Postprandial State Research Articles

Oseltamivir phosphate for suspension is bioequivalent to TAMIFLU in healthy volunteers: a randomized, open-label clinical study

PurposeThe study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects.MethodsA single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group.ResultsThe Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00–125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively.ConclusionTwo Oseltamivir phosphate for suspensions are safe and bioequivalent.

Aging Is Associated With Impaired Postprandial Response of Skeletal Muscle Protein Synthesis to High-Intensity Muscle Contraction in Mice.

The purpose of this study was to investigate whether aging alters the effect of nutritional status on contraction-induced muscle protein metabolism. In an overnight fasted or fed states, the right gastrocnemius muscle of young (3 months) and aged (24 months) male C57BL/6J mice was isometrically contracted via percutaneous electrical stimulation. The left gastrocnemius muscle served as a control. In the fasted state, there were no differences in basal or contraction-induced muscle protein synthesis between young and old mice. However, in the fed state, basal muscle protein synthesis was greater in young mice, and contraction increased muscle protein synthesis only in young mice. In the fed state, although phosphorylation of 4E-BP1 was similarly increased by contraction in both ages, the increase in phosphorylation of p70S6K was greater in young mice. Our results indicate that aging impairs the ability to integrate signals from muscle contraction and nutrition, leading to aging-induced anabolic resistance to muscle contraction in the postprandial state.

Association between Fasting and Postprandial Levels of Liver Enzymes with Metabolic Syndrome and Suspected Prediabetes in Prepubertal Children.

Elevated liver enzyme activity may be associated with metabolic syndrome (MetS); however, it is not included in the MetS definition for children. Postprandial changes in the levels of biochemistry tests are related to manifestations of metabolic abnormalities. We assessed the association between fasting and postprandial liver enzymes levels with MetS and elevated hemoglobin A1c (HbA1c) in children aged 9-11. The study included 51 girls and 48 boys, all presumably healthy. In all participants' anthropometric indices, fasting glucose, insulin, lipid profile and HbA1c were measured. Enzymes, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were assayed in fasting and postprandial states. Individuals were divided into subgroups: with (MetS(+): n = 26); without MetS (MetS(-): n = 73); with HbA1c levels ≤ 5.3% (n = 39); and ≥5.7% (n = 11). Elevated fasting GGT levels were found in 23% of MetS(+) children and rarely in MetS(-) children; increased postprandial GGT was noted in 35% of MetS(+) individuals. Postprandial GGT changes tend to predict MetS (OR = 1.16; p = 0.092). Increased fasting ALT was found rarely in MetS(+) children, but did not occur in MetS(-) children. HbA1c ≥ 5.7% occurred rarely and neither fasting ALT nor GGT were related to elevated HbA1c. However, postprandial change of ALT was a good positive predictor of increased HbA1c (OR = 1.33; p = 0.021). Postprandial GGT performs better as an indicator of metabolic syndrome occurrence, and instead postprandial ALT may predict prediabetes in prepubertal children.

Protein-based nutritional strategies to manage the development of diabetes: evidence and challenges in human studies.

Type 2 diabetes mellitus (T2DM) is one of the most prevalent diseases in modern society, governed by both genetic and environmental factors, such as nutritional habits. This metabolic disorder is characterized by insulin resistance, which is related to high blood glucose levels, implying negative health effects in humans, hindering the healthy ageing of people. The relationship between food and health is clear, and the ingestion of specific nutrients modulates some physiological processes, potentially implying biologically relevant changes, which can translate into a health benefit. This review aims to summarize human studies published in which the purpose was to investigate the effect of protein ingestion (in native state or as hydrolysates) on human metabolism. Overall, several studies showed how protein ingestion might induce a decrease of glucose concentration in the postprandial state (area under the curve), although it is highly dependent on the source and the dose. Other studies showed no biological effects upon protein consumption, mostly with fish-derived products. In addition, the major challenges and perspectives in this research field are highlighted, suggesting the future directions, towards which scientists should focus on. The dietary intake of proteins has been proven to likely exert a beneficial effect on diabetes-related parameters, which can have a biological relevance in the prevention and pre-treatment of diabetes. However, the number of well-designed human studies carried out to date to demonstrate the effects of specific proteins or protein hydrolysates in vivo is still scarce.

