A randomized double blind placebo controlled trial to assess the safety and efficacy of a patented fenugreek (Trigonella foenum-graecum) seed extract in Type 2 diabetics.

Background: Fenugreek plant (Trigonella foenum-graecum) 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.

Retrospective observational study on real world use of the Minimed™ 780G automated insulin delivery system: Impact of the settings on autocorrection and omitted meal boluses.

INTRODUCTION: The Medtronic MiniMed™ 780G (MM780G) system uses an algorithm that includes autocorrection bolus (AB) delivery. This study evaluates the impact of omitted meal boluses and the system settings, glucose target and active insulin time (AIT), on the AB. METHOD: Retrospective observational study on data uploaded by all MiniMed 780G users in our healthcare area, obtained through the remote monitoring platform Care Connect, from April to August 2023. Downloads with a sensor usage time <95% were excluded. RESULTS: 235 downloads belonging to 235 users were analysed. AB delivery was significantly higher at 2 h AIT (36.08 ±â€¯13.17%) compared to the rest of settings (2.25-4 h) (26.43 ±â€¯13.2%) (p < 0.001). AB differences based on the glucose target were not found. Patients with <3 meal boluses per day had higher AB delivery (46.91 ±â€¯19.00% vs 27.53 ±â€¯11.54%) (p < 0.001) and had more unfavourable glucometric parameters (GMI 7.12 ±â€¯0.45%, TIR 67.46 ±â€¯12.89% vs GMI 6.78 ±â€¯0.3%, TIR 76.51 ±â€¯8.37%) (p < 0.001). However, the 2-h AIT group presented similar TAR, TIR and GMI regardless of the number of meal boluses. CONCLUSION: The fewer user-initiated boluses, the greater the autocorrection received. The active insulin time of 2 h entails a more active autocorrection pattern that makes it possible to more effectively compensate for the omission of meal boluses without increasing hypoglycaemias.

Polyphenols mediated attenuation of diabetes associated cardiovascular complications: A comprehensive review.

Background: Diabetes mellitus is a common chronic metabolic disorder that is characterized by increased levels of glucose for prolonged periods of time. Incessant hyperglycemia leads to diabetic complications such as retinopathy, nephropathy, and neuropathy, and cardiovascular complications such as ischemic heart disease, peripheral vascular disease, diabetic cardiomyopathy, stroke, etc. There are many studies that suggest that various polyphenols affect glucose homeostasis and can help to attenuate the complications associated with diabetes. Objective: This review focuses on the possible role of various dietary polyphenols in palliating diabetes-induced cardiovascular complications. This review also aims to give an overview of the interrelationship among ROS production (due to diabetes), inflammation, glycoxidative stress, and cardiovascular complications as well as the anti-hyperglycemic effects of dietary polyphenols. Methods: Various scientific databases including Scopus, Web of Science, Google Scholar, PubMed, Science Direct, Springer Link, and Wiley Online Library were used for searching articles that complied with the inclusion and exclusion criteria. Results: This review lists several polyphenols based on various pre-clinical and clinical studies that have anti-hyperglycemic potential as well as a protective function against cardiovascular complications. Conclusion: Several pre-clinical and clinical studies suggest that various dietary polyphenols can be a promising intervention for the attenuation of diabetes-associated cardiovascular complications.

Postprandial effects following a semielemental critical-care diet lead to changes in uric acid, bile acids, and glucose in the central bearded dragon (Pogona vitticeps).

