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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 Jul 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 shows no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study.
AIM
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 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 were 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 6-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 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 (P < 0.05) were observed after acarbose treatment.
CONCLUSION
In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only minor effects on GM as seen in increased relative abundances of Klebsiella spp. and Escherichia coli.
PubMed: 38842918
DOI: 10.1530/EC-24-0052 -
Obesity (Silver Spring, Md.) Jul 2024The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in...
OBJECTIVE
The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity.
METHODS
A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis.
RESULTS
After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger.
CONCLUSIONS
A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.
Topics: Humans; Obesity; Magnetic Resonance Imaging; Male; Female; Weight Loss; Adult; Caloric Restriction; Middle Aged; Hunger; Brain; Diabetes Mellitus, Type 2; Leptin; Blood Glucose; Eating
PubMed: 38831482
DOI: 10.1002/oby.24046 -
JAMA Internal Medicine Jul 2024Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes.
OBJECTIVE
To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled.
INTERVENTION
Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died.
MAIN OUTCOMES AND MEASURES
The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness.
RESULTS
A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group.
CONCLUSIONS AND RELEVANCE
The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities.
TRIAL REGISTRATION
Chinese Clinical Trial Register: ChiCTR1900023241.
Topics: Humans; Middle Aged; Female; Male; Diabetes Mellitus, Type 2; Glucose Intolerance; Double-Blind Method; Adult; Drugs, Chinese Herbal; Blood Glucose; Aged; China; Glycated Hemoglobin; Insulin Resistance; Glucose Tolerance Test
PubMed: 38829648
DOI: 10.1001/jamainternmed.2024.1190 -
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 -
Food Research International (Ottawa,... Jul 2024Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of chickpea hummus on postprandial blood glucose, insulin and gut hormones in healthy humans combined with mechanistic studies of food structure, rheology and digestion kinetics.
Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is increasing evidence that food structure plays a crucial role in influencing the bioaccessibility and digestion kinetics of macronutrients. The aims of this study were to compare the effects of two hummus meals, with different degrees of cell wall integrity, on postprandial metabolic responses in relation to the microstructural and rheological characteristics of the meals. A randomised crossover trial in 15 healthy participants was designed to compare the acute effect of 27 g of starch, provided as hummus made from either intact chickpea cells (ICC) or ruptured chickpea cells (RCC), on postprandial metabolic responses. In vitro starch digestibility, microstructural and rheological experiments were also conducted to evaluate differences between the two chickpea hummus meals. Blood insulin and GIP concentrations were significantly lower (P < 0.02, P < 0.03) after the consumption of the ICC meal than the meal containing RCC. In vitro starch digestion for 90 min was slower in ICC than in RCC. Microscopic examination of hummus samples digested in vitro for 90 min revealed more intact chickpea cells in ICC compared to the RCC sample. Rheological experiments showed that fracture for ICC hummus samples occurred at smaller strains compared to RCC samples. However, the storage modulus for ICC was higher than RCC, which may be explained by the presence of intact cells in ICC. Food structure can affect the rate and extent of starch bioaccessibility and digestion and may explain the difference in the time course of metabolic responses between meals. The rheological properties were measured on the two types of meals before ingestion, showing significant differences that may point to different breakdown mechanisms during subsequent digestion. This trial was registered at clinicaltrial.gov as NCT03424187.
Topics: Humans; Cicer; Postprandial Period; Insulin; Blood Glucose; Digestion; Cross-Over Studies; Rheology; Adult; Male; Female; Young Adult; Starch; Gastric Inhibitory Polypeptide; Healthy Volunteers; Kinetics
PubMed: 38823849
DOI: 10.1016/j.foodres.2024.114517 -
Journal of Diabetes and Its... Jul 2024Postprandial hyperglycemia can be problematic for people with type 1 diabetes (T1DM) following carbohydrate-restricted diets. Bolus insulin calculated for meal protein... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A randomised controlled trial of additional bolus insulin using an insulin-to-protein ratio compared with insulin-to-carbohdrate ratio alone in people with type 1 diabetes following a carbohydrate-restricted diet.
AIMS
Postprandial hyperglycemia can be problematic for people with type 1 diabetes (T1DM) following carbohydrate-restricted diets. Bolus insulin calculated for meal protein plus carbohydrate may help. This study evaluated the effect of additional bolus insulin using an insulin-to-protein ratio (IPR) on glycaemic control.
MATERIALS AND METHODS
Participants with T1DM aged ≥18-years were randomly allocated (1:1) to either carbohydrate and protein-based, or carbohydrate-based insulin dosing alone for 12 weeks while following a carbohydrate-restricted diet (50-100 g/day). Measurement of HbA1c and continuous glucose monitoring occurred at baseline and 12 weeks, with assessment of participant experience at 12 weeks.
