Reduction In Area Under The Curve Research Articles

Abstract 4116298: Once Weekly Utreglutide (GL0034), a Glucagon-like Peptide-1 Receptor Agonist, at 4 × 450 µg Doses Reduces Blood Pressure, Lipids, and Body Weight in Post-menopausal Females: A Phase I Study

Background: Utreglutide (GL0034), a novel, once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated significant reductions in body weight (BW) after a single dose ascending study in individuals with obesity . BW reductions after pharmacological treatment of obesity with GLP-1RA is associated with blood pressure (BP) lowering effects. Aim: This phase I study assessed the safety, tolerability, and cardio-metabolic effects of utreglutide after multiple ascending doses in post-menopausal female volunteers with overweight and obesity. Methods: In this randomized, double-blind, placebo-controlled study 12 post-menopausal female volunteers with overweight/obesity, aged 18 to 65 years old with a body mass index (BMI) ≥26 kg/m 2 were randomized (9:3) to subcutaneous utreglutide fixed doses (4 × 450 µg); or placebo once weekly for four weeks. Safety, tolerability, and key cardio-metabolic parameters were assessed. Biomarker measurements included oral glucose tolerance test (OGTT) insulin and glucose area under the curve (AUC), systolic- and diastolic BP, lipid profile (triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL), creatinine, potassium, BW and leptin. Results: Utreglutide was generally well tolerated and related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Reductions in OGTT AUCs of insulin ( p <0.05) and glucose ( p <0.01) were noted on Day 23 after four weeks treatment with Utreglutide. This was accompanied by a decrease ( p <0.001) in mean systolic and diastolic BP on Day 23 from baseline (BL). On Day 23, significant reductions in TC ( p <0.01), LDL ( p <0.05) and non-HDL ( p <0.05) were observed. BW reduction versus BL ( p <0.001) was 2.0 kg and 1.8 kg respectively on Day 29 and End of Study (EoS). Leptin levels significantly reduced from BL on Day 23 ( p< 0.01) and EoS ( p <0.001). No significant changes were observed for TG, creatinine and potassium (Table). Conclusions: Once weekly utreglutide dosing for four weeks at a dose of 450 µg in post-menopausal females with overweight and obesity, demonstrated clinically relevant reductions of systolic and diastolic BP. This was associated with improved performance of OGTT AUC of insulin and glucose, lipids, BW and leptin with an overall good tolerability and with potential to demonstrate cardio-metabolic benefits.

NIMG-46. UNDERSTANDING PERMEABILITY CHANGES IN VESTIBULAR SCHWANNOMAS AS PART OF THE DYNAMIC RESPONSE TO RADIOSURGERY USING GOLDEN-ANGLE RADIAL SPARSE PARALLEL IMAGING, A RETROSPECTIVE STUDY

Abstract Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on post contrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. Consecutive patients with vestibular schwannoma who underwent SRS between 2017-2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 12, and 24-36 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS, an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 12, and 24 months after SRS (corrected p < 0.05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak (p = 0.013) and AUC (p = 0.029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at median 62 months. These patients showed a strong correlation between changes in peak, AUC, and wash-in phase slope at 6 months and tumor volume at last follow-up. After SRS and loss of internal contrast uptake within the vestibular schwannomas, a slow vascular permeability dynamic found on GRASP studies persisted, suggesting the internal development of scar tissue. Moreover, the degree of reduction in GRASP parameters at 6 months positively predicted the degree of tumor regression long-term.

Effects of aerobic, resistance, and combined exercise training on body fat and glucolipid metabolism in inactive middle-aged adults with overweight or obesity: a randomized trial

