Test Meal Research Articles

Apparent Saturation of Branched-Chain Amino Acid Catabolism After High Dietary Milk Protein Intake in Healthy Adults

Abstract Context Milk protein contains high concentrations of branched-chain amino acids (BCAA) that play a critical role in anabolism and are implicated in the onset of obesity and chronic disease. Characterizing BCAA catabolism in the postprandial phase could elucidate the impact of protein intake on obesity risk established in the “early protein hypothesis.” Objective To examine the acute effects of protein content of young child formulas as test meals on BCAA catabolism, observing postprandial plasma concentrations of BCAA in relation to their degradation products. Methods The TOMI Add-On Study is a randomized, double-blind crossover study in which 27 healthy adults consumed 2 isocaloric young child formulas with alternating higher (HP) and lower (LP) protein and fat content as test meals during separate interventions, while 9 blood samples were obtained over 5 hours. BCAA, branched-chain α-keto acids (BCKA), and acylcarnitines were analyzed using a fully targeted HPLC-ESI-MS/MS approach. Results Mean concentrations of BCAA, BCKA, and acylcarnitines were significantly higher after HP than LP over the 5 postprandial hours, except for the BCKA α-ketoisovalerate (KIVA). The latter metabolite showed higher postprandial concentrations after LP. With increasing mean concentrations of BCAA, concentrations of corresponding BCKA, acylcarnitines, and urea increased until a breakpoint was reached, after which concentrations of degradation products decreased (for all metabolites except valine and KIVA and Carn C4:0-iso). Conclusion BCAA catabolism is markedly influenced by protein content of the test meal. We present novel evidence for the apparent saturation of the BCAA degradation pathway in the acute postprandial phase up to 5 hours after consumption.

Plasma Endocannabinoids Are Independently Associated With the Metabolic Function of White Adipose Tissue

Abstract Context Little is known about the link between the endocannabinoid (EC) system and the in vivo metabolic function of white adipose tissue (WAT). Objective We aimed to evaluate whether ECs are linked to postprandial fatty acid metabolism and WAT metabolic function. Methods Men and women, with (IGT, n = 20) or without impaired glucose tolerance (NGT, n = 20) underwent meal testing with oral and intravenous stable isotope palmitate tracers and positron emission tomography with intravenous [11C]-palmitate and oral [18F]-fluoro-thia-heptadecanoic acid to determine systemic and organ-specific dietary fatty acid (DFA) and nonesterified fatty acid (NEFA) metabolism and partitioning. We determined fasting and postprandial plasma levels of EC by ultra-high performance liquid chromatography–tandem mass spectrometry. Results All ECs of the 2-monoacylglycerol (2-MAG) family displayed a progressive postprandial increase up to 360 minutes after meal intake that was more pronounced in women with IGT. N-acylethanolamine (NAE) levels decreased between fasting and 180 minutes, followed by a return to preprandial values at 360 minutes and were also increased in women with IGT. Postprandial area under the curve (AUC) of palmitate appearance rate was significantly and independently associated with postprandial AUC of anandamide (AEA; P = .0003) and total energy expenditure (P = .0009). DFA storage in abdominal subcutaneous adipose tissue was positively predicted by fasting 2-arachidonoylglycerol (2-AG; P < .04). Conclusion EC levels of the NAE family independently follow plasma NEFA metabolism, whereas 2-MAG closely follow the spillover of triglyceride-rich lipoprotein intravascular lipolytic products. Whether these associations are causal requires further investigation.

