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Contemporary Clinical Trials Feb 2024Aging is associated with gut dysbiosis, low-grade inflammation, and increased risk of type 2 diabetes (T2D). Prediabetes, which increases T2D and cardiovascular disease...
BACKGROUND
Aging is associated with gut dysbiosis, low-grade inflammation, and increased risk of type 2 diabetes (T2D). Prediabetes, which increases T2D and cardiovascular disease risk, is present in 45-50% of mid-life adults. The gut microbiota may link ultra-processed food (UPF) with inflammation and T2D risk.
METHODS
Following a 2-week standardized lead-in diet (59% UPF), adults aged 40-65 years will be randomly assigned to a 6-week diet emphasizing either UPF (81% total energy) or non-UPF (0% total energy). Measurements of insulin sensitivity, 24-h and postprandial glycemic control, gut microbiota composition/function, fecal short chain fatty acids, intestinal inflammation, inflammatory cytokines, and vascular function will be made before and following the 6-week intervention period. Prior to recruitment, menus were developed in order to match UPF and non-UPF conditions based upon relevant dietary factors. Menus were evaluated for palatability and costs, and the commercial additive content of study diets was quantified to explore potential links with outcomes.
RESULTS
Overall diet palatability ratings were similar (UPF = 7.6 ± 1.0; Non-UPF = 6.8 ± 1.5; Like Moderately = 7, Like Very Much = 8). Cost analysis (food + labor) of the 2000 kcal menu (7-d average) revealed lower costs for UPF compared to non-UPF diets ($20.97/d and $40.23/d, respectively). Additive exposure assessment of the 2000 kcal UPF diet indicated that soy lecithin (16×/week), citric acid (13×/week), sorbic acid (13×/week), and sodium citrate (12×/week) were the most frequently consumed additives.
CONCLUSIONS
Whether UPF consumption impairs glucose homeostasis in mid-life adults is unknown. Findings will address this research gap and contribute information on how UPF consumption may influence T2D development.
Topics: Adult; Humans; Food, Processed; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Inflammation; Homeostasis; Glucose; Diet; Fast Foods
PubMed: 38184104
DOI: 10.1016/j.cct.2024.107427 -
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 -
Molecular Metabolism May 2024In the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes,...
OBJECTIVE
In the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes, for systemic energy delivery. These digestion products can also bind receptors on endocrine cells to stimulate the release of hormones capable of influencing systemic energy metabolism. The initial phase of intestinal FA absorption involves the acylation of FAs to acyl-CoA by the acyl-CoA long chain synthetase (ACSL) enzymes. ACSL5 is abundantly expressed in the small intestinal epithelium where it is the major ACSL isoform, contributing approximately 80% of total ACSL activity. In mice with whole body deficiency of ACSL5, the rate of dietary fat absorption is reduced and energy expenditure is increased. However, the mechanisms by which intestinal ACSL5 contributes to intestinal FA metabolism, enteroendocrine signaling, and regulation of energy expenditure remain undefined. Here, we test the hypothesis that intestinal ACSL5 regulates energy metabolism by influencing dietary fat absorption and enteroendocrine signaling.
METHODS
To explore the role of intestinal ACSL5 in energy balance and intestinal dietary fat absorption, a novel mouse model of intestine specific ACSL5 deficiency (ACSL5) was generated by breeding ACSL5 floxed (ACSL5) to mice harboring the tamoxifen inducible, villin-Cre recombinase. ACSL5 and control, ACSL5 mice were fed chow (low in fat) or a 60% high fat diet (HFD), and metabolic phenotyping was performed including, body weight, body composition, insulin and glucose tolerance tests, energy expenditure, physical activity, and food intake studies. Pair-feeding studies were performed to determine the role of food intake in regulating development of obesity. Studies of dietary fat absorption, fecal lipid excretion, intestinal mucosal FA content, and circulating levels of glucagon like peptide 1 (GLP-1) and peptide YY (PYY) in response to a TAG challenge were performed. Treatment with a GLP-1 receptor antagonist was performed to determine the contribution of GLP-1 to acute regulation of food intake.