MethodTwenty inactive males (BMI 27.67 ± 0.88 kg/m2, age 49.15 ± 2.58 years) participated in an eight-week were randomly assigned to one of three intervention groups (combined (CT), resistance (RT), and aerobic (AT)) exercise modalities to assess within-subject and between group changes in glycolipid profile. Data were analyzed using repeated measures ANCOVA.ResultPre-post mean values of body fat percentage (%BF), area under the curve (AUC), low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol (TC) decreased in all three groups. The main effect of exercise modality on the AUC (F (2, 26) = 10.577, P = 0.001, η2 = 0.569) was significant. Post-hoc analyses revealed that the RT group (-30.653 ± 6.766, p = 0.001) with 11.53% and the CT group (M = -0.896, SE = 3.347, P = 0.015) with 3.79% exhibited significantly greater reductions in AUC compared to the AT group. LDL levels showed significant different between groups (F (2, 26) = 6.33, p = 0.009, η2 = 0.442), specially significantly 3.7% lowered in AT (MD = 4.783, SE = 1.563, P = 0.002) and 3.79% lower in CT (MD = 4.57, SE = 1.284, P = 0.008) groups compared to the RT group. AT significantly reduced TC by 17.716 ± 5.705 mg/dL (p = 0.02) compared to RT, representing a 7.97% decrease.ConclusionExercise type significantly influences lipid profiles and glycemic control. Notably, both aerobic and combined training demonstrated a superior ability to modulate the lipid profile, and resistance training and combined training were more effective in reducing the AUC.Trial registrationMay, 31st 2024. Registration no: PACTR202405463745521 “Retrospectively registered”.

The Effect of Adding Protein to a Carbohydrate Meal on Postprandial Glucose and Insulin Responses: A Systematic Review and Meta-Analysis of Acute Controlled Feeding Trials

BackgroundProtein influences acute postprandial glucose and insulin responses, but the effects of dose, protein type, and health status are unknown. ObjectivesWe aimed to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers. MethodsWe searched MEDLINE, EMBASE, and Cochrane databases through 30 July, 2023 for acute, crossover trials comparing acute postprandial responses elicited by carbohydrate-containing test meals with and without added protein in adults without diabetes or with type 2 (T2DM) or type 1 (T1DM) diabetes mellitus. Group data were pooled separately using generic inverse variance with random-effects models and expressed as the ratio of means with 95% confidence interval. Risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. ResultsIn 154 trial comparisons of animal, dairy, and plant proteins (without diabetes, n = 22, 67, 32, respectively; T2DM, n = 14, 16, 3, respectively), each gram protein per gram available carbohydrate (g/g) reduced the glucose area under the curve (AUC) less in adults with T2DM than in those without diabetes (−10% compared with −50%, P < 0.05) but increased the insulin AUC similarly (+76% compared with +56%). In subjects without diabetes, each g/g of dairy and plant protein reduced glucose AUC by 52% and 55%, respectively, and increased the insulin AUC by 64% and 45%, respectively (all P < 0.05). Animal proteins significantly reduced the glucose AUC by 31% and increased the insulin AUC by 37% (pooled effects) but without a significant dose-response. In adults with T2DM, animal protein reduced the glucose AUC by 13% and increased the insulin AUC by 105%, with no significant dose-response. Dairy protein reduced the glucose AUC by 18% (no dose-response), but each g/g increased the insulin AUC by 34% (P < 0.05). In adults with T1DM, protein increased the glucose AUC by 40% (P < 0.05, n = 5). Data source (reported AUC compared with calculated AUC) and study methodology quality significantly modified some outcomes and contributed to high between-study heterogeneity. ConclusionsIn people without diabetes, adding dairy or plant protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose AUC and increases insulin AUC. Animal protein may slightly reduce the glucose AUC and may increase the insulin AUC. In people with T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein source.This study was registered at PROSPERO as CRD42022322090.

Advanced hybrid closed loop (artificial pancreas) and carbohydrate count in type 1 diabetes

