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PloS One 2024We overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical...
We overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads. To assess WRIC validity seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events. Sixteen participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose in a crossover design. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and carbohydrate oxidation. Postprandial carbohydrate oxidation trajectories for each participant and condition were modeled using Bayesian Hierarchical Modeling. Mean total error in infusions were 1.27 ± 0.67% and 0.42 ± 0.70% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions ([Formula: see text] = 1.05 ± 0.03 kcal/min, p = 0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p = 0.29), postprandial carbohydrate oxidation parameters were significantly lower for dextrose compared with sucrose or fructose. We provide evidence validating our WRIC and a novel application of statistical methods useful for research using WRIC.
Topics: Humans; Calorimetry, Indirect; Male; Female; Adult; Reproducibility of Results; Bayes Theorem; Postprandial Period; Cross-Over Studies; Young Adult; Energy Intake; Energy Metabolism; Oxidation-Reduction; Fasting
PubMed: 38900814
DOI: 10.1371/journal.pone.0304030 -
Drug Design, Development and Therapy 2024This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
OBJECTIVE
This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.
METHODS
A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (C), the areas under the plasma concentration-time curve (AUC, AUC), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.
RESULTS
Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09-103.44% for C, 94.05-103.51% for AUC, and 94.56-103.86% for AUC under fasting conditions, and 99.18-112.48% for C, 98.79-106.02% for AUC, and 98.95-105.89% for AUC under postprandial conditions, all of which were within the bioequivalence range of 80.00-125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.
CONCLUSION
The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.
CLINICAL TRIAL REGISTRATION
chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).
Topics: Humans; Therapeutic Equivalency; Thalidomide; Fasting; Postprandial Period; Adult; Male; Cross-Over Studies; Healthy Volunteers; Tablets; Young Adult; Female; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Area Under Curve; Administration, Oral
PubMed: 38895175
DOI: 10.2147/DDDT.S461771 -
Nutrients Jun 2024Nutritional bars (NBs) are gaining popularity among healthy and athletic individuals, but postprandial antioxidative response has not been investigated. Therefore, the...
Nutritional bars (NBs) are gaining popularity among healthy and athletic individuals, but postprandial antioxidative response has not been investigated. Therefore, the current study examined the postprandial alterations in total phenolic content (TPC), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and Superoxide dismutase (SOD) in the plasma of healthy individuals after the ingestion of 140 g (510 Kcal) from formulated date-based bars (DBBs) or fruit-based bars (FBBs). Firstly, the free and bound phenolic contents (PCs) were determined to be 10.15 and 12.98 and 6.19 and 3.57 mg GAE g, respectively. FBBs were significantly higher in free PC than DBBs, while DBBs were considerably higher in bound PC than FBBs. Secondly, twenty participants with age, height, weight, body mass index (BMI), fat mass, and fat-free mass averages of 21.4 years, 170.0 cm, 66.3 kg, 22.9 kg m, 14.5, and 29.2 kg, respectively, were subjected to metabolic experiments (ISRCTN19386758). Ingestion of 140 g of FBB or DBB resulted in 288.50 or 302.14 µg TPC mL blood, respectively. Postprandial TPC content increased with time progression and peaked after 120 min. T-AOC contents averaged 22.63 and 23.61 U mL before ingestion of FBBs or DBBs, respectively. The T-AOC content increased significantly 120 and 180 min after ingestion of DBBs, while no significant change was noted after consuming FBBs. A significant decrease in MDA content was observed 180 min after consuming DBBs, while no significant change was noted after consuming FBBs. SOD concentrations ranged from 193.99 to 201.07 U L in FBBs and DBBs, respectively. No considerable response was noted up to 3 h after ingestion of FBBs. On the contrary, a significant response was found 120 min after consuming DBBs. Pearson's correlation coefficient indicated a highly significant positive correlation coefficient ( < 0.01) between T-AOC and either MDA or SOD, as well as between MDA and SOD. The principal component analysis demonstrated a strong and positive relationship between SOD and TPC at 60 and 120 min after DBB ingestion. In conclusion, the relative changes in postprandial responses in T-AOC and MDA did not significantly ( > 0.05) differ between DBBs and FBBs, except for TPC ( = 0.04, paired -test) and SOD ( = 0.003, paired -test). Further studies with an extended experimental time are needed to confirm the current findings.
