Postprandial Excursions Research Articles

Can Metabolite and Hormone Profiles Provide a Rationale for Choosing Between Bariatric Procedures?

There are no formal guidelines for choosing among different bariatric surgery procedures for obesity treatment. So, our aim was to evaluate whether post-absorptive metabolite and hormone profiles could aid the surgeon decision when considering bariatric surgery interventions. Subjects (N=38) previously submitted to biliopancreatic diversion with duodenal switch (BPD-DS, n=9), single anastomosis duodenal-ileum bypass with sleeve gastrectomy (SADI-S, n= 9), long biliopancreatic limb Roux-en-Y gastric bypass (RYGB-M, n= 11), and classic RYGB (RYGB-C, n= 9) underwent a mixed meal test to evaluate post-absorptive glucose, total amino acid (AA), insulin, and GLP-1 profiles. Glucose, AA, insulin, and GLP-1 excursions were lower after BPD-DS when compared to other surgeries. SADI-S resulted in lower glucose but similar AA and insulin excursions when compared to RYGB-M. The highest GLP-1 excursion was observed after RYGB-M. There were no significant differences in glucose or AA post-prandial excursions between RYGB procedures, yet insulin excursion was higher after RYGB-C when compared to RYGB-M. Post-prandial metabolite excursions diverge across bariatric procedures being lowest after BPD-DS, intermediate after SADI-S, and highest after RYGB, in parallel with the anti-diabetic efficacy and malabsorption risk reported for each type of intervention. SADI-S and RYGB-M seem to elicit similar post-prandial hormonal profiles, with potentially lower risk of protein malnutrition when compared to BPD-DS. Post-absorptive metabolite and hormone profiles could provide a rationale as decision-aid when choosing among bariatric surgery interventions, as long as these findings are validated in future trials.

Micronutrients and phytochemicals content in various rice (Oryza sativa Linn.) samples control carbohydrate digestion variedly and present differential antioxidant activities: an in vitro appraisal

High starch and carbohydrate content in rice ( Oryza sativa Linn.) disparages this food responsible for postprandial hyperglycemic excursions. However, rice is an Asian food synonym. Additionally, in traditional Indian healing practices, rice is used for treatment of various disorders. In this research, we analyzed micronutrient and phytochemical contents in different rice samples available in market. Effect of aqueous-ethanol extract of each type of rice was evaluated against intestinal α-glucosidase to examine extract’s influence on carbohydrate digestion. Free-radicals scavenging activities as a measure of antioxidant potential in different rice were also examined. Brown-rice presented highest (54%) α-glucosidase inhibition followed by parboiled-rice (52%), idly-rice (48%), hand-pounded rice (42%), dosa-rice (40%) and basmati-rice (39%). Polished white sona-masoori rice presented least enzyme inhibitory (31%) activity. Presence of higher α-glucosidase inhibitory activity was regarded as slow digesting rice that would impart lesser postprandial glycemic excursion. Brown and parboiled-rice presented highest ABTS֗ + radical scavenging (74%) activity whereas; idly-rice displayed highest DPPH scavenging (50%) activity. Higher polyphenol and niacin contents in rice were found significantly (p<0.0001 and p<0.01 respectively) correlated with enzyme inhibitory activity. Higher polyphenol content was found responsible for enhanced free-radicals scavenging activity. Increasing concentrations of niacin and pantothenic acid correlated with ABTS֗ + radical scavenging activity.

Food order and glucose excursion in Indian adults with normal and overweight/obese Body Mass Index: A randomised crossover pilot trial.