The correlation between patients with type 2 diabetes mellitus and chronic microvascular complications during the glucose peak time

IntroductionTo assess the Type 2 Diabetes Mellitus (T2DM) patients in association with Chronic Microvascular Complications at Glucose Peak Time and the association among chronic microvascular complications in T2DM patients and the glucose peak period in the typical steamed bread meal test. MethodsOverall 1095 T2DM patients were classified as three groups: (1) Group G1: glucose peak time ≤ 1 h (n = 84), Group G2: 1 h < glucose peak time ≤ 2 h (n = 648) and Group G3: glucose peak time > 2 h (n = 363). The clinical characteristics, insulin characteristics and glucose peak time and chronic microvascular complications markers of patients in each group was analyzed and compared. Statistical analyses were performed using SPSS 23.0, employing chi-square tests, Kruskal-Wallis tests, one-way ANOVA, and binary logistic regression analysis, with significance set at P < 0.05. ResultsAge, length of disease, glycated hemoglobin (HbA1c), urine albumin-creatinine ratio (UACR), and the number of patients with diabetic retinopathy (DR) increased (all P < 0.05) in those with postponed glucose peak time, while insulinogenic indexes, the AUC for C-p (AUCC-p), fasting, and 120-min C-peptide (C-p) decreased (all P < 0.05). Only age was connected to patients with diabetic kidney disease (DKD) independently in binary logistic regression analysis, although delayed glucose peak time was related to the presence of patients with DR. (all P < 0.05). ConclusionDelayed glucose peak time contributed to DR. Attention should be paid to condition of chronic microvascular complications in T2DM patients with a postponed peak glucose timing.

Magnetic Resonance Imaging of Gastric Motility in Conscious Rats.

Gastrointestinal (GI) magnetic resonance imaging (MRI) can simultaneously capture gastric peristalsis, emptying, and intestinal filling and transit. Performing GI MRI with animals requires anesthesia, which complicates physiology and confounds interpretation and translation from animals to humans. This study aims to enable MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions. We acclimated rats to remain awake, still, and minimally stressed during MRI. We scanned 14 Sprague-Dawley rats in both awake and anesthetized conditions after voluntarily consuming a contrast-enhanced test meal. Awake rats remained physiologically stable during MRI, showed gastric emptying of 23.7±1.4% after 48 minutes, and exhibited strong peristaltic contractions propagating through the antrum with a velocity of 0.72±0.04 mm/s, a relative amplitude of 40.7±2.3%, and a frequency of 5.1±0.1 cycles per minute. In the anesthetized condition, gastric emptying was about half of that in the awake condition, likely due to the effect of anesthesia in halving the amplitudes of peristaltic contractions rather than their frequency (not significantly changed) or velocity. In awake rats, the intestine filled more quickly and propulsive contractions were more occlusive. We demonstrated the effective acquisition and analysis of GI MRI in awake rats. Awake rats show faster gastric emptying, stronger gastric contraction with a faster propagation speed, and more effective intestinal filling and transit, compared to anesthetized rats. Our protocol is expected to benefit future preclinical studies of GI physiology and pathophysiology.

The effects of acute exercise on food intake and appetite in adolescents with and without obesity: A systematic review and meta-analysis.

This systematic review and meta-analysis synthesized evidence pertaining to consummatory and appetitive responses to acute exercise in children and adolescents with and without obesity (5-18 years). Articles reporting on supervised, controlled trials of any modality, duration, or intensity with laboratory-measured food intake were found using MEDLINE, EMBASE, and Cochrane up to July 2023. Differences between conditions in laboratory energy and macronutrient intake, appetite sensations, and food reward were quantitatively synthesized using random-effects meta-analyses. Thirty-five studies were eligible for the systematic review of energy intake, consisting of 60 distinct intervention arms with lean (n = 374) and overweight/obesity participants (n = 325; k = 51 eligible for meta-analysis). Study quality as indicated by the Effective Public Healthy Practice Project tool was rated as low and moderate risk of bias for 80% and 20% of studies, respectively. Acute exercise had no significant effect on energy intake during an ad libitum test meal (mean difference [MD] = -4.52 [-30.58, 21.54] kcal, p = .729). Whilst absolute carbohydrate intake was lower after exercise (23 arms; MD = -6.08 [-11.26, -0.91] g, p = .023), the proportion of carbohydrate was not (30 arms; MD = -0.62 [-3.36, 2.12] %, p = .647). A small elevation in hunger (27 arms; MD = 4.56 [0.75, 8.37] mm, p = .021) and prospective food consumption (27 arms; PFC; MD = 5.71 [1.62, 9.80] mm, p = .008) was observed post-exercise, but not immediately prior to the test meal (Interval: Mdn = 30 min, Range = 0-180). Conversely, a modest decrease in explicit wanting for high-fat foods was evident after exercise (10 arms; MD = -2.22 [-3.96, -0.47] mm, p = .019). Exercise intensity (p = .033) and duration (p = .013) moderated food intake only in youth with overweight/obesity, indicating lower intake at high intensity and short duration. Overall, acute exercise does not lead to compensation of energy intake or a meaningful elevation of appetite or food reward and might have a modest benefit in youth with overweight/obesity if sufficiently intense. However, conclusions are limited by substantial methodological heterogeneity and the small number of trials employing high-intensity exercise, especially in youth with overweight/obesity.