RESULTS
Thirty-four participants were randomised, 22 female, mean(SD): age 39.2 years (12.6) years; diabetes duration 20.6 years (12.9); HbA1c 7.3 % (0.8), 56.7 mmol/mol (9.2). Seven in each group used insulin pump therapy. HbA1c reduced at 12 weeks with no difference between treatments: mean (SD) control 7.2 % (1.0), 55.7 mmol/mol (10.6); intervention 6.9 % (0.7), 52.3 mmol/mol (7.2) (p = 0.65). Using additional protein-based insulin dosing compared with carbohydrate alone, there was no difference in glycaemic variability, time spent in euglycemic range (TIR), or below range. Participants using IPR reported more control of their diabetes, but varying levels of distress.
CONCLUSIONS
Additional bolus insulin using an IPR did not improve glycaemic control or TIR in patients with well controlled T1DM following a carbohydrate-restricted diet. Importantly, the use of the IPR does not increase the risk of hypoglycemia and may be preferred.
Topics: Humans; Diabetes Mellitus, Type 1; Female; Adult; Insulin; Male; Middle Aged; Diet, Carbohydrate-Restricted; Dietary Proteins; Hypoglycemic Agents; Blood Glucose; Glycated Hemoglobin; Hyperglycemia; Glycemic Control; Postprandial Period
PubMed: 38820834
DOI: 10.1016/j.jdiacomp.2024.108778 -
Endoscopy May 2024Previous studies suggest that anti-reflux mucosectomy (ARMS) is effective in reducing reflux symptoms and total acid exposure, although the mechanism is unknown. Our... (Clinical Trial)
Clinical Trial
UNLABELLED
Previous studies suggest that anti-reflux mucosectomy (ARMS) is effective in reducing reflux symptoms and total acid exposure, although the mechanism is unknown. Our objective was to investigate the effect of ARMS on reflux parameters and mechanism of action.
METHODS
Gastroesophageal reflux (GERD) patients with insufficient symptom control despite twice daily proton pump inhibitor (PPI) underwent a piecemeal multiband mucosectomy of 50% of the circumference of the esophago-gastric-junction (EGJ), extending 2cm into the cardia. The primary endpoint was the total number of reflux episodes during 24-h pH-impedance studies.
RESULTS
11 patients were treated (8 men, age 37 (32-57) years), one patient is lost to follow-up after treatment. ARMS reduced the total number of reflux episodes from 74 (50-82) to 37 (28-66) p=0.008) and total acid exposure from 8.7% (6.4-12.7) to 5.3% (3.5-6.7) (p=0.008). Treatment reduced the number of transient lower esophageal sphincter relaxations (TLESRs) (from 4 (1-8) to 2 (1-4), p=0.027) during a 90-minute postprandial period. Reflux symptoms were reduced substantially (from 3.6 (3.6-3.9) to 1.6 (0.7-2.7), p=0.007). Treatment did not increase dysphagia (Brief Esophageal Dysphagia Questionnaire)of 8.2 (±7.3) to 8.5 (±6.5) (p=0.879). Impedance planimetry showed no changes in EGJ distensibility after treatment (4.4 (±2.1) mm2/mmHg to 4.3 (±2.2) mm2/mmHg), p=0.952). One delayed post-procedural bleeding (10%, (1/10)) occurred requiring repeat endoscopy, no strictures developed.
CONCLUSION
ARMS is an effective treatment option in PPI refractory GERD patients reducing acid exposure, reflux episodes and symptoms. While its working mechanism could not be explained by a difference in distensibility, a reduction in TLSERs might play a role.
PubMed: 38802103
DOI: 10.1055/a-2333-5232 -
The Journal of Nutrition May 2024Infant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps that may impact protein...
BACKGROUND
Infant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps that may impact protein digestion and subsequent amino acid (AA) absorption.
OBJECTIVES
The objective was to understand the impact of the protein ingredient quality within IFs on postprandial plasma AA profiles.
METHODS
Four isonitrogenous and isocaloric IFs were produced at a semi-industrial scale using whey proteins from different origins (cheese compared with ideal whey) and denaturation levels (IF-A, -B, -C), and caseins with different supramolecular organizations (IF-C, -D). Ten Yucatan minipiglets (12- to 27-d-old) were used as a human infant model and received each IF for 3 d according to a Williams Latin square followed by a 2-d wash-out period. Jugular plasma was regularly sampled from 10 min preprandial to 4 h postprandial on the third day to measure free AAs, urea, insulin, and glucose concentrations. Data were statistically analyzed using a mixed linear model with diet (IFs), time, and sex as fixed factors and piglet as random factor.
RESULTS
IFs made with cheese whey (IF-A and -B) elicited significantly higher plasma total and essential AA concentrations than IFs made with ideal whey (IF-C and -D), regardless of the pre- and postprandial times. Most of the differences observed postprandially were explained by AA homeostasis modifications. IFs based on cheese whey induced an increased plasma concentration of Thr due to both a higher Thr content in these IFs and a Thr-limiting degrading capability in piglets. The use of a nonmicellar casein ingredient led to reduced plasma content of AA catabolism markers (IF-D compared with IF-C).
CONCLUSIONS
Overall, our results highlight the importance of the protein ingredient quality (composition and structure) within IFs on neonatal plasma AA profiles, which may further impact infant protein metabolism.
PubMed: 38801861
DOI: 10.1016/j.tjnut.2024.05.009