Postprandial Lipid Metabolism Research Articles

The Impact of Pinus koraiensis Leaf Extract Consumption on Postprandial ApoB100 and Lipid Metabolism: A Randomized, Double-Blind, Placebo-Controlled Trial in Healthy Participants Subjected to an Oral High-Fat Challenge.

Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0-4 h and 2-4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake.

Chinese migrants exhibit impaired postprandial lipaemia compared to Caucasian counterparts following both high fat and high carbohydrate test meals.

People of Chinese ethnicity develop type 2 diabetes mellitus (T2DM) at a younger age and lower body mass index (BMI) than their Caucasian counterparts. Furthermore, Chinese migrants to Westernised countries have an increased risk of metabolic diseases compared to those in their country of origin(1,2). We propose that this increased risk is due to a greater manifestation of metabolic abnormalities in response to altered diet and lifestyle behaviours. Although fasting lipaemia and glycaemia are commonly used to predict risk of CVD and T2DM, assessment of impaired postprandial metabolism has been found to be a more sensitive indicator of risk(3). We hypothesised that Chinese migrants, at risk of T2DM, exhibit impaired postprandial lipid and lipoprotein metabolism compared to Australian-born Caucasian counterparts. Chinese and Caucasian adults at risk of T2DM were recruited to the study in which postprandial lipaemia and glycaemia were monitored following consumption of a high fat and high carbohydrate breakfast meal followed by a mixed, lunch meal. In a nonrandomised acute crossover trial, 15 adults (n = 8 Chinese and n = 7 Caucasian) aged ≥ 18 and ≤ 65 years at risk of T2DM (AUSDRISK score > 12 (median = 14.0, IQR = 3.0)), attended two postprandial test days separated by ≥ 7-day washout period. Test breakfast meals were isocaloric (3.6 MJ), high fat (46% energy from fat, 46% energy from carbohydrates) or high carbohydrate (74% E carbohydrates, 17.5% E fat). Blood samples were collected at baseline (fasting), 180 min and 360 min after consumption of the breakfast meal. The lunch meal (3.7 MJ, 18% E fat, 76% E carbohydrates) was consumed 240 min after baseline. Samples were analysed for lipaemia and glycaemia. Additionally, chylomicron-rich, and VLDL-rich lipoprotein fractions were isolated by sequential ultracentrifugation and chylomicron particle number (apolipoprotein (apo) B48), triacylglycerol (TAG), and total cholesterol were assessed in these fractions. Data were analysed using a mixed between-within-subject analysis of variance. There were no differences in age, and baseline anthropometric measures between groups, apart from the Chinese group exhibiting significantly lower waist circumference and BMI compared to the Caucasian group. There were no differences between groups in blood measures, apart from a higher total- and LDL-cholesterol concentration in the Caucasian compared to the Chinese group (P<0.05). Despite identical fasting TAG concentrations, the Chinese group, compared with the Caucasian group exhibited significantly elevated serum TAG and chylomicron-apo-B48 concentrations at 360 min following both test meals (P<0.01). All other postprandial measures were not different between groups. These findings show that despite having identical or improved fasting glycaemia and lipid profile, the Chinese group exhibited impaired postprandial lipid metabolism which may contributes to their increased risk of metabolic diseases.

The chylomicron saga: time to focus on postprandial metabolism.

Since statins have had such tremendous therapeutic success over the last three decades, the field of atherosclerosis has become somewhat LDL-centric, dismissing the relevance of triglycerides (TG), particularly chylomicrons, in atherogenesis. Nonetheless, 50% of patients who take statins are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and are unable to achieve their goal LDL-C levels. This residual risk is mediated, in part by triglyceride rich lipoproteins (TRL) and their remnants. Following his seminal investigation on the subject, Zilversmit proposed that atherosclerosis is a postprandial event in 1979 (1-4). In essence, the concept suggests that remnant cholesterol-rich chylomicron (CM) and very-low density lipoprotein (VLDL) particles play a role in atherogenesis. Given the foregoing, this narrative review addresses the most recent improvements in our understanding of postprandial dyslipidemia. The primary metabolic pathways of chylomicrons are discussed, emphasizing the critical physiological role of lipoprotein lipase and apoCIII, the importance of these particles' fluxes in the postprandial period, their catabolic rate, the complexities of testing postprandial metabolism, and the role of angiopoietin-like proteins in the partition of CM during the fed cycle. The narrative is rounded out by the dysregulation of postprandial lipid metabolism in insulin resistance states and consequent CVD risk, the clinical evaluation of postprandial dyslipidemia, current research limits, and potential future study directions.