Greater oxidation of dietary linoleate compared to palmitate in humans following an acute high-carbohydrate diet

We have previously demonstrated that dietary saturated fatty acids (SFA), when compared to polyunsaturated fatty acids (PUFA), are preferentially partitioned into oxidation pathways. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated. To investigate whether an acute upregulation of hepatic DNL influences dietary FA partitioning into oxidation pathways. 20 healthy volunteers (11 females) underwent a fasting baseline visit followed by two study days, 2-weeks apart. Prior to each study day, participants consumed an isocaloric high-carbohydrate diet (to upregulate hepatic DNL) for 3-days. On the two study days, participants consumed an identical standardised test meal that contained either [U13C]palmitate or [U13C]linoleate, in random order, to trace the fate of dietary FA. Blood and breath samples were collected over a 6h postprandial period and 13C enrichment in breath CO2 and plasma lipid fractions were measured using gas-chromatography-combustion-isotope ratio mass spectrometry. Compared to the baseline visit, fasting plasma triglyceride concentrations and markers of hepatic DNL, the lipogenic and stearyl-CoA desaturase indices, were significantly (p<0.05) increased after consumption of the high-carbohydrate diet. Appearance of 13C in expired CO2 and tracer recovery were significantly (p<0.05) higher after consumption of the meal containing [U13C]linoleate compared to [U13C]palmitate (5.1±0.5% vs. 3.7±0.4%), respectively. Incorporation of 13C into the plasma triglyceride and non-esterified fatty acid pool was significantly (p<0.001) greater for [U13C]palmitate compared to [U13C]linoleate. Dietary PUFA compared to SFA appear to be preferentially partitioned into oxidation pathways during an acute upregulation of hepatic DNL, thus consumption of a PUFA-enriched diet may help mitigate intrahepatic triglyceride accumulation in individuals at risk of cardiometabolic disease.

Effect of adding &lt;i&gt;fenugreek&lt;/i&gt; and &lt;i&gt;Nigella sativa&lt;/i&gt; to white rice on postprandial glycemic and appetite responses in healthy individuals

White rice is a high glycemic index food, and therefore different approaches are adopted to reduce its glycemic effect. The present study investigated the effect of adding fenugreek and Nigella sativa seed powder to white rice on glycemia, appetite, palatability, and gastrointestinal clinical manifestations in healthy subjects. In a randomized crossover design, 16 healthy subjects consumed white rice alone (control group), white rice with 2-g fenugreek seed powder, or white rice with 4-g nigella seed powder on different occasions. Each test meal provided 50 g of available carbohydrates. Blood glucose, subjective appetite, and gastrointestinal manifestations were measured at fasting and postprandially for 2 h. Palatability of the test meals was also measured using a 9-point hedonic scale. The nigella meal resulted in significantly lower blood glucose concentration (31.25 mg/dL) at 30 min (p = 0.022), compared to the control meal (43.88 mg/dL) whereas fenugreek meal showed no significant effect. Moreover, the nigella meal significantly increased satiety ratings at 30 and 90 min (p = 0.035 and 0.018, respectively). The results demonstrated that the addition of nigella powder to white rice reduced its glycemic response and increased satiety, compared to the control meal. All test meals were judged as acceptable by the subjects and their consumption didn’t cause any gastrointestinal discomfort. Results of the current study demonstrated promising implications for reducing glycemic response of white rice, a commonly consumed high-glycemic index food.

