Mixed-macronutrient Meal Research Articles

Fat burning capacity in a mixed macronutrient meal protocol does not reflect metabolic flexibility in women who are overweight or obese.

Metabolic flexibility, the ability to switch from glucose to fat as a fuel source, is considered a marker of metabolic health. Higher fat oxidation is often associated with greater flexibility and insulin sensitivity, while lower fat oxidation is linked to metabolic inflexibility and insulin resistance. However, our study challenges the universal validity of this relationship, uncovering a more nuanced understanding of the complex interplay between fuel source switching and fat oxidation, especially in the presence of insulin resistance. In an 8-week controlled feeding intervention, overweight to obese women with insulin resistance (as defined by McAuley's index) were randomized to consume either a diet based on the Dietary Guidelines for Americans 2010 (DGA) or a 'Typical' American Diet (TAD), n = 22 each. Participants were given a high-fat mixed macronutrient challenge test (MMCT) (60% fat, 28% carbohydrates, and 12% protein) at weeks 0, 2, and 8. Plasma lipids, metabolome, and lipidome were measured at 0, 0.5, 3, and 6h postprandial (PP); substrate oxidation measures were also recorded at 0,1 3, and 6h PP. Metabolic flexibility was evaluated as the change in fat oxidation from fasting to PP. Mixed model and multivariate analyses were used to evaluate the effect of diet on these outcomes, and to identify variables of interest to metabolic flexibility. Intervention diets (DGA and TAD) did not differentially affect substrate oxidation or metabolic flexibility, and equivalence tests indicated that groups could be combined for subsequent analyses. Participants were classified into three groups based on the % of consumed MMCT fat was oxidized in the 6h post meal period at weeks 0, 2 and 8. Low fat burners (LB, n = 6, burned <30% of fat in MMCT) and high fat burners (HB, n = 7, burned > 40% of fat in MMCT) at all weeks. Compared to LB, HB group had higher fat mass, total mass, lean mass, BMI, lower HDLc and lower RER (p < 0.05), but not different % body fat or % lean mass. During week 0, at 1h PP, LB had an increase in % fat oxidation change from 0h compared to HB (p<0.05), suggesting higher metabolic flexibility. This difference disappeared later in the PP phase, and we did not detect this beyond week 0. Partial least squares discriminant analysis (PLSDA (regular and repeated measures (sPLSDA)) models identified that LB group, in the late PP phase, was associated with higher rates of disappearance of acylcarnitines (AC) and lysophosphatidylcholines (LPC) from plasma (Q2: 0.20, R2X: 0.177, R2Y: 0.716). In women with insulin resistance, a high fat burning capacity does not imply high metabolic flexibility, and not all women with insulin resistance are metabolically inflexible. LPCs and ACs are promising biomarkers of metabolic flexibility.

Elevations in plasma glucagon are associated with reduced insulin clearance after ingestion of a mixed-macronutrient meal in people with and without type 2 diabetes

Aims/hypothesisThe temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear.MethodsIn a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model.ResultsThere were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min−1 m−2) and type 2 diabetes (1.4 ± 0.7 l min−1 m−2) groups compared with Lean-NGT (1.9 ± 0.5 l min−1 m−2; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R2=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ −0.75 l min−1 m−2; p<0.001).Conclusions/interpretationThe ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted.Trial registrationISRCTN17563146 and ISRCTN95281775Graphical

Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SIT-LESS randomised controlled trial.

To examine the impact of interrupting prolonged sitting with frequent short bouts of light-intensity activity on glycaemic control in people with type 1 diabetes (T1D). In total, 32 inactive adults with T1D [aged 27.9 ± 4.7 years, 15 men, diabetes duration 16.0 ± 6.9 years and glycated haemoglobin 8.4 ± 1.4% (68 ± 2.3 mmol/mol)] underwent two 7-h experimental conditions in a randomised crossover fashion with >7-day washout consisting of: uninterrupted sitting (SIT), or, interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals (SIT-LESS). Standardised mixed-macronutrient meals were administered 3.5 h apart during each condition. Blinded continuous glucose monitoring captured interstitial glucose responses during the 7-h experimental period and for a further 48-h under free-living conditions. SIT-LESS reduced total mean glucose (SIT 8.2 ± 2.6 vs. SIT-LESS 6.9 ± 1.7 mmol/L, p = .001) and increased time in range (3.9-10.0 mmol/L) by 13.7% (SIT 71.5 ± 9.5 vs. SIT-LESS 85.1 ± 7.1%, p = .002). Hyperglycaemia (>10.0 mmol/L) was reduced by 15.0% under SIT-LESS (SIT 24.2 ± 10.8 vs. SIT-LESS 9.2 ± 6.4%, p = .002), whereas hypoglycaemia exposure (<3.9 mmol/L) (SIT 4.6 ± 3.0 vs. SIT-LESS 6.0 ± 6.0%, p = .583) was comparable across conditions. SIT-LESS reduced glycaemic variability (coefficient of variation %) by 7.8% across the observation window (p = .021). These findings were consistent when assessing discrete time periods, with SIT-LESS improving experimental and free-living postprandial, whole-day and night-time glycaemic outcomes (p < .05). Interrupting prolonged sitting with frequent short bouts of light-intensity activity improves acute postprandial and 48-h glycaemia in adults with T1D. This pragmatic strategy is an efficacious approach to reducing sedentariness and increasing physical activity levels without increasing risk of hypoglycaemia in T1D.