Effects of a 4-week pecan-enriched diet on cognitive function in healthy older adults

BACKGROUND: Pecans are rich in nutrients known to benefit cognition. OBJECTIVE: To examine the effect of daily pecan consumption on cognitive function in older adults. METHODS: In this randomized controlled trial, 42 adults (50–75y) either consumed 68 g of pecans/day for 4-weeks (pecan; n = 21) or avoided all nuts (control; n = 21). At pre- (V1) and post-intervention (V2) visits, cognitive function was assessed using a fluid composite score and four subtests from the NIH Toolbox-Cognitive Battery (NIHTB-CB) (Flanker Test, Digital Change Card Sort Test (DCCS), Picture Sequence Memory Test (PSMT), NIHTB Auditory Verbal Learning Test (RAVLT)) at fasting, 30- and 210-min after a high-saturated fat meal void of pecans. RESULTS: From V1 to V2, fasting and postprandial cognitive performance did not differ between groups. There were improvements in both groups for fasting fluid composite score (p < 0.001) and performance on RAVLT, PSMT, DCCS, and Flanker tests from V1 to V2 (p < 0.001 for all), with no differences between groups. Additionally, postprandial performance on RAVLT, PSMT, and Flanker tests improved at V2 (p < 0.01 for each), with no differences between groups. CONCLUSIONS: A short-term pecan-enriched diet did not provide additional cognitive benefits in healthy older adults in the fasted or postprandial state.

Human fasting modulates macrophage function and upregulates multiple bioactive metabolites that extend lifespan in Caenorhabditis elegans: a pilot clinical study

BackgroundPeriodic prolonged fasting (PF) extends lifespan in model organisms and ameliorates multiple disease states both clinically and experimentally owing, in part, to its ability to modulate the immune system. However, the relationship between metabolic factors, immunity, and longevity during PF remains poorly characterized especially in humans. ObjectiveThis study aimed to observe the effects of PF in human subjects on the clinical and experimental markers of metabolic and immune health and uncover underlying plasma-borne factors that may be responsible for these effects. MethodsIn this rigorously controlled pilot study (ClinicalTrial.gov identifier, NCT03487679), 20 young males and females participated in a 3-d study protocol including assessments of 4 distinct metabolic states: 1) overnight fasted baseline state, 2) 2-h postprandial fed state, 3) 36-h fasted state, and 4) final 2-h postprandial re-fed state 12 h after the 36-h fasting period. Clinical and experimental markers of immune and metabolic health were assessed for each state along with comprehensive metabolomic profiling of participant plasma. Bioactive metabolites identified to be upregulated in circulation after 36 h of fasting were then assessed for their ability to mimic the effects of fasting in isolated human macrophage as well as the ability to extend lifespan in Caenorhabditis elegans. ResultsWe showed that PF robustly altered the plasma metabolome and conferred beneficial immunomodulatory effects on human macrophages. We also identified 4 bioactive metabolites that were upregulated during PF (spermidine, 1-methylnicotinamide, palmitoylethanolamide, and oleoylethanolamide) that could replicate these immunomodulatory effects. Furthermore, we found that these metabolites and their combination significantly extended the median lifespan of C. elegans by as much as 96%. ConclusionsThe results of this study reveal multiple functionalities and immunological pathways affected by PF in humans, identify candidates for the development of fasting mimetic compounds, and uncover targets for investigation in longevity research.

Interorgan Metabolism of Ganglioside Is Altered in Type 2 Diabetes.