OBJECTIVE: To assess the prandial effects of a semielemental diet on plasma uric acid, bile acid, and glucose concentrations in the central bearded dragon (Pogona vitticeps). ANIMALS: 13 healthy adult male bearded dragons. METHODS: Following a 72-hour fasting period, blood was collected to measure preprandial uric acid, bile acid, and glucose concentrations. The animals were then gavage fed 1.2% body weight of an omnivore critical-care diet containing 20% protein, 9.5% fat, 2.5% fiber, and 2.39 kcal/mL. Blood was collected for repeat concentrations at 4 and 24 hours. RESULTS: Median (IQR) uric acid concentration (mg/dL) increased from 3.8 preprandial (2.8 to 4.3) to 4.7 4 hours postprandial (4 to 7; P = .0001). Median (IQR) bile acid concentration (mg/dL) increased from 1.8 preprandial (1 to 3.4) to 9.5 24 hours postprandial (5.6 to 10.4; P = .004). Median (IQR) glucose concentration (mg/dL) was 209 at time 0 (193 to 216), 287 at 4 hours (258 to 312), and 393 at 24 hours (361 to 464). Significant increases were seen between pre- and 4-hours-postprandial (P < .0001), pre- and 24-hours-postprandial (P < .0001), and 4-hours- and 24-hours-postprandial (P < .0001) glucose concentrations. CLINICAL RELEVANCE: Results suggest that postprandial status and diet composition should be considered during the interpretation of some biochemical analytes in the bearded dragon.

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

The Impact of Time-Restricted Meal Intake on Glycemic Control and Weight Management in Type 2 Diabetes Mellitus Patients: An 18-Month Longitudinal Study.

AIMS: This study aimed to investigate the impact of time-restricted meal intake (TRM) on anthropometric and biochemical parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 400 patients diagnosed with T2DM were selected from the Endocrinology Department at King George's Medical University (KGMU), Lucknow, based on the American Diabetes Association (ADA) guidelines and specific criteria. A total of 127 patients were lost to follow-up, resulting in 273 patients who completed the study. The patients were randomly assigned to two groups: the TRM group (consenting to have an early dinner at 7 pm) and the control group (non-TRM/late-night eater group). Baseline data were recorded, and follow-up assessments were conducted at six months, 12 months, and 18 months. Informed consent was obtained, and a diet chart was regularly maintained and updated. RESULTS:  The TRM group experienced a significant weight loss of 3.88 kg (5.45%) and a substantial reduction in BMI by 1.5 units (5.26%). In contrast, the non-TRM/control group had smaller reductions in weight (1.36 kg, 1.77%) and BMI (0.5 units, 1.65%). TRM group showed significant reductions in fasting blood sugar levels by 33.9 mg/dl (21.17%), postprandial blood sugar levels by 94.6 mg/dl (38.88%), and glycosylated hemoglobin (HbA1c) levels by 1.37 (15.87%). These improvements were significantly greater than the reductions observed in the control group, which had decreases of 29.3 mg/dl (17.85%) in fasting blood sugar levels, 41.6 mg/dl (16.84%) in postprandial blood sugar levels, and 0.59 (6.89%) in HbA1c levels. CONCLUSION: Our findings underscore the potential of TRM as an effective strategy for weight management and glycemic control in patients with T2DM, even in a long-term context. These results support time-restricted eating as a sustainable lifestyle modification for managing chronic metabolic diseases.

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry.

Introduction: Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays. Method: A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary. Results: Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels. Discussion: This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.

The Association of Macronutrient Consumption and BMI to Exhaled Carbon Dioxide in Lumen Users: Retrospective Real-World Study.