ODP626 Weekend Hypoglycemia: A Case of Intermittent Endogenous Hyperinsulinemic Hypoglycemia Caused by Prolonged Interval Between Hemodialysis Sessions in ESRD

Abstract Background Hypoglycemia is a common clinical dilemma with burden of risk to life, bothersome symptoms and expensive workup. With many different causes for hypoglycemia, initial workup includes differentiating insulin-dependent versus non-insulin dependent causes. Elevated insulin levels correlated with a C-peptide level can separate endogenous versus exogenous hyperinsulinemic hypoglycemia. If endogenous hyperinsulinism is discovered, further investigation into a wide array of pathology is warranted. We highlight a case of hyperinsulinemic hypoglycemia in a patient with end-stage renal disease on hemodialysis. Given limited treatment options, this case illustrates the importance of patient specific behavioral modifications. Case A 43-year-old man with T2DM with ESRD on hemodialysis (MWF) presents with recurrent episodes of severe hypoglycemia with altered mental status. On admission, serum glucose was 29 mg/dL and patient was treated with IV dextrose with resolution of symptoms. Patient denied taking anti-hyperglycemic medications. Patient was recently and similarly admitted two weeks prior where his insulin regimen (patient confirmed compliance) was discontinued due to severe hypoglycemia. Serum insulin and C-peptide at the time of this admission were 93.8 mg/dLand 29.57 nmol/L respectively. Insulin antibodies were negative. Although both values indicate an endogenous source for hyperinsulinemia, exact interpretation is unclear given his ESRD. Patient underwent hemodialysis on hospital day one. On hospital day two, patient's labs indicated hyperinsulinemic hypoglycemia again, with glucose of 56 mg/dL and an insulin of 24 mg/dL. Subsequently, an abdominal CT scan with triple phase washout was negative for an intra-pancreatic process. He had normal thyroid function, and history of adrenal insufficiency which was stable on maintenance doses of glucocorticoids. Patient also confirmed good appetite, stable weight, and albumin levels were appropriate. On hospital day 3, patient underwent his normally scheduled dialysis. Both pre- and post-dialysis insulin and C-peptide levels were collected, and insulin levels decreased &amp;gt;50% following dialysis. Patient was also started on diazoxide to reduce endogenous hyperinsulinemia after this session. No further hypoglycemia occurred during hospital stay. He was subsequently discharged home on hospital day 4 and educated on the increased likelihood of hypoglycemia during extended periods of time without dialysis, which in his case was weekends. In order to address this, he was instructed to have small, frequent mixed macronutrient meals and snacks on Sundays, leading up to Monday's dialysis session. Conclusion This case of "weekend hypoglycemia" highlights a perplexing presentation in a patient with ESRD on HD, of hyperinsulinemic hypoglycemia occurring only during prolonged interval (&amp;gt;2 days) between hemodialysis sessions. This is postulated secondary to a combination of ESRD with associated impaired renal clearance of insulin and impaired renal gluconeogenesis and resultant hyperinsulinemia that improved with dialysis sessions. Patient education on compliance with dialysis sessions and dietary counseling to reduce risk of hypoglycemia is key in management. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Acute Cannabidiol Administration Does Not Increase the Thermic Effect of Feeding in Men with Overweight and Obesity