Acute exercise might not affect subsequent appetite responses to a fixed meal in adolescents with obesity: The SMASH exploratory study

While an intensity-dependent post-exercise decrease in energy intake (EI) has been described in adolescents with obesity, studies invariably used ad libitum meals, limiting then any conclusions regarding the effect of exercise on post-meal appetitive responses that can be also impacted by the ad libitum nature of the meal. This study analyses appetite and food-reward related responses to a fixed meal after an acute exercise, also exploring the associations between substrate use during exercise and overall daily EI in adolescents with obesity. Thirteen adolescents with obesity (12–16 years, 5 males) randomly complete 2 experimental sessions: (i) a control condition (CON); (ii) a 30-min moderate intensity (65% VO2peak) cycling condition (EX). Energy expenditure and substrate oxidation were measured during both 30 min of rest (CON) or exercise (EX). Ad libitum EI, macronutrient intake and relative EI were assessed at dinner, subjective appetite sensations taken at regular intervals and food reward measured before and after lunch as well as before dinner. Energy and macronutrient intake did not differ between conditions, as well as appetite feelings. A time effect (p = 0.012) was observed between pre and post meal for choice fat bias in both conditions but was only significant within the CON condition (p = 0.004). CHO oxidation during exercise was found correlated with both EI (r = 0.586, p = 0.045), pre-lunch hunger (r = 0.624, p = 0.030), daily AUC for hunger and DTE (r = 0.788, p = 0.002 and r = 0.695; p = 0.012 respectively). This exploratory study highlights that acute exercise might not affect subsequent appetite responses when using a fixed test meal in adolescents with obesity.

Post-Bariatric Hypoglycemia: an Impaired Metabolic Response to a Meal

Aims/HypothesisPost-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH.MethodsWe performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH.ResultsOut of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH.ConclusionOverall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH.Graphical

Effects of Red, Green and Black Pepper on Intestinal Motility and Post-Prandial Bicarbonate Concentration in Guinea Pigs

Pepper is one of the most commonly used spices in most food cultures because of its many dietary and medicinal uses. The aim of the present study was to investigate and compare the effects of different varieties of pepper on intestinal motility and post-prandial serum bicarbonate concentration in guinea pigs. The study was carried out using 50 adult guinea pigs weighing 800-1000g, separated into groups of 5 each including group 1 which served as control. The experimental groups received respectively black, green and red pepper extracts in concentrations of 25mg/kg, 50mg/kg and 75mg/kg. For each experimental group, pepper was administered together with a mixture of Evans blue dye and Arabic gum and allowed for one hour. Each animal was thereafter, anesthetized and the intestines dissected out. For each animal, the total length of the intestine as well as the distance travelled by the test meal from the pyloric sphincter were measured and recorded. Intestinal transit was expressed as the percentage of the distance travelled by the test meal to the total length of the intestine. Concomitantly, blood samples were collected to determine the post-prandial bicarbonate concentration. The result showed that all three varieties of pepper caused significant rise in percentage intestinal transit (in 1hr) and by implication reduction in the intestinal transit time. However, a significant dose-dependent effect was observed in the groups receiving black and green pepper respectively but not in the red category. This suggests an inverse relationship between the concentrations of black and green pepper with the intestinal transit time. Pepper did not cause any significant change in the plasma post-prandial bicarbonate concentrations. Conclusively, the results suggest that black, green and red pepper respectively increased intestinal motility without possibly causing any significant effect on gastric acid secretion.

Modeling the acceptance of vegetarian diets to promote sustainable food systems.

