Early Postprandial Period Research Articles

High-Moisture Extrusion of a Dietary Protein Blend Impairs In Vitro Digestion and Delays In Vivo Postprandial Plasma Amino Acid Availability in Humans

BackgroundIndustrial processing can alter the structural complexity of dietary proteins and, potentially, their digestion and absorption upon ingestion. High-moisture extrusion (HME), a common processing method used to produce meat alternative products, affects in vitro digestion, but human data are lacking. We hypothesized that HME of a mycoprotein/pea protein blend would impair in vitro digestion and in vivo postprandial plasma amino acid availability. MethodsIn Study A, 9 healthy volunteers completed 2 experimental trials in a randomized, double-blind, crossover design. Participants consumed a beverage containing 25 g protein from a “dry” blend (CON) of mycoprotein/pea protein (39%/61%) or an HME content-matched blend (EXT). Arterialized venous blood samples were collected in the postabsorptive state and regularly over a 5-h postprandial period to assess plasma amino acid concentrations. In Study B, in vitro digestibility of the 2 beverages were assessed using bicinchoninic acid assay and optical fluorescence microscopy at baseline and during and following gastric and intestinal digestion using the INFOGEST model of digestion. ResultsProtein ingestion increased plasma total, essential (EAA), and branched-chain amino acid (BCAA) concentrations (time effect, P < 0.0001) but more rapidly and to a greater magnitude in the CON compared with the EXT condition (condition × time interaction, P < 0.0001). This resulted in greater plasma availability of EAA and BCAA concentrations during the early postprandial period (0–150 min). These data were corroborated by the in vitro approach, which showed greater protein availability in the CON (2150 ± 129 mg/mL) compared with the EXT (590 ± 41 mg/mL) condition during the gastric phase. Fluorescence microscopy revealed clear structural differences between the 2 conditions. ConclusionsThese data demonstrate that HME delays in vivo plasma amino acid availability following ingestion of a mycoprotein/pea protein blend. This is likely due to impaired gastric phase digestion as a result of HME-induced aggregate formation in the pea protein.This trial was registered at clinicaltrials.gov as NCT05584358.

Acute Microbial Protease Supplementation Increases Net Postprandial Plasma Amino Acid Concentrations After Pea Protein Ingestion in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundDigestibility is a primary factor in determining the quality of dietary protein. Microbial protease supplementation may be a strategy for improving protein digestion and subsequent postprandial plasma amino acid availability. ObjectivesTo assess the effect of co-ingesting a microbial protease mixture with pea protein on postprandial plasma amino acid concentrations. DesignA mixture of 3 microbial protease preparations (P3) was tested for proteolytic efficacy in an in vitro static simulation of gastrointestinal digestion. Subsequently, in a randomized, double-blind, placebo-controlled crossover trial, 24 healthy adults (27 ± 4 y; 12 females, 12 males) ingested 25 g pea protein isolate (20 g protein, 2.2 g fat) with either P3 or maltodextrin placebo (PLA). Blood samples were collected at baseline and throughout a 0‒5 h postprandial period and both the early (0–2 h) iAUC and total (0–5 h) iAUC were examined. ResultsPlasma glucose concentrations decreased in both conditions (P < 0.001), with higher concentrations after P3 ingestion compared with PLA (P < 0.001). Plasma insulin concentrations increased for both conditions (P < 0.001) with no difference between conditions (P = 0.331). Plasma total amino acid (TAA) concentrations increased over time (P < 0.001) with higher concentrations observed for P3 compared with PLA (P = 0.010) during the 0‒5 h period. There was a trend for elevated essential amino acid (EAA) concentrations for P3 compared with PLA (P = 0.099) during the 0‒5 h postprandial period but not for leucine (P = 0.282) or branched-chain amino acids (BCAA, P = 0.410). The early net exposure (0‒2 h iAUC) to amino acids (leucine, BCAA, EAA, and TAA) was higher for P3 compared with PLA (all, P < 0.05). ConclusionsMicrobial protease co-ingestion increases plasma TAA concentrations (0–5 h) and leucine, BCAA, EAA, and TAA availability in the early postprandial period (0‒2 h) compared with ingesting pea protein with placebo in healthy adults.

Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals

Aims/hypothesisPost-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes during insulin-induced postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia after Roux-en-Y gastric bypass vs surgical and non-surgical control individuals.MethodsIn this case–control study, 32 adults belonging to four groups with comparable age, sex and BMI (patients with post-bariatric hypoglycaemia, Roux-en-Y gastric bypass, sleeve gastrectomy and non-surgical control individuals) underwent a postprandial hypoglycaemic clamp in our clinical research unit to reach the glycaemic target of 2.5 mmol/l 150–170 min after ingesting 15 g of glucose. Glucose fluxes were assessed during the postprandial and hypoglycaemic period using a dual-tracer approach. The primary outcome was the incremental AUC of glucagon during hypoglycaemia. Catecholamines, cortisol, growth hormone, pancreatic polypeptide and endogenous glucose production were also analysed during hypoglycaemia.ResultsThe rate of glucose appearance after oral administration, as well as the rates of total glucose appearance and glucose disappearance, were higher in both Roux-en-Y gastric bypass groups vs the non-surgical control group in the early postprandial period (all p<0.05). During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups vs the non-surgical control group (all p<0.01). Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia vs the non-surgical control group (median [IQR]: 24.7 [10.9, 38.7] pmol/l vs 238.7 [186.3, 288.9] pmol/l) (p=0.005). Other hormonal responses to hypoglycaemia and endogenous glucose production did not significantly differ between the groups.Conclusions/interpretationThe glucagon response to insulin-induced postprandial hypoglycaemia is lower in post-bariatric surgery individuals compared with non-surgical control individuals, irrespective of the surgical modality. No significant differences were found between patients with post-bariatric hypoglycaemia and surgical control individuals, suggesting that impaired counter-regulation is not a root cause of post-bariatric hypoglycaemia.Trial registrationClinicalTrials.gov NCT04334161Graphical abstract

An evaluation of the rat intestinal monoamine biogeography days following exposure to acute stress.

Stress-induced abnormalities in gut monoamine levels (e.g., serotonin, dopamine, norepinephrine) have been linked to gastrointestinal (GI) dysfunction, as well as the worsening of symptoms in GI disorders. However, the influence of stress on changes across the entire intestinal monoamine biogeography has not been well-characterized, especially in the days following stress exposure. Therefore, the aim of this study was to comprehensively assess changes to monoamine neurochemical signatures across the entire rat intestinal tract days after exposure to an acute stressor. To the end, adult male F344 rats were subjected to an episode of unpredictable tail shocks (acute stress) or left undisturbed. Forty-eight hours later rats were euthanized either following a 12h period of fasting or 30min of food access to evaluate neurochemical profiles during the peri- and early postprandial periods. Monoamine-related neurochemicals were measured via UHPLC in regions of the small intestine (duodenum, jejunum, ileum), large intestine (cecum, proximal colon, distal colon), cecal contents, fecal contents, and liver. The results suggest a relatively wide-spread increase in measures of serotonin activity across intestinal regions can be observed 48h after exposure to acute stress, however some evidence was found supporting localized differences in serotonin metabolization. Moreover, acute stress exposure reduced catecholamine-related neurochemical concentrations most notably in the ileum, and to a lesser extent in the cecal contents. Next, stress-related fecal serotonin concentrations were consistent with intestinal profiles. However, fecal dopamine was elevated in association with stress, which did not parallel findings in any other intestinal area. Finally, stress exposure and the food access period together only had minor effects on intestinal monoamine profiles. Taken together, these data suggest nuanced differences in monoaminergic profiles exist across intestinal regions the days following exposure to an acute stressor, highlighting the importance of assessments that consider the entire intestinal tract biogeography when investigating stress-related biological outcomes that may be relevant to GI pathophysiology.

151-LB: Postprandial Glucose Metabolism Differs between Early Adolescents and Adults with Type 1 Diabetes

