Postprandial Triacylglycerol Response Research Articles

A fructose-based meal challenge to assess metabotypes and their metabolic risk profile: A randomized, crossover, controlled trial.

The first aim of this study was to determine the metabolic type of individuals based on the postprandial metabolic response after the ingestion of a meal challenge that was high protein and either high glucose (high GI) or fructose (low GI). The second aim was to compare the baseline characteristics between the different metabolic types (metabotypes). The third aim was to assess whether the inclusion of fructose or glucose in a high-protein breakfast modulated the glucose, insulin, and TG response over a 4-h period. The study included 46 Asian women with a body mass index between 17 and 28 kg/m2 in a randomized crossover design. Metabolic typing was based on the assessment of the postprandial glycemic, insulin and triacylglycerol (TG) response after the ingestion of two high-protein meal challenges either high in fructose or glucose. Baseline characteristics were compared between the different metabolic types. Baseline and 4-h postprandial blood samples were collected and glucose, insulin, and TG levels were analyzed. Cluster analysis was used to phenotype the participants in distinct groups. Baseline characteristics including anthropometry, glycemic, and lipid profiles and resting metabolic rate were compared among the metabolic types. Cluster analysis revealed that women could be grouped into three metabolic types based on postprandial glucose, insulin, and TG response after the fructose meal challenge: cluster 1 with an average glucose + high TG response (highTG; n = 12), cluster 2 with a high glucose + average TG response (highGLU; n = 8), and cluster 3 with an average glucose + average TG response (Avg; n = 26). Post hoc analysis revealed significantly greater waist-to-hip ratio and a worse lipid profile for the highTG cluster and a higher fasting blood glucose, body mass index, fat percentage, and hip circumference in the highGLU cluster. Three metabolic types with a distinct metabolic response could be distinguished after a high fructose meal. The results suggest a different risk profile and may indicate why some people develop diabetes in an obesogenic environment. Improved metabolic-type assessments will enable us to develop and optimize nutritional and medical interventions for individuals with differing diabetes risk.

Interesterification of a commonly consumed palm-based hard fat blend does not affect postprandial lipoprotein metabolism in healthy older adults

AbstractInteresterified (IE) fats are widely used to replace partially-hydrogenated fats as hard fats with functional and sensory properties needed for spreads/margarines, baked goods, and confectionary, while avoiding the health hazards of trans fats. Detailed mechanistic work to determine the metabolic effects of interesterification of commonly-consumed hard fats has not yet been done. Earlier studies using fats less commonly consumed have shown either neutral or a lowering effect on postprandial lipaemia. We investigated postprandial lipaemia, lipoprotein remodelling, and triacylglycerol-rich lipoprotein (TRL) fraction apolipoprotein concentrations following a common IE blend of palm oil/kernel fractions versus its non-IE counterpart, alongside a reference monounsaturated (MUFA) oil. A 3-armed, double blind, randomized controlled trial (clinicaltrials.gov NCT03191513) in healthy adults (n = 20; 10 men, 10 women) aged 45–75 y, assessed effects of single meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate) on postprandial plasma triacylglycerol (TAG) concentrations, lipoprotein profiles, and TRL fraction apolipoprotein B48 and TAG concentrations. Test fats were IE 80:20 palm stearin/palm kernel fat, the equivalent non-IE fat, and a high-MUFA reference oil (rapeseed oil, RO). Blood was collected at baseline and hourly for 8 h. Linear mixed modelling was performed, adjusting for treatment order and baseline values (ver. 24.0; SPSS Inc., Chicago, IL, USA). Total 8 h incremental area under the curves (iAUC) for plasma TAG concentrations were lower following IE and non-IE compared with RO (mean difference in iAUC: non-IE vs. RO -1.8 mmol/L.h (95% CI -3.3, -0.2); IE vs. RO -2.6 mmol/L.h (95% CI -5.3, 0.0)), but iAUCs for IE and non-IE were not significantly different. There were no differences between IE and non-IE for chylomicron fraction apoB48 concentrations nor TAG:apoB48 ratio. No differences were observed between IE and non-IE for lipoprotein (VLDL, HDL, LDL) particle size or sub-class particle concentrations. However, LDL particle diameters were reduced at 5 and 6 h following IE vs RO (P < 0.05). XXL- (including chylomicron remnants and VLDL particles), XL- and L-VLDL particle concentrations (average diameters > 75, 64, and 53.6 nm respectively) were higher following IE and non-IE vs. RO at 6 h (P < 0.05) and 8 h postprandially (P < 0.005–0.05). In conclusion, both IE and non-IE palmitic acid-rich fats generated a greater preponderance of pro-atherogenic large TRL remnant particles in the late postprandial phase relative to an oleic acid-rich oil. However, the process of interesterification did not modify postprandial TAG response or lipoprotein metabolism.