Postprandial glycaemia has an impact on health but there is limited data about the effect of food order on postprandial glycaemia by body weight status. To investigate the effects of food order on postprandial glucose (PPG) excursion, in Indian adults with normal (NL) and overweight/obese (OW) Body Mass Index. This randomised crossover study was conducted at a Malaysian university among Indian adults without diabetes. The participants consumed isocaloric test meals at three study visits based on randomised food orders: carbohydrate first/protein last (CF); protein first/carbohydrate last (CL); and a composite meal containing carbohydrate and protein (CM). Capillary blood glucose was measured at baseline, 30, 60, 90 and 120 minutes after starting the meal. The CL food order had a blunting effect on PPG excursion at 30 and 60 minutes (p < 0.01). The CL food order resulted in lower glucose peak when compared with the CF and CM food order (p < 0.001). The CL food order resulted in lower incremental glucose peak (mmol/L) (NL: CF 3.9 ± 0.3, CM 3.0 ± 0.3, CL 2.0 ± 0.2; OW: CF 2.9 ± 0.3, CM 2.5 ± 0.3, CL 1.8 ± 0.2) and iAUC 0-120 min (mmol/Lxmin) (NL: CF 272.4 ± 26.7, CM 206.2 ± 30.3, CL 122.0 ± 14.8; OW: CF 193.2 ± 23.1, CM 160.1 ± 21.7, CL 113.6 ± 15.3) when compared with the CF food order (p < 0.001). The effect of food order on postprandial excursion did not differ between the NL (n = 14) and the OW (n = 17) groups. In participants with normal and overweight/obese BMI, consuming food in the protein first/carbohydrate last order had the biggest effect in reducing PPG excursion.

Abstract 16511: Isocaloric Fructose Restriction Improves Postprandial Chylomicron and VLDL Excursions in Adolescents With Obesity by Reducing Angiopoietin-Like Protein 3 and Apolipoprotein CIII

Introduction: Delayed postprandial triglyceride-rich lipoprotein (TRL) metabolism is associated with increased atherogenic risk. Dietary fructose is a preferred lipogenic substrate which contributes to NAFLD and dyslipoproteinemia. Hypothesis: Isocaloric fructose restriction reduces postprandial TRL excursions in part by affecting the modulation of lipoprotein lipase (LPL) activity and peripheral clearance rates. Methods: We determined the effect of 9 days of isocaloric fructose restriction on fasting and postprandial TRL metabolism markers in obese Latino and African American children (9-18 years old; n=30) with high habitual sugar consumption (&gt;50 g/d). Metabolic assessments were performed on day 0 and day 10 of isocaloric fructose restriction (starch substituted for sugar, same macronutrient composition). To follow postprandial TRL metabolism, after an initial double-sized meal, single-sized meals (providing 67% of daily calories, 15% protein, 35% fat, 50% carbohydrate) were fed every 30 minutes, with blood sampled every hour for 8 hours. Fructose content of meals reduced from 12% on day 0 to 4% on day 10. Paired t-tests compared change from day 0 to day 10 within each child. Results: Fasting TG, apoCIII, and ANGPTL3 reduced by 25%, 28% and 26% respectively (p &lt;0.01). Postprandial AUC of TG, apoCIII, ANGPTL3, VLDL, chylomicrons (apoB48) reduced by 35%, 34%, 40%, 17%, 19% (p &lt;0.01), while no changes were found in fasting or AUC for ANGPTL4, ANGPTL8 nor LPL mass. Conclusions: Short-term isocaloric fructose restriction improved postprandial chylomicron and VLDL metabolism in children with obesity. Specific and selective improvements in ANGPTL3 and apoCIII suggest differential modulation of LPL activity as a putative mechanism that deserves further exploration.

The Clinical Application of Mealtime Whey Protein for the Treatment of Postprandial Hyperglycaemia for People With Type 2 Diabetes: A Long Whey to Go.

Mitigating postprandial hyperglycaemic excursions may be effective in not only enhancing glycaemic control for people with type 2 diabetes but also reducing the onset of diabetes-related complications. However, there are growing concerns over the long-term efficacy of anti-hyperglycaemic pharmacotherapies, which coupled with their rising financial costs, underlines the need for further non-pharmaceutical treatments to regulate postprandial glycaemic excursions. One promising strategy that acutely improves postprandial glycaemia for people with type 2 diabetes is through the provision of mealtime whey protein, owing to the slowing of gastric emptying and increased secretion of insulin and the incretin peptides. The magnitude of this effect appears greater when whey protein is consumed before, rather than with, a meal. Herein, this dietary tool may offer a simple and inexpensive strategy in the management of postprandial hyperglycaemia for people with type 2 diabetes. However, there are insufficient long-term studies that have investigated the use of mealtime whey protein as a treatment option for individuals with type 2 diabetes. The methodological approaches applied in acute studies and outcomes reported may also not portray what is achievable long-term in practice. Therefore, studies are needed to refine the application of this mealtime strategy to maximize its clinical potential to treat hyperglycaemia and to apply these long-term to address key components of successful diabetes care. This review discusses evidence surrounding the provision of mealtime whey protein to treat postprandial hyperglycaemia in individuals with type 2 diabetes and highlights areas to help facilitate its clinical application.