Postprandial glucose turnover in adolescents with type 1 diabetes (T1D) has not been investigated. To do so, we studied adolescents (n=15, age 11.5±0.5 yrs, BMI 19±2.3 kg/m2, HbA1c 7.5±1%, diabetes duration 4.6±3 yrs) and adults (n=15, age 36.3±9.4 yrs, BMI 27.1±2.1 kg/m2, HbA1c 6.9±1.1%, diabetes duration 18.1±9.6 yrs) with T1D after a mixed meal. Healthy adults (n=14, age 26.9 ± 7 yrs, BMI 24.9±2.5 kg/m2, HbA1c 5.0±0.3%) served as controls. T1D subjects administered their customary insulin bolus dose at meal onset. Rates of endogenous glucose production (EGP) , meal glucose appearance (MRa) and glucose disappearance (Rd) were calculated by the triple tracer method with stable isotopes ([1-13C] glucose, [2-13C] glucose and [6, 6-2H2] glucose) . Integrated glucose excursions did not differ between adolescents and adults with T1D during early (0-120 min) and total (0-300 min) postprandial periods. While basal EGP at start of the meal was higher (p&amp;lt;0.01) , integrated rates of EGP, MRa, Rd and glucose clearance were all lower (p&amp;lt;0.03) in adolescents than in adults with T1D during the early postprandial period and were numerically lower (p=0.08) during the total postprandial period (Figure1) . Taken together, the data demonstrates significant differences in postprandial glucose metabolism between adolescents and adults with T1D. Additional studies are ongoing to determine the causes of these differences. Disclosure F. Ruchi: None. D. Romeres: None. S. Gururaj: None. M. D. Deboer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. R. Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A. Basu: Speaker's Bureau; Zealand Pharma A/S. Funding DK 124886, DK 085516, DK 029953

Postmeal optogenetic inhibition of dorsal hippocampal principal neurons increases future intake in a time-dependent manner

Research involving human participants indicates that memories of recently eaten meals limit how much is eaten during subsequent eating episodes; yet, the brain regions that mediate the inhibitory effects of ingestion-related memory on future intake are largely unknown. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memories of personal experiences, mediate the inhibitory effects of ingestion-related memory on future intake. Our research program aimed at testing this hypothesis has been influenced in large part by our mentor James McGaugh and his research on posttraining manipulations. In the present study, we used an activity-guided optogenetic approach to test the prediction that if dHC glutamatergic neurons limit future intake through a process that requires memory consolidation, then inhibition should increase subsequent intake when given soon after the end of a meal but delayed inhibition should have no effect. Viral vectors containing CaMKIIα-eArchT3.0-eYFP and fiber optic probes were placed in the dHC of male Sprague-Dawley rats. Compared to intake on a day when no inhibition was given, postmeal inhibition of dHC glutamatergic neurons given for 10 min after the end of a saccharin meal increased the likelihood that rats would consume a second meal 90 min later and significantly increased the amount of saccharin solution consumed during that next meal when the neurons were no longer inhibited. Importantly, delayed inhibition given 80 min after the end of the saccharin meal did not affect subsequent intake of saccharin. Given that saccharin has minimal postingestive gastric consequences, these effects are not likely due to the timing of interoceptive visceral cues generated by the meal. These data show that dHC glutamatergic neural activity is necessary during the early postprandial period for limiting future intake and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.

Inhibiting ventral hippocampal NMDA receptors and Arc increases energy intake in male rats.

Research into the neural mechanisms that underlie higher-order cognitive control of eating behavior suggests that ventral hippocampal (vHC) neurons, which are critical for emotional memory, also inhibit energy intake. We showed previously that optogenetically inhibiting vHC glutamatergic neurons during the early postprandial period, when the memory of the meal would be undergoing consolidation, caused rats to eat their next meal sooner and to eat more during that next meal when the neurons were no longer inhibited. The present research determined whether manipulations known to interfere with synaptic plasticity and memory when given pretraining would increase energy intake when given prior to ingestion. Specifically, we tested the effects of blocking vHC glutamatergic N-methyl-D-aspartate receptors (NMDARs) and activity-regulated cytoskeleton-associated protein (Arc) on sucrose ingestion. The results showed that male rats consumed a larger sucrose meal on days when they were given vHC infusions of the NMDAR antagonist APV or Arc antisense oligodeoxynucleotides than on days when they were given control infusions. The rats did not accommodate for that increase by delaying the onset of their next sucrose meal (i.e., decreased satiety ratio) or by eating less during the next meal. These data suggest that vHC NMDARs and Arc limit meal size and inhibit meal initiation.

Additional Insulin Is Required in Both the Early and Late Postprandial Periods for Meals High in Protein and Fat: A Randomized Trial.