Topics: Humans; Postprandial Period; Antioxidants; Fruit; Male; Young Adult; Malondialdehyde; Female; Superoxide Dismutase; Adult; Phenols; Food, Formulated; Healthy Volunteers
PubMed: 38892726
DOI: 10.3390/nu16111794 -
Nutrients May 2024The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not...
Examining the Direct and Indirect Effects of Postprandial Amino Acid Responses on Markers of Satiety following the Acute Consumption of Lean Beef-Rich Meals in Healthy Women with Overweight.
The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not well-characterized. The objective of this study was to identify the direct and indirect effects of postprandial amino acid (AA) responses on satiety. Seventeen women (mean ± SEM, age: 33 ± 1 year; BMI: 27.8 ± 0.1 kg/m) consumed a eucaloric, plant-based diet containing two servings of lean beef/day (i.e., 7.5 oz (207 g)) for 7 days. During day 6, the participants completed a 12 h controlled-feeding, clinical testing day including repeated satiety questionnaires and blood sampling to assess pre- and postprandial plasma AAs, PYY, and GLP-1. Regression and mediation analyses were completed to assess AA predictors and hormonal mediators. Total plasma AAs explained 41.1% of the variance in perceived daily fullness ( < 0.001), 61.0% in PYY ( < 0.001), and 66.1% in GLP-1 ( < 0.001) concentrations, respectively. Several individual AAs significantly predicted fluctuations in daily fullness, PYY, and GLP-1. In completing mediation analyses, the effect of plasma leucine on daily fullness was fully mediated by circulating PYY concentrations (indirect effect = B: 0.09 [Boot 95% CI: 0.032, 0.17]) as no leucine-fullness direct effect was observed. No other mediators were identified. Although a number of circulating AAs predict satiety, leucine was found to do so through changes in PYY concentrations in middle-aged women.
Topics: Humans; Female; Adult; Postprandial Period; Amino Acids; Red Meat; Peptide YY; Satiation; Overweight; Glucagon-Like Peptide 1; Biomarkers; Meals; Animals; Cattle; Satiety Response
PubMed: 38892651
DOI: 10.3390/nu16111718 -
Nutrients May 2024Non-communicable diseases (NCDs) are becoming an increasingly important health concern due to a rapidly ageing global population. The fastest growing NCD, type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
Understanding the Impact of Different Doses of Reducose Mulberry Leaf Extract on Blood Glucose and Insulin Responses after Eating a Complex Meal: Results from a Double-Blind, Randomised, Crossover Trial.
Non-communicable diseases (NCDs) are becoming an increasingly important health concern due to a rapidly ageing global population. The fastest growing NCD, type 2 diabetes mellitus (T2DM), is responsible for over 2 million deaths annually. Lifestyle changes, including dietary changes to low glycemic response (GR) foods, have been shown to reduce the risk of developing T2DM. The aim of this study was to investigate whether three different doses of Reducose, a mulberry leaf extract, could lower the GR and insulinemic responses (IR) to a full meal challenge in healthy individuals. A double-blind, randomised, placebo-controlled, repeat-measure, crossover design trial was conducted by the Oxford Brookes Centre for Nutrition and Health; 37 healthy individuals completed the study. Participants consumed capsules containing either 200 mg, 225 mg, 250 mg Reducose or placebo before a test meal consisting of 150 g white bread and egg mayo filler. Capillary blood samples were collected at 15-min intervals in the first hour and at 30-min intervals over the second and third hours to determine glucose and plasma insulin levels. The consumption of all three doses of Reducose resulted in significantly lower blood glucose and plasma insulin levels compared to placebo. All three doses of Reducose (200 mg, 225 mg, 250 mg) significantly lowered glucose iAUC 120 by 30% ( = 0.003), 33% ( = 0.001) and 32% ( = 0.002), respectively, compared with placebo. All three doses of Reducose (200 mg, 225 mg, 250 mg) significantly lowered the plasma insulin iAUC 120 by 31% ( = 0.024), 34% ( = 0.004) and 38% ( < 0.001), respectively. The study demonstrates that the recommended dose (250 mg) and two lower doses (200 mg, 225 mg) of Reducose can be used to help lower the GR and IR of a full meal containing carbohydrates, fats and proteins.