The thermic effect of feeding (the increase in energy expenditure above resting metabolic rate following ingestion of food) is lower in adult humans with overweight and obesity compared to their lean counterparts. In animal models of obesity, the endocannabinoid system is upregulated and is thought to contribute to an unfavorable metabolic phenotype. The influence of cannabidiol, a non‐psychoactive component of Cannabis sativa L., on the thermogenic properties of the endocannabinoid system in humans is unclear. Accordingly, the purpose of the current study was to explore the hypothesis that acute administration of cannabidiol would increase the thermic effect of feeding. Metabolic rate, via indirect calorimetry, was determined at rest and over 4‐hours following ingestion of a liquid, mixed macronutrient meal (22% fat, 62% carbohydrate, 16% protein) equivalent to 40% of resting metabolism, in 11 adult men with body mass index greater than 25 kg/m2 (age: 26 ± 9 years; body mass: 93.7 ± 13.0 kg; body mass index: 29.8 ± 3.0 kg/m²; body fat: 29.4% ± 4.6% (mean ± SD)) on two separate occasions. Immediately following meal ingestion, participants were administered either 30 mg of cannabidiol or placebo, in a randomized, single‐blind crossover fashion. Resting metabolic rate did not differ between trials (1745 ± 311 vs. 1744 ± 288 kcal/day; P=0.98). Compared with rest, energy expenditure was increased after ingestion of the liquid meal (P&lt;0.01) but was unaffected by cannabidiol (Time x Placebo vs. Cannabidiol: P = 0.21). The area under the thermic effect of feeding response curve was also unaffected by cannabidiol (57 ± 24 vs. 58 ± 16 kcal/min x min; P=0.92). Respiratory exchange ratio, an indicator of substrate utilization, was not different between trials at rest (0.81 ± 0.04 vs. 0.79 ± 0.04; P=0.09). Ingestion of the meal increased respiratory exchange ratio (P&lt;0.01), indicative of increased reliance on carbohydrate oxidation, but again this response was unaffected by cannabidiol (Time x Placebo vs. Cannabidiol: P=0.08). These preliminary data suggest that a single 30 mg dose of cannabidiol does not influence the thermic effect of feeding, a significant contributor to total daily energy expenditure, in men with overweight or obesity. Cannabidiol has been purported to have multiple beneficial effects on physiological function, it appears that these effects may be independent of any influence on the thermic effect of feeding.

Postprandial Responses of Energy Substrates in Dogs Fed High Fat‐ vs High Protein‐Low Carbohydrate Ketogenic Foods Relative to a High Carbohydrate Food

ObjectiveReduction of dietary carbohydrate (CHO) can increase circulating ketone availability and may aid disease management including inflammatory bowel disease, cancer, diabetes and cognitive decline. Companion animal dogs are prone to all of these maladies. Postprandial to a mixed macronutrient meal, non‐esterified fatty acids (NEFA) and beta‐hydroxybutyrate (BHB) decrease. In contrast, both glucose and blood urea nitrogen (BUN) increase. Triglycerides (TG) comprise circulating fat energy after a fat‐containing meal although medium chain TG (MCT) are preferentially catabolized to ketones. The postprandial responses of dogs to habitual feeding of high fat versus high protein low CHO foods, relative to high CHO foods, is not known. Therefore, we compared fasting (0 hr) and 2‐0 hr delta values for BHB, NEFA, TG, glucose, BUN as markers of available energy for these foods in dogs.MethodsDogs housed in pairs, with daily group exercise in outdoor grassy runs. Dogs returned to the colony healthy after the study; no invasive procedures. Blood collections under approved protocols at 0 hours (immediately before a meal) and at 2 hours postprandial. Macronutrients (P/F/C; % energy) for the 3 foods: HiCHO (25/37/38); LoCHOprot (50/44/6); LoCHOfat (28/68/4). The LoCHOfat food further contained 22% of dietary fat energy as MCT. Prospective randomized crossover trial (2 groups, n = 18). HiCHO was the wash‐in food followed by LoCHOprot or LoCHOfat in randomized order (5 wk feeding each food). Foods analyzed according to AOAC methods. Energy substrates BHB, NEFA, TG, glucose and BUN measured by Cobas or enzymatic reaction. Individual diet differences by dependent samples t‐test, linear mixed modeling for overall diet effect. Significance at α = 0.05.ResultsAnalyzed ketogenic ratios of the foods: HiCHO (0.46), LoCHOprot (1.1), and LoCHOfat (1.7). At fasting, LoCHOprot and LoCHOfat elevated circulating BHB above HiCHO food with LoCHOfat BHB higher than LoCHOprot. Between 0‐2 hours postprandial, BHB decreased for HiCHO (‐23%) and increased more for LoCHOfat (+100%) than LoCHOprot (+33%). Fasting NEFA were higher in LoCHOprot than LoCHOfat, and not different otherwise. From 0‐2 hours postprandial all foods showed decreased NEFA: HiCHO (‐43%), LoCHOprot (‐57%), LoCHOfat (‐12%). Fasting glucose was not different between groups. From 0‐2 hours postprandial LoCHOprot (‐4%) and LoCHOfat (‐8%) showed decreased glucose while HiCHO was unchanged. Fasting TG levels were different between all foods with the LoCHOprot (‐45%) and LoCHOfat (‐37%) lower than HiCHO. From 0‐2 hours postprandial all dogs showed increased TG with all values different between groups: HiCHO (+135%), LoCHOprot (+356%), LoCHOfat (+591%). Fasting BUN was higher with LoCHOprot than either HiCHO (‐27%) or LoCHOfat (‐26%). From 0‐2 hours postprandial all dogs showed increased BUN with all changes different: HiCHO (+17%), LoCHOprot (+42%), LoCHOfat (+23%).ConclusionsThe LoCHOfat food increased postprandial availability of BHB, NEFA and TG energy while decreasing glucose energy. LoCHOprot primarily enhanced available energy from protein as shown by increased amino acid catabolism to BUN, with additional contributions from BHB, NEFA and TG. The HiCHO food presented only glucose and TG as energy postprandial. Together these data show that a moderate protein, high fat, low CHO food with added MCT can selectively apportion postprandial energy toward ketone and fats while decreasing availability of glucose.