GM3 is implicated in cell signaling, inflammation and insulin resistance. The intestinal mucosa metabolizes ganglioside and provides gangliosides for uptake by peripheral tissues. Gangliosides downregulate acute and chronic inflammatory signals. It is likely that transport of intestinal derived gangliosides to other tissues impact the same signals characteristic of inflammatory change in other chronic conditions such as Type 2 Diabetes (T2DM). The postprandial ceramide composition of GM3 and other gangliosides in plasma and chylomicrons has not been examined in T2DM. The present study assessed if diet or T2DM alters ganglioside components in plasma and chylomicrons secreted from the intestinal mucosa after a meal. GD1, GD3, and GM3 content of chylomicrons and plasma was determined by LC/triple quad MS in non-diabetic (control) and T2DM individuals in the fasting and postprandial state after 2 days of consuming a low or high fat diet in a randomized blinded crossover design. Diet fat level did not alter baseline plasma or chylomicron ganglioside levels. Four hours after the test meal, plasma monounsaturated GD3 was 75% higher, plasma saturated GD3 was 140% higher and plasma polyunsaturated GM3 30% lower in diabetic subjects compared to control subjects. At 4 h, chylomicron GD1 was 50% lower in T2DM compared to controls. The proportion of d34:1 in GD3 was more abundant and d36:1 in GD1 less abundant in T2DM compared to control subjects at 4 h. The present study indicates that T2DM alters ceramide composition of ganglioside available for uptake by peripheral tissues.

Magnetic Resonance Imaging and Spectroscopy Methods to Study Hepatic Glucose Metabolism and Their Applications in the Healthy and Diabetic Liver.

The liver plays an important role in whole-body glucose homeostasis by taking up glucose from and releasing glucose into the blood circulation. In the postprandial state, excess glucose in the blood circulation is stored in hepatocytes as glycogen. In the postabsorptive state, the liver produces glucose by breaking down glycogen and from noncarbohydrate precursors such as lactate. In metabolic diseases such as diabetes, these processes are dysregulated, resulting in abnormal blood glucose levels. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are noninvasive techniques that give unique insight into different aspects of glucose metabolism, such as glycogenesis, glycogenolysis, and gluconeogenesis, in the liver in vivo. Using these techniques, liver glucose metabolism has been studied in regard to a variety of interventions, such as fasting, meal intake, and exercise. Moreover, deviations from normal hepatic glucose metabolism have been investigated in both patients with type 1 and 2 diabetes, as well as the effects of antidiabetic medications. This review provides an overview of current MR techniques to measure hepatic glucose metabolism and the insights obtained by the application of these techniques in the healthy and diabetic liver.

Amyloid‐β plus cholesterol treatment impairs the ability of microglia to efflux excess cholesterol

AbstractBackgroundMicroglia, specialized phagocytic cells of the brain, play a critical role in the clearance of amyloid beta (Aβ), which is involved in the pathogenesis of Alzheimer’s disease. The ability of microglia to remove Aβ is influenced by their cellular cholesterol clearance capacity. It is not known to what extent Aβ impairs microglial cholesterol efflux capacity, especially in the context of excess cholesterol.MethodHMC3 microglia were treated with Aβ‐oligomer (AβO, 2µM), cholesterol loading (20µg), or AβO + cholesterol in combination, and with or without cholesterol acceptor, high‐density lipoprotein (HDL), at 0.1 mg/mL. Pooled HDL from 18 individuals in a 2‐hour postprandial state and a 36‐hour fasted state were compared. The cellular content of unesterified and esterified cholesterol was measured.ResultsThe addition of cholesterol, AβO, and cholesterol+AβO increased cellular cholesterol content, which was attenuated by the addition of HDL. Importantly, cells treated with cholesterol plus AβO had the highest overall cholesterol content (27.80+/‐2.85µM), and both fasted (20.67+/‐3.04µM, p≥0.05) and postprandial HDL (21.95+/‐3.84µM, p<0.05) were not able to reduce the cellular cholesterol content as well as in the untreated (fasted: 16.17+/‐2.28µM, p<0.05; postprandial: 18.55+/‐2.01µM, p>0.05), cholesterol only (fasted: 17.72+/‐2.17µM, p<0.05; postprandial: 18.14+/‐3.19µM, p<0.05), or AβO only condition (fasted: 16.80+/‐1.40µM, p<0.05; postprandial: 18.42+/‐2.05µM, p>0.05). Fasted HDL more efficiently removed cellular cholesterol in the untreated and in AβO+cholesterol treated cells. Intriguingly, cellular esterified cholesterol content was significantly lowered with fasted HDL but not postprandial HDL in both AβO alone (fasted: 5.73+/‐2.27 µM, p<0.05; postprandial: 10.32+/‐2.70µM, p>0.05) and AβO + cholesterol (fasted: 2.87+/‐2.13µM, p<0.05; postprandial: 9.03+/‐1.74µM, p>0.05).ConclusionThese findings suggest that microglia exposed to a double‐hit of AβO and excess cholesterol experience an impaired ability to efflux excess cholesterol. Additionally, HDL from fasted individuals displayed an enhanced capacity to efflux cholesterol, especially in microglia dually encumbered by AβO + cholesterol. Further studies are needed to examine the impact of this diminished cholesterol efflux capacity and cholesterol accumulation on the phagocytic capacity of microglia.