BACKGROUND: Metabolic flexibility is the ability of the body to rapidly switch between fuel sources based on their accessibility and metabolic requirements. High metabolic flexibility is associated with improved health outcomes and a reduced risk of several metabolic disorders. Metabolic flexibility can be improved through lifestyle changes, such as increasing physical activity and eating a balanced macronutrient diet. Lumen is a small handheld device that measures metabolic fuel usage through exhaled carbon dioxide (CO2), which allows individuals to monitor their metabolic flexibility and make lifestyle changes to enhance it. OBJECTIVE: This retrospective study aims to examine the postprandial CO2 response to meals logged by Lumen users and its relationship with macronutrient intake and BMI. METHODS: We analyzed deidentified data from 2607 Lumen users who logged their meals and measured their exhaled CO2 before and after those meals between May 1, 2023, and October 18, 2023. A linear mixed model was fitted to test the association between macronutrient consumption, BMI, age, and gender to the postprandial CO2 response, followed by a 2-way ANOVA. RESULTS: The model demonstrated significant associations (P<.001) between CO2 response after meals and both BMI and carbohydrate intake (BMI: ß=-0.112, 95% CI -0.156 to -0.069; carbohydrates: ß=0.046, 95% CI 0.034-0.058). In addition, a 2-way ANOVA revealed that higher carbohydrate intake resulted in a higher CO2 response compared to low carbohydrate intake (F2,2569=24.23; P<.001), and users with high BMI showed modest responses to meals compared with low BMI (F2,2569=5.88; P=.003). CONCLUSIONS: In this study, we show that Lumen's CO2 response is influenced both by macronutrient consumption and BMI. The results of this study highlight a distinct pattern of reduced metabolic flexibility in users with obesity, indicating the value of Lumen for assessing postprandial metabolic flexibility.

Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist.

INTRODUCTION: We assessed the effect of the prandial state on the pharmacokinetics, safety, and tolerability of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide 1 receptor agonist (GLP-1 RA), in two studies (A and B). METHODS: Study A and study B were phase 1, randomized, crossover studies in healthy adults aged 18-65 years and 21-70 years, respectively. Participants received single (3 mg, study A) or multiple (16 mg, study B) oral doses of orforglipron under fasted and fed conditions. Blood samples were collected pre- and postdose to assess area under the concentration-time curve (AUC), maximum observed drug concentration (Cmax), time of Cmax (tmax), and half-life (t1/2) associated with terminal rate constant. AUC and Cmax were analyzed using a linear mixed-effects model. Treatment differences were presented as ratios of geometric least squares means (GLSM). Treatment-emergent adverse events (TEAEs), adverse events of special interest, and serious adverse events were assessed. RESULTS: Study A included 12 participants (mean age 45.0 years; male 66.7%); study B included 34 participants (mean age 42.8 years; male 88.2%). GLSM AUC and Cmax were lower by 23.7% and 23.2% in study A, and 17.6% and 20.9% in study B, in the fed versus fasted states, respectively. In both studies, t1/2 and median tmax were comparable between fed and fasted states. The majority of TEAEs in both studies were gastrointestinal tract-related conditions. No serious adverse events or deaths were reported in either study. CONCLUSION: The observed pharmacokinetic differences due to the prandial state are unlikely to contribute to clinically meaningful differences in the efficacy of orforglipron. The safety profile was consistent with the known profiles of other GLP-1 RAs. Given the absence of prandial restrictions, orforglipron may emerge as a convenient oral treatment option for patients with type 2 diabetes or obesity. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03929744 and NCT05110794.

Real-world management of chronic and postprandial hyperkalemia in CKD patients treated with patiromer: a single-center retrospective study.

INTRODUCTION: Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. METHODS: We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2 h after the main meal for the evaluation of postprandial potassium concentrations. RESULTS: Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41 mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36 mmol/L; p = 0.15). CONCLUSIONS: In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.

Delayed prandial insulin boluses are an important determinant of blood glucose control and relate to fear of hypoglycemia in people with type 1 diabetes on advanced technologies.

AIMS: Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH). METHODS: In the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH. RESULTS: Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1-23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045). CONCLUSIONS: In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia.

Synthesis and Biological Evaluation of Some New 3-Aryl-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones and 3-Aryl-2-(benzylthio)quinazolin-4(3H)-ones as Antioxidants; COX-2, LDHA, α-Glucosidase and α-Amylase Inhibitors; and Anti-Colon Carcinoma and Apoptosis-Inducing Agents.