Hematopoietic cell- versus enterocyte-derived dipeptidyl peptidase-4 differentially regulates triglyceride excursion in mice.

Postprandial triglycerides (TGs) are elevated in people with type 2 diabetes (T2D). Glucose-lowering agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, also reduce postprandial TG excursion. Although the glucose-lowering mechanisms of DPP-4 have been extensively studied, how the reduction of DPP-4 activity improves lipid tolerance remains unclear. Here, we demonstrate that gut-selective and systemic inhibition of DPP-4 activity reduces postprandial TG excursion in young mice. Genetic inactivation of Dpp4 simultaneously within endothelial cells and hematopoietic cells using Tie2-Cre reduced intestinal lipoprotein secretion under regular chow diet conditions. Bone marrow transplantation revealed a key role for hematopoietic cells in modulation of lipid responses arising from genetic reduction of DPP-4 activity. Unexpectedly, deletion of Dpp4 in enterocytes increased TG excursion in high-fat diet–fed (HFD-fed) mice. Moreover, chemical reduction of DPP-4 activity and increased levels of GLP-1 were uncoupled from TG excursion in older or HFD-fed mice, yet lipid tolerance remained improved in older Dpp4–/– and Dpp4EC–/– mice. Taken together, this study defines roles for specific DPP-4 compartments, age, and diet as modifiers of DPP-4 activity linked to control of gut lipid metabolism.

Different Malabsorptive Obesity Surgery Interventions Result in Distinct Postprandial Amino Acid Metabolomic Signatures.

Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1years earlier. Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis.

OR30-07 Mixed Meal Tolerance Test (MMTT) Results from Revita-2, the First Randomized, Sham-Controlled, Double-Blind, Prospective, Multicenter Study of Duodenal Mucosal Resurfacing (DMR) Safety and Efficacy in Patients with Sub-Optimally Controlled Type 2 Diabetes (T2D)

BACKGROUND: The duodenum is a key metabolic signaling center and regulator of metabolic homeostasis. Duodenal mucosal hyperplasia is therefore a potential therapeutic target for metabolic diseases related to insulin-resistance. Previous reports demonstrated that DMR, a minimally invasive, endoscopic mucosal ablative procedure, safely improves hepatic and glycemic parameters. Primary endpoints from REVITA-2, the first randomized, sham-controlled, double-blind, prospective, multicenter study of DMR safety and efficacy in patients with T2D, were met and previously reported. Here we further explore mechanisms underlying the beneficial effects of DMR on hepatic and glucose metabolism by analyzing mixed meal tolerance test (MMTT) data from the REVITA-2 study. Methods: Eligible patients (HbA1c 7.5–10%, BMI ≥ 24 to ≤ 40 kg/m2, on stable treatment with ≥1 oral anti-diabetic medication) received DMR or sham procedure (1:1). Exploratory endpoints included median change in fasting plasma glucose (FPG), MMTT glucose area under the curve (AUC) over 2 hours, and change in MMTT C-peptide and glucagon over 2 hours, from baseline to 12 weeks post-DMR. One-sided P value based on ANCOVA model on ranks without imputation assessed treatment difference at the 0.05 significance level. The modified intent to treat primary analysis population included randomized patients in whom study procedure was attempted. Results: A total of 70 patients (DMR, N = 35; sham, N = 35) were included in the analysis, of which 57% and 54% (DMR, n = 20; sham, n = 19) had baseline FPG ≥ 180 mg/dL. Median MMTT AUC for glucose was significantly reduced post-DMR (-36.38 mg/dL) compared with sham (-4.94 mg/dL; P = 0.009), driven by a significant decrease in FPG (DMR, -41.0 mg/dL; sham, -15.0 mg/dL; P = 0.003) rather than median MMTT postprandial glucose excursion (DMR, -4.63 mg/dL; sham, 5.34 mg/dL; P = 0.209). AUC glucose reductions were more pronounced in patients with baseline FPG ≥ 180 (DMR, -63.03 mg/dL; sham, -20.31 mg/dL; P = 0.007) compared with baseline FPG < 180 (DMR, -26.81 mg/dL; sham, 13.81 mg/dL; P = 0.271). In patients with baseline FPG ≥ 180, postprandial C-peptide excursion was significantly increased (DMR, 0.41 ng/mL; sham, 0.02 ng/mL; P = 0.012) and postprandial glucagon excursion was significantly decreased (DMR, -8.03 pg/mL; sham, 2.13 pg/mL; P = 0.027). Conclusion: DMR markedly improves glucose responses to a mixed meal challenge, primarily driven by a decrease in FPG, suggesting a primary effect on insulin resistance. Increases in C-peptide and reductions in glucagon levels suggest improvement in beta cell function in addition to improvements in hepatic insulin sensitivity, and ratifies the position of the duodenum as both a culprit endocrine organ and therapeutic target for patients with T2D.