The pattern and quantity of insulin required for high-protein high-fat (HPHF) meals is not well understood. This study aimed to determine the amount and delivery pattern of insulin required to maintain euglycemia for 5 hours after consuming a HPHF meal compared with a low-protein low-fat (LPLF) meal. This randomized crossover clinical trial, conducted at 2 Australian pediatric diabetes centers, included 10 patients (12-21 years of age) with type 1 diabetes for ≥ 1 year. Participants were randomized to HPHF meal (60 g protein, 40 g fat) or LPLF meal (5 g protein, 5 g fat) with identical carbohydrate content (30 g). A modified insulin clamp technique was used to determine insulin requirements to maintain postprandial euglycemia for 5 hours. Total mean insulin requirements over 5 hours were measured. The total mean insulin requirements for the HPHF meal were significantly greater than for the LPLF meal (11.0 [CI 9.2, 12.8] units vs 5.7 [CI 3.8, 7.5] units; P = 0.001). Extra intravenous insulin was required for HPHF: 0 to 2 hours (extra 1.2 [CI 0.6, 1.6] units/h), 2 to 4 hours (extra 1.1 [CI 0.6, 1.6] units/h), and 4 to 5 hours (extra 0.6 [CI 0.1, 1.1] units/h) after the meal. There were marked inter-individual differences in the quantity of additional insulin (0.3 to 5 times more for HPHF) and the pattern of insulin delivery (0%-85% of additional insulin required in the first 2 hours). The addition of protein and fat to a standardized carbohydrate meal almost doubled the mean insulin requirement, with most participants requiring half of the additional insulin in the first 2 hours.

Fortificación con fibra dietética como estrategia para aumentar la saciedad: ensayo aleatorizado doble ciego controlado

Introducción: Se ha descrito que las fibras dietéticas (FD) podrían tener efectos favorables en el control de sentimientos subjetivos relacionados a sensaciones postprandiales de apetito y saciedad, propiedad que en el contexto epidemiológico actual podrían ser beneficiosos. Objetivo: Evaluar el efecto agudo de 3 tipos de FD sobre la percepción subjetiva de sensaciones postprandiales. Material y métodos: Estudio randomizado, doble ciego, controlado, cruzado. 21 sujetos sanos con índice de masa corporal entre 18.5-24.9 Kg/m2, fueron asignados aleatoriamente para consumir 4 desayunos separados por a lo menos 2 días. Los desayunos fueron fortificados con 3 g de: β-glucano de avena (BETA), pectinas de manzana (PECT), celulosa microcristalina (CELL) y maltodextrina como control (MALT). Los sentimientos subjetivos postprandiales se determinaron con una Encuesta Visual Análoga (EVA) antes del desayuno y a los 15, 30, 60, 90 y 120 min. Resultados: En análisis de varianzas (ANOVA) mostró una diferencia significativa a los 15 minutos (p&lt;0,05) en la percepción de saciedad subjetiva de los desayunos fortificados con pectina de manzana versus β-glucano de avena. β-glucano de avena produjo el menor efecto en la saciedad subjetiva (p&lt;0,05). Un ANOVA de medidas repetidas no mostró efectos de los tipos de fibras adicionadas a los desayunos en el sentimiento subjetivo de apetito. Conclusiones: Las pectinas de manzana parecen ser más efectiva que otros tipos de FD para aumentar la percepción subjetiva de saciedad y disminuir el apetito, especialmente en el periodo postprandial temprano.

Acute Running and Coronary Heart Disease Risk Markers in Male Cigarette Smokers and Nonsmokers: A Randomized Crossover Trial.