Olive Oil's Attenuating Effects on Lipotoxicity.

Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.

Acute Deletion of the Glucocorticoid Receptor in Hepatocytes Disrupts Postprandial Lipid Metabolism in Male Mice.

Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, β-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription.

The Implementation and Testing of a Reliable and Valid Oral Fat Tolerance Test (OFTT) for Research and Clinical Purposes

Background: Increased fat intake leads to a greater risk of atherosclerosis due to the increase in circulating triglycerides (TG), which damages the endothelial lining. An oral fat tolerance test (OFTT) is usually employed to evaluate postprandial lipid metabolism. However, there has yet to be a standardized procedure for doing an OFTT. This investigation assists in the determination of a standardized, reliable, and valid OFTT. Methods: All participants (n=20) were free of any known cardiovascular or metabolic disease. Participants were allotted 20 minutes to complete the OFTT. Baseline and subsequent blood analyses postfeeding were collected at 1, 2, 3, and 4 hours. One of the three OFTT loads of varying fat concentrations was administered to each participant in a randomized crossover design, containing fat loads of 150 g, 100 g, and 50 g of fat. A single-measure consistency intraclass correlation coefficient was used to determine significance (r>0.75). Results: The test-retest reliability of the OFTT loads (150 g, 100 g, and 50 g) were all significant (p<0.001), with ICC at 0.745, 0.923, and 0.715, respectively. Face Validity was confirmed upon repeat analysis. Conclusions: The 100 g OFTT load was the most reliable and valid measure for observing TG elevation. It is proposed that the 100 g load would be a reliable tool for further research investigation and eventual use for clinical purposes.

Effects of a novel medium-long-medium-type structured lipid synthesized using a two-step enzymatic method on lipid metabolism and obesity protection in experimental mice.

We synthesized a novel, structured lipid containing caprylic acid at its sn-1,3 position and docosahexaenoic acid at its sn-2 position (1,3C-2D-TAG) by using a two-step enzymatic method and then investigated the relationship between the types of fatty acids in the structured lipid and their physiological functions. Furthermore, we compared the effects of similarly structured lipids on postprandial lipid metabolism and obesity protection. The results revealed that the novel structured lipid synthesized using the enzymatic method not only exhibited better physical properties than traditional oils but also had high oxidation stability and crystallization degree. In terms of physiological function, the low-dose 1,3C-2D-TAG group exhibited higher cholesterol and triglyceride levels, lower kidney weight or body weight, and higher serum aspartate aminotransferase and blood urea nitrogen levels than control group, whereas the high-dose 1,3C-2D-TAG group exhibited higher triglyceride levels. Moreover, the medium-dose 1,3C-2D-TAG group had remarkably higher high-density lipoprotein cholesterol levels and lower low-density lipoprotein cholesterol levels than the high-lipid, control, and 1,2,3C-TAG groups; however, the cholesterol and triglyceride levels and kidney and liver functions did not differ significantly among these groups. The study results suggest that 1,3C-2D-TAG can not only facilitate the effective utilization of the energy supplied by medium-chain fatty acids but also help overcome difficulties in the absorption of long-chain polyunsaturated fatty acids.

Analysis of Chemical Constituents of Chrysanthemum morifolium Extract and Its Effect on Postprandial Lipid Metabolism in Healthy Adults.

Chrysanthemum extract possesses antioxidant potential and carbohydrate and fat digestive enzyme inhibitory in vitro. However, no evidence supporting chrysanthemum in modulation of postprandial lipemia and antioxidant status in humans presently exists. This study was to analyze the composition of Imperial Chrysanthemum (IC) extract and determine the effect on changes in postprandial glycemic and lipemic response and antioxidant status in adults after consumption of a high-fat (HF) meal. UHPLC-MS method was used to analyze the components of two kinds of IC extracts (IC-P/IC-E) and in vitro antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydraxyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Hydroxyl radical (HR) radical scavenging assays. Following a randomized design, 37 healthy adults (age, 25.2 ± 2.6 years, and BMI, 20.9 ± 1.5 kg/m2) were assigned to two groups that consumed the HF meal, or HF meal supplemented by IC extract. Blood samples were collected at fasting state and then at 0.5, 1, 2, 4, 6 and 8 h after the meal consumption. There were 12 compounds with relative content of more than 1% of the extracts, of which amino acid and derivatives, flavonoids, carboxylic acids and derivatives were the main components. Compared with IC-E, the contents of flavonoids in IC-P increased significantly (p < 0.05), and the cynaroside content exceeded 30%. In addition, IC-P showed strong free radical scavenging activity against DPPH, ABTS and HR radicals. Furthermore, according to repeated−measures ANOVA, significant differences were observed in the maximal changes for postprandial glucose, TG, T-AOC and MDA among the two groups. Postprandial glucose has significant difference between the two groups at 1 h after meal and the level in IC group was significantly lower than that in control group. No significant differences were observed in the incremental area under the curve (iAUC) among the two groups. IC significantly improved the serum antioxidant status, as characterized by increased postprandial serum T-AOC, SOD, GSH and decreased MDA. This finding suggests that IC can be used as a natural ingredient for reducing postprandial lipemia and improving the antioxidant status after consuming a HF meal.