RESULTS
We found that ACSL5 mice experienced rapid and sustained protection from body weight and fat mass accumulation during HFD feeding. While intestine specific deficiency of ACSL5 delayed gastric emptying and reduced dietary fat secretion, it did not result in increased excretion of dietary lipid in feces. Energy expenditure and physical activity were not increased in ACSL5 mice. Mice deficient in intestinal ACSL5 display significantly reduced energy intake during HFD, but not chow feeding. When HFD intake of control mice was matched to ACSL5 during pair-feeding studies, no differences in body weight or fat mass gain were observed between groups. Postprandial GLP-1 and PYY were significantly elevated in ACSL5 mice secondary to increased FA content in the distal small intestine. Blockade of GLP-1 signaling by administration of a long-acting GLP-1 receptor antagonist partially restored HFD intake of ACSL5.
CONCLUSIONS
These data indicate that intestinal ACSL5 serves as a critical regulator of energy balance, protecting mice from diet-induced obesity exclusively by increasing satiety and reducing food intake during HFD feeding. The reduction in food intake observed in ACSL5 mice is driven, in part, by increased postprandial GLP-1 and PYY secretion. These effects are only observed during HFD feeding, suggesting that altered processing of dietary fat following intestinal ACSL5 ablation contributes to GLP-1 and PYY mediated increases in satiety.
Topics: Animals; Coenzyme A Ligases; Mice; Obesity; Diet, High-Fat; Male; Glucagon-Like Peptide 1; Peptide YY; Mice, Inbred C57BL; Eating; Postprandial Period; Energy Metabolism; Mice, Knockout
PubMed: 38499083
DOI: 10.1016/j.molmet.2024.101918 -
Endocrine Journal Nov 2023Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and...
Residual pancreatic endocrine function is important for maintaining metabolic status after pancreatectomy and is closely related to patient nutritional status and prognosis. In contrast to insulin secretion, the significance of glucagon secretion following pancreatectomy remains unclear. In this study, we assessed the changes in pancreatic glucagon secretion during pancreatectomy to determine their pathophysiological significance. We evaluated glucagon and insulin secretion using a liquid meal tolerance test before and after pancreatectomy in patients scheduled to undergo pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). After pancreatectomy, fasting plasma glucagon levels were significantly decreased in both the PD (n = 10) and DP (n = 5) groups (PD: from 18.4 to 10.5 pg/mL, p = 0.037; DP: from 21.0 to 12.1 pg/mL, p = 0.043), whereas postprandial plasma glucagon levels were not changed. In the liquid meal tolerance test after pancreatectomy, 60-min plasma glucagon levels and the area under the curve (AUC) for 0-120 min of PD were significantly higher than those for DP (60-min plasma glucagon: PD 49.0 vs. DP 21.7 pg/mL, p = 0.040; AUC: PD 4,749 vs. DP 3,564 μg min/mL, p = 0.028). Postoperative plasma glucose, serum insulin, and serum C-peptide levels during the liquid meal tolerance test were not significantly different between the two groups. Although fasting plasma glucagon levels decreased, postprandial glucagon responses were maintained after both PD and DP. The difference in residual meal-stimulated glucagon response between PD and DP suggests that a relative excess of postprandial glucagon is involved in the postoperative nutritional status after PD through its impact on systemic metabolic status.
Topics: Humans; Glucagon; Pancreatectomy; Blood Glucose; Pancreas; Insulin Secretion; Insulin; Postprandial Period
PubMed: 37704414
DOI: 10.1507/endocrj.EJ23-0032 -
JMIR Research Protocols Aug 2023Prolonged bouts of sedentary time, independent from the time spent in engaging in physical activity, significantly increases cardiometabolic risk. Nonetheless, the...