Cigarette smoking is an independent risk factor for coronary heart disease and is associated with impaired postprandial metabolism. Acute exercise reduces postprandial lipemia and improves other coronary heart disease risk markers in nonsmokers. Less is known about responses in cigarette smokers. Twelve male cigarette smokers (mean ± SD; age = 23 ± 4 yr, body mass index = 24.9 ± 3.0 kg·m-2) and 12 male nonsmokers (age = 24 ± 4 yr, body mass index = 24.1 ± 2.0 kg·m-2) completed two, 2-d conditions (control and exercise) in a randomized crossover design. On day 1, participants rested for 9 h (0800-1700) in both conditions except a 60-min treadmill run (65% ± 7% peak oxygen uptake, 2.87 ± 0.54 MJ) was completed between 6.5 and 7.5 h (1430-1530) in the exercise condition. On day 2 of both conditions, participants rested and consumed two high-fat meals over 8 h (0900-1700) during which 13 venous blood samples and nine resting arterial blood pressure measurements were collected. Smokers exhibited higher postprandial triacylglycerol and C-reactive protein than nonsmokers (main effect group effect size [Cohen's d] ≥ 0.94, P ≤ 0.034). Previous day running reduced postprandial triacylglycerol, insulin, and systolic and diastolic blood pressure (main effect condition d ≥ 0.28, P ≤ 0.044) and elevated postprandial nonesterified fatty acid and C-reactive protein (main effect condition d ≥ 0.41, P ≤ 0.044). Group-condition interactions were not apparent for any outcome across the total postprandial period (0-8 h; all P ≥ 0.089), but the exercise-induced reduction in postprandial triacylglycerol in the early postprandial period (0-4 h) was greater in nonsmokers than smokers (-21%, d = 0.43, vs -5%, d = 0.16, respectively; group-condition interaction P = 0.061). Acute moderate-intensity running reduced postprandial triacylglycerol, insulin, and resting arterial blood pressure the day after exercise in male cigarette smokers and nonsmokers. These findings highlight the ability of acute exercise to augment the postprandial metabolic health of cigarette smokers and nonsmokers.

1773-P: Postprandial Hyperglycemia after a High–Glycemic Index Meal Activates Brain Areas Associated with Food Cravings and Overeating in T1D

High vs. low glycemic index (GI) foods elicit late postprandial activation of mesolimbic brain areas, which may contribute to the associated increases in hunger, food intake and cravings. It is unknown whether changes in blood glucose or higher insulin levels mediate this activation and its potential adverse downstream effects. Fifteen men with T1D, mean (SD) BMI 21 (1.4) kg/m2, aged 21 (1.6) yr underwent three conditions in random order: C1 - high GI (GI=84) meal with IV insulin to maintain euglycemia; C2 - macronutrient matched low GI (37) meal with IV insulin to maintain euglycemia; C3 - high GI meal with IV insulin to match C2. Insulin was algorithmically adjusted for 4.5 hr with blood glucose checks every 5 min. Brain imaging (arterial spin labeling) was obtained at baseline, in the early (1 hr) and late (4 hr) postprandial period. This design allowed us to compare high vs. low GI meals with similar glucose response (incremental area under the curve 192 [22] vs. 41 [12], p=0.6) but different insulin doses (25 [2] vs. 17 [1] units, p=0.003; C1 vs. C2) or similar insulin doses (17 [1] units each, p=0.5) with different glucose response (1257 [37] vs. 41 [12] mg/dl*h, p&amp;lt;0.001, C3 vs. C2). As expected, a high GI meal elicits increased hunger and late postprandial activation of brain areas linked to food cravings. This activation was mediated by postprandial hyperglycemia rather than insulin level. Thus, a high GI meal may promote overeating with insulin dose deviations in either direction: 1) via mesolimbic signaling if hyperglycemia results from inadequate insulin coverage, or 2) via compensatory carbohydrate intake if excessive coverage causes hypoglycemia. Disclosure B.S. Lennerz: None. F. Munsch: None. D.C. Alsop: Other Relationship; Self; General Electric, Hitachi America, Ltd., Philips Healthcare, Siemens Corporation. G.M. Steil: Consultant; Self; Eli Lilly and Company. D.C. Simonson: Stock/Shareholder; Self; GI Windows. Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. D.S. Ludwig: None.

Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial.

The American Diabetes Association recommends individuals with type 1 diabetes (T1D) adjust insulin for dietary fat; however, optimal adjustments are not known. This study aimed to determine 1) the relationship between the amount and type of dietary fat and glycemia and 2) the optimal insulin adjustments for dietary fat. Adults with T1D using insulin pump therapy attended the research clinic on 9-12 occasions. On the first six visits, participants consumed meals containing 45 g carbohydrate with 0 g, 20 g, 40 g, or 60 g fat and either saturated, monounsaturated, or polyunsaturated fat. Insulin was dosed using individual insulin/carbohydrate ratio as a dual-wave 50/50% over 2 h. On subsequent visits, participants repeated the 20-60-g fat meals with the insulin dose estimated using a model predictive bolus, up to twice per meal, until glycemic control was achieved. With the same insulin dose, increasing the amount of fat resulted in a significant dose-dependent reduction in incremental area under the curve for glucose (iAUCglucose) in the early postprandial period (0-2 h; P = 0.008) and increase in iAUCglucose in the late postprandial period (2-5 h; P = 0.004). The type of fat made no significant difference to the 5-h iAUCglucose. To achieve glycemic control, on average participants required dual-wave insulin bolus: for 20 g fat, +6% insulin, 74/26% over 73 min; 40 g fat, +6% insulin, 63/37% over 75 min; and 60 g fat, +21% insulin, 49/51% over 105 min. This study provides clinical guidance for mealtime insulin dosing recommendations for dietary fat in T1D.