Oxidative stress, COX-2, LDHA and hyperglycemia are interlinked contributing pathways in the etiology, progression and metastasis of colon cancer. Additionally, dysregulated apoptosis in cells with genetic alternations leads to their progression in malignant transformation. Therefore, quinazolinones 3a-3h and 5a-5h were synthesized and evaluated as antioxidants, enzymes inhibitors and cytotoxic agents against LoVo and HCT-116 cells. Moreover, the most active cytotoxic derivatives were evaluated as apoptosis inducers. The results indicated that 3a, 3g and 5a were efficiently scavenged DPPH radicals with lowered IC50 values (mM) ranging from 0.165 ± 0.0057 to 0.191 ± 0.0099, as compared to 0.245 ± 0.0257 by BHT. Derivatives 3h, 5a and 5h were recognized as more potent dual inhibitors than quercetin against α-amylase and α-glucosidase, in addition to 3a, 3c, 3f and 5b-5f against α-amylase. Although none of the compounds demonstrated a higher efficiency than the reference inhibitors against COX-2 and LDHA, 3a and 3g were identified as the most active derivatives. Molecular docking studies were used to elucidate the binding affinities and binding interactions between the inhibitors and their target proteins. Compounds 3a and 3f showed cytotoxic activities, with IC50 values (µM) of 294.32 ± 8.41 and 383.5 ± 8.99 (LoVo), as well as 298.05 ± 13.26 and 323.59 ± 3.00 (HCT-116). The cytotoxicity mechanism of 3a and 3f could be attributed to the modulation of apoptosis regulators (Bax and Bcl-2), the activation of intrinsic and extrinsic apoptosis pathways via the upregulation of initiator caspases-8 and -9 as well as executioner caspase-3, and the arrest of LoVo and HCT-116 cell cycles in the G2/M and G1 phases, respectively. Lastly, the physicochemical, medicinal chemistry and ADMET properties of all compounds were predicted.

Post-prandial secretion of glucagon-like peptide-2 (GLP-2) after carbohydrate-, fat- or protein enriched meals in healthy subjects.

Glucagon-like peptide 2 (GLP-2) is an important regulator of intestinal growth and function. In adherable mixed meals the macronutrient composition with the best potential for stimulating GLP-2 secretion is not known. We compared the effect of 3 iso-energetic meals, where approximately 60 % of the energy ratio was provided as either carbohydrate, fat, or protein, respectively, on the post-prandial endogenous GLP-2 secretion. The responses were compared to secretion profiles of peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP). Ten healthy subjects were admitted on three occasions, at least a week apart, after a night of fasting. In an open-label, crossover design, they were randomized to receive a high carbohydrate (HC), high fat (HF) or high protein (HP) meal. The meals were approximately ∼3.9 MJ. Venous blood was collected for 240 min, and plasma concentrations of GLP-2, GIP and PYY were measured with specific radioimmunoassays. Mean GLP-2 levels peaked already at 30 min for the HC meal, however the HP meal induced the highest mean GLP-2 peaking levels, resulting in significantly higher mean GLP-2 area under the curve (AUC) from baseline of 7279 pmol*min/L, 95 %-CI [6081;8477] compared to the HC meal: 4764 pmol*min/L, 95 %-CI [3498;6029], p = 0.020 and the HF meal: 4796 pmol*min/L, [3385;6207], p = 0.011. Findings were similar for the PYY. The HC meal provided a greater AUC for GIP compared to the HP- and HF meals. The HP meal was most effective with respect to stimulation of the postprandial GLP-2 and PYY secretion, whereas the HC meal was more effective for GIP.

Insights on the Hypoglycemic Potential of Crocus sativus Tepal Polyphenols: An In Vitro and In Silico Study.