Effects of Increased Standing and Light-Intensity Physical Activity to Improve Postprandial Glucose in Sedentary Office Workers: Protocol for a Randomized Crossover Trial.
BACKGROUND
Prolonged bouts of sedentary time, independent from the time spent in engaging in physical activity, significantly increases cardiometabolic risk. Nonetheless, the modern workforce spends large, uninterrupted portions of the day seated at a desk. Previous research suggests-via improved cardiometabolic biomarkers-that this risk might be attenuated by simply disrupting sedentary time with brief breaks of standing or moving. However, this evidence is derived from acute, highly controlled laboratory experiments and thus has low external validity.
OBJECTIVE
This study aims to investigate if similar or prolonged cardiometabolic changes are observed after a prolonged (2-week) practice of increased brief standing and moving behaviors in real-world office settings.
METHODS
This randomized crossover trial, called the WorkWell Study, will compare the efficacy of two 2-week pilot intervention conditions designed to interrupt sitting time in sedentary office workers (N=15) to a control condition. The intervention conditions use a novel smartphone app to deliver real-time prompts to increase standing (STAND) or moving (MOVE) by an additional 6 minutes each hour during work. Our primary aim is to assess intervention-associated improvements to daily postprandial glucose using continuous glucose monitors. Our secondary aim is to determine whether the interventions successfully evoke substantive positional changes and light-intensity physical activity (LPA). Other outcomes include the feasibility and acceptability of the intervention conditions, fasting blood glucose concentration, femoral artery flow-mediated dilation (f-FMD), and systolic and diastolic blood pressure.
RESULTS
The trial is ongoing at the time of submission.
CONCLUSIONS
This study is a novel, randomized crossover trial designed to extend a laboratory-based controlled study design into the free-living environment. By using digital health technologies to monitor and prompt participants in real time, we will be able to rigorously test the effects of breaking up sedentary behavior over a longer period of time than is seen in traditional laboratory-based studies. Our innovative approach will leverage the strengths of highly controlled laboratory and free-living experiments to achieve maximal internal and external validity. The research team's multidisciplinary expertise allows for a broad range of biological measures to be sampled, providing robust results that will extend knowledge of both the acute and chronic real-life effects of increased standing and LPA in sedentary office workers. The WorkWell Study uses a rigorous transdisciplinary protocol that will contribute to a more comprehensive picture of the beneficial effects of breaking up sitting behavior.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04269070; https://clinicaltrials.gov/study/NCT04269070.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/45133.
PubMed: 37610800
DOI: 10.2196/45133 -
The American Journal of Clinical... Mar 2024Ketone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute ingestion of a ketone monoester, whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of myofibrillar protein synthesis rates in young males: a double-blind randomized trial.
BACKGROUND
Ketone bodies may have anabolic effects in skeletal muscle via their capacity to stimulate protein synthesis. Whether orally ingested exogenous ketones can stimulate postprandial myofibrillar protein synthesis (MyoPS) rates with and without dietary protein co-ingestion is unknown.
OBJECTIVES
This study aimed to evaluate the effects of ketone monoester intake and elevated blood β-hydroxybutyrate (β-OHB) concentration, with and without dietary protein co-ingestion, on postprandial MyoPS rates and mechanistic target of rapamycin complex 1 (mTORC1) pathway signaling.
METHODS
In a randomized, double-blind, parallel group design, 36 recreationally active healthy young males (age: 24.2 ± 4.1 y; body fat: 20.9% ± 5.8%; body mass index: 23.4 ± 2 kg/m) received a primed continuous infusion of L-[ring-H]-phenylalanine and ingested one of the following: 1) the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET+PRO). Blood and muscle biopsy samples were collected during basal and postprandial (300 min) conditions to assess β-OHB, glucose, insulin, and amino acid concentrations, MyoPS rates, and mTORC1 pathway signaling.
RESULTS
Capillary blood β-OHB concentration increased similarly during postprandial conditions in KET and KET+PRO, with both being greater than PRO from 30 to 180 min (treatment × time interaction: P < 0.001). Postprandial plasma leucine and essential amino acid (EAA) incremental area under the curve (iAUC) over 300 min was greater (treatment: both P < 0.001) in KET+PRO compared with PRO and KET. KET, PRO, and KET+PRO stimulated postprandial MyoPS rates (0-300 min) higher than basal conditions [absolute change: 0.020%/h; (95% CI: 0.013, 0.027%/h), 0.014%/h (95% CI: 0.009, 0.019%/h), 0.019%/h (95% CI: 0.014, 0.024%/h), respectively (time: P < 0.001)], with no difference between treatments (treatment: P = 0.383) or treatment × time interaction (interaction: P = 0.245). mTORC1 pathway signaling responses did not differ between treatments (all P > 0.05).
CONCLUSIONS
Acute oral intake of a ketone monoester, 10 g whey protein, or their co-ingestion in the overnight postabsorptive state elicit a similar stimulation of postprandial MyoPS rates in healthy young males. This trial was registered at clinicaltrials.gov as NCT04565444 (https://clinicaltrials.gov/study/NCT04565444).
Topics: Adult; Humans; Male; Young Adult; Dietary Proteins; Eating; Ketones; Mechanistic Target of Rapamycin Complex 1; Muscle, Skeletal; Postprandial Period; Whey Proteins; Double-Blind Method
PubMed: 38215886
DOI: 10.1016/j.ajcnut.2024.01.004 -
Annals of Medicine and Surgery (2012) Sep 2023Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes, is a chronic autoimmune condition in which the pancreas makes little or no insulin...
INTRODUCTION
Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes, is a chronic autoimmune condition in which the pancreas makes little or no insulin leading to resultant hyperglycemia. The incidence of type 1 diabetes in India is 0.26 per 1000 children.
MATERIALS AND METHODS
The author treated 25 patients with type 1 diabetes with autologous intrapancreatic stem cell therapy in the last 5 years. A group of 26 patients of type 1 diabetes with conventional treatment of insulin injections was put as a control group in the same period.
RESULTS
The results of the therapy group were substantially superior to the control group, which came statistically highly significant. The variable compared were weight gain, the daily requirement of insulin and its drop after therapy, the rise of C-peptide levels and drop in anti-glutamic acid decarboxylase antibody, drop in HbA1c levels, and drop in fasting and postprandial blood sugar.
DISCUSSION
When stem cells are given intravenously, the majority are engulfed by the lungs and only a small fraction is delivered to the pancreas. When injected into the pancreas, through its arterial blood supply, due to the larger size and irregular shape of stem cells, they are retained in tissue spaces and do not escape from the venous side, thus achieving far higher concentration in the pancreas compared to the intravenous route.
CONCLUSIONS
Intrapancreatic stem cell therapy for type 1 diabetes is safe, affordable, and effective. It has the potential to become a viable treatment option for type 1 diabetes patients.
PubMed: 37663700
DOI: 10.1097/MS9.0000000000000837 -
Journal of Applied Physiology... Jun 2024Feeding and resistance exercise stimulate myofibrillar protein synthesis (MPS) rates in healthy adults. This anabolic characterization of "healthy adults" has been...
Feeding and resistance exercise stimulate myofibrillar protein synthesis (MPS) rates in healthy adults. This anabolic characterization of "healthy adults" has been namely focused on males. Therefore, the purpose of this study was to examine the temporal responses of MPS and anabolic signaling to resistance exercise alone or combined with the ingestion of protein in postmenopausal females and compare postabsorptive rates with young females. Sixteen females [60 ± 7 yr; body mass index (BMI) = 26 ± 12 kg·m] completed an acute bout of unilateral resistance exercise before consuming either: a fortified whey protein supplement (WHEY) or water. Participants received primed continuous infusions of L-[-C]phenylalanine with bilateral muscle biopsies before and after treatment ingestion at 2 h and 4 h in nonexercised and exercised legs. Resistance exercise transiently increased MPS above baseline at 0-2 h in the water condition ( = 0.007). Feeding after resistance exercise resulted in a late phase (2-4 h) increase in MPS in the WHEY condition ( = 0.005). In both conditions, resistance exercise did not enhance the cumulative (0-4 h) MPS response. In the nonexercised leg, MPS did not differ at 0-2 h, 2-4 h, or 0-4 h of the measurement periods (all, > 0.05). Likewise, there were no changes in the phosphorylation of p70S6K, AMPKα, or total and phosphorylated yes-associated protein on Ser127. Finally, postabsorptive MPS was lower in premenopausal versus postmenopausal females ( = 0.023). Our results demonstrate that resistance exercise-induced changes in MPS are temporally regulated, but do not result in greater cumulative (0-4 h) MPS in postmenopausal women. An adequate quality and quantity of skeletal muscle is relevant to support physical performance and metabolic health. Muscle protein synthesis (MPS) is an established remodeling marker, which can be hypertrophic or nonhypertrophic. Importantly, protein ingestion and resistance exercise are two strategies that support healthy muscle by stimulating MPS. Our study shows postmenopause modulates baseline MPS that may diminish the MPS response to the fundamental anabolic stimuli of protein ingestion and resistance exercise in older females.
Topics: Humans; Female; Postmenopause; Resistance Training; Middle Aged; Postprandial Period; Myofibrils; Muscle Proteins; Whey Proteins; Muscle, Skeletal; Rest; Aged; Phenylalanine; Protein Biosynthesis; Dietary Supplements; Adult; Exercise; Phosphorylation
PubMed: 38385186
DOI: 10.1152/japplphysiol.00886.2023 -
Frontiers in Endocrinology 2023The aim of this study is to discuss the postpartum anxiety disorder and influencing factors in puerperae with gestational diabetes mellitus (GDM) to provide a clinical...
OBJECTIVE
The aim of this study is to discuss the postpartum anxiety disorder and influencing factors in puerperae with gestational diabetes mellitus (GDM) to provide a clinical basis for better early identification and intervention of adverse mood.
METHODS
Convenient sampling method was adopted to investigate 205 pregnant women as the observation group and 201 normal healthy pregnant women in the same period as the control group. The self-rating anxiety scale (SAS) was used to investigate and observe the respondents, evaluate the postpartum anxiety status of patients with GDM, and analyze the related influencing factors. Statistical analysis of the data was performed using SAS 3.0 software. A proposed P < 0.05 was considered as statistically significant.
RESULTS
Patients with GDM had a higher risk than normal maternal anxiety, related to years of education, triglycerides, 1-h postprandial blood glucose, and a history of induced abortion.
CONCLUSION
GDM can lead to the occurrence of postpartum anxiety, and the poor psychological state is not conducive to the maternal and infant health. Early identification and early intervention can reduce the harm caused by anxiety and promote the progress of maternal and infant health and clinical research.
Topics: Infant; Pregnancy; Humans; Female; Diabetes, Gestational; Postpartum Period; Puerperal Disorders; Anxiety; Anxiety Disorders
PubMed: 38089633
DOI: 10.3389/fendo.2023.1202884 -
The Journal of Clinical Endocrinology... Jul 2023Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear.
OBJECTIVE
To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function.
METHODS
This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured.
RESULTS
β-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133).
CONCLUSION
In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146.
Topics: Adult; Humans; Insulin; Diabetes Mellitus, Type 2; Whey Proteins; Kinetics; Single-Blind Method; Blood Glucose; Postprandial Period; Cross-Over Studies
PubMed: 36734166
DOI: 10.1210/clinem/dgad069