BACKGROUND: Postprandial Glucose Excursion (PPGE) control is one of the goals of diabetes therapy. Patients should count meal carbohydrates but it is often inaccurate. Automated Advanced Hybrid Closed Loop (AHCL) systems may overcome carbohydrate count mistakes and aid to improve PPGE control. OBJECTIVE: To evaluate the effect of switching from manual Sensor Augmented Pump (SAP) to AHCL on PPGE in Type 1 Diabetic (T1D) subjects. METHODS: In 15 T1D patients using manual SAP, the Area Under the Curve (AUC) after breakfast, lunch and dinner was calculated for two weeks before (T0), immediately (T1) and 3 months (T2) after switching to 780 G AHCL system. Total Daily Dose (TDD), Time Above/Below/In Range (TAR, TBR, TIR), BMI, A1c, lipid profile and Treatment Satisfaction Questionnaire (DTSQ) were considered. RESULTS: A significant reduction in AUC was observed for breakfast and dinner at T2 and for lunch and dinner at T1. TIR increased, while TAR and TBR reduced significantly from T0 to T1 and T2. For A1c, BMI and plasma lipids no statistically significant differences were observed, although A1c decreased from 7.2% to 6.8%. TDD increased significantly, due to the automatic correction boluses. DTSQ score at T2 was 33 (range 32–34, max 36). CONCLUSIONS: After switching to AHCL, PPGE decreased rapidly by automatic correction boluses, without weight gain. Meal management simplification and glucose control improvement were associated with high satisfaction scores.

Efficacy of Postprandial Exercise in Mitigating Glycemic Responses in Overweight Individuals and Individuals with Obesity and Type 2 Diabetes-A Systematic Review and Meta-Analysis.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in overweight individuals and individuals with obesity and type 2 diabetes (T2DM). A literature search was conducted through databases such as PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. A random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24 h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analyses were conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and the disease status of participants. This study revealed a significantly reduced glucose AUC (Hedges' g = -0.317; SE = 0.057; p < 0.05) and 24 h mean glucose levels (Hedges' g = -0.328; SE = 0.062; p < 0.05) following PPE compared to CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min compared to ≤30 min. The reduction in 24 h mean glucose levels was also greater (p < 0.05) following PPE for ≥60 min compared to <60 min post-meal and in those with T2DM compared to those without T2DM. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE is a promising strategy, particularly for patients with T2DM. This manuscript is registered with Research Registry (UIN: reviewregistry1693).

Quantifying Change in Perfusion after Genicular Artery Embolization with Parametric Analysis of Intraprocedural Digital Subtraction Angiograms

PurposeTo quantify perfusion changes during genicular artery embolization (GAE) with the qualitatively described “pruning” technique using parametric analysis. Materials and MethodsA total of 12 patients underwent unilateral GAE with a total of 36 vessels embolized. Among 34 of the 36 vessels embolized, regions of interest (ROIs) were placed on parent vessels (PVs) and hyperemic target vessels (TVs) before and after GAE. For each ROI, peak intensity (PI), time to arrival (TTA), and area under the curve (AUC) were computed and compared between PV and TV. Volume of embolic administered was correlated with adverse events. ResultsNo change was seen in PI, TTA, and AUC in the PV after GAE. Reduction in AUC (1,495.7 ± 521.5 vs 1,667.4 ± 574.0; P << .01) and PI (195.1 ± 43.8 vs 224.3 ± 49.2; P << .01) with increase in TTA (3.42 s ± 1.70 vs 1.92 s ± 1.45; P << .01) within the TV were observed after GAE. Median follow-up time was 89 days (range, 21–254 days). Reduction in clinical symptoms was also noted based on the Western-Ontario and McMaster Universities Arthritis Index total and pain scale at 1 month (total, 42.9% ± 23.0; pain, 54.4% ± 9.8; P << .01) and 3 months (total, 42.5% ± 14.9; pain, 57.8% ± 10.6; P << .01). Eight total mild adverse events (minor/self-limiting) were noted per Society of Interventional Radiology guidelines. A larger volume of embolic was observed in knees with skin changes (3.4 mL ± 0.4 vs 1.7 mL ± 0.4; P << .001). Furthermore, all skin changes were seen with embolic volumes >3.0 mL. ConclusionsQuantification of intraprocedural perfusion changes with GAE demonstrated reduced flow to the TV with maintained flow in the PV and acceptable clinical outcomes. A potential relationship between embolic volume and nontarget embolization was also highlighted.