Large Inter-individual Variation in Postprandial Lipemia Following a Mixed Meal in over 1000 Twins and Singletons from the UK and US: The PREDICT I Study (OR19-06-19)

ObjectivesPostprandial lipemia is an important risk factor for cardiovascular disease, independent of fasting levels, and is influenced by multiple factors including; environmental, genetic, metabolic, metagenomic and the meal-context. Postprandial lipemic responses may therefore differ between individuals, however previously this has only been studied in limited numbers. The PREDICT I study is the largest study to date to measure inter-individual variability in postprandial lipemic responses using a standardized test meal model. MethodsA multi-center postprandial study of 1000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from US, assessed postprandial (hourly 0–6h) lipemic responses to sequential mixed-nutrient dietary challenges (50g fat and 85g carbohydrate at 0h; 22g fat and 71g carbohydrate at 4h) in a clinical setting. Inter-individual variability in postprandial triacylglycerol (TG) responses was measured for incremental area under the curve (iAUC), Cmax, Tmax and increase above fasting at 5h (mean peak concentration time-point). ResultsAnalysis showed high inter-individual variability in postprandial lipemic responses (Figures 1–3) in the tightly controlled clinic setting (interim analysis of n = 537); IQR (median) was; iAUC (0-6h) 2.34 (2.38) mmol/L.h; Cmax 1.32 (2.02) mmol/L; Tmax 30.0 (300) min; and increase above fasting at 5h 0.92 (0.95). TG variation was higher in the non-fasting versus the fasting state; fasting TG concentration IQR (median); 0.57 (0.91) mmol/L. ConclusionsThe large variation in the magnitude and pattern of lipemic responses to identical meals in healthy people demonstrates the limitations of using the group mean and the importance of individualized dietary approaches. Ongoing exploration in PREDICT I of the determinants of postprandial lipemic responses considering environmental, genetic, metagenomic and microbiome variables will significantly advance our ability to predict an individual’s postprandial response. Funding SourcesNIHR, Wellcome Trust, Zoe Global Ltd. Supporting Tables, Images and/or Graphs▪▪

Effect of Night Time Eating on Postprandial Triglyceride Metabolism in Healthy Adults: A Systematic Literature Review.

Eating at night time, as is frequent in shift workers, may contribute to increased cardiovascular disease (CVD) risk through a disruption in usual lipid metabolism, resulting in repeated and sustained hyperlipidemia at night. This systematic review aimed to investigate the impact of eating a meal at night compared with the same meal eaten during the day on postprandial lipemia. Six databases were searched: CINAHL Plus, Cochrane Library, EMBASE, Ovid MEDLINE, Informit, and SCOPUS. Eligible studies were original research cross-over design with a minimum fasting period of 5 h before testing preceded by a standardized control meal; measured postprandial triacylglycerol (TAG) for 5 h or greater; had meal time between 0700 h and 1600 h for day time and between 2000 h and 0400 h for night time; and had within-study test meals (food or drink) that were identical in macronutrient composition and energy. Two authors independently completed eligibility and quality assessment using the American Dietetic Association Quality Criteria Checklist for Primary Research. After removing duplicates, 4,423 articles were screened, yielding 5 studies for qualitative synthesis. All studies identified at least one parameter of the postprandial TAG response that was different as a result of meal time (e.g., the total concentration or the time course kinetics). Two studies reported a greater total TAG concentration (area under curve) at night compared with day, and 3 studies found no difference. Four studies reported that the kinetics of the postprandial time course of TAGs was different at night compared with during the day. Inconsistent reporting in the primary studies was a limitation of the review. Night eating may negatively affect postprandial lipemia and this review shows there is a need to rigorously test this using standardized methods and analysis with larger sample sizes. This is critical for informing strategies to lower CVD risk for shift workers.