Post-prandial hyperglycemia typical of diabetes mellitus could be alleviated using plant-derived compounds such as polyphenols, which could influence the activities of enzymes involved in carbohydrate digestion and of intestinal glucose transporters. Here, we report on the potential anti-hyperglycemic effect of Crocus sativus tepals compared to stigmas, within the framework of valorizing these by-products of the saffron industry, since the anti-diabetic properties of saffron are well-known, but not those of its tepals. In vitro assays showed that tepal extracts (TE) had a greater inhibitory action than stigma extracts (SE) on α-amylase activity (IC50: TE = 0.60 ± 0.09 mg/mL; SE = 1.10 ± 0.08 mg/mL; acarbose = 0.051 ± 0.07) and on glucose absorption in Caco-2 differentiated cells (TE = 1.20 ± 0.02 mg/mL; SE = 2.30 ± 0.02 mg/mL; phlorizin = 0.23 ± 0.01). Virtual screening performed with principal compounds from stigma and tepals of C. sativus and human pancreatic α-amylase, glucose transporter 2 (GLUT2) and sodium glucose co-transporter-1 (SGLT1) were validated via molecular docking, e.g., for human pancreatic α-amylase, epicatechin 3-o-gallate and catechin-3-o-gallate were the best scored ligands from tepals (-9.5 kcal/mol and -9.4 kcal/mol, respectively), while sesamin and episesamin were the best scored ones from stigmas (-10.1 kcal/mol). Overall, the results point to the potential of C. sativus tepal extracts in the prevention/management of diabetes, likely due to the rich pool of phytocompounds characterized using high-resolution mass spectrometry, some of which are capable of binding and interacting with proteins involved in starch digestion and intestinal glucose transport.

Microinjection of NMDA-neurotoxin into the superior salivatory nucleus of the rat: Short-term secretory and long-term drinking behavior effects.

The anatomical location of the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the submandibular-sublingual salivary glands, is well established in rats. However, as of yet there is no functional data that convincingly shows the secretory nature of this region. Previous studies have not been able to differentiate between interventions on efferent or afferent fibers connected to the SSN versus interventions on the salivatory nucleus itself. Taking advantage of the fact that salivatory neurons express NMDA-receptors on their somas, in the present study SSN cell bodies were activated and lesioned sequentially by means of intracerebral application of NMDA-neurotoxin. In exp. 1 two effects, a short- and a long-term effect, were observed following NMDA administration. The first effect was high submandibular-sublingual saliva secretion during the hour following administration of the neurotoxin and the second was a profound change in drinking behavior once the animals recovered from the lesion. Thus, on post-surgery days 16, 17 and 18, the rats exhibited hyperdipsia in the presence of dry food but not in the presence of wet food. In expt. 2 results showed that saliva hypersecretion observed after NMDA-microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after the administration of dihydroergotamine plus propranolol (α and ß-adrenergic blockers, respectively). From a functional perspective, these data suggest that the somata of the parvocellular reticular formation control the secretory activity of the submandibular-sublingual salivary glands and thus constitute the SSN.

No acute hyperglycemia induced impairment in brachial artery flow-mediated dilation before or after aerobic exercise training in young recreationally active males.

There is some evidence that transient endothelial dysfunction induced by acute hyperglycemia may be attenuated by a single bout of aerobic exercise. However, the impact of aerobic exercise training on acute hyperglycemia-induced endothelial dysfunction has not been explored. The purpose of this study was to determine the impact of aerobic exercise training on the endothelial function response to acute hyperglycemia. Brachial artery flow-mediated dilation (FMD) was assessed in 24 healthy males (21 ± 1 years) pre-, 60 and 90 min post ingestion of 75 g of glucose. Participants completed a four-week control (CON; n = 13) or exercise training (EX; n = 11) intervention. The EX group completed four weeks of cycling exercise (30 min, 4×/week at 65% work rate peak). Cardiorespiratory fitness ([Formula: see text]O2peak) increased and resting HR decreased in EX, but not CON post-intervention (p < 0.001). Glucose and insulin increased (p < 0.001) following glucose ingestion, with no significant difference pre- and post-intervention. In contrast to previous research, FMD was unaffected by glucose-ingestion, pre- and post-intervention in both groups. In conclusion, acute hyperglycemia did not impair endothelial function, before or after exercise training. Relatively high baseline fitness ([Formula: see text]O2peak ~ 46 mL/kg/min) and young age may have contributed to the lack of impairment observed. Further research is needed to examine the impact of exercise training on hyperglycemia-induced impairments in endothelial function in sedentary males and females.