Prior arm-crank exercise has no effect on postprandial lipaemia in nondisabled adults

A single bout of cycling or running performed in the evening can reduce postprandial lipaemia (PPL) the following morning, although this is currently unknown for upper-body exercise. The aim of this study was to determine if a bout of arm crank exercise (high-intensity interval [HIIE] or moderate-intensity continuous [MICE]), can attenuate PPL in non-injured individuals. Eleven healthy and recreationally active participants (eight males, three females; age: 27 ± 7 yr; body mass index: 23.5 ± 2.5 kg · m-2) volunteered to participate in three trials: HIIE (10 x 60 s at 80% peak power output), MICE (50% peak power output of isocaloric duration), and a no-exercise control condition. Each exercise bout was performed at 18:00, and participants consumed a standardized evening meal at 20:00. Following an overnight fast, a 5-h mixed-macronutrient tolerance test was performed at 08:00. There were no significant differences in triglyceride incremental area under the curve between HIIE (192 ± 94 mmol. L-1 per 300 min), MICE (184 ± 111 mmol. L-1 per 300 min), and the no-exercise condition (175 ± 90 mmol. L-1 per 300 min) (P=0.46). There were no significant differences in incremental area under the curve for glucose (P=0.91) or insulin (P=0.59) between conditions. Upper-body MICE and HIIE performed in the evening do not influence PPL the following morning, in normotriglyceridemic individuals. Clinical Trials Registration: NCT04277091 Novelty: • Arm crank exercise has no effect on PPL when performed the evening prior to a mixed-macronutrient meal test • Upper-body sprint interval exercise should be investigated as a potential solution to reduce PPL.

Metabolic flexibility differs by body composition in adults.

With the rise of global cardiometabolic diseases, it is important to investigate risk factors such as obesity. Metabolic flexibility, the ability to maintain metabolic homeostasis following an acute challenge, can reflect cardiometabolic health. We investigated the association between body composition and the metabolic flexibility following meal consumption in an adult population. In this study of 1027 participants (mean age 44.0y±SD 4.2y), we administered a mixed-macronutrient meal challenge. Fasting and 2-h postprandial plasma were assayed for lipids, glycemic, and inflammation biomarkers. We characterized metabolic flexibility through meal-induced biomarker responses (%Δ, the difference between postprandial and fasting concentrations, divided by fasting concentration). We then compared the responses by sex-specific tertiles of body mass index (BMI) and percent body fat. With every unit (kg/m2) increase in BMI, %Δ (95% confidence interval) increased by 0.17% (0.09, 0.26%) for total cholesterol, 0.31% (0.07, 0.54%) for triglycerides, and 0.11% (0.01, 0.20%) for apoA-I, whereas insulin elevation was reduced (-6.30%;-8.41,-4.20%), and the reduction in leptin was attenuated (0.64%; 0.25, 1.05%). With each unit (percent) increase in body fat, we observed similar changes in the %Δ of total cholesterol and leptin but not in triglycerides, apoA-I, or insulin. Glucose response increased by 0.29% (0.06, 0.51%) as body fat increases by one unit. Metabolic flexibility, as assessed by biomarker responses to an acute physiological meal challenge, differed by body composition. These findings may help elucidate the pathways through which obesity contributes to cardiometabolic diseases.

Comparison of aspartame- and sugar-sweetened soft drinks on postprandial metabolism.

