaemic dysregulation progressed. Interestingly, 53.4% of the NGT group had a monophasic type of curve in the OGTT and a QUICKI index of 0.32. Subsequently, associative models of 2-h PG were performed, and 4 models were obtained. The best model had a coefficient of determination of 0.747 (p = 0.001) and included the variables A1c, C-reactive protein (CRP), body fat mass, and total cholesterol. ConclusionsThe use of A1c, CRP, body fat mass, and total cholesterol in a model might associate with 2-h PG without the need for a 2-h OGTT.

Cluster analysis based on fasting and postprandial plasma glucose and insulin concentrations

Cluster analysis based on fasting and postprandial plasma glucose and insulin concentrations

Study on the effectiveness of postprandial blood glucose control and glycemic index of acetylated wheat flour in healthy volunteers

Background: The study was conducted to determine the ability to control postprandial blood glucose response and glycemic index of acetylated wheat starch cakes containing 31,2% of resistant starch on 12 healthy volunteers. Material and methods: Research designed using experimental and double-blind methods. During the two days of the clinical trial, after more than 12 hours of overnight fasting, each volunteer consumed a diet consisting of 1 cake containing 50 g of acetylated wheat starch or 50 g of natural wheat starch and 330 ml of filtered water in 15 minutes. Volunteers had determined their capillary blood glucose concentrations at times before meals, 60 and 120 minutes after meals. Results: Blood glucose concentration at 60 minutes after eating acetylated wheat starch cake (G1= 8.6 ± 0.8 mmol/L) was lower than natural wheat starch cake (G1= 11.7 + 1.1 mmol/L) (p &lt; 0.05). Similarly, blood glucose concentration at 120 minutes after eating acetylated wheat starch cake (G2= 7.1 ± 0.7 mmol/L) was lower than natural wheat starch cake (G2= 9.2 ± 1.7 mmol/L) (p &lt; 0.05). The area under the curve of blood glucose concentration after 120 minutes of eating natural wheat starch cake (AUC0-120min= 337.0 min*mmol/L) is doulble times larger than the acetylated wheat starch cake (AUC0-120min= 175.5 min*mmol/L) (p &lt; 0.05). Glycemic index of acetylated wheat starch cake is 52.0. Conclusion: Acetylated wheat starch cake has a low glycemic index, possessing the ability to control postprandial blood glucose effectively, limiting the increase of postprandial blood glucose concentration within the safe range, and it did not cause any digestive disorders in volunteers. This is very meaningful in the application of acetylated wheat starch to process foods not only for diabetic patients but also for pre-diabetic or overweight and obese people to support treatment and improve quality of life. Key words: resistant starch, blood glucose, glycemic index, volunteers.

The Role of the Glycemic Index and Glycemic Load in the Dietary Approach of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic disorder that often develops during pregnancy, characterized by glucose intolerance and insulin resistance (IR). To ensure the well-being of both the mother and the fetus, the body undergoes multiple metabolic and immunological changes that result in peripheral IR and, under certain hereditary or acquired abnormalities, GDM in predisposed women. The adverse short- and long-term effects of GDM impact both the mother and the fetus. Nutrition seems to play an important role to prevent GDM or improve its evolution. An emphasis has been given to the proportion of carbohydrates (CHO) relative to protein and lipids, as well as dietary patterns, in GDM. The effects of CHO on postprandial glucose concentrations are reflected in the glycemic index (GI) and glycemic load (GL). Diets rich in GI and GL may induce or exacerbate IR, whereas diets low in GI and GL appear to enhance insulin sensitivity and improve glycemic control. These positive outcomes may be attributed to direct interactions with insulin and glucose homeostasis or indirect effects through improved body composition and weight management. This comprehensive narrative review aims to explore the significance of nutrition, with a focus on the critical evaluation of GI and GL in the dietary management of women with GDM.