Continuous glucose monitoring in a healthy population: understanding the post-prandial glycemic response in individuals without diabetes mellitus.

Continuous glucose monitoring has become a common adjunct in the management of Diabetes Mellitus. However, there has been a recent trend among individuals without diabetes using these devices as a means of monitoring their health. The increased visibility of glucose data has allowed users to study the effect lifestyle has upon post-prandial glucose levels. Although post-prandial hyperglycemia is well understood in the setting of diabetes, its impact in individuals without diabetes is less well defined. This article reviews the factors which contribute to post-prandial hyperglycemia in individuals without diabetes and how the data obtained from continuous glucose monitoring can be used to improve an individual's metabolic health.

Syncope in Aortic Stenosis: Not Always What It Seems.

Aortic stenosis is a common valvular pathology and may also have atypical presentations outside the classic triad of chest pain, syncope, and shortness of breath. Some patients may not present with the symptoms of the triad. This patient instead presented with syncope and vomiting. Statistically, the most common cause of syncope at rest in the setting of aortic stenosis is due to an arrhythmia rather than the valve itself limiting cardiac output. In a comorbid Alzheimer's patient who has developed hyperorality, postprandial hypotension can also result in syncope at rest. Therefore, syncope at rest should raise alarm for nonvalvular etiologies such as arrhythmia. This case study also aims to establish an association between syncope at rest and hyperorality in the setting of aortic stenosis, a first study so far. Additionally, it highlights an unusual presentation of aortic stenosis where syncope occurs at rest associated with vomit in the absence of chest pain or shortness of breath.

Effects of low-GI biscuits as pre-loads or mid-meal snacks on post-prandial glycemic excursions in women with recent gestational diabetes: A protocol for a randomized crossover trial and an extended tailored intervention.

Background: Increased post-prandial glycemic excursions contribute to the development of diabetes and have been observed in women with recent gestational diabetes mellitus (GDM) and with normal glucose tolerance at post-partum. As a convenient meal replacement, low-GI biscuits are helpful for improving glycemic excursions in patients with type 2 diabetes. However, it is unknown whether low-GI biscuits as pre-loads or mid-meal snacks have a better effect in diminishing post-prandial glycemic excursions from the individual level in women with recent GDM. Therefore, the aim of this trial is to tailor a better dietary strategy utilizing low-GI biscuits (Fitmeal) to improve post-prandial glycemic excursions through within-subject comparison in such a population and observe the long-term effect of a tailored dietary approach in glycemic control. Methods: We have designed a two-phase trial including a randomized, crossover, non-blinded trial in the first phase, followed by a 4-week tailored intervention in the second phase. A total of 52 post-partum women with recent GDM will be allocated into four meal plans: (1) Fitmeal pre-load 30 min before standard lunch meal (P+L), (2) Fitmeal as a mid-meal snack 2 h before standard lunch meal (S+L), (3) isocaloric standard control with co-ingestion of Fitmeal and standard lunch meal (CL) at the same time, and (4) placebo control with 200 ml of water taken 30 min before standard lunch meal (W + L), on four consecutive days. Acute post-prandial glycemic response (PGR) measured by continuous glucose monitoring (CGM) will be compared among the four meals. In the second phase, all participants will receive a 4-week tailored intervention using Fitmeal as pre-loads or mid-meal snacks based on within-subject PGR results from the first phase. Glycemic metrics, dietary behaviors, and psychosocial factors (e.g., quality of life, self-efficacy, perceived stress, and depression) will be examined at baseline and end-point. Discussion: This trial is expected to optimize the use of low-GI biscuits as pre-loads or mid-meal snacks in improving individual post-prandial glycemic excursions among women with recent GDM. Furthermore, the findings of this study will provide novel information on how to deliver an effective dietary intervention at the individual level and guide future clinical practice of medical nutrition therapy for diabetes prevention. Trial registration number: Chinese clinical trial registry, ChiCTR2200060923.