Aim: We compared the impact of artificially- and sugar-sweetened beverages co-ingested with a mixed meal on postprandial fat and carbohydrate oxidation, blood glucose, and plasma insulin and triglyceride concentrations. Methods: Eight college-aged, healthy males completed three randomly assigned trials, which consisted of a mixed macronutrient meal test with 20oz of Diet-Coke (AS), Coca-Cola (NS), or water (CON). One week separated each trial and each participant served as his own control. Resting energy expenditure (REE) via indirect calorimetry, blood pressure, and blood samples were obtained immediately before, 5, 10, 30, 60, 120, and 180 min after meal and beverage ingestion. A two-way (treatment × time) repeated-measures ANOVA was conducted to assess REE, fat and carbohydrate oxidation rates, blood glucose, and plasma insulin and triglyceride concentrations. Results: There was a significant main effect of treatment on total fat oxidation (P = 0.006), fat oxidation was significantly higher after AS (P = 0.006) and CON (P = 0.001) compared to following NS. There was a significant main effect of treatment on total carbohydrate oxidation (P = 0.005), carbohydrate oxidation was significantly lower after AS (P = 0.014) and CON (P = 0.001) compared to following NS. Plasma insulin concentration AUC was significantly lower after AS (P = 0.019) and trended lower in CON (P = 0.054) compared to following NS. Conclusion: Ingestion of a mixed meal with an artificially-sweetened beverage does not impact postprandial metabolism, whereas a sugar-sweetened beverage suppresses fat oxidation and increases carbohydrate oxidation compared to artificially-sweetened beverage and water.

Application of Machine Learning to Assess Interindividual Variability in Rapid-Acting Insulin Responses After Subcutaneous Injection in People With Type 1 Diabetes

ObjectivesCirculating insulin concentrations mediate vascular-inflammatory and prothrombotic factors. However, it is unknown whether interindividual differences in circulating insulin levels are associated with different inflammatory and prothrombotic profiles in type 1 diabetes (T1D). We applied an unsupervised machine-learning approach to determine whether interindividual differences in rapid-acting insulin levels associate with parameters of vascular health in patients with T1D. MethodsWe re-analyzed baseline pretreatment meal-tolerance test data from 2 randomized controlled trials in which 32 patients consumed a mixed-macronutrient meal and self-administered a single dose of rapid-acting insulin individualized by carbohydrate counting. Postprandial serum insulin, tumour necrosis factor (TNF)-alpha, plasma fibrinogen, human tissue factor (HTF) activity and plasminogen activator inhibitor-1 (PAI-1) were measured. Two-step clustering categorized individuals based on shared clinical characteristics. For analyses, insulin pharmacokinetic summary statistics were normalized, allowing standardized intraindividual comparisons. ResultsDespite standardization of insulin dose, individuals exhibited marked interpersonal variability in peak insulin concentrations (48.63%), time to peak (64.95%) and insulin incremental area under the curve (60.34%). Two clusters were computed: cluster 1 (n=14), representing increased serum insulin concentrations; and cluster 2 (n=18), representing reduced serum insulin concentrations (cluster 1: 389.50±177.10 pmol/L/IU h−1; cluster 2: 164.29±41.91 pmol/L/IU h−1; p<0.001). Cluster 2 was characterized by increased levels of fibrinogen, PAI-1, TNF-alpha and HTF activity; higher glycated hemoglobin; increased body mass index; lower estimated glucose disposal rate (increased insulin resistance); older age; and longer diabetes duration (p<0.05 for all analyses). ConclusionsReduced serum insulin concentrations are associated with insulin resistance and a prothrombotic milieu in individuals with T1D, and therefore may be a marker of adverse vascular outcome.

Postprandial vascular-inflammatory and thrombotic responses to high-fat feeding are augmented by manipulating the lipid droplet size distribution

Background and aimsPostprandial responses are influenced not only by the type and amount of fat ingested, but also lipid droplet size distribution. However, little research has investigated the impact of differential lipid size distributions within a mixed-macronutrient meal context on postprandial vascular health. Therefore, we examined whether manipulating the lipid droplet size distribution within a mixed-macronutrient meal impacts vascular-inflammatory and thrombotic parameters. Methods and resultsIn a randomised and counterbalanced fashion, sixteen adults (8 males; age 34 ± 7 years; BMI of 25.3 ± 4.5 kg/m2) completed three separate fasted morning-time feeding challenges, each separated by a minimum washout of 7-days. On each occasion, test-meals matched for carbohydrate and protein content differing only in fat amount and the lipid droplet size distribution were administered, such that participants consumed (1) a low-fat meal (LF) with negligible fat content, (2) an emulsified-high-fat meal with a fine lipid droplet size (FE), or (3) an emulsified-high-fat meal with a coarse lipid droplet size (CE). Periodic blood samples were retrospectively analysed for plasma triglycerides, tumour necrosis factor alpha (TNFα), tissue factor (TF), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). Triglyceride concentrations increased rapidly overtime under FE (P-time<0.05); this rise was attenuated under CE (P-time>0.05) and was comparable to LF (P-condition>0.05). Similarly, FE induced a significant rise in TNFα, TF, fibrinogen, and PAI-1 (P-time<0.05); these parameters remained unchanged under LF and CE (P-time>0.05). ConclusionA high-fat mixed-macronutrient meal with a larger lipid droplet size distribution ameliorates the associated rise in vascular-inflammatory and thrombotic parameters. Trial registrationISRCTN88881254.