With increasing concerns about health, animal welfare, and the environment, changes in dietary patterns are emerging, as evidenced by the gradual shift toward plant-rich diets. To appropriately plan vegetarian meals with high consumer satisfaction that would help promote this dietary pattern and ultimately improve the sustainability of food systems, meal acceptability testing would be crucial. The present work aims to investigate the influence of individual food components' acceptability on the overall meal acceptability in vegetarian diets. Over four taste-testing periods, 94 panelists of US nationality recruited from Cornell University staff (47 males and 47 females; 30-50 years of age) were asked to rate the acceptability of 41 vegetarian meals containing various food category items, including a main dish, side dish, appetizer, salad, soup, bread, dessert, beverage, and a control food. Each meal included six menu items to ensure the tested foods resembled a typical meal. Consequently, some meals lacked one or more of the nine total food categories. Participants were asked to rate the acceptability of the six meal items and the overall meal acceptability on a 9-point hedonic scale. Multiple imputation was used to fill in any missing data, and multiple linear regression analysis was then performed. Through this study, a model that predicts the overall meal acceptability of vegetarian diets based on individual meal category components was developed with an R-squared value of .7033, suggesting that around 70.33% of the variation in overall meal acceptability could be explained by the nine food category predictors. The findings also suggested that the most influential food item on overall meal acceptability was the main dish followed by the side dish. For every unit increase in the acceptability score of the main dish on a 9-point hedonic scale, the overall meal acceptability increased by 0.324 points. The positive findings would be beneficial to food service providers in designing a vegetarian meal with high meal acceptability. By focusing on optimizing the acceptability of these two key categories, menu planners can effectively elevate customers' satisfaction of their meals.

Gut-derived appetite hormones do not explain energy intake differences in humans following low-carbohydrate versus low-fat diets.

The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake. A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low-fat (LF) diet (10% fat, 75% carbohydrate) and a low-carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient-representative breakfast test meals, and 6-h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day. The LC meal resulted in greater mean postprandial plasma active glucagon-like peptide-1 (GLP-1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose-dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001). In the short term, endogenousgut-derived appetite hormones do not necessarily determine ad libitum energy intake.

Randomized, crossover trial: comparing the effects of standardized egg-white meal and Vital® on global gastric emptying parameters and intragastric meal distribution in healthy Asian participants.

Measurements of gastric emptying and accommodation for alternative test-meal protocol during gastric emptying scintigraphy (GES), such as high-calorie nutrient drinks, are not fully established. We aimed to compare the effects of standardized egg-white meal (EWM) versus high-calorie nutrient drink (Vital®; Abbott Laboratories) on global GES parameters and intragastric meal distribution at immediate scan (IMD0h). Of 84 screened participants, 60 asymptomatic healthy Asian population (38 females; 24.0±1.5years; 23.8±2.6kg/m2) were recruited in this 2×2 (AB/BA) crossover trial. Participants were randomized to a 4-h GES with 99mTc-radiolabeled EWM (~255.8kcal), followed by a 200mL Vital® (300kcal), or vice versa, separated by a 2-week washout period. Global meal retention (GMR), power-exponential model emptying parameters (half-emptying [T1/2], lag phases [Tlag2%, Tlag5%, Tlag10%]), and IMD0h were determined and compared. GMRs for both test meals were within the international standard references for solid GES. Compared to EWM, Vital® exhibited significantly lower GMRs (faster emptying) from 0.5 to 3h (all P<0.001) but comparable at 4h (P=0.153). Similar observations were found for the model-based T1/2 and the different Tlag thresholds (all P<0.001). Furthermore, IMD0h was found to be lower with Vital®, indicating lower gastric accommodation (faster antral filling) immediately post-ingestion (P<0.001). Both test meals showed significant moderate-to-strong positive associations at the late-phase GE (GMR 2-4h, T1/2) (all P<0.05). Overall, Vital® is an acceptable alternative test meal to the EWM for GES; however, exercise caution when interpreting early-phase GE. The normative values for global GES parameters and IMD0h are also established.

Reduced Capacity of High-Density Lipoprotein to Acquire Free Cholesterol From Triglyceride-Rich Lipoproteins Is Associated With Elevated Postprandial Hypertriglyceridemia in Healthy Men.