Does postprandial lipemia interfere with blood gas analysis and assessment of acid-base status in dogs?

To evaluate the interference of postprandial lipemia on blood gas parameters and to assess the acid-base status by the quantitative approach of the strong ion model blood samples of 15 healthy dogs were collected during fasting (0 h) and at one (1 h), three (3 h) and five (5 h) hours after the induction of lipemia with a hypercaloric diet. Total cholesterol (TC) and triglyceride (TG) levels were used to assess lipemia and these were correlated with the parameters evaluated accordingly. Anion gap decreased at 5 h without correlation with TC and TG, whereas other parameters measured by the blood gasometer did not change. In the evaluation of the acid base state, the apparent strong ion difference (SIDa) and the strong ion gap (SIG) showed a decrease at 5 h without correlation with lipemia. Lipid levels correlated with the effective strong ion difference (SIDe), the concentration of total non-volatile weak acids (Atot), albumin, phosphate, and magnesium. The SIDe increased at 1 h and at 3 h; the Atot at 1 h, 3 h, and 5 h; albumin increased at 1 h and 3 h; phosphate increased at 1 h, 3 h and 5 h; and magnesium decreased at 5 h. Though postprandial lipemia does not interfere with blood gas analysis, it can cause errors in the variables used to assess the acid-base status, which are dependent on biochemical analytes. Therefore, caution is required when interpreting electrolyte disturbances that result from the postprandial state.

Non-invasive vagus nerve stimulation in a hungry state decreases heart rate variability

Vagus nerve signals from the gut to brain carry information about nutrients and drive food reward. Such signals are disrupted by consuming large amounts of high-calorie foods, necessitating greater food intake to elicit a similar neural response. Non‐invasive vagus nerve stimulation (nVNS) via a branch innervating the ear is a candidate treatment for obesity in humans. There is disagreement on the optimal location of nVNS in the ear for experimental and clinical studies. There are also no studies comparing nVNS in hungry and post-prandial states. We aimed to compare ear position(s) for nVNS and explore the effects of nVNS during hungry and post-prandial states on proxies for autonomic outflow (heart-rate variability) and efferent metabolism (gastric wave frequency and resting energy expenditure).In a within-subject design, 14 participants (10 women, on average 29.4 +/- 6.7 years old) received nVNS in four different locations (cymba conchae, tragus, earlobe, or tragus AND cymba conchae) on separate days. In each session, participants were asked to consume a palatable chocolate flavored milk. With electrography on the abdomen and indirect calorimetry in a canopy, we measured electro-cardiogram, electro-gastrogram and resting energy expenditure for 15 min before and at least 35 min after consumption of the palatable drink. We also collected ratings of the palatable drink and internal and other states.Pre-drink consumption (in a hungry state) we observed no differences in the effect of location of acute nVNS on resting energy expenditure and gastric wave measures. However, nVNS in cymba conchae decreases heart-rate variability (relative to sham) and ratings of how much participants want to consume the drink (relative to tragus AND cymba conchae and a trend relative to sham). After drink consumption and with continued nVNS, gastric wave frequency is unchanged, and resting energy expenditure increases regardless of stimulation location. Heart-rate variability decreases in all locations, except cymba conchae. We also observe a trend for an increase in gastric wave amplitude in late post-drink consumption time-points in cymba conchae. We observe no support for the combined stimulation of tragus AND cymba conchae being more effective than either of the individual locations.These results suggest that nVNS in the cymba conchae in a hungry state has a similar acute effect on vagal tone as food consumption: to decrease heart rate variability. This effect then negates the usual postprandial effects of a decrease in heart rate variability as seen in the other nVNS locations. These preliminary observations suggest that nVNS in cymba conchae may act primarily on vagal afferent autonomic (and only modestly on metabolic output) in a similar way as food consumption does.

ODP553 Hypoglycemia after sleeve gastrectomy: a rare case of an insulinoma

Abstract Background The obesity pandemic has become a great topic of interest due its implications for quality of life, comorbidities, increasing mortality and the economic impact on health services worldwide(1). Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, achieving weight loss due to its restrictive and humoral effects (2). Its prevalence has increased from 5 to 37% since 2008 (3). One common complication after bariatric surgery (BS) is the postprandial hyperinsulinemic hypoglycemic state (4). While rare, insulinomas can cause it, where symptoms are more common during the fasting state; thus, evaluation of insulin secretion is needed to exclude dumping syndrome or nesidioblastosis. Until now, this is the first report of insulinoma after LSG. Clinical Case We here present 43-year-old women who was referred to the Obesity Clinic two years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state with a documented glycemic level of less than 30 mg/dl, compatible with Whipple's Triad. Initially, we suspected dumping syndrome but after documentation of a second low fasting plasma glucose, we decided to perform a 72-hour fasting test, which tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. A laparoscopic enucleation of insulinoma was performed, and after that, the hypoglycemic symptoms and blood sugar levels improved, remaining asymptomatic until now. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. Conclusion This is the first case of insulinoma after sleeve gastrectomy, the suggested physiopathology is due to a combination of increased plasma concentrations of incretins, mainly glucagon-like peptide 1 (GLP-1), and an accelerated release of nutrients in the proximal duodenum (5). Although this is a very rare case condition, clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Postprandial Metabolome Following a Low Glycaemic Index Meal-Challenge Test: A Narrative Review.

The Identifying the dynamic metabolome of the individual in response to a particular stimulus using a metabolomic approach is an emerging research area. Measuring the postprandial metabolite response utilising a meal-challenge test (MCT) provides information beyond the fasting state, which is especially important since human beings spend most of their time in the postprandial state. This is pertinent as an excessive rise in postprandial glycaemia is common in individuals with type 2 diabetes mellitus (T2DM), which puts them at a high risk of developing cardiovascular disease (CVD). While a low glycaemic index (GI) meal improves postprandial glycaemia and insulin levels in MCT studies among individuals with T2DM, its effect on metabolite changes in the postprandial state is unclear. This review summarises the perturbation in postprandial metabolites following a low GI meal in comparison to that following a usual or high GI meal and maps the metabolites in their metabolic pathways. We undertook a literature review using electronic databases, with the Medical Subject Headings (MeSH) terms, to retrieve relevant studies based on specific criteria. A total of seven related studies were documented. For the majority of metabolites studied, it was identified that metabolic regulation following an MCT extends beyond the glucose pathway. Altered metabolic pathways after the consumption of a low GI meal include: i) essential amino acid metabolism by altering the levels of plasma phenylalanine, tyrosine, lysine, leucine, isoleucine and valine; ii) glycolysis and tricarboxylic acid (TCA) metabolism by altering citrate and alanine, and iii) gut microbiota metabolism by altering betaine and acetate. The altered metabolites regulated the pancreatic insulin secretion and related to other dietary factors beyond GI modifications. These metabolomics data need to be interpreted cautiously because the metabolic changes analysed might not be due to the beneficial effects of a low GI meal. Validation of the putative metabolomic biomarkers following a dietary intervention MCT is suggested because researchers need to fully understand the kinetics and metabolism of individuals metabolite before reaching a solid conclusion. Further research characterising the metabotype based on habitual dietary patterns is warranted.

Remnant cholesterol and atherosclerotic cardiovascular disease: Metabolism, mechanism, evidence, and treatment.

This review aimed to summarize the evidence of elevated remnant cholesterol and the risks of atherosclerotic cardiovascular disease (ASCVD) and to search for further guidance in clinical therapy. The lipids-lowering treatments such as statins and ezetimibe targeted on low-density lipoprotein cholesterol (LDL-C) have always been the first-line therapy for ASCVD. However, even after statins or new lipid-lowering drugs lowered LDL-C to recommended concentrations, and with other risk factors well-controlled, such as high blood pressure, the risks of developing ASCVD remained. Remnant cholesterol (RC) referred to the cholesterol contained in all remnant lipoprotein particles, which was the cholesterol in the hydrolyzed very-low-density lipoprotein and intermediate-density lipoprotein in the fasting state, and the cholesterol in the chylomicron remnants in the postprandial state. Evidence from in vitro and animal pathogenic mechanisms studies, epidemiology, and genetic studies all indicated that RC played an important role in predicting the incidence of ASCVD. As a new indicator to reflect atherosclerosis, especially when LDL-C has been controlled to a recommended level, RC was considered as a priority treatment target for people at high risk of ASCVD. The use of statins, fibrates, APOC3 inhibitors, PCSK9 inhibitors, and omega-3 fatty acids to reduce RC levels in the plasma may provide long-term benefits. However, the standardized detection of RC was still controversial, and more studies on appropriate treatments of elevated RC are urgently needed. These positive trials may benefit more patients at high ASCVD risks worldwide in the future.

Pharmacokinetics and safety of the two oral cefaclor formulations in healthy chinese subjects in the fasting and postprandial states.

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%–100.63%), 97.92% (96.49%–99.38%) and 97.95% (96.52%–99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%–97.22%), 97.31% (95.98%–98.65%) and 97.31% (95.93%–98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80–125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

The LIPL study lipid panels and platelet activity in coronary heart disease

Abstract Introduction Measuring lipid panel in the fasting state can be inconvenient for patients and may aggravate their compliance. Moreover, people spend most of the day in the nonfasting state. Hence, it suggests that the changes in the process of atherosclerosis happen mainly under the influence of nonfasting lipids. Up to date, the studies in the postprandial state were primarily performed in healthy subjects. Aim This exploratory study investigates the change in lipid profile and platelet activity in patients with different cardiovascular risk profiles in the postprandial state. Methods The studied population consists of 66 patients with different cardiovascular risks: patients with coronary artery disease (CAD) and diabetes mellitus type 2 (DM2) (n=20), CAD without DM2 (n=25), and a healthy control group (n=21). Lipid variables and markers of platelet function were assessed during the fasting state and 3 and 5 hours after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90g of fat. The platelet activity was measured with a Multiplate test using ADP, ASPI and TRAP reagents. Results Patients with CAD and DM2 were significantly older and had the highest BMI. All patients with CAD were on acetylsalicylic acid, and 95% of CAD patients were on high-dose statins. Total cholesterol, LDL-c, Apolipoprotein A1, and Apolipoprotein B did not change during the OFTT, irrespective of the group. However, HDL-c decreased statistically significantly three and five hours after the fat loading with a peak after five hours (3.46±0.4 mg/dL, p<0.001). The lowest HDL-c was in the CAD and DM2 group (p=0.006). Triglycerides (TG) increased significantly during the OFTT, with a peak after 5 hours (130.2±14.5 mg/dL, p<0.001) irrespective of the group. There was no difference in TG concentration between the groups. Differences stayed statistically significant even after adjustment for age and BMI. Platelet activity increased after fat loading, as shown by a significantly increased thrombocyte count after three hours (p<0.001). Platelet activity measured by multiplate test with ADP (7.16±2.17 AU, p=0.005), ASPI (4.60±1.40 AU, p=0.005), and TRAP (11.41±3.10 AU, p=0.001) reagents increased statistically significant three hours after the fat loading. The platelet activity measured by all three reagents remained increased even after the adjustment for age and BMI (ADP: 7.14±2.10 AU, p=0.004, ASPI: 4.60±1.40 AU, p=0.006, TRAP: 11.40±3.10 AU, p=0.002). Moreover, the platelet activity measured by ADP (−13.12±4.93, p=0.030), and TRAP (−14.6±15.51, p=0.031) reagents was lower in the control group. When adjusted for age and BMI, there was no difference in the platelet activity between the three groups. Conclusion This study showed that fatty meal causes worsening of lipid profile and leads to increased platelet activity in subjects irrespective of cardiovascular risk profile. Funding Acknowledgement Type of funding sources: None.

The Difference in Glucagon Response to Breakfast Between Non-Obese Patients With Long-Duration Type 1 and Type 2 Diabetes

Background: A balanced action of insulin and glucagon is essential for treating diabetes. This study aimed to assess the change in blood glucagon levels from fasting to a postprandial state and to compare them between patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Methods: This study enrolled patients with T1DM (n = 13) who had undetectable serum C-peptide levels (< 0.02 ng/mL) and patients with T2DM (n = 13) whose age, gender, and body mass index were matched to cases (1:1) as controls. Plasma glucose, serum C-peptide, and plasma glucagon in fasting and 2 h after consuming a standard breakfast for diabetic patients were measured and compared between groups. Results: There were no significant differences in plasma glucose and hemoglobin A1c levels between patients with T1DM and T2DM. However, fasting plasma glucagon levels were significantly lower in patients with T1DM than those in patients with T2DM (19.2 ± 13.0 pg/mL vs. 31.6 ± 18.3 pg/mL, P = 0.029). Furthermore, the glucagon’s response to a standardized meal for diabetic patients differed between patients with T1DM and T2DM. Conclusions: The significant difference in glucagon response to the meal may be caused by the abnormal postprandial secretion of glucagon in patients with T1DM. The nutrient ratio of the meal may also influence glucagon secretion. J Endocrinol Metab. 2022;12(4-5):134-139 doi: https://doi.org/10.14740/jem834

Postprandial triglyceride-rich lipoproteins promote the adipogenic differentiation of adipose-derived mesenchymal stem cells via the LRP1/caveolin-1/AKT1 pathway

Diet-induced obesity (OB) is usually accompanied by hypertriglyceridemia, which is characterized by the accumulation of triglyceride (TG)-rich lipoprotein (TRL) particles in the circulation. We previously found that postprandial TRL combined with insulin induced the adipogenic differentiation of 3T3-L1 preadipocytes, which may represent a key mechanism underlying obesity. However, the specific mechanism and signaling pathway involved in this process remain to be fully elucidated. In this study, we found that, in the postprandial state, patients with obesity had significantly higher levels of TG and remnant cholesterol (RC) than normal-weight controls. In vitro, we found that postprandial TRL, together with insulin, promoted the adipogenic differentiation of adipose-derived mesenchymal stem cells (AMSCs), as evidenced by the increased expression of lipogenesis-related genes and their protein products, including low-density lipoprotein related protein 1 (LRP1). Besides, caveolin-1 (Cav-1) expression was also significantly upregulated under this condition. Cav-1 and LRP1 were observed to interact, and then led to the activation of the PI3K/AKT1 signaling pathway. Meanwhile, the inhibition of LRP1 or Cav-1 significantly attenuated the adipogenic differentiation of AMSCs and downregulated AKT1 phosphorylation levels. Moreover, treatment with a selective AKT1 inhibitor significantly suppressed postprandial TRL and insulin-induced adipogenesis in AMSCs. Combined, our results demonstrated that, in association with insulin, postprandial TRL can promote the adipogenic differentiation of AMSCs in a manner that is dependent on the LRP1/Cav-1-mediated activation of the PI3K/AKT1 signaling pathway. Our findings indicated that a postprandial increase in TRL content is a critical factor in the pathogenesis of hypertriglyceridemia and diet-induced obesity.

A Standardized Protocol for Measuring Bioelectrical Impedance in Green Turtles (Chelonia mydas).

AbstractBioelectrical impedance analysis (BIA) is gaining popularity in wildlife studies as a portable technology for immediate and nondestructive predictions of body composition components, such as fat-free and fat masses. Successful application of BIA for field-based research requires the identification and control of potential sources of error, as well as the creation of and adherence to a standardized protocol for measurement. The aim of our study was to determine sources of error and to provide a standardization protocol to improve measurement precision of BIA on juvenile green turtles (Chelonia mydas; ). We assessed the effects of altered environmental temperature (20°C-30°C), postprandial state (2-72 h), and time out of the water (2 h) on five impedance parameters (resistance at infinite frequency [Rinf], resistance at zero frequency [R0], resistance at 50 kHz [R50], phase angle at 50 kHz [PhA50], and intracellular resistance [Ri]) using a bioimpedance spectroscopy device. Technical reproducibility of measurements and interanimal variability were also assessed. We found an inverse exponential relationship between change in environmental temperature and impedance parameters Rinf, R0, and R50. Postprandial state significantly increased Rinf and Ri 72 h after feeding. BIA measurements were reproducible within individual juvenile green turtles at temperatures from 20°C to 30°C. Significant variation in impedance values was found between animals at all temperatures, sampling times, and postprandial states, but the relative differences (%) were small in magnitude. Our study suggests that measurement precision is improved by measuring animals at consistent environmental temperatures close to their preferred thermal range. We propose a standardized protocol of measurement conditions to facilitate laboratory and field use of BIA for body composition assessment studies in turtles.

Relationship between psychological stress and ghrelin concentrations in pregnant women with overweight or obesity

Exposure to, perception of, and response to stress have all been shown to influence appetite and dietary behaviors in non-pregnancy human and animal studies, mediated in part by the appetite stimulating hormone ghrelin. Yet, the impact of prenatal stress on biological pathways associated with appetite in the context of pregnancy is not well understood. The objective of this study was to assess the relationship between these layered dimensions of stress with fasting and postprandial plasma ghrelin concentrations among Hispanic pregnant women with overweight or obesity, a population known to experience heightened levels of stress. Thirty-three non-diabetic Hispanic women with pre-pregnancy body mass index of 25.0–34.9 kg/m2 participated in a crossover study at 28–32 weeks’ gestation. At each visit, participants provided fasting blood and saliva samples, consumed a standardized mixed-meal, and completed a 15-minute task: friendly conversation (control) or the Trier Social Stress Test (experimental stress exposure). Six timed blood and saliva samples were collected up to 2 h from baseline and assayed for ghrelin and cortisol, respectively, and area-under-the-curve (AUC) values were computed. Day-to-day stress levels were assessed by the Perceived Stress Scale. Physiological and psychological stress reactivity was determined by cortisol AUC and change in self-reported affect state, respectively, during the experimental stress visit. Maternal perceived stress was positively associated with ghrelin concentrations in the fasted (β = 0.06, p = 0.02) and postprandial state (β = 0.05, p = 0.02). Mean ghrelin AUC was not significantly different following acute stress versus control. Measures of acute stress reactivity were not associated with ghrelin AUC. Contrary to our hypothesis, among Hispanic pregnant women with overweight and obesity, exposure to an acute stress induction task did not alter postprandial ghrelin concentrations, and changes in individual psychological and physiological stress reactivity did not associate with postprandial ghrelin. However, our findings suggest that maternal report of general perceived stress over the last month is associated with higher fasting and postprandial ghrelin concentrations. Differences in the effects of short-term stress exposure versus day-to-day perception of stress on appetite and food intake in pregnancy deserves further investigation.