New faster-acting insulin Fiasp® — do we need a new meal-time insulin?

Studies aiming at improving the treatment of patients on insulin therapy are conducted bidirectionally. On the one hand, there are attempts to find modified insulin that acts even faster and has shorter effect than currently used short-acting insulin analogs, and on the other hand researchers work to develop more stable basal insulins. Fiasp® is one of the new developments in this field. Addition of two excipients — niacinamide and L-arginine — resulted in faster hypoglycemic effect of insulin aspart while maintaining the stability of drug formulation. Clinical trials assessing pharmacokinetic parameters of Fiasp® showed a 2 times faster onset of action (4 vs. 9 min), 2 times higher exposure to insulin 30 minutes after its administration and 74% more hypoglycemic activity during the first 30 minutes following subcu­taneous injection. Clinical trials of Fiasp® were conducted under the acronym Onset. Overall, these studies included over 3,000 patients with diabetes, both type 1 and type 2. In patients with type 1 diabetes (DM1) comparable or better diabetes control was observed in the Fiasp® groups compared with groups treated with Novorapid, with significantly lower blood glucose levels in the early postprandial period. It has also been demon­strated that administration of insulin Fiasp® within 20 min of the beginning of the meal was associated with comparable results to Novorapid administered before the meal. Fiasp® is commercially available in Poland, but it is not yet widely used due to the high price and no reimburse­ment from NFZ.

Pectin gelling in acidic gastric condition increases rheological properties of gastric digesta and reduces glycaemic response in mice

The rheological characteristics and transit time of gastric digesta and the postprandial glycaemic response in mice orally administered with water (control) or pectin solutions supplemented (AP-Ca) or not supplemented (AP) with CaCO3 were elucidated. AP and AP-Ca increased viscosity, storage and loss moduluses (G’ and G’’) of mice gastric digesta. The gelling capacity of AP-Ca in acidic gastric conditions appeared to provide a greater enhancement of gastric digesta viscosity compared with AP. The postprandial blood glucose concentration was lower in mice orally administered with AP or AP-Ca compared with control mice. The transit time of gastric digesta and the blood glucose concentration were affected in mice orally administered with AP during the early postprandial period. The effect of AP-Ca on the gastric digesta rheology and transit time was stronger than that of AP. Both of the pectin solutions failed to reduce food intake in mice.

Gastric emptying of different meal volumes of identical composition in preterm infants: a time series analysis.

BackgroundPreterm infants' meals typically progress to higher volumes over time. Knowledge of gastric emptying (GE) responses to differing meal volumes may inform enteral feeding management. We examined the effect of meal volume and composition on preterm GE.MethodsForty infants were studied at 33.3±1.4 (29.7-35.6) weeks postmenstrual age when fully enteral fed (target 150 ml/kg/day). Intraindividual comparisons of GE were made for paired meals of 100% and 75% prescribed volume and identical composition of mother's own milk (n=21) and pasteurized donor human milk (n=19). Serial stomach ultrasound images were used to calculate gastric residual volumes (GRVs) and remaining meal proportions (% meal).ResultsGE was faster in the early postprandial period and slowed over time (P<0.001). Reduced volume meals had slower GE rates and lower GRV (P<0.001). Serial postprandial % meal was similar between reduced and full volume meals (P=0.41). Higher milk casein concentration was associated with slower GE (P=0.04). Complete gastric emptying (GRV=0 ml) was more common in infants fed at 3 h intervals compared with those fed every 2 h (P=0.002).ConclusionEarly postprandial GE is more rapid for larger meal volumes. Stable preterm infants may tolerate feeding of a 3 h meal volume at shorter intervals.

HNF1α defect influences post-prandial lipid regulation.