A high sucrose detection threshold is associated with increased energy intake and improved post-prandial glucose response independent of the sweetness intensity of isocaloric sucrose solutions

Several studies proposed a role for the sweet taste receptor in energy intake and blood glucose regulation, but little is yet known about the impact of the individual sweet taste perception. Here, we found in a cross-over human intervention study with 29 male participants that modulating the sweetness of an isocaloric sucrose solution did not influence postprandial plasma concentrations of blood glucose and associated hormones over 120 min and 2 h post-load energy intake. Independent of the sweetness of the test solution, tests persons with a higher sucrose detection threshold had an average of 402 ± 78.8 kcal (39 ± 21%) higher energy intake and a higher glucose/insulin ratio, combined with a higher liking for sweet tasting food, than the test persons of the low threshold group. The body composition suggested a higher fat-free mass in the high threshold group that may have influenced energy intake and post-prandial glucose responses.

Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology

The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications1,2, stressing the need for more personalized treatment1. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown3. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium–glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol−1; 95% confidence interval, −10.0 to −6.3 mmol mol−1), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups (NCT04451837).

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.

Effect of micronization and meal size of corn grain on glycemic response and in vitro hindgut acidosis potential in horses

This study aimed to 1) evaluate the interaction of corn grain micronization and starch levels per meal on equine plasma glucose, and 2) determine if micronization affects the risk of hindgut acidosis. Six mature (aged 6 to 10 years), healthy, non-pregnant mares (initial body weight [BW]: 301 to 463 kg) were used in a 2×3 factorial cross-over design. The treatments included two forms of corn grain (ground and micronized flaked) at three levels of starch (1, 1.5, and 2 g/kg BW per meal). The blood was sampled before and 30, 60, 90, 120, 180, 240, and 300 min after morning feeding and the glucose concentration in the plasma was determined. Small intestine and hindgut dry matter (DM) disappearances of ground and micronized corn were also compared using in vitro techniques. Micronized flaked corn grain showed three times more in vitro enzymatic DM disappearance (p < 0.001) compared with ground corn. Residues of in vitro enzymatic digestion of micronized flaked corn fermented 38.59 % faster than ground corn during in vitro hindgut incubation. The horses that consumed micronized flaked corn had higher post-prandial plasma glucose concentrations (p < 0.001). Increasing starch levels per meal from 1–2 g/kg BW resulted in higher plasma glucose concentrations (P = 0.005). However, no interaction of processing and starch meal size was found. Overall, processing the corn grain by micronization or increasing starch level per meal increased the plasma glucose concentrations, but the magnitude of the increases did not match that expected from in vitro studies.

Glycemic and Satiety Response to Three Mexican Honey Varieties.

Honey is considered one of the last untreated natural food substances, with a complex composition. It is produced by bees (Apis mellifera) from nectar. The glycemic index (GI) is a physiological assessment of a food's carbohydrate content via its effect on postprandial blood glucose concentrations. This study evaluated the GI and the satiety response to three Mexican types of honey administered to 26 healthy volunteers. The fructose values ranged from 272.40 g/kg to 395.10 g/kg, while the glucose value ranged from 232.20 g/kg to 355.50 g/kg. The fructose/glucose (F/G) ratio of honey was 1.45, 1.00, and 1.17 for highland, multifloral, and avocado honey, respectively. Highland and avocado honey were classified as medium-GI (69.20 ± 4.07 and 66.36 ± 5.74, respectively), while multifloral honey was classified as high-GI (74.24 ± 5.98). Highland honey presented a higher satiety values response than glucose. The difference in GI values and the satiety response effect of highland honey could be explained by its different carbohydrate composition and the possible presence of other honey components such as phytochemicals. Honey, especially avocado, could therefore be used as a sweetener without altering significantly the blood glucose concentration.