Whey protein lowers systolic blood pressure and Ca-caseinate reduces serum TAG after a high-fat meal in mildly hypertensive adults

Epidemiological studies show an inverse association between dairy consumption and blood pressure (BP) but there are few data on the postprandial effects of milk proteins. This study examined their effects, compared to maltodextrin, on postprandial BP and other CVD risk markers in volunteers with mild and pre-hypertension over an 8 h period. In this double-blinded, randomised, cross-over, controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein reduced systolic BP compared with Ca-caseinate (−15.2 ± 13.6 mmHg) and maltodextrin (−23.4 ± 10.5 mmHg) up to 5 h post-ingestion. There was an improvement in arterial stiffness after whey protein compared with maltodextrin (incremental Area Under the Curve- iAUC0–8h: +14.4 ± 6.2%). Despite similar glucose levels after both whey protein and Ca-caseinate, whey protein induced a higher insulin response than Ca-caseinate (iAUC0–8h: +219.5 ± 54.6 pmol/L). Ca-caseinate induced less suppression of non-esterified fatty acids than whey protein (iAUC0–5h: −58.9 ± 135.5 μmol/L) and maltodextrin (iAUC0–5h: −106.9 ± 89.4 μmol/L) and induced a smaller postprandial triacylglycerol response than whey protein (iAUC0–8h: −1.68 ± 0.6 mmol/L). Milk proteins co-ingestion with high-fat meals may have the potential to maintain or improve CVD risk factors.

Assessment of the Validity and Reproducibility of a Novel Standardized Test Meal for the Study of Postprandial Triacylglycerol Concentrations

Lipotest® is a standardized fat-rich meal designed for use as a test meal during a fat tolerance test (FTT) for the study of postprandial triacylglycerol (TAG) concentrations. Herein we examined the precision and reproducibility of examination using Lipotest® on postprandial TAG levels. A total of 26 healthy consenting subjects were examined twice after 8–10 h fasting with an interval of approximately 1 week apart. Blood samples were collected at baseline and 1, 2, 3, and 4 h after consumption of the test meal for measurement of plasma total TAG levels. We examined agreement, precision, and accuracy between the two visits using the Altman plots and correlation coefficient. Reproducibility was tested using the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Moreover, the area under the curve (AUC) as a summary measure of the overall postprandial TAG levels was calculated. The agreement, precision (r ≥ 0.74, p < 0.001), and accuracy (≥0.99) between the measurements in plasma TAG during Lipotest® testing in the two visits were high. In terms of reproducibility, the values of CV were 15.59–23.83% while those of ICC were ≥0.75. The values of the AUCs in the visits were not different (p = 0.87). A single measurement of plasma TAG levels at 4 h after Lipotest® consumption depicted peak postprandial TAG concentration. A FTT using Lipotest® as a standardized meal has good precision and reproducibility for the study of postprandial TAG levels in healthy individuals. A single determination of plasma TAG concentration at 4 h after Lipotest® consumption captures peak postprandial TAG response.

Concordant and divergent strategies to improve postprandial glucose and lipid metabolism

AbstractFollowing ingestion of a mixed‐macronutrient meal, blood glucose and triacylglycerol (TAG) concentrations are elevated for approximately 2 and 8 hours, respectively, depending on factors such as the amount and type of food ingested. For many individuals who consume at least three meals per day, the majority of waking hours are thus spent in a postprandial state. Exaggerated postprandial glycaemia and triglyceridemia are associated with cardiovascular and metabolic diseases, and so strategies to alleviate such perturbations are desirable (e.g. exercise and/or diet). An acute bout of endurance, resistance or high‐intensity and interval exercise typically mitigates postprandial glucose and TAG responses to subsequent meals. Regular exercise training also facilitates adaptations that beneficially alter postprandial metabolism. The health benefits of various dietary protocols have been debated in research and in the media over recent decades. To complicate matters, these strategies may be beneficial for glucose metabolism but simultaneously impair TAG metabolism or vice versa. Finally, despite the finding that diet and exercise can independently alter postprandial metabolism, there are fewer investigations of their ability to act synergistically to achieve a prophylactic response on postprandial blood glucose and TAG concentrations. This may provide the basis for future public health guidelines and is an important consideration in the context of the current worldwide prevalence of cardiovascular and metabolic diseases.