Effects of high-carbohydrate versus mixed-macronutrient meals on female soccer physiology and performance

Athletes are often told to minimize intakes of fiber, fat, and protein in pre-competition meals to avoid gut distress, but this guidance is based on scant direct evidence. This study evaluated the physiological and perceptual effects of pre-competition mixed-macronutrient (MM) and high-carbohydrate (HCHO) meals in collegiate female soccer players. Fifteen players participated in this randomized, investigator-blinded, crossover study involving two ~ 1000-kcal meals (HCHO and MM) consumed 4h prior to 70-min scrimmages. Assessments included global positioning system (GPS) tracking, heart rate (HR), perceived exertion (RPE), ratings of fatigue (ROF), gut symptoms, and perceptions of satiety, hunger, and fullness. Differences between conditions for HR, RPE, ROF, and gut symptoms were evaluated with Wilcoxon signed-rank tests. GPS data and hunger, satiety, and fullness scores were compared using within-subjects repeated measures ANOVAs. No statistically significant differences were found between the conditions at any time point for HR, RPE, ROF, or gut symptoms. Significant time effects were found for two GPS variables (total distance covered and high-speed running), indicating that participants covered less distance during the second half of the scrimmages in comparison to the first half. However, there were no significant condition or condition × time interactions for GPS data. Finally, there were no condition or condition × time interactions for hunger, fullness, and satiety, though significant time effects were observed. A MM meal consumed 4h prior to 70min of soccer competition does not increase gut symptoms and can be similarly ergogenic as a HCHO meal.

Essential amino acid-enriched whey enhances post-exercise whole-body protein balance during energy deficit more than iso-nitrogenous whey or a mixed-macronutrient meal: a randomized, crossover study

BackgroundThe effects of ingesting varying essential amino acid (EAA)/protein-containing food formats on protein kinetics during energy deficit are undetermined. Therefore, recommendations for EAA/protein food formats necessary to optimize both whole-body protein balance and muscle protein synthesis (MPS) during energy deficit are unknown. We measured protein kinetics after consuming iso-nitrogenous amounts of free-form essential amino acid-enriched whey (EAA + W; 34.7 g protein, 24 g EAA sourced from whey and free-form EAA), whey (WHEY; 34.7 g protein, 18.7 g EAA), or a mixed-macronutrient meal (MEAL; 34.7 g protein, 11.4 g EAA) after exercise during short-term energy deficit.MethodsTen adults (mean ± SD; 21 ± 4 y; 25.7 ± 1.7 kg/m2) completed a randomized, double-blind crossover study consisting of three, 5 d energy-deficit periods (− 30 ± 3% of total energy requirements), separated by 14 d. Whole-body protein synthesis (PS), breakdown (PB), and net balance (NET) were determined at rest and in response to combination exercise consisting of load carriage treadmill walking, deadlifts, and box step-ups at the end of each energy deficit using L-[2H5]-phenylalanine and L-[2H2]-tyrosine infusions. Treatments were ingested immediately post-exercise. Mixed-muscle protein synthesis (mixed-MPS) was measured during exercise through recovery.ResultsChange (Δ postabsorptive + exercise to postprandial + recovery [mean treatment difference (95%CI)]) in whole-body (g/180 min) PS was 15.8 (9.8, 21.9; P = 0.001) and 19.4 (14.8, 24.0; P = 0.001) greater for EAA + W than WHEY and MEAL, respectively, with no difference between WHEY and MEAL. ΔPB was − 6.3 (− 11.5, − 1.18; P = 0.02) greater for EAA + W than WHEY and − 7.7 (− 11.9, − 3.6; P = 0.002) greater for MEAL than WHEY, with no difference between EAA + W and MEAL. ΔNET was 22.1 (20.5, 23.8; P = 0.001) and 18.0 (16.5, 19.5; P = 0.00) greater for EAA + W than WHEY and MEAL, respectively, while ΔNET was 4.2 (2.7, 5.6; P = 0.001) greater for MEAL than WHEY. Mixed-MPS did not differ between treatments.ConclusionsWhile mixed-MPS was similar across treatments, combining free-form EAA with whey promotes greater whole-body net protein balance during energy deficit compared to iso-nitrogenous amounts of whey or a mixed-macronutrient meal.Trial registrationClinicalTrials.gov, Identifier no. NCT04004715. Retrospectively registered 28 June 2019, first enrollment 6 June 2019

Nocturnal whey protein ingestion impairs post-prandial glucose tolerance at breakfast.

Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.

Walking Or Body Weight Squats May Improve Muscle Dietary Amino Acid Sensitivity During Prolonged Sitting

Low physical activity (e.g. reduced daily steps) reduces the ability of dietary amino acids (AA) to support muscle protein synthesis, leading to eventual muscle loss. Interrupting prolonged sitting with short bouts of intermittent exercise can improve carbohydrate and lipid metabolism, however its ability to sensitize skeletal muscle to dietary AA has yet to be investigated. PURPOSE: To determine the ability of interrupting prolonged sitting with practical ‘activity snacks’ to enhance the postprandial incorporation of dietary AA into myofibrillar protein. METHODS: As a subset of a larger study, twelve participants (7 males and 5 females; ~23y; ~40.0mlO2/kg/min; ~25.1kg/m2; ~4676 steps/d) completed three 7.5 hr trials in a randomized order consisting of prolonged sitting (SIT), sitting with intermittent walking (WLK; 2 min at 3.1mph every 30 min) or sitting with intermittent squatting (SQT; 15 ‘chair stands with calf raise’ every 30 min). Mixed-macronutrient meals (~55:30:15% carbohydrate:fat:protein) were provided at 20% (breakfast) and 30% (lunch) of daily energy requirements to be consistent with Western feeding patterns. Meals were enriched to 15% with ring-[2H5]phenylalanine or ring-[13C6]phenylalanine to model the metabolic fate of dietary AA. Muscle biopsies taken at the end of each trial as well as at the beginning of trial 2 were used to determine change in AA enrichment (LC/MS/MS) in the myofibrillar protein fraction (ΔMyo). RESULTS: ΔMyo was 0.032±0.004MPE in SIT and tended to be greater with SQT (0.038±0.003; P=0.10) and WLK (0.047±0.006; P=0.06) according to a prior comparisons (paired one-tail T-test). Relative to SIT, effect sizes were large for WLK (ES=0.88; 95% CI -0.30 - 2.07) and moderate for SQT (ES=0.55; 95% CI -0.60 - 1.71). CONCLUSION: Interrupting prolonged periods of sitting with intermittent bouts of body weight-dependent activity has the potential to improve the utilization of dietary AA for de novo muscle protein synthesis in young healthy adults. Our results add to the evidence that reducing sedentary time through ‘activity snacks’ may help maintain muscle mass and quality. Future research should determine whether at risk populations (e.g. aging, obese) may obtain a greater benefit from this simple lifestyle modification. Supported in part by an ACSM Research Endowment Grant.

Physiological responses to maximal eating in men.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Postprandial regulation of prouroguanylin in humans of a healthy weight and those who are overweight or with obesity

Uroguanylin is a peptide gut hormone proposed to have a role in signalling post meal satiety. Uroguanylin circulates as its pro-hormone, prouroguanylin. There has been limited investigation of the regulation of prouroguanylin by food; therefore we investigated prouroguanylin regulation following meals. In separate experiments we investigated the effects of high calorie (1451 kcal) and medium calorie (725 kcal), high fat meals, on plasma prouroguanylin concentrations. We then examined the effect of a 722.5 kcal high carbohydrate breakfast on prouroguanylin concentrations, comparing the response in healthy weight adults versus those who are overweight/ with obesity. The 1451 kcal meal increased prouroguanylin concentrations, versus fasting at 60 (P < 0.05), 90 (P < 0.01) and 120 (P < 0.001) minutes. After the 725 kcal meal hormone concentrations rose more slowly and were significant versus fasting concentrations at 120 min (P < 0.01). The high carbohydrate breakfast 722.5 kcal, led to an initial suppression of hormone concentrations at 30 min. post meal (P < 0.05) followed by an increase in concentrations until they were significant versus fasting at 120 min. (P < 0.01). Participants overweight/ with obesity had lower fasting prouroguanylin concentrations (P < 0.05), but post meal concentrations did not differ between the groups. Our results suggest there is a delayed increase in prouroguanylin concentrations following, large and regular sized mixed macronutrient meals rich in fat or carbohydrate. Fasting levels are suppressed in people who are overweight/ with obesity, but the post meal response remains intact. There may be potential to target post meal release of prouroguanylin in obesity.

Impact of dietary protein on postprandial glycaemic control and insulin requirements in Type 1 diabetes: a systematic review.