SAT-640 Glycemic Profile of Intravenous Glucocorticoid Induced Hyperglycemia Using Continuous Glucose Monitoring

Background: Intravenous (IV) steroids are widely used in critically ill patients and with chemotherapy. It is well known that glucocorticoid-induced hyperglycemia (GCIH) occurs within 3 hours following oral administration of steroids with typical postprandial glycemic excursions lasting 24-36 hours. The recent increased availability of Continuous Glucose Monitoring (CGM) has allowed a detailed description of glycemic fluctuations in patients receiving steroids in different settings, however there is no reported observation of CGM findings following a single dose of IV Dexamethasone in a patient with diabetes. We present a case of glycemic pattern documented on CGM of a patient with type 2 diabetes, who had received 11 cycles of a single dose Dexamethasone-containing chemotherapy. Clinical Case: The patent is 70 years old female with history of type 2 DM of 19 years duration and metastatic pancreatic adenocarcinoma, diagnosed in November 2018, and treated with Fluorouracil and Dexamethasone 6mg IV on every other Wednesday since December 2018. Her diabetes was fairly controlled on Metformin, Repaglinide, Pioglitazone and Detemir insulin. Premeal Lispro was added while Metformin and Repaglinide were discontinued with the beginning of chemotherapy. She started using Freestyle Libre CGM in January 2019. During her visit in March 2019, the patient was taking Detemir Insulin 50 units in AM and 30 units at night, and Lispro 15 units before meals, in addition to correction insulin based on an Insulin Sensitivity Factor (ISF) of 1:25 for Blood Glucose (BG) above 200mg/dl. Unlike the reported postprandial hyperglycemic excursions associated with oral steroids, the patient’s CGM data showed a reproducible triphasic glycemic pattern following IV Dexamethasone, consisting of a steady state of hyperglycemia reached within 3 hours and lasting around 18-30 hours, followed by a transient BG improvement for 18-20 hours, and ending with another hyperglycemic plateau of 10-16 hours on day 3 post chemotherapy, with no association to meal intake. Given this recurrent pattern, the patient was advised to increase her bedtime Detemir insulin from 30 to 45 units and her correction ISF from 1:25 to 1:18 on days 1 and 2 after chemotherapy, with subsequent attenuation and shortening of GCIH. Conclusion: Our case report is the first one to describe CGM documented glycemic profile following a single dose of IV Dexamethasone in a patient with type 2 diabetes treated with insulin. The CGM data reveals a consistent steady GCIH, lasting around 48 hours, and reflecting the prolonged action of Dexamethasone. The transient BG improvement seen on day 2 is likely due to the Detemir dose self-increase and the carbohydrates intake decrease in response to day 1 hyperglycemia. A 48 hours modified insulin regimen based on higher dose of long acting and correction insulin improved Dexamethasone induced hyperglycemia.

Multi-Hour Blood Glucose Prediction in Type 1 Diabetes: A Patient-Specific Approach Using Shallow Neural Network Models.