Platycodi Radix Beverage Improves Postprandial Lipemic Response Associated With Plasma Bacteria-Derived Extracellular Vesicles in Healthy Adults With an Oral Fat Load

ObjectivesThis study aimed to examine the responsiveness of postprandial triglyceride-rich lipoprotein (TRL) metabolism to Platycodi radix beverage (PR) is associated with the alterations in plasma bacteria-derived extracellular vesicles (EVs) composition.MethodsNinety-six healthy and normolipidemic adults were randomly divided into two groups and consumed PR or placebo for 8 weeks. An oral fat tolerance test was performed before and after the 8-week intervention to access the postprandial lipid response. Plasma TG, chylomicron TG (CM-TG), and lipoprotein lipase (LPL) mass levels were measured at fasting, 3, and 6 hours during the oral fat tolerance test and summarized by computing the area under the curve (AUC). EVs isolated from fasting plasma samples were identified using 16S rRNA sequencing. A linear mixed-effect model was used to analyze the difference between the two groups. TLR clearance responder to PR consumption was defined by QUalitative INteraction Trees (QUINT). Lasso regularized generalized linear model (GLM) was used to find genera associated with the responsiveness.ResultsPR consumption for 8 weeks noticeably decreased AUC (0–3h) values for TG and CM-TG compared to the placebo group. Responders for TRL clearance were defined as subjects having higher LPL mass (150.6 ng/mL) and dietary fat intake (38.5 g/day) at baseline. Responders showed remarkable reductions in AUC (0–6h) values for TG and CM-TG in the PR group compared to the placebo group. Furthermore, GLM analysis demonstrated that the responsiveness of postprandial TRL clearance was accurately predicted by the model consisting of changes in the relative abundance of 16 genera, suggesting the close association between them.ConclusionsThese findings suggest that PR consumption modulates postprandial TRL clearance by altering plasma EV composition in normolipidemic adults with habitually higher fat intake over 38.5 g/day.Funding SourcesThis work was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (2012M3A9C4048761).

Blink reflex: A practical test to evaluate the trigeminal nerve injury following percutaneous balloon compression for the treatment of trigeminal neuralgia.

To evaluate the blink reflex (BR) in estimating the potential injury of trigeminal nerve following percutaneous balloon compression (PBC) surgery, and to determine the association between BR alterations and early surgical outcomes. In this single-center, prospective before-and-after study, a total of 74 patients who had primary trigeminal neuralgia and scheduled for PBC between October 2020 and June 2021 were prospectively included. BR testing and facial sensory assessment were performed pre- and post-PBC. The latency and the area under the curve (AUC) of pre- and postoperative R1 (R1pre /R1post ) and R2 (R2pre /R2post ) were measured. The BR components were noticeably delayed or diminished following PBC. R1post was elicited in only 26 patients, and absent in 48 patients. The residual R1post had markedly reduced AUC (median difference [Hodges-Lehmann]: -59.5, 95% confidence interval [CI]: -217.5 to -6.9, p=0.023). Compared with R2pre , the latency of R2post was considerably delayed (mean difference: 4.3, 95% CI: 2.9 to 5.7, p<0.001) and the AUC was greatly suppressed (median difference [Hodges-Lehmann]: -388.4, 95% CI: -548.4 to -259.5, p<0.001). After PBC, 58 patients had immediate total pain relief, and 16had partial relief. The absence of R1post was found in 46 of 58 (79.3%) patients with complete remission, whereas in only 2 of 16 (12.5%) patients with partial relief. Association analysis showed that the absence of R1post was strongly associated with total pain relief (46/58 [79.3%] vs. 2/16 [12.5%], odds ratio [OR]: 26.8, 95% CI: 5.4 to 134.5, Cramér's V: 0.6, p<0.001). The latency of R2post in patients with total relief was significantly delayed (mean difference: 2.5, 95% CI: 0.3 to 4.6, p=0.028). Patients experienced graded facial numbness after PBC, of whom 31 reported mild numbness (Grades I-II) and 43 reported more severe numbness (Grades III-IV). The absence of R1post was significantly associated with facial numbness severity, 33/43 (76.7%) in Grades III-IV vs. 15/31 (48.4%) in Grades I-II (OR: 0.284, 95% CI: 0.105 to 0.771, Cramér's V: 0.3, p=0.012). In patients with more severe numbness, the latency of R2post was significantly delayed (mean difference: 2.7, 95% CI: 0.1 to 5.3, p=0.043), and the reduction of AUC was much greater (median difference [Hodges-Lehmann]: 17.2, 95% CI: 0.5 to 35.4, p=0.041). Both R1 and R2 were significantly diminished after PBC and these alterations were associated with early surgical outcomes, suggesting that the BR is useful in evaluating trigeminal injury following PBC and could provide objective information about early prognosis.