PurposeHepatocyte nuclear factor 1 alpha (HNF1α) defects cause Mature Onset Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell insulin secretion. However, HNF1α is involved in many other metabolic pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to investigate gut hormones, lipids, and insulin regulation in response to a meal test in HNF1α defect carriers (MODY3) compared to non-diabetic subjects (controls) and type 2 diabetes (T2D).MethodsWe administered a standardized liquid meal to each participant. Over 6 hours, we measured post-meal responses of insulin regulation (blood glucose, c-peptide, insulin), gut hormones (ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1) and lipids (non-esterified fatty acids [NEFA] and triglycerides).ResultsWe found that MODY3 participants had lower insulin secretion indices than controls and T2D participants, showing the expected β-cell defect. MODY3 had similar glycated hemoglobin levels (HbA1c median [IQR]: 6.5 [5.6–7.6]%) compared to T2D (median: 6.6 [6.2–6.9]%; P<0.05). MODY3 had greater insulin sensitivity (Matsuda index: 71.9 [29.6; 125.5]) than T2D (3.2 [4.0; 6.0]; P<0.05). MODY3 experienced a larger decrease in the ratio of NEFA to insulin (NEFA 30–0 / insulin 30–0: -39 [-78; -30] x104) in the early post-prandial period (0–30 minutes) compared to controls and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05). MODY3 had lower fasting (0.66 [0.46; 1.2] mM) and post-meal triglycerides levels compared to T2D (fasting: 2.3 [1.7; 2.7] mM; P<0.05). We did not detect significant post-meal differences in ghrelin and incretins between MODY3 and other groups.ConclusionIn response to a standard meal test, MODY3 showed greater early post-prandial NEFA diminution in response to relatively low early insulin secretion, and they maintained very low post-prandial triglycerides levels.

Increasing the protein quantity in a meal results in dose-dependent effects on postprandial glucose levels in individuals with Type 1 diabetes mellitus.

To determine the glycaemic impact of increasing protein quantities when consumed with consistent amounts of carbohydrate in individuals with Type 1 diabetes on intensive insulin therapy. Participants with Type 1 diabetes [aged 10-40 years, HbA1c ≤ 64 mmol/mol (8%), BMI ≤ 91st percentile] received a 30-g carbohydrate (negligible fat) test drink daily over 5 days in randomized order. Protein (whey isolate 0 g/kg carbohydrate, 0 g/kg lipid) was added in amounts of 0 (control), 12.5, 25, 50 and 75 g. A standardized dose of insulin was given for the carbohydrate. Postprandial glycaemia was assessed by 5 h of continuous glucose monitoring. Data were collected from 27 participants (15 male). A dose-response relationship was found with increasing amount of protein. A significant negative relationship between protein dose and mean excursion was seen at the 30- and 60-min time points (P = 0.007 and P = 0.002, respectively). No significant relationship was seen at the 90- and 120-min time points. Thereafter, the dose-response relationship inverted, such that there was a significant positive relationship for each of the 150-300-min time points (P < 0.004). Mean glycaemic excursions were significantly greater for all protein-added test drinks from 150 to 300 min (P < 0.005) with the 75-g protein load, resulting in a mean excursion that was 5 mmol/l higher when compared with the control test drink (P < 0.001). Increasing protein quantity in a low-fat meal containing consistent amounts of carbohydrate decreases glucose excursions in the early (0-60-min) postprandial period and then increases in the later postprandial period in a dose-dependent manner.