Cannabidiol (CBD) ingestion increases ad libitum energy intake in healthy adults but does not affect postprandial glucose or lipid metabolism

Cannabidiol (CBD) ingestion increases ad libitum energy intake in healthy adults but does not affect postprandial glucose or lipid metabolism

Dietary treatment of type 1 diabetes: Beyond carbohydrate counting to fight cardiovascular risk

Aims.Type 1 diabetes (T1D) is tied to an increased risk of cardiovascular morbidity and mortality. Dietary treatment would be an elective therapeutic strategy to fight this risk. However, it is not known what the best dietary approach is.We revisited the currently available literature on the nutritional treatment of T1D in the light of their potential comprehensive effects on the management of cardio-metabolic risk factors (body weight, fasting and postprandial glucose and lipid metabolism). Data synthesis.Nutritional research in T1D is mainly focused on blood glucose control, with most of the trials aiming at evaluating the acute effects of nutrients on postprandial glycemic response. The effects of the quantity and quality of nutrients and some specific foods on other metabolic risk factors have been explored mainly in cross-sectional analysis. Very few well-designed nutritional trials evaluated the best dietary approach to comprehensively manage cardiovascular risk by targeting along with blood glucose control, overweight, fasting and postprandial dyslipidemia. Therefore, the current best practice guidance for the dietary management of cardiovascular risk in T1D is generally based on evidence from patients with type 2 diabetes. ConclusionsWell-conducted nutritional trials specifically designed for T1D are needed to identify the best dietary treatment to fight cardiovascular risk in these patients.

The Location of Missense Variants in the Human GIP Gene Is Indicative for Natural Selection.

The intestinal hormone, glucose-dependent insulinotropic polypeptide (GIP), is involved in important physiological functions, including postprandial blood glucose homeostasis, bone remodeling, and lipid metabolism. While mutations leading to physiological changes can be identified in large-scale sequencing, no systematic investigation of GIP missense variants has been performed. Here, we identified 168 naturally occurring missense variants in the human GIP genes from three independent cohorts comprising ~720,000 individuals. We examined amino acid changing variants scattered across the pre-pro-GIP peptide using in silico effect predictions, which revealed that the sequence of the fully processed GIP hormone is more protected against mutations than the rest of the precursor protein. Thus, we observed a highly species-orthologous and population-specific conservation of the GIP peptide sequence, suggestive of evolutionary constraints to preserve the GIP peptide sequence. Elucidating the mutational landscape of GIP variants and how they affect the structural and functional architecture of GIP can aid future biological characterization and clinical translation.

A wheat aleurone-rich diet improves oxidative stress but does not influence glucose metabolism in overweight/obese individuals: Results from a randomized controlled trial

Background and aimsAleurone is the innermost layer of wheat bran, rich in fiber, minerals, vitamins, phenolic compounds, and betaine. The metabolic effects of aleurone rich foods are still unknown. Our aim was to investigate the effects of consuming a Wheat Aleurone rich diet vs. a Refined Wheat diet for 8 weeks on fasting and postprandial glycemic and lipid metabolism, inflammation, and oxidative stress in overweight/obese individuals. Methods and resultsAccording to a randomized cross-over study design, 23 overweight/obese individuals, age 56 ± 9 years (M±SD), were assigned to two isoenergetic diet – Wheat Aleurone and Refined Wheat diets – for 8 weeks. The diets were similar for macronutrient composition but different for the aleurone content (40–50 g/day in the Wheat Aleurone diet). After each diet, fasting and postprandial plasma metabolic profile, ferulic acid metabolites and 8-isoprostane concentrations in 24-h urine samples were evaluated. Compared with the Refined Wheat Diet, the Wheat Aleurone Diet increased fasting plasma concentrations of betaine by 15% (p = 0.042) and decreased the excretion of 8-isoprostane by 33% (p = 0.035). Conversely, it did not affect the fasting and postprandial glucose, insulin and triglyceride responses, homocysteine, and C-Reactive Protein concentrations, nor excretion of phenolic metabolites. ConclusionAn 8-week Wheat Aleurone Diet improves the oxidative stress and increases plasma betaine levels in overweight/obese individuals with an increased cardiometabolic risk. However, further studies with longer duration and larger sample size are needed to evaluate the benefits of aleurone-rich foods on glucose and lipid metabolism in individuals with more severe metabolic abnormalities. Clinical trial registry numberNCT02150356, (https://clinicaltrials.gov).