Topics: Humans; Cross-Over Studies; Plant Extracts; Double-Blind Method; Morus; Blood Glucose; Male; Insulin; Female; Adult; Plant Leaves; Postprandial Period; Middle Aged; Meals; Young Adult; Glycemic Index; Diabetes Mellitus, Type 2
PubMed: 38892603
DOI: 10.3390/nu16111670 -
Food & Nutrition Research 2024Fenugreek plant () constitutes a traditionally acclaimed herbal remedy for many human ailments including diabetes, obesity, neurodegenerative diseases, and reproductive...
BACKGROUND
Fenugreek plant () constitutes a traditionally acclaimed herbal remedy for many human ailments including diabetes, obesity, neurodegenerative diseases, and reproductive disorders. It is also used as an effective anti-oxidative, anti-inflammatory, antibacterial, and anti-fungal agent. The seed of the plant is especially enriched in several bioactive molecules including polyphenols, saponins, alkaloids, and flavonoids and has demonstrated potential to act as an antidiabetic phytotherapeutic. A novel patented formulation (Fenfuro) was developed in our laboratory from the fenugreek seeds which contained >45% furostanolic saponins (HPLC).
OBJECTIVE
A placebo-controlled clinical compliance study was designed to assess the effects of complementing Fenfuro on a randomized group of human volunteers on antidiabetic therapy (Metformin and sulphonylurea) in controlling the glycemic index along with simultaneous safety assessment.
STUDY METHODOLOGY AND TRIAL DESIGN
In a randomized double-blind, placebo-controlled trial, 42 individuals (21 male and 21 female volunteers) in the treatment group (out of 57 enrolled) and 39 individuals (17 male and 22 female volunteers) in the placebo group (out of 47 enrolled), all on antidiabetic therapy with Metformin/Metformin with sulphonyl urea within the age group of 18-65 years were administered either 1,000 mg (500 mg × 2) (Fenfuro) capsules or placebo over a period of 12 consecutive weeks. Fasting and postprandial glucose along with glycated hemoglobin were determined as primary outcomes to assess the antidiabetic potential of the formulation. Moreover, in order to evaluate the safety of the formulation, C-peptide and Thyroid Stimulating Hormone (TSH) levels as well as immunohematological parameters were assessed between the treatment and placebo groups at the completion of the study.
RESULTS
After 12 weeks of administration, both fasting as well as postprandial serum glucose levels decreased by 38 and 44% respectively in the treatment group. Simultaneously, a significant reduction in glycated hemoglobin by about 34.7% was also noted. The formulation did not have any adverse effect on the study subjects as there was no significant change in C- peptide level and TSH level; liver, kidney, and cardiovascular function was also found to be normal as assessed by serum levels of key immunohematological parameters. No adverse events were reported.
CONCLUSION
This clinical compliance study re-instated and established the safety and efficacy of Fenfuro as an effective phytotherapeutic to treat hyperglycemia.
PubMed: 38863744
DOI: 10.29219/fnr.v68.10667 -
Animal : An International Journal of... Jun 2024To avoid a high body protein mobilization in modern lean sows during lactation, an adequate dietary amino acid (AA) supply and an efficient AA utilization are crucial....