The total amount of CRP within the first 72 h after STEMI is crucial for the outcome

Abstract Background The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality. Methods 66 STEMI patients were enrolled following complete coronary revascularization (2–12 h after AMI). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. A specific CRP adsorber removed ≤79% of the original CRP. 6000 ml of plasma was treated via peripheral venous access. Primary endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 3–9 days after STEMI. Results Aphereses sessions were well tolerated with no relevant side effects. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24h after the onset of symptoms (CRP gradient). The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP gradients. The mean CRP gradient does not differ between both groups, whereas the mean area under the curve (AUC) of CRP within the first 72 h after AMI does. Thus, there was no bias in CRP kinetics between the two groups. The AUC of CRP is a significant indicator for infarct size (p=0.002), LVEF (p&amp;lt;0.001), circumferential strain (p&amp;lt;0.001), longitudinal strain (p=0.021). Therefore, the aphereses patients performed significantly better at all endpoints than the controls. The CRP apheresis significantly reduced myocardial damage by a reduction of the AUC of CRP. To our surprise, two apheresis patients had an infarct size of 0%. Conclusions For the first time we find an unequivocal association between myocardial infarct size and the AUC of CRP. The results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry). Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pentracor GmbH

47 Quantitative evaluation of hunger in pregnant sows: metabolic and hormonal responses to feeding frequency under limit-fed regime

Abstract The objectives of the study were to determine the pattern of glucose, insulin, active ghrelin, and total PYY responses and indirectly quantify perceived hunger in pregnant sows under-limit fed conditions. Eighteen sows [(Landrace × Yorkshire); BW 211.86 ± 1.29 kg; parity 3.80 ± 0.16; backfat 13.50 ± 0.25 mm)] were sampled from 180 sows. Sows were blocked by parity and BW and randomly assigned to 1 of 3 treatments in a RCBD. Treatments included sows fed once at [0730 h (Control, T1), twice [half ration at 0730 and 1530 h (T2)], or thrice [one-third portion at 0730, 1130, and 1530 h (T3)]. The daily feed quantity was kept at 1.25× maintenance energy intake (100 × (BW)0.75) kcal ME/d. Sows received corn-soybean meal-based diet which provided 6935 kcal ME/d and SID Lys:ME of 1.71 g/Mcal from d 30 to 60 of gestation. Hunger was quantified using total area under the curve (AUC) of the hormonal responses. Data analysis was done using PROC MIXED and GLIMMIX procedure of SAS. Sow was the experimental unit. Adjustment for multiple comparisons was by Tukey’s method. The control sows had greater 23-h mean glucose concentration than sows fed 3× daily (P = 0.002). Active ghrelin concentration for sows fed 3× daily tended to be lower (P = 0.063) compared with control sows but reduced (P = 0.018) relative to sows fed 2× daily. In conclusion, sows fed 3× daily had 9.0% reduction in 23-h glucose total AUC, 42.5% greater 23-h insulin total AUC, 27.4% reduction in active ghrelin total AUC, and 14.2% greater PYY total AUC compared with pregnant sows fed 1× daily. It is suggested that hunger in pregnant sows occurs at active ghrelin/total PYY ratio of 5.06 ± 0.20 and at a mean plasma glucose concentration of 70.37 ± 1.39 mg/dL and below.

Dynamic Glucose Disposal is Driven by Reduced Endogenous Glucose Production in Response to Voluntary Wheel Running: A Stable Isotope Approach.