In vivo response to an oral fat load of ectopic lipids and acetylcarnitine in skeletal muscle in subjects with obesity

Rationale: Acetylcarnitine plays a pivotal role in the regulation of mitochondrial and cellular lipid trafficking. The aim of the present study was to investigate the postprandial response to an oral fat load in terms of changes in skeletal muscle acetylcarnitine and intramyocellular lipid content (IMCL) in subjects with obesity through proton magnetic resonance spectroscopy (1H-MRS), in association with changes in postprandial lipid metabolism.

Milk fat as a source of bioactive compounds

Milk fat as a source of bioactive compounds

Eating Dinner Early Improves 24-h Blood Glucose Levels and Boosts Lipid Metabolism after Breakfast the Next Day: A Randomized Cross-Over Trial.

Aim: To examine whether mild early time-restricted eating (eating dinner at 18:00 vs. at 21:00) improves 24-h blood glucose levels and postprandial lipid metabolism in healthy adults. Methods: Twelve participants (2 males and 10 females) were included in the study. In this 3-day (until the morning of day 3) randomized crossover study, two different conditions were tested: eating a late dinner (at 21:00) or an early dinner (at 18:00). During the experimental period, blood glucose levels were evaluated by each participant wearing a continuous blood glucose measuring device. Metabolic measurements were performed using the indirect calorimetry method on the morning of day 3. The study was conducted over three days; day 1 was excluded from the analysis to adjust for the effects of the previous day’s meal, and only data from the mornings of days 2 and 3 were used for the analysis. Results: Significant differences were observed in mean 24-h blood glucose levels on day 2 between the two groups (p = 0.034). There was a significant decrease in the postprandial respiratory quotient 30 min and 60 min after breakfast on day 3 in the early dinner group compared with the late dinner group (p < 0.05). Conclusion: Despite a difference of only 3 h, eating dinner early (at 18:00) has a positive effect on blood glucose level fluctuation and substrate oxidation compared with eating dinner late (at 21:00).

Postprandial Lipid Metabolism in Normolipidemic Subjects and Patients with Mild to Moderate Hypertriglyceridemia: Effects of Test Meals Containing Saturated Fatty Acids, Mono-Unsaturated Fatty Acids, or Medium-Chain Fatty Acids.

Fasting and postprandial hypertriglyceridemia are causal risk factors for atherosclerosis. The prevalence of hypertriglyceridemia is approximately 25–30% and most hypertriglyceridemic patients suffer from mild to moderate hypertriglyceridemia. Data regarding dietary interventions on postprandial triglyceride metabolism of mildly to moderately hypertriglyceridemic patients is, however, sparse. In a randomized controlled trial, eight mildly hypertriglyceridemic patients and five healthy, normolipidemic controls received three separate standardized fat-meals containing either saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), or medium-chain fatty acids (MCFA) in a randomized order. Fasting and postprandial lipid parameters were determined over a 10 h period and the (incremental) area under the curve (AUC/iAUC) for plasma triglycerides and other parameters were determined. MCFA do not lead to a significant elevation of postprandial total plasma triglycerides and other triglyceride parameters, while both SFA (patients: p = 0.003, controls: p = 0.03 compared to MCFA) and MUFA (patients: p = 0.001; controls: p = 0.14 compared to MCFA) do lead to such an increase. Patients experienced a significantly more pronounced increase of plasma triglycerides than controls (SFA: patients iAUC = 1006 mg*h/dL, controls iAUC = 247 mg*h/dL, p = 0.02; MUFA: patients iAUC = 962 mg*h/dL, controls iAUC = 248 mg*h/dL, p = 0.05). Replacing SFA with MCFA may be a treatment option for mildly to moderately hypertriglyceridemic patients as it prevents postprandial hypertriglyceridemia.

Urinary Medium-Chained Acyl-Carnitines Sign High Caloric Intake whereas Short-Chained Acyl-Carnitines Sign High -Protein Diet within a High-Fat, Hypercaloric Diet in a Randomized Crossover Design Dietary Trial.

The western dietary pattern is known for its frequent meals rich in saturated fat and protein, resulting in a postprandial state for a large part of the day. Therefore, our aim was to investigate the postprandial glucose and lipid metabolism in response to high (HP) or normal (NP) protein, high-fat hypercaloric diet and to identify early biomarkers of protein intake and hepatic lipid accumulation. In a crossover design, 17 healthy subjects were randomly assigned to consume a HP or NP hypercaloric diet for two weeks. In parallel, a control group (CD; n = 10) consumed a weight-maintaining control diet. Biomarkers of postprandial lipid and glucose metabolism were measured in 24 h urine and in plasma before and following a meal challenge. The metabolic profile of urine but not plasma, showed increased excretion of 13C, carnitine and short chain acyl-carnitines after adaptation to the HP diet. Urinary excretion of decatrienoylcarnitine and octenoylcarnitine increased after adaptation to the NP diet. Our results suggest that the higher excretion of short-chain urinary acyl-carnitines could facilitate the elimination of excess fat of the HP diet and thereby reduce hepatic fat accumulation previously reported, whereas the higher excretion medium-chains acyl-carnitine could be early biomarkers of hepatic lipid accumulation.

The Effect of Partly Replacing Vegetable Fat with Bovine Milk Fat in Infant Formula on Postprandial Lipid and Energy Metabolism: A Proof-of-principle Study in Healthy Young Male Adults.

ScopeInfant formula (IF) uses besides vegetable fats also bovine milk fat, which differs in triacylglycerol (TAG) structure. Furthermore, it differs in fatty acid (FA) composition. Whether changing fat source in IF affects postprandial energy metabolism, lipemic response, and blood lipid profile is unknown.Methods and ResultsA proof‐of‐principle study, with a randomized controlled double‐blind cross‐over design, is conducted. Twenty healthy male adults consumed drinks with either 100% vegetable fat (VEG) or 67% bovine milk fat and 33% vegetable fat (BOV), on 2 separate days. For a detailed insight in the postprandial responses, indirect calorimetry is performed continuously, and venous blood samples are taken every 30 min, until 5 h postprandially. No differences in postprandial energy metabolism, serum lipids, lipoprotein, or chylomicron concentrations are observed between drinks. After consumption of VEG‐drink, C18:2n‐6 in serum increased. Observed differences in chylomicron FA profile reflect differences in initial FA profile of test drinks. Serum ketone bodies concentrations increase following consumption of BOV‐drink.ConclusionsThe use of bovine milk fat in IF does neither affect postprandial energy metabolism nor lipemic response in healthy adults, but alters postprandial FA profiles and ketone metabolism. Whether the exact same effects occur in infants requires experimental verification.

Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes.

AimTo assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D).Materials and MethodsIn this randomized, double‐blind, single‐centre, crossover trial, subjects with T2D received once‐daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12‐week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat‐rich) at the end of each treatment period. The primary endpoint was area under the glucose 0–5‐h curve (AUC0–5h) after the standard breakfast.ResultsFifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C‐peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC0–5h) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC0–5h/5h) and glucagon AUC0–5h were also significantly reduced, with similar results after the fat‐rich breakfast. Fasting concentrations of triglycerides, very low‐density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC0–8h for triglycerides, VLDL and ApoB48, and triglycerides iAUC0–8h/8h, were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC0–1h) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment.ConclusionOral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying.

Improvement of Postprandial Lipid Metabolism After Ileal Transposition in Non-obese Diabetic Rats.

Ileal transposition (IT) could reduce obesity and improve type 2 diabetes mellitus (T2DM). The main aim of our study was to investigate lipid metabolism changes in T2DM rats after IT without a weight reduction effect. Thirty male diabetic rats were randomly divided into IT, sham IT (SI), and control groups. The levels of plasma cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), and bile acid were measured. After sacrifice, the white adipose tissue, brown adipose tissue and liver were weighed. IT induced significant improvement in glucose and lipid metabolism. There were no significant differences in the levels of cholesterol (P = 0.87), HDL (P = 0.70), LDL (P = 0.96), or TGs (P = 0.97) among the groups before surgery. After IT, the levels of cholesterol (P = 0.019), LDL (P = 0.004), and TGs (P < 0.001) were lower than those in the SI and control groups, while the level of HDL was not significantly different compared to those of the other groups (P = 0.437). Higher bile acid level (P = 0.001), lower white adipose tissue/total body weight ratio (P < 0.001), and lower liver/total body weight ratio (P = 0.003) were found in the IT group. The BAT/total body weight ratio in the IT group was higher than that in the SI or control groups (P = 0.002). IT could improve lipid metabolism in diabetic rats.