To avoid a high body protein mobilization in modern lean sows during lactation, an adequate dietary amino acid (AA) supply and an efficient AA utilization are crucial. This study evaluated the effects of dietary CP and in vitro protein digestion kinetics on changes in sow body condition, litter weight gain, milk composition, blood metabolites, protein utilization efficiency and subsequent reproductive performance. We hypothesized that a slower digestion of dietary protein would improve AA availability and utilization. In total, 110 multiparous sows were fed one of four lactation diets in a 2 × 2 factorial design, with two CP concentrations: 140 g/kg vs 180 g/kg, and two protein digestion kinetics, expressed as a percentage of slow protein (in vitro degradation between 30 and 240 min): 8 vs 16% of total protein. Feeding sows the high CP diets reduced sow weight loss (Δ = 7.6 kg, P < 0.01), estimated body fat loss (Δ = 2.6 kg, P = 0.02), and estimated body protein loss (Δ = 1.0 kg, P = 0.08), but only at a high percentage of slow protein. A higher percentage of slow protein increased litter weight gain throughout lactation (Δ = 2.6 kg, P = 0.04) regardless of CP concentrations, whereas a higher CP only increased litter weight gain during week 3 of lactation (Δ = 1.2 kg, P = 0.01). On Day 15 postfarrowing, serial blood samples were taken from a subsample of sows fed with the high CP diets. In these sows, a high percentage of slow protein resulted in higher plasma AA concentrations at 150 and 180 min after feeding (Δ = 0.89, P = 0.02, Δ = 0.78, P = 0.03, mmol/L, respectively) and lower increases in urea at 90 and 120 min after feeding (Δ = 0.67, P = 0.04, Δ = 0.70, P = 0.03, mmol/L, respectively). The higher dietary CP concentration increased total nitrogen loss to the environment (Δ = 604 g, P < 0.01) with a reduction of protein efficiency (Δ = 14.8%, P < 0.01). In the next farrowing, a higher percentage of slow protein increased subsequent liveborn litter size (Δ = 0.7, P < 0.05). In conclusion, feeding sows with a high dietary CP concentration alleviated maternal weight loss during lactation when the dietary protein digestion rate was slower, but lowered protein efficiency. A slower protein digestion improved litter weight gain, possibly by reducing AA oxidation and improving plasma AA availability, thus, improving protein efficiency.
Topics: Animals; Female; Lactation; Amino Acids; Weight Gain; Animal Feed; Diet; Swine; Reproduction; Digestion; Postprandial Period; Weight Loss; Dietary Proteins; Animal Nutritional Physiological Phenomena; Milk; Pregnancy
PubMed: 38843665
DOI: 10.1016/j.animal.2024.101184 -
Endocrine Connections Jun 2024The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and...
Two weeks of acarbose treatment show no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study.
AIMS
The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and thereby possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D.
METHODS
Faecal samples collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57-85 years, HbA1c 40-74 mmol/mol, BMI 23.6 - 34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing.
RESULTS
The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to both the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (β-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp and Escherichia coli were observed after acarbose treatment (P < 0.05).
CONCLUSIONS
In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only physiologically unimportant effects on GM.
PubMed: 38842918
DOI: 10.1530/EC-24-0052 -
Frontiers in Pharmacology 2024The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects.
A single-dose, randomized, open-label, four-period, crossover equivalence trial comparing the clinical similarity of the proposed biosimilar rupatadine fumarate to reference Wystamm in healthy Chinese subjects.
PURPOSE
The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects.
METHODS
A total of 72 subjects were randomly assigned to the fasting cohort ( = 36) and fed cohort ( = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC-MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a reference-scaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations.
RESULTS
For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (C; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration-time curve from time 0 to the last detectable concentration (AUC) and from time 0 to infinity (AUC). The geometric mean ratio (GMR) of the test/reference for C was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC and AUC comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%-103.90%) and 98.71% (93.93%-103.75%), respectively. For the fed status, the subject standard deviation values of C, AUC, and AUC were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for C, AUC, and AUC were 101.19% (91.64%-111.74%), 98.80% (94.47%-103.33%), and 98.63% (94.42%-103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3-hydroxydesloratadine was also within 80%-125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient.
CONCLUSION
The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status.
CLINICAL TRIAL REGISTRATION
http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213217.
PubMed: 38828454
DOI: 10.3389/fphar.2024.1328142 -
Frontiers in Endocrinology 2024Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically...
Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test.
INTRODUCTION
Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT).
PATIENTS AND METHODS
In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed.
RESULTS
Serum FGF21 significantly increased in the fasting state ( < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD ( < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC ( < 0.05) and was an independent factor for MAFLD ( < 0.05, OR=1.403).
CONCLUSION
Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.
Topics: Humans; Fibroblast Growth Factors; Male; Female; Postprandial Period; Middle Aged; Adult; Inflammation; Lipids; Non-alcoholic Fatty Liver Disease; Triglycerides; Dietary Fats; Biomarkers; Fatty Acids, Nonesterified
PubMed: 38828414
DOI: 10.3389/fendo.2024.1343853