The capacity of high-density lipoprotein cholesterol (HDL) to acquire free cholesterol (FC) from triglyceride-rich lipoproteins during lipoprotein lipase-dependent lipolysis in a process of reverse remnant cholesterol transport, has been proposed as a key biological function of HDL particles that underlies the U-shaped relationship between HDLcholesterol and cardiovascular diseases. Although reverse remnant cholesterol transport has been evaluated in a fasting state, it has never been explored under nonfasting conditions. FC transfer was evaluated in healthy men (n=78) before and throughout the postprandial phase up to 8 hours after consumption of a test meal. Postprandially, the capacity of HDL to acquire FC increased progressively, reaching a maximal mean value of 98.5%±22.5% 6 hours after meal intake (P<0.05). Analysis of the study population according to tertiles of postprandial variation of FC transfer identified subjects exhibiting reduced capacity of HDL to acquire FC (tertile 1), those for whom the capacity of HDL to acquire FC remained unchanged (tertile 2), and subjects characterized by an enhanced FC transfer during the postprandial phase (tertile 3). Across the tertiles, we found an inverse relationship between the maximal postprandial change in FC transfer to HDL and the degree of postprandial triglyceride response. Healthy individuals exhibiting exacerbated postprandial triglyceride response and reduced HDL cholesterol levels feature reduced FC transfer to HDL during the postprandial state. These data suggest that to normalize postprandial triglyceride response, 2 conditions need to be fulfilled: notably elevated FC transfer to HDL in the postprandial phase and increased levels of acceptor HDL particles.

Effect of ghrelin on glucose tolerance, gut hormones, appetite, and food intake after sleeve gastrectomy.

Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown. We investigated the effects of ghrelin infusion on appetite and glucose tolerance in individuals with obesity before and 3 mo after SG. Twelve participants scheduled for SG were included. Before and 3 mo after surgery, a mixed-meal test followed by an ad libitum meal test was performed with concomitant infusions of acyl-ghrelin (1 pmol/kg/min) or placebo. Infusions began 60 min before meal intake to reach a steady state before the mixed-meal and were continued throughout the study day. Two additional experimental days with 0.25 pmol/kg/min and 10 pmol/kg/min of acyl-ghrelin infusions were conducted 3 mo after surgery. Both before and after SG, postprandial glucose concentrations increased dose dependently during ghrelin infusions compared with placebo. Ghrelin infusions inhibited basal and postprandial insulin secretion rates, resulting in lowered measures of β-cell function, but no effect on insulin sensitivity was seen. Ad libitum meal intake was unaffected by the administration of ghrelin. In conclusion, ghrelin infusion increases postprandial plasma glucose concentrations and impairs β-cell function before and after SG but has no effect on ad libitum meal intake. We speculate that the lower concentration of ghrelin after SG may impact glucose metabolism following this procedure.NEW & NOTEWORTHY Ghrelin's effect on glucose tolerance and food intake following sleeve gastrectomy (SG) was evaluated. Acyl-ghrelin was infused during a mixed-meal and ad libitum meals before and 3 mo after surgery. Postprandial glucose concentrations increased during ghrelin infusions, both before and after surgery, while insulin production was inhibited. However, ad libitum meal intake did not differ during ghrelin administration compared with placebo. The decreased ghrelin concentration following SG may contribute to the glycemic control after surgery.

The role of glucagon-like peptide 1 in the postprandial effects of metformin in type 2 diabetes: a randomized crossover trial.

Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D. In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.7%], body mass index 30.1 kg/m2, age 71 years) underwent, in randomized order, 14 days of metformin and placebo treatment, respectively. Each treatment period was preceded by 14 days without any glucose-lowering medicine and concluded by two 4 h mixed meal tests performed in randomized order and separated by >24 h with either continuous intravenous exendin(9-39)NH2 or saline infusion. Compared to placebo, metformin treatment lowered fasting plasma glucose (mean of differences [MD] 1.4 mmol/L × min [95% CI 0.8-2.0]) as well as postprandial plasma glucose excursions during both saline infusion (MD 186 mmol/L × min [95% CI 64-307]) and exendin(9-39)NH2 infusion (MD 268 mmol/L × min [95% CI 108-427]). The metformin-induced improvement in postprandial glucose tolerance was unaffected by GLP-1R antagonization (MD 82 mmol/L × min [95% CI -6564-170]). Metformin treatment increased fasting plasma GLP-1 (MD 1.7 pmol/L × min [95% CI 0.39-2.9]) but did not affect postprandial GLP-1 responses (MD 820 pmol/L × min [95% CI -1750-111]). Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin's beneficial effect on fasting plasma glucose in T2D. Trial registration: Clinicaltrials.gov NCT03246451.

The Effect of Adding Protein to a Carbohydrate Meal on Postprandial Glucose and Insulin Responses: A Systematic Review and Meta-Analysis of Acute Controlled Feeding Trials

BackgroundProtein influences acute postprandial glucose and insulin responses, but the effects of dose, protein type, and health status are unknown. ObjectivesWe aimed to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers. MethodsWe searched MEDLINE, EMBASE, and Cochrane databases through 30 July, 2023 for acute, crossover trials comparing acute postprandial responses elicited by carbohydrate-containing test meals with and without added protein in adults without diabetes or with type 2 (T2DM) or type 1 (T1DM) diabetes mellitus. Group data were pooled separately using generic inverse variance with random-effects models and expressed as the ratio of means with 95% confidence interval. Risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. ResultsIn 154 trial comparisons of animal, dairy, and plant proteins (without diabetes, n = 22, 67, 32, respectively; T2DM, n = 14, 16, 3, respectively), each gram protein per gram available carbohydrate (g/g) reduced the glucose area under the curve (AUC) less in adults with T2DM than in those without diabetes (−10% compared with −50%, P < 0.05) but increased the insulin AUC similarly (+76% compared with +56%). In subjects without diabetes, each g/g of dairy and plant protein reduced glucose AUC by 52% and 55%, respectively, and increased the insulin AUC by 64% and 45%, respectively (all P < 0.05). Animal proteins significantly reduced the glucose AUC by 31% and increased the insulin AUC by 37% (pooled effects) but without a significant dose-response. In adults with T2DM, animal protein reduced the glucose AUC by 13% and increased the insulin AUC by 105%, with no significant dose-response. Dairy protein reduced the glucose AUC by 18% (no dose-response), but each g/g increased the insulin AUC by 34% (P < 0.05). In adults with T1DM, protein increased the glucose AUC by 40% (P < 0.05, n = 5). Data source (reported AUC compared with calculated AUC) and study methodology quality significantly modified some outcomes and contributed to high between-study heterogeneity. ConclusionsIn people without diabetes, adding dairy or plant protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose AUC and increases insulin AUC. Animal protein may slightly reduce the glucose AUC and may increase the insulin AUC. In people with T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein source.This study was registered at PROSPERO as CRD42022322090.

The ‘Carrot Test’: An approach to characterize individual differences in oral processing behaviour and eating rate