The effect of longer-term plant sterol and stanol consumption on apolipoprotein CII and apolipoprotein CIII concentrations in humans

Background: Elevated fasting and postprandial serum levels of triacylglycerol (TAG) are a risk factor for cardiovascular disease (CVD). The dietary components plant sterols and stanols can be used as strategy against elevated TAG levels. In a recent study it was found that longer-term plant stanol consumption resulted in a higher postprandial TAG response compared to sterol consumption after a second meal. The explanation for this observed difference remained unclear. Possibly the clearance of TAG from the blood might be affected differently. Specialized particles are responsible for the transportation of TAG in the blood, called the lipoproteins. These particles contain apolipoproteins CII (apoCII) and CIII (apoCIII) which have an activating and inhibiting effect on the enzyme lipoprotein lipase (LPL) responsible for the clearance of TAG from the blood. Objective: The objective was to examine if postprandial apoCII and apoCIII responses could explain observed differences in postprandial TAG response after longer-term sterol and stanol consumption. Methods: Healthy subjects (n=42) participated in a randomized control trial consisting of three intervention periods during which the participants consumed either control margarine, or margarine enriched with plant sterols or plant stanols. Blood was sampled under fasting conditions and after the consumption of breakfast and lunch. ApoCII and apoCIII concentrations in serum were measured by an immunoturbimetric immunoassay. Results: Both iAUC and iAUCmin of postprandial apoCII concentrations were similar between all three conditions ( p=0.965 and p=0.563 respectively). Postprandial iAUC and iAUCmin of apoCIII concentrations also showed no difference between conditions (p=0.342 and p=0.955 respectively). In the control group, the iAUC of postprandial apoCIII concentrations was higher after the second meal compared to the first meal. (p=0.037).Conclusion: Postprandial apoCII and apoCIII responses were not affected by longer-term plant sterol and stanol consumption, therefore changes in concentrations of these two apolipoproteins can be ruled out as explanation for the observed differences in TAG response

Association of the tumor necrosis factor-alpha promoter polymorphism with change in triacylglycerol response to sequential meals.

BackgroundReported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant’s body weight. Hence, we investigated the association of TNFA polymorphism (−308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia.MethodsThe study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders.ResultsThe -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts.ConclusionsOur findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies.Trial registration NCT01172951.

The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults.

BackgroundApolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults.FindingsHealthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively.ConclusionsIn summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake.

The Postprandial Chylomicron Triacylglycerol Response to Dietary Fat in Healthy Male Adults Is Significantly Explained by a Combination of Single Nucleotide Polymorphisms in Genes Involved in Triacylglycerol Metabolism

The postprandial chylomicron (CM) triacylglycerol (TG) response to dietary fat, which is positively associated with atherosclerosis and cardiovascular disease risk, displays a high interindividual variability. This is assumed to be due, at least partly, to polymorphisms in genes involved in lipid metabolism. Existing studies have focused on single nucleotide polymorphisms (SNPs), resulting in only a low explained variability. We aimed to identify a combination of SNPs associated with the postprandial CM TG response. Thirty-three healthy male volunteers were subjected to 4 standardized fat tolerance test meals (to correct for intraindividual variability) and genotyped using whole-genome microarrays. The plasma CM TG concentration was measured at regular interval times after each meal. The association of SNPs in or near candidate genes (126 genes representing 6225 SNPs) with the postprandial CM TG concentration (0-8 h areas under the curve averaged for the 4 test meals) was assessed by partial least squares regression, a multivariate statistical approach. Data obtained allowed us to generate a validated significant model (P = 1.3 × 10(-7)) that included 42 SNPs in 23 genes (ABCA1, APOA1, APOA5, APOB, BET1, CD36, COBLL1, ELOVL5, FRMD5, GPAM, INSIG2, IRS1, LDLR, LIPC, LPL, LYPLAL1, MC4R, NAT2, PARK2, SLC27A5, SLC27A6, TCF7L2, and ZNF664) and explained 88% of the variance. In 39 of these SNPs, univariate analysis showed that subjects with different genotypes exhibited significantly different (q < .05) postprandial CM TG responses. Using a multivariate approach, we report a combination of SNPs that explains a significant part of the variability in the postprandial CM TG response.

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

ObjectiveStudies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. MethodsMen classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. ResultsMetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥5.6mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P<0.001). Following the test meals, there were higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P<0.001) and insulin maxC (P=0.010) were also observed in these individuals after the test meals. Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response. ConclusionOur data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.

Within-person variation in the postprandial lipemic response of healthy adults

The response to dietary fat plays a key role in metabolic health. Although this can vary widely between individuals, variation within an individual and the associated contribution of phenotypic and genotypic factors to this variation are less defined. The objectives were to quantify within-person variation in triacylglycerol response by means of a novel variation score (S(v)) and to explore the phenotypic and genotypic factors associated with this score. Two consecutive 5-h oral-lipid-tolerance tests (OLTTs) were conducted in 51 healthy adults aged 18-60 y with a BMI (in kg/m²) of 18.5 to 49.8. Detailed body composition, physical function, biochemistry, and genotype data were gathered. The postprandial triacylglycerol response profile did not differ (P = 0.64) across OLTTs for the group; nor did average concentrations of functional markers apolipoprotein C2 (P = 0.73) and apolipoprotein C3 (P = 0.74). S(v) was low in most (82%) of the adults and was significantly (P < 0.05) associated with age, fasting triacylglycerol, triacylglycerol AUC, and fasting nonessential fatty acids. Significant associations were also observed between S(v) and single nucleotide polymorphisms in 7 genes (APOA1, IL1α, IL1β, TLR4, TCF7L2, CCK1Rec, and STAT3) after correction for phenotypic differences. This work showed that the within-person variability in postprandial lipemic response is low in most healthy adults. It also showed that variability in this response is associated with a defined set of phenotypic and genotypic characteristics.

The leptin receptor Gln223Arg polymorphism (rs1137101) mediates the postprandial lipaemic response, but only in males

ObjectiveAn exaggerated postprandial triacylglycerol (TAG) response is an important determinant of cardiovascular disease risk. With increased recognition of the role of leptin in systemic macronutrient metabolism, we used a candidate gene approach to examine the impact of the common leptin receptor (LEPR) Gln223Arg polymorphism (rs1137101) on postprandial lipaemia. Methods and resultsHealthy adults (n = 251) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0) and lunch (t = 330 min). Fasting total- and low-density lipoprotein cholesterol were 9% lower in the ArgArg than GlnArg group (P < 0.04), whereas fasting TAG was 27% lower in the ArgArg than GlnGln group (P < 0.02). The magnitude of the postprandial TAG response was also significantly lower in the ArgArg compared with the GlnArg and GlnGln genotypes, with a 26% lower area under the curve (AUC) and incremental AUC in the ArgArg individuals (P ≤ 0.023). Genotype*gender interactions were evident for fasting and postprandial TAG responses (P < 0.05), with the genotype effect only evident in males. Regression analysis indicated that the LEPR genotype and genotype*gender interactions were independent predictors of the TAG AUC, accounting for 6.3% of the variance. Our main findings were replicated in the independent LIPGENE-Cordoba postprandial cohort of metabolic syndrome subjects (n = 75), with a 52% lower TAG AUC in the ArgArg than GlnGln male subjects (P = 0.018). ConclusionWe report for the first time that the common LEPR Gln223Arg genotype is an important predictor of postprandial TAG in males. The mechanistic basis of these associations remains to be determined.

Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study

Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. Seventy-one patients (age 18-70 years), who did not reach HbA(1c) 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n = 25), Alo/Pio (n = 22) or Pbo (n = 24). Blood was sampled at pre-specified intervals, starting at 15 min before and ending 8 h after meal ingestion. At week 16, Alo (n = 25) and Alo/Pio (n = 21) vs Pbo (n = 24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p < 0.001), as well as in chylomicron TG (p < 0.001) and VLDL1 TG iAUCs (p < 0.001 and p = 0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p = 0.028), and a non-significant trend towards a decrease with Alo/Pio (p = 0.213). The incidence of adverse events was low and consistent with previous studies. Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. ClinicalTrials.gov number NCT00655863.

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

ObjectiveTo examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia. MethodsHealthy men (n=112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0min) and lunch (330min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples. ResultsSubjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P≤0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (maxC) were significantly greater in men with ≥3 than <3 components (P<0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P<0.04). For glucose, maxC after the test breakfast (0–330min) and total AUC (0–480min) were higher in men with ≥3 than <3 components (P≤0.001). ConclusionsOur data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components.

Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects. In this multi-center study, insulin sensitivity and β-cell function were assessed (n=102), using a euglycemic-hyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n=35). A total of 102 subjects with IFG (n=48), IGT (n=12), IFG/IGT (n=26) and NGT (n=16). IFG, IGT and IFG/IGT subjects had lower insulin sensitivity with no differences between groups, and lower impaired β-cell function compared with NGT controls. The early postprandial increase in triacylglycerol (TAG) concentration was higher (iAUC(0-2 h) IFG: 238.4±26.5, IGT: 234.0±41.0 and NGT: 82.6±13.8 μmol l(-1) min(-1), both P<0.05) and early TAG extraction was increased (AUC(0-2 h) IFG: 56.8±9.0, IGT: 52.2±12.0 and NGT: 3.8±15.4 nmol·100 ml(-1) min(-1), P<0.05 and P=0.057, respectively) in both IFG and IGT subjects. IFG, IGT and IFG/IGT subjects have lower insulin sensitivity and impaired β-cell function compared with age- and BMI-matched NGT controls. The increased postprandial TAG response and higher muscle TAG extraction in both IFG and IGT compared with NGT may lead to ectopic fat accumulation in the skeletal muscle, thereby contributing to insulin resistance.

Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.

Is the beneficial effect of prior exercise on postprandial lipaemia partly due to redistribution of blood flow?

Preprandial aerobic exercise lowers postprandial lipaemia (a risk factor for coronary heart disease); however, the mechanisms responsible are still not clear. The present study investigated whether blood flow to skeletal muscle and/or the liver was increased in the postprandial period after exercise, relative to a control trial, and whether this resulted from increased cardiac output or redistribution of flow. Eight overweight inactive males, aged 49.4±10.5years (mean±S.D.), acted as their own controls in a counterbalanced design, either walking briskly for 90min at 60% V̇O2max (maximal oxygen uptake), or resting in the lab, on the evening of day 1. The following morning, a fasting blood sample was collected, participants consumed a high-fat breakfast, and further venous blood samples were drawn hourly for 6h. Immediately after blood sampling, Doppler ultrasound was used to measure cardiac output and blood flow through both the femoral artery of one leg and the hepatic portal vein, with the ultrasonographer blinded to trial order. The total postprandial triacylglycerol response was 22% lower after exercise (P=0.001). Blood flow through the femoral artery and the hepatic portal vein was increased by 19% (P<0.001) and 16% (P=0.033), respectively, during the 6-h postprandial period following exercise; however, postprandial cardiac output did not differ between trials (P=0.065). Redistribution of blood flow, to both exercised skeletal muscle and the liver, may therefore play a role in reducing the plasma triacylglycerol response to a high-fat meal on the day after an exercise bout.

Post-prandial capillary triacylglycerol responses to moderate exercise in centrally obese middle-aged men

In this study, we wished to determine whether 30 min of moderate-intensity exercise, corresponding to minimal recommended guidelines, attenuates post-prandial capillary triacylglycerol concentrations in obese men. Ten middle-aged, centrally obese men (age 46 ± 2 years, body mass index 31.6 ± 1.0 kg · m−2, waist circumference 104.6 ± 2.2 cm) completed two 2-day trials (exercise and control) at least one week apart in a randomized, repeated-measures design. On day 1, participants either cycled for 30 min at approximately 60% of maximal heart rate in the afternoon or rested (no exercise). On day 2 of both trials, after a 10-h overnight fast, participants consumed a test meal of moderate fat content (35%) for breakfast. Capillary blood samples were collected in the fasted state (0 h) and at 2, 4, and 6 h post-prandially on day 2. Total area under the capillary triacylglycerol concentration versus time curve was significantly lower on the exercise than control trial (P = 0.023). One 30-min session of moderate-intensity cycling is effective in lowering post-prandial capillary triacylglycerol concentration in obese middle-aged men. These findings may have important implications for exercise recommendations as a means to reduce the risk of cardiovascular disease if such exercise is performed for an extended period.