Background: Considering current insulin action profiles and the nature of glycemic responses to insulin, there is an acute need for longer term, accurate, blood glucose predictions to inform insulin dosing schedules and enable effective decision support for the treatment of type 1 diabetes (T1D). However, current methods achieve acceptable accuracy only for prediction horizons of up to 1 h, whereas typical postprandial excursions and insulin action profiles last 4-6 h. In this study, we present models for prediction horizons of 60-240 min developed by leveraging "shallow" neural networks, allowing for significantly lower complexity compared with related approaches. Methods: Patient-specific neural network-based predictive models are developed and tested on previously collected data from a cohort of 24 subjects with T1D. Models are designed to avoid serious pitfalls through incorporating essential physiological knowledge into model structure. Patient-specific models were generated to predict glucose 60, 90, 120, 180, and 240 min ahead, and a "transfer learning" approach to improve accuracy for patients where data are limited. Finally, we determined subgroup characteristics that result in higher model accuracy overall. Results: Root mean squared error was 28 ± 4, 33 ± 4, 38 ± 6, 40 ± 8, and 43 ± 12 mg/dL for 60, 90, 120, 180, and 240 min, respectively. For all prediction horizons, at least 93% of predictions were clinically acceptable by the Clarke error grid. Variance of historic continuous glucose monitor (CGM) values was a strong predictor for the need of transfer learning approaches. Conclusions: A shallow neural network, using features extracted from past CGM data and insulin logs, can achieve multi-hour glucose predictions with satisfactory accuracy. Models are patient specific, learnt on readily available data without the need for additional tests, and improve accuracy while lowering complexity compared with related approaches, paving the way for new advisory and closed loop algorithms able to encompass most of the insulin action timeframe.

Circulating Triglycerides Gate Dopamine-Associated Behaviors through DRD2-Expressing Neurons

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system andcan promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

Bile acid treatment and FXR agonism lower postprandial lipemia in mice.

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.

Ambulatory glucose profile in managing post-prandial hyperglycaemia in patients with type 2 diabetes mellitus: a case report

The case report describes the potential role of real-time Ambulatory Glucose Profile (AGP) in identifying and managing a patient with hyperglycemia. This 55-years-old male patient with type 2 Diabetes Mellitus (T2DM) was presented to the clinic with weakness, increased urinary frequency, with constipation for the past 3 months. The patient was a known case of T2DM for 10 years, along with dyslipidemia, hypertension, and obesity. The profile obtained from AGP revealed glucose fluctuations with post-prandial excursions. Consequently, the patient’s treatment regimen was changed. The use of glimepiride was discontinued, and the patient was recommended with voglibose 0.2 mg bid with two meals, metformin 100 mg + dapagliflozin 10 mg combination with morning meals, and metformin 1000 mg with evening meals. The treatment for hypertension and dyslipidemia was continued. This case study indicates that CGM can help improve our understanding of glycemic patterns and can have a beneficial effect on glycemic control.

Postprandial Dyslipidemia, Hyperinsulinemia, and Impaired Gut Peptides/Bile Acids in Adolescents with Obesity.

With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (ie, GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance. In this cross-sectional study, normal weight adolescents and adolescents with obesity underwent a 6-hour oral fat tolerance test. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoproteins. GLP-1 and GLP-2 were quantified by electrochemiluminescent immunoassays. Total bile acids were measured by an automated enzymatic cycling colorimetric method and the bile acid profile by mass spectrometry. Adolescents with obesity exhibited fasting and postprandial dyslipidemia, particularly augmented postprandial excursion of large triglyceride-rich lipoproteins. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia and insulin resistance. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion. Blunted postprandial GLP and bile acid response to dietary fat ingestion strongly associates with marked postprandial dyslipidemia. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity.

Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans

BackgroundOur previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans. PurposeThe purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation. MethodsThirteen normal weight young adult males (BMI 23.1 ± 0.8 kg/m2, age 22.2 ± 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD. Main findingsIntestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (−24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD. ConclusionThese findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity.