BackgroundEating rate is a modifiable risk factor for obesity and efficient methods to objectively characterise an individual’s oral processing behaviours could help better identify people at risk of increased energy consumption. Many previous approaches to characterise oral processing and eating rate have relied on specialised equipment or wearable devices that are time consuming, expensive or require expertise to administer. The current trial used video-coding of the consumption of a standardised test food (the ‘carrot test’) to measure oral processing. ObjectiveWe sought (i) to test whether self-reported eating rate (SRER) is predictive of food oral processing derived from coded eating behaviours captured in the laboratory with a standardised test food, and (ii) to test whether differences in SRER are predictive of oral processing behaviours, eating rate and intake of a test meal. MethodsTwo hundred and fifty-three volunteers (86 male and 167 female, mean age 39.5 ± 13.6 years, mean BMI 22.2 ± 3.4 kg/m2) provided their SRER and anthropometric measurements of height, weight and dual-energy X-ray absorptiometry (DEXA) percentage fat mass. Participants were also video recorded eating a fixed 50 g portion of carrot and an ad libitum lunch meal of fried rice. Average eating rate (g/min), bite size (g) and number of chews per bite for the carrot and lunch were derived through behavioural coding of the videos. Energy intake (kcal) was recorded at lunch and a later afternoon snack. ResultsFaster SRER significantly predicted faster eating rate, larger bite size and more chews per bite observed during intake of the carrot (ß = −0.26–0.21, p ≤ 0.001) and the lunch (ß = −0.26–0.35, p ≤ 0.014). SRER did not significantly predict intake at lunch or during the afternoon snack (ß = 0.05–0.07, p ≥ 0.265). Participants’ oral processing of the carrot significantly predicted oral processing of the lunch (ß = −0.25–0.40, p ≤ 0.047) and faster eating rate of the carrot significantly predicted increased lunch intake (ß = 0.119, p = 0.045). None of the oral processing behaviours predicted afternoon snack intake (ß = −0.01–0.05, p ≥ 0.496). None of these associations were moderated by BMI or body composition. ConclusionWe confirm that SRER is a valid measure of group level differences in individual oral processing behaviours, but did not predict an individual’s energy intake at a lunch-time meal. With this approach, it is possible to characterise differences in eating rate by coding eating behaviours for a standardized test food (in this case, a fixed portion of raw carrot). This approach could be used to provide an objective measure of a person’s habitual oral processing behaviour, and was shown to be a significant predictor of eating rate and energy intake for a later test meal.

Combined antiallodynic effects of Neurotropin®–tramadol and Neurotropin®–mirogabalin in rats with L5-spinal nerve ligation

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50–200 NU/kg, p.o.), tramadol (7.5–60 mg/kg, p.o.), and mirogabalin (3–30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100–400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30–100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100–400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10–100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin–tramadol or Neurotropin–mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

Effects of Different Protein Sources on Amino Acid Absorption and Plasma Appearance of Tryptophan, Large Neutral Amino Acids, and Tryptophan Metabolites in Pigs

BackgroundAbsorption of tryptophan (TRP) across the gut epithelium is potentially modulated by competing large neutral amino acids (LNAAs), which could affect the appearance of TRP and its metabolites in the bloodstream. ObjectivesThis study aimed to determine, in a growing pig model of an adult human, the absorption of TRP and other LNAAs from the gastrointestinal tract, and plasma appearance of TRP, LNAAs, and TRP metabolites, in response to dietary proteins varying in TRP content. MethodsPigs were adapted for 7 d to each of 4 diets that differed in their protein source and TRP content: 1) alpha-lactalbumin (AL; 9.95 mg TRP/g diet DM), 2) whey protein (6.59 mg TRP/g), 3) casein (3.73 mg TRP/g), or 4) zein (0.14 mg TRP/g). On day 8, pigs were euthanised after a 12-h fast (baseline), or 1, 2, 3, 4, or 6 h after they received a test meal consisting of 45 g protein, or a protein-free meal (n = 6 pigs at each time in each meal group). Tryptophan and LNAA absorption from the small intestine, and appearance of TRP, LNAAs, and TRP metabolites (melatonin, serotonin, kynurenine pathway metabolites), in the portal vein and systemic circulation, were determined. ResultsAL intake resulted in sustained elevated plasma TRP concentrations after an overnight fast. The amount of TRP absorbed was dose-dependently related to protein TRP content (P = 0.028), with fastest rates for pigs fed AL (371 mg/h). Portal and systemic plasma TRP, TRP/LNAA, and the TRP metabolites were highest (P ≤ 0.05) after AL intake, and remained above baseline levels for ∼4 h postprandially. Absorption rates of TRP correlated with postprandial plasma TRP and TRP metabolites (P ≤ 0.05). ConclusionsIn adult humans, postprandial plasma TRP and TRP metabolite concentrations can likely be modulated by the TRP content of the meal.