Empagliflozin Normalizes Fasting Hyperglycemia and Improves Postprandial Glucose Tolerance in Totally Pancreatectomized Patients: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Insulin remains the only glucose-lowering treatment modality recommended for totally pancreatectomized patients. We investigated the effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on fasting and postprandial glucose concentrations in pancreatectomized patients and matched healthy control participants. In a randomized, double-blind, placebo-controlled crossover study, 10 pancreatectomized patients and 10 matched control participants underwent two 3-h liquid mixed meal tests preceded by two doses of 25 mg empagliflozin (administered the night before and in the morning of the meal test) or placebo, respectively. Basal insulin was administered as usual, but bolus insulin was omitted before the meal test during experimental days. Compared with placebo, empagliflozin lowered fasting plasma glucose (5.0 ± 0.4 vs. 7.9 ± 0.9 mmol/L [mean ± SEM], P = 0.007) and postprandial plasma glucose excursions as assessed by baseline-subtracted area under the curve (1,080 [733; 1,231] vs. 1,169 [1,036; 1,417] pmol/L × min [median (25th and 75th percentiles)], P = 0.014) in the pancreatectomized patients. In the control participants, empagliflozin lowered fasting plasma glucose compared with placebo (5.1 ± 0.1 vs. 5.5 ± 0.1 mmol/L, P = 0.008) without affecting postprandial glucose excursions significantly. The pancreatomy group exhibited greater postprandial glucagon excursions compared with the control group on both experimental days (P ≤ 0.015); no within-group differences between days were observed. Empagliflozin administered the day before and immediately before a standardized liquid mixed meal test normalized fasting hyperglycemia and improved postprandial glucose tolerance in pancreatectomized patients.

Dietary Approach of Patients with Hormone-Related Cancer Based on the Glycemic Index and Glycemic Load Estimates.

Hormone-related cancers, namely breast, endometrial, cervical, prostate, testicular, and thyroid, constitute a specific group of cancers dependent on hormone levels that play an essential role in cancer growth. In addition to the traditional risk factors, diet seems to be an important environmental factor that partially explains the steadily increased prevalence of this group of cancer. The composition of food, the dietary patterns, the endocrine-disrupting chemicals, and the way of food processing and preparation related to dietary advanced glycation end-product formation are all related to cancer. However, it remains unclear which specific dietary components mediate this relationship. Carbohydrates seem to be a risk factor for cancer in general and hormone-related cancers, in particular, with a difference between simple and complex carbohydrates. Glycemic index and glycemic load estimates reflect the effect of dietary carbohydrates on postprandial glucose concentrations. Several studies have investigated the relationship between the dietary glycemic index and glycemic load estimates with the natural course of cancer and, more specifically, hormone-related cancers. High glycemic index and glycemic load diets are associated with cancer development and worse prognosis, partially explained by the adverse effects on insulin metabolism, causing hyperinsulinemia and insulin resistance, and also by inflammation and oxidative stress induction. Herein, we review the existing data on the effect of diets focusing on the glycemic index and glycemic load estimates on hormone-related cancers.

Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-and-diabetic adults.

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre- and - type 2 diabetes (T2D). Eight T2D adults (60±4 years) with overweight/obesity (32±4 kg·m-2) under chronic metformin treatment (9±6 years; 1281±524 mg·day-1) underwent four trials; a) taking their habitual metformin treatment (MET), b) substituting during 96 h their metformin medication by placebo (PLAC), c) placebo combined with 50 min bout of high-intensity interval exercise (PLAC+EX), and d) metformin combined with exercise (MET+EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (i.e., OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET+EX lower than PLAC and PLAC+EX, respectively; P=0.023). MET+EX increased MATSUDAindex above PLAC (4.8±1.4 vs 3.3±1.0, respectively; P=0.018) and OGISindex above PLAC (358±52 vs 306±46 mL·min-1·m-2, respectively; P=0.006). Metformin decreased plasma appearance of the ingested glucose (Ra OGTT; MET vs PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg-1·min-1; P=0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre- and - type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise.

Breaking prolonged sitting increases 24-h physical activity and self-perceived energy levels but does not acutely affect cognition in healthy adults.