Postprandial hyperglycaemia is a challenge for people living with Type 1 diabetes. In addition to carbohydrate, dietary protein has been shown to contribute to postprandial glycaemic excursions with recommendations to consider protein when calculating mealtime insulin doses. The aim of this review is to identify and synthesize evidence about the glycaemic impact of dietary protein and insulin requirements for individuals with Type 1 diabetes. A systematic literature search of relevant biomedical databases was performed to identify research on the glycaemic impact of dietary protein when consumed alone, and in combination with other macronutrients in individuals with Type 1 diabetes. The review included 14 published studies dated from 1992 to 2018, and included studies that researched the impact of protein alone (n=2) and protein in a mixed meal (n=12). When protein was consumed alone a glycaemic effect was not seen until ≥75g. In a carbohydrate-containing meal ≥12.5g of protein impacted the postprandial glucose. Inclusion of fat in a high-protein meal enhanced the glycaemic response and further increased insulin requirements. The timing of the glycaemic effect from dietary protein ranged from 90 to 240min. Studies indicate that the postprandial glycaemic response and insulin requirements for protein are different when protein is consumed alone or with carbohydrate and/or fat. This systematic review provides evidence that dietary protein contributes to postprandial glycaemic excursions and insulin requirements. These insights have important implications for the education of people with Type 1 diabetes and highlights the need for more effective insulin dosing strategies for mixed macronutrient meals.

A small dose of whey protein co-ingested with mixed-macronutrient breakfast and lunch meals improves postprandial glycemia and suppresses appetite in men with type 2 diabetes: a randomized controlled trial

Large doses of whey protein consumed as a preload before single high-glycemic load meals has been shown to improve postprandial glycemia in type 2 diabetes. It is unclear if this effect remains with smaller doses of whey co-ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed whey offers further benefit under these conditions is unclear. The aim of this study was to investigate postprandial glycemic and appetite responses after small doses of intact and hydrolyzed whey protein co-ingested with mixed-nutrient breakfast and lunch meals in men with type 2 diabetes. In a randomized, single-blind crossover design, 11 men with type 2 diabetes [mean±SD age: 54.9±2.3 y; glycated hemoglobin: 6.8%±0.3% (51.3±3.4 mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control) immediately before mixed-macronutrient breakfast and lunch meals, separated by 3 h. Blood samples were collected periodically and were processed for insulin, intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), leptin, peptide tyrosine tyrosine (PYY3-36), and amino acid concentrations. Interstitial glucose was measured during and for 24 h after each trial. Subjective appetite was assessed with the use of visual analog scales. Total postprandial glycemia area under the curve was reduced by 13%±3% after breakfast following the intact whey protein when compared with control (P<0.05). Hydrolyzed whey attenuated early glucose after breakfast when compared with control (P<0.05). Glycemia was improved postlunch after the intact whey protein only when compared with control (P<0.05). Greater satiety was observed after the intact whey protein only after both meals when compared with control (P<0.05). Insulin concentrations increased after both the intact and hydrolyzed whey protein, showing strong positive correlations with increases in valine and isoleucine (P<0.05). Incretin and appetite regulatory hormone responses were similar across trials (P>0.05). The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes. This trial was registered at www.clinicialtrials.gov as NCT02903199.

Translocation and protein complex co-localization of mTOR is associated with postprandial myofibrillar protein synthesis at rest and after endurance exercise.

Translocation and colocalization of mechanistic target of rapamycin complex 1 (mTORC1) with regulatory proteins represents a critical step in translation initiation of protein synthesis in vitro. However, mechanistic insight into the control of postprandial skeletal muscle protein synthesis rates at rest and after an acute bout of endurance exercise in humans is lacking. In crossover trials, eight endurance‐trained men received primed‐continuous infusions of L‐[ring‐2H5]phenylalanine and consumed a mixed‐macronutrient meal (18 g protein, 60 g carbohydrates, 17 g fat) at rest (REST) and after 60 min of treadmill running at 70% VO2peak (EX). Skeletal muscle biopsies were collected to measure changes in phosphorylation and colocalization in the mTORC1‐pathway, in addition to rates of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis. MyoPS increased (P < 0.05) above fasted in REST (~2.1‐fold) and EX (~twofold) during the 300 min postprandial period, with no corresponding changes in MitoPS (P > 0.05). TSC2/Rheb colocalization decreased below fasted at 60 and 300 min after feeding in REST and EX (P < 0.01). mTOR colocalization with Rheb increased above fasted at 60 and 300 min after feeding in REST and EX (P < 0.01), which was consistent with an increased phosphorylation 4E‐BP1Thr37/46 and rpS6ser240/244 at 60 min. Our data suggest that MyoPS, but not MitoPS, is primarily nutrient responsive in trained young men at rest and after endurance exercise. The postprandial increase in MyoPS is associated with an increase in mTOR/Rheb colocalization and a reciprocal decrease in TSC2/Rheb colocalization and thus likely represent important regulatory events for in vivo skeletal muscle myofibrillar mRNA translation in humans.