The Dopamine Receptor Subtype 2 (DRD2) Regulates the Central Reinforcing Actions of Dietary Lipids in Humans and Rodents

Emerging evidence suggests that energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote the development of compulsive-like feeding, reward dysfunction, and ultimately weight gain. Yet the mechanisms by which metabolic signals influence MCL circuitry to control behavior remain poorly understood. Circulating triglycerides (TG) are a conserved post-prandial metabolic signature among mammals and high plasma TG are associated with reduced reward responsiveness in humans. Here, we show that the TG-processing enzyme lipoprotein lipase (LPL) is enriched throughout the MCL of both mouse and human, including DA-releasing neurons in the ventral tegmental area and DA-receptive neurons in the striatum. Using brain-specific TG delivery in mice, we show that nutritional TG are metabolized within the MCL system where they acutely control D2 DA receptor (DRD2) signaling. We also show that TG are directly reinforcing in mice, and that central TG sensing relies on LPL activity in the MCL. Likewise, in humans, post-prandial TG excursions modulate brain response to food cues in MCL with the direction of the association determined by a DRD2 dependent genotype. Collectively, these findings reveal a mechanism by which dietary TG directly alter MCL signaling to regulate behavior, providing a new mechanistic basis by which energy-rich diets can lead to adaptations in DA signaling that underlie compulsive behavior.

Reduced Postprandial Serum Triglyceride After a Meal Prepared Using an Airfryer: A Randomized Crossover Trial (P08-103-19)

ObjectivesElevated circulating non-fasting triglyceride (TG) or postprandial triglyceride (ppTG) is as an independent contributor to risk for coronary heart disease. We hypothesized that a commonly consumed fried meal (including French fries and chicken nuggets) prepared by airfrying would result in a significantly lower ppTG response than the same meal prepared using a conventional deep fat frying approach. MethodsWe conducted a randomized crossover trial to evaluate the effect of airfryer cooking compared to conventional deep fat frying preparation in young healthy male (n = 10) and female subjects (n = 6). A 7-day washout period was included between meal test days. All study participants were blinded to the method of meal preparation. ResultsThe airfryer resulted in a significantly lower postprandial triglyceride response compared to deep fat frying of the same meal (P < 0.001). Glucose, insulin, and free fatty acid response differences were not found. Self-reported satiety did not differ after the meals. Furthermore, air-frying did not influence circulating inflammatory biomarkers, cholesterol, or apolipoproteins. ConclusionsAir frying of common fried meals results in lower postprandial triglyceride excursions in young healthy volunteers in the absence of any effects on satiety. Air-frying represents a useful and practical method to reduce meal fat content in line with current dietary recommendations on triglyceride management and general healthy eating. Funding SourcesThis research was funded by Philips Research China, Philips (China) Investment Co., Ltd., Shanghai, China. Supporting Tables, Images and/or Graphs▪▪▪

Restricting carbohydrates at breakfast is sufficient to reduce 24-hour exposure to postprandial hyperglycemia and improve glycemic variability

The breakfast meal often results in the largest postprandial hyperglycemic excursion in people with type 2 diabetes. Our purpose was to investigate whether restricting carbohydrates at breakfast would be a simple and feasible strategy to reduce daily exposure to postprandial hyperglycemia. Adults with physician-diagnosed type 2 diabetes [n=23; mean ± SD age: 59±11 y; glycated hemoglobin: 6.7%±0.6%; body mass index (kg/m2): 31±7] completed two 24-h isocaloric intervention periods in a random order. Participants consumed one of the following breakfasts: 1) a very-low-carbohydrate high-fat breakfast (LCBF;<10% of energy from carbohydrate, 85% of energy from fat, 15% of energy from protein) or 2) a breakfast with dietary guidelines-recommended nutrient profile (GLBF; 55% of energy from carbohydrate, 30% of energy from fat, 15% of energy from protein), with the same lunch and dinner provided. Continuous glucose monitoring was used to assess postprandial glucose responses over 24 h, and visual analog scales were used to assess ratings of hunger and fullness. The LCBF significantly reduced postprandial hyperglycemia after breakfast (P<0.01) and did not adversely affect glycemia after lunch or dinner. As such, overall postprandial hyperglycemia (24-h incremental area under the glucose curve) and glycemic variability (mean amplitude of glycemic excursions) were reduced with the LCBF (24-h incremental area under the glucose curve: -173±361 mmol/L; P=0.03; mean amplitude of glycemic excursions: -0.4±0.8 mmol/L · 24 h; P=0.03) compared with the GLBF. Premeal hunger was lower before dinner with the LCBF than with the GLBF (P-interaction=0.03). A very-low-carbohydrate high-fat breakfast lowers postbreakfast glucose excursions. The effects of this simple strategy appear to be sufficient to lower overall exposure to postprandial hyperglycemia and improve glycemic variability. Longer-term interventions are warranted. This trial was registered at clinicaltrials.gov as NCT02982330.