It is unknown whether predetermined (un)interrupted sitting within a laboratory setting will induce compensatory changes in human behaviours (energy intake and physical activity) once people return to a free-living environment. The effects of breaking up prolonged sitting on cognition are also unclear. Twenty-four (male = 13) healthy participants [age 31 ± 8 y, BMI 22.7 ± 2.3kg/m2 (mean ± SD)] completed 320min mixed-feeding trials under prolonged sitting (SIT) or with 2min walking at 6.4km/h every 20min (ACTIVE), in a randomised crossover design. Human behaviours were recorded post-trial under free-living conditions until midnight. Cognitive performance was evaluated before and immediately after SIT and ACTIVE trials. Self-perceived sensations (appetite, energy and mood) and finger prick blood glucose levels were collected at regular intervals throughout the trials. There were no differences between trials in eating behaviour and spontaneous physical activity (both, p > 0.05) in free-living conditions, resulting in greater overall total step counts [11,680 (10740,12620) versus 6049 (4845,7253) steps] and physical activity energy expenditure (PAEE) over 24-h period in ACTIVE compared to SIT (all, p < 0.05). Greater self-perceived levels of energy and lower blood glucose iAUC were found in ACTIVE trial compared to SIT trial (both, p < 0.05). No differences were found in cognitive performance between trials (all, p > 0.05). Breaking up sitting does not elicit subsequent behavioural compensation, resulting in greater 24-h step counts and PAEE in healthy adults. Breaking up sitting reduces postprandial glucose concentrations and elicits greater self-perceived energy levels, but these positive effects do not acutely translate into improved cognitive function.

Obesity wars: hypothalamic sEVs a new hope.

There are currently several pharmacological therapies available for the treatment of obesity, targeting both the central nervous system (CNS) and peripheral tissues. In recent years, small extracellular vesicles (sEVs) have been shown to be involved in many pathophysiological conditions. Because of their special nanosized structure and contents, sEVs can activate receptors and trigger intracellular pathways in recipient cells. Notably, in addition to transferring molecules between cells, sEVs can also alter their phenotypic characteristics. The purpose of this review is to discuss how sEVs can be used as a CNS-targeted strategy for treating obesity. Furthermore, we will evaluate current findings, such as the sEV-mediated targeting of hypothalamic AMP-activated protein kinase (AMPK), and discuss how they can be translated into clinical application.

Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water—The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis

BackgroundServing whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate. ObjectivesThe objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)]. MethodsWe searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022. ResultsWhey protein premeals lowered peak glucose concentration by −1.4 mmol/L [−1.9 mmol/L; −0.9 mmol/L], and the area under the curve for glucose was −0.9 standard deviation (SD) [−1.2 SD; −0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects. ConclusionsIn conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.

1645-P: Diabetes-Associated Variation in TCF7L2 Is Associated with a Longitudinal Decline in Glucose Tolerance Accompanied by Impaired Suppression of Postprandial Glucagon Secretion

Diabetes-associated alleles in TCF7L2 increase the rate of conversion from prediabetes to type 2 diabetes (T2DM). Multiple studies have shown an association of the T allele at rs7903146 with impaired β-cell function and more recently with defective suppression of α-cell secretion by glucose. However, the temporal relationship of these abnormalities is uncertain. To study the longitudinal changes in islet function, we recruited 140 individuals half of whom were homozygous for the diabetes-associated allele (TT) at rs7903146. The remainder were homozygous for the protective allele (CC). Subjects were studied on 2 occasions, 3 years apart using an oral 75g glucose challenge. This was labelled with 13C-glucose, in concert with intravenously infused tracers to enable measurement of endogenous glucose production, meal appearance and glucose disposal. Indices for insulin secretion and action were estimated using the oral minimal model. Fasting, peak and integrated (443 ± 27 vs. 428 ± 50 mmol/l per 6hr, p = 0.54) post-prandial glucose concentrations did not differ over time in people with the CC genotype. In contrast, post-prandial integrated glucose concentrations increased (441 ± 29 vs. 544 ± 37 mmol/l per 6hr, p &amp;lt; 0.01) in people with the TT genotype. This was accompanied by an increase in integrated postprandial glucagon concentrations (526 ± 39 vs. 618 ± 61 pmol/l per 2hr, p = 0.04) that was not observed in the CC genotype (537 ± 50 vs. 525 ± 65 pmol/l per 2hr, p = 0.07). There were no baseline differences in β-cell function between genotype groups. Disposition Index in both TT (950 ± 130 vs. 868 ± 92 10-4 dl/kg/min per μU/ml, baseline vs. follow-up study respectively, p=0.42) and CC (896 ± 177 vs. 1062 ± 289 10-4 dl/kg/min per μU/ml, p=0.65) groups did not change. This data would suggest that α-cell dysfunction associated with the TT genotype (rs7903146) precedes β-cell dysfunction in people prior to the development of T2DM. Disclosure M.Zeini: None. K.Muthusamy: None. A.M.Egan: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. A.Vella: Advisory Panel; Rezolute, Inc., Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S, Other Relationship; Novo Nordisk. Funding National Institutes of Health (DK116723)

285-LB: LEAP2 Reduces Preprandial and Postprandial Glucose Levels and Ad Libitum Food Intake in Obese Men

The naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP2) has gained interest as a ghrelin receptor antagonist. Recently, we reported food intake and plasma glucose-lowering effects of exogenous LEAP2 in lean healthy males. Here, we investigated the effects of LEAP2 infusion on ad libitum food intake and postprandial glucose tolerance in obese men. Twenty obese men (mean (SEM) age 44.2 (2.2) years; BMI 36.3 (0.8) kg/m2; body fat percentage 37.4 (0.9)%) were enrolled in this randomized, double-blind, placebo-controlled, crossover study comprising two experimental days. Experimental days involved a ~5-hour intravenous (iv) infusion of LEAP2 or placebo during which a liquid mixed meal test (MMT) and a subsequent ad libitum meal test were performed. Plasma glucose measures included fasted (preprandial), Cmax and Tmax values as well as area under the curve (AUC) during MMT. Ad libitum food intake was measured in kilojoule (kJ) and kJ/kg body weight. Compared to placebo, LEAP2 infusion lowered preprandial plasma glucose (mean (SEM): 5.03 (0.08) vs. 5.19 (0.06) mmol/L, P=0.0095) as well as Cmax (6.58 (0.18) vs. 6.98 mmol/L (0.18), P=0.0001) and AUC for plasma glucose during MMT (1,506 (33.4) vs. 1564 (30.4) min×mmol/L, P=0.0005), but not Tmax. Ad libitum food intake was reduced by ~13% during LEAP2 infusion compared to placebo (2,939 (266) vs. 3,378 (258) kJ, P=0.0118; 25.0 (2.4) vs. 28.4 (2.0) kJ/kg body weight, P=0.0140). We conclude that a continuous iv LEAP2 infusion reduces pre- and postprandial plasma glucose concentrations as well as ad libitum food intake in obese men. Disclosure A. Englund: None. C. A. Hagemann: Employee; Gubra ApS. L. S. Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. F. K. Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.

235-LB: Incretin-Linked Adipose Tissue Microvascular Blood Flow in Healthy People With and Without a Family History of Type 2 Diabetes

Adipose tissue microvascular blood flow (ATMBF) increases in response to a mixed meal challenge (MMC) to promote nutrient storage. This vascular action is impaired in apparently healthy people with a parent with type 2 diabetes (FH+). The mechanisms for this vascular impairment in FH+ are unknow. We aimed to investigate whether incretins [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)] are associated with ATMBF responses to a MMC. Thirteen healthy (FH-, no parents or grandparents with type 2 diabetes) and fourteen FH+ underwent a 2-hr MMC after an overnight fast. Age, BMI, fasting and peak postprandial blood glucose and plasma insulin concentrations were similar between FH- and FH+ (Table 1). Baseline ATMBF, assessed by contrast ultrasound, was similar between groups, but was impaired in FH+ in response to the MMC (Table 1). Peak plasma GLP-1 and GIP concentrations, but not their ratio (GLP-1:GIP), were higher in FH+ in response to the MMC (Table 1). GLP-1 and GIP concentrations were not associated with ATMBF, however, GLP-1:GIP was significantly associated with postprandial ATMBF at 1-hr (p=0.025, r=0.46). We conclude that impaired postprandial ATMBF in FH+ is not exclusively linked to incretin levels. However, lower GLP-1:GIP ratios may be linked to impaired ATMBF responses in the postprandial state. Disclosure K. Roberts-thomson: None. L. Parker: None. M. Keske: None.