The Effect of Casein Ingestion within a Milk Matrix on Muscle Protein Synthesis

Isolated micellar casein has been classified as a slow protein because of its slow digestion and amino acid absorption kinetics. These result further in a more moderate and sustained amino acid availability in the plasma and subsequently lower muscle protein synthesis (MPS) rate when, for example, compared with whey. However, the milk matrix with lactose, fat and various minerals may modulate the effect of casein on MPS. Therefore, this study aimed to compare the effects of the ingestion of casein dissolved in bovine milk serum to the ingestion of isolated casein on myofibrillar protein synthesis. In this parallel group randomized trial, 32 healthy older men (age: 71 ± 1 y) received a primed continuous infusion of L-[ring-2 H5 ]phenylalanine, L-[1-13C]leucine, and L-[ring-3,5-2 H2 ]tyrosine and blood and muscle samples were taken to assess myofibrillar fractional synthetic rate (FSR) under basal postabsorptive conditions and after a single bolus of 25 g intrinsically L-[1-13C]phenylalanine and L-[1-13C]leucine-labeled casein either in an isolated form (ISOCAS; n = 16) or dissolved in bovine milk serum (MILK-CAS; n = 16). The ingestion of 25 g of casein significantly (P &lt; 0.05) increased MPS rates in both groups when assessed over the late postprandial period (t = 120 – 300 min). Ingestion of MILK-CAS and ISO-CAS did not significantly stimulate MPS rates when assessed over the early (t = 0 – 120 min) and overall (t = 0 – 300 min) postprandial FSR compared to postabsorptive (t = -120 – 0 min) FSR. No significant differences were observed between the two groups over the early, late or entire postprandial period (P &gt; 0.05). The ingestion of additional normal milk matrix to micellar casein does not modulate overall myofibrillar protein synthesis rates in older men when compared to the ingestion of micellar casein dissolved in water. Therefore, there is neither a benefit, nor a detrimental effect of ingesting micellar casein within a normal milk matrix instead of the isolated form to increase MPS.

Gastric Volvulus Presenting as Chronic, Intermittent Chest Pain and Retching of Unclear Etiology

AIM: To describe a case of gastric volvulus which presented as chronic, intermittent chest pain and retching. CASE REPORT: A 59 yo female presented for further evaluation after relocating from another area. Her past medical history was unremarkable and she was taking only pantoprazole each day. She related a one year history of severe, intermittent lower chest pain with associated retching. Symptoms occurred exclusively in the intraprandial and early postprandial period. Symptoms occurred a few times each week and led to multiple ER visits. She underwent extensive cardiac evaluation, blood testing, gallbladder sonography, abdominal CT scanning and upper GI endoscopy (EGD). Her prior gastroenterologist detected a “moderate-sized” hiatal hernia and non-dysplastic, ultra-short-segment Barrett's esophagus (“irregular z-line”) at the time of EGD. Given her symptoms and her new diagnosis of Barrett's esophagus one year earlier, I recommended repeat EGD which revealed a large hiatal hernia (with approximately half of the stomach being intrathoracic) and there appeared to be a paraesophageal component. At this point, it was strongly suspected that her symptoms were related to the endoscopic findings. An upper GI series confirmed that a large portion of the stomach was intrathoracic, and there was organoaxial gastric volvulus (see Figure 1). The patient was urgently referred for surgical consultation and she underwent intervention. After nearly 2 years of follow-up, she has had durable resolution of all of her previous symptoms.Figure 1CONCLUSION: Chronic episodic chest pain in association with meal-related retching should raise the specter of intermittent gastric volvulus, especially in a patient with a history of a hiatal hernia. Although a bit less usual, in this case, the chronic symptoms were related to an organoaxial, as opposed to a mesenteroaxial gastric volvulus. Surgical repair was successful in alleviating the patient's symptoms.

Adaptation to a high-protein diet progressively increases the postprandial accumulation of carbon skeletons from dietary amino acids in rats.

We aimed to determine whether oxidative pathways adapt to the overproduction of carbon skeletons resulting from the progressive activation of amino acid (AA) deamination and ureagenesis under a high-protein (HP) diet. Ninety-four male Wistar rats, of which 54 were implanted with a permanent jugular catheter, were fed a normal protein diet for 1 wk and were then switched to an HP diet for 1, 3, 6, or 14 days. On the experimental day, they were given their meal containing a mixture of 20 U-[15N]-[13C] AA, whose metabolic fate was followed for 4 h. Gastric emptying tended to be slower during the first 3 days of adaptation. 15N excretion in urine increased progressively during the first 6 days, reaching 29% of ingested protein. 13CO2 excretion was maximal, as early as the first day, and represented only 16% of the ingested proteins. Consequently, the amount of carbon skeletons remaining in the metabolic pools 4 h after the meal ingestion progressively increased to 42% of the deaminated dietary AA after 6 days of HP diet. In contrast, 13C enrichment of plasma glucose tended to increase from 1 to 14 days of the HP diet. We conclude that there is no oxidative adaptation in the early postprandial period to an excess of carbon skeletons resulting from AA deamination in HP diets. This leads to an increase in the postprandial accumulation of carbon skeletons throughout the adaptation to an HP diet, which can contribute to the sustainable satiating effect of this diet.