A role for foregut tyrosine metabolism in glucose tolerance

ObjectiveWe hypothesized that DA and L-DOPA derived from nutritional tyrosine and the resultant observed postprandial plasma excursions of L-DOPA and DA might affect glucose tolerance via their ability to be taken-up by beta cells and inhibit glucose-stimulated β-cell insulin secretion. MethodsTo investigate a possible circuit between meal-stimulated 3,4-dihydroxy-L-phenylalanine (L-DOPA) and dopamine (DA) production in the GI tract and pancreatic β-cells, we: 1) mapped GI mucosal expression of tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC); 2) measured L-DOPA and DA content of GI mucosal tissues following meal challenges with different L-tyrosine (TYR) content, 3) determined whether meal TYR content impacts plasma insulin and glucose excursions; and 4) characterized postprandial plasma excursions of L-DOPA and DA in response to meal tyrosine content in rodents and a population of bariatric surgery patients. Next, we characterized: 1) the metabolic transformation of TYR and L-DOPA into DA in vitro using purified islet tissue; 2) the metabolic transformation of orally administrated stable isotope labeled TYR into pancreatic DA, and 3) using a nuclear medicine technique, we studied endocrine beta cells in situ release and binding of DA in response to a glucose challenge. ResultsWe demonstrate in rodents that intestinal content and circulatory concentrations L-DOPA and DA, plasma glucose and insulin are responsive to the tyrosine (TYR) content of a test meal. Intestinal expression of two enzymes, Tyrosine hydroxylase (TH) and Aromatic Amino acid Decarboxylase (AADC), essential to the transformation of TYR to DA was mapped and the metabolism of metabolism of TYR to DA was traced in human islets and a rodent beta cell line in vitro and from gut to the pancreas in vivo. Lastly, we show that β cells secrete and bind DA in situ in response to glucose stimulation. ConclusionsWe provide proof-of-principle evidence for the existence of a novel postprandial circuit of glucose homeostasis dependent on nutritional tyrosine. DA and L-DOPA derived from nutritional tyrosine may serve to defend against hypoglycemia via inhibition of glucose-stimulated β-cell insulin secretion as proposed by the anti-incretin hypothesis.

Medium-chain fatty acids lower postprandial lipemia: A randomized crossover trial

Epidemiological and interventional studies have linked saturated fatty acids (SFA) with elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased CVD risk. However, the effects of the SFA chain length on postprandial lipemia in humans are not well elucidated. The aim of this study was to investigate the impact of short, medium and long-chain SFA on postprandial blood lipids in healthy volunteers. Sixteen healthy volunteers consumed test biscuits containing 40g of either butter (BB), coconut oil (CB) or lard (LB) in a single-blinded, randomized crossover design. Blood samples were collected fasting and 2, 3, 4, and 6 hours postprandially and assessed for blood lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; LDL-C and triglyceride, TG). The postprandial TG response following CB was 59.8% lower than following BB (p<0.01) and 58.8% lower than LB (p<0.01), although no difference was observed between the BB and the LB responses. The net area under the LDL-C concentration curve was significantly larger after consumption of the CB compared to the BB, despite no significant differences in postprandial net area under the TC and HDL-C concentration curves. Consumption of medium-chain SFA as CB resulted in lower postprandial TG excursions compared to short-chain SFA as BB and long-chain SFA as LB, despite their identical fat and caloric content. These results suggest that SFA differ in their potential to elevate postprandial lipid levels, and that coconut oil, a rich source of medium-chain SFA may not be as hyperlipidemic as animal fats rich in long chain SFA. ANZCTR IDENTIFIER: 12617000903381. CLINICAL TRIAL REGISTRY NUMBER: The study was registered with the Australia New Zealand Trial registry as ACTRN12617000903381.