To resolve both the systems level and molecular mechanisms responsible for exercise induced improvements in glucose tolerance, we sought to test the effect of voluntary wheel running exercise on postprandial glucose dynamics. We utilized a stable isotope labeled oral glucose tolerance test (SI-OGTT) incorporating complimentary deuterium glucose tracers at 1:1 ratio (2-2H-glucose and 6-6 2H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose production (EGP) and whole-body glucose disposal. SI-OGTT was performed in C57BL/6J mice after 8 weeks on a high fat diet (45% fat). Mice were then randomized to either a wheel running cage (n=13, HFD Ex) or normal cage (n=13, HFD Sed) while maintaining the HFD for 4 weeks prior to performing a SI-OGTT. HFD Ex mice demonstrated improvements in whole blood glucose total AUC that was attributed primarily to a reduction in EGP AUC. Serum insulin levels measured at 0 and 15-minutes post glucose gavage were significantly elevated in the HFD Sed mice, whereas HFD Ex mice demonstrated the expected reduction in insulin at both time points. Overall, exercise improved hepatic insulin sensitivity by reducing postprandial EGP, but also increased whole-body glucose disposal. Finally, these results demonstrate the benefits of exercise on hepatic insulin sensitivity by combining a more physiological route of glucose administration (oral glucose) with the resolution of stable isotope tracers. These novel observations clearly demonstrate that SI-OGTT is a sensitive and cost-effective method to measure exercise adaptations in obese mice with as little as 2 µl of tail blood.

Glycemic and Insulinemic Responses of Vegetables and Beans Powders Supplemented Chapattis in Healthy Humans: A Randomized, Crossover Trial.

Vegetables and beans are nutrient-dense foods with innate potential to mediate diabetes in a variety of cultures. The present study aims at evaluating vegetables and beans for assessing their glycemic index and response in raising glucose levels in human model. Powdered formulations of vegetables and beans were designed to modulate glycemic response of carbohydrate-rich staples. A randomized, crossover trial was conducted in healthy young adults (n = 24) who were challenged with vegetable powder-supplemented chapatti (VPSC), bean powder-supplemented chapatti (BPSC) and all-purpose wheat flour chapatti (APFC) to evaluate their postprandial glucose (PPG) and postprandial insulin (PPI) responses. In comparison with APFC, feeding VPSC and BPSC to healthy volunteers anticipated significant reduction in PPG (44% reduction in incremental area under the curve (AUC) for VPSC and 46% reduction in incremental AUC for BPSC, p = 0.005). Likewise, significant reduction in PPI levels was observed for VPSC (59%, p = 0.012) and BPSC (47%, p = 0.002) compared to APFC-treated group. The study concludes wheat flour enrichment with vegetables and beans powder as a viable approach to develop cost effective and culturally acceptable low glycemic foods bearing acceptable sensory attributes.

Hypoglycemic effect of Phaleria macrocarpa (Scheff.) Boerl dry extract in healthy adults

BackgroundThe prevalence of diabetes in Indonesia continues to increase and causes many complications. Fruits of Phaleria macrocarpa (Scheff.) Boerl. (PM) are used in the traditional health system of the Indonesians, as effective remedy in the management of diabetes mellitus. The aim of this study was to evaluate the effect and magnitude of doses of PM dry fruit extract (PME) on blood glucose levels in healthy adults.MethodsThis research was of pre-posttest design involving 30 healthy volunteer subjects aged 20-55 years receiving glucose loads. At pre-test the subjects were given orally 75 g glucose, and at post-test they were given PME at doses of 125 mg and 250 mg. Data collection included anthropometric examination and blood glucose level. The area under the curve (AUC) of blood glucose levels was measured at 0, 15, 30, 60, 120 and 180 minutes. Data analysis was performed using paired t-test with p &lt;0.05.ResultsThe percentage of reduction in AUC between pre- and post-test after administration of PME 125 mg was 12.1% and significant (p=0.000). But the percentage of reduction in AUC between pre- and post-test after administration of PME 250 mg was 4.07% and not significant (p=0.06). The reduction in AUC between post-test PME 125 mg vs PME 250 mg showed significant results (p=0.011).Conclusion This study demonstrated that a dose of 125 mg Phaleria macrocarpa (Scheff.) Boerl. dry extract has a hypoglycemic effect in healthy adults, and may therefore be suitable for use as traditional anti-diabetic drug.

Identification of a select metabolite panel for measuring metabolic perturbation in response to heavy exertion.

Databases from three global metabolomics-based studies (N = 59) (PMID: 25409020, 26561314, 29566095) were evaluated for metabolite shifts following heavy exertion (75-km cycling) to generate a representative, select panel of metabolites identified by variable importance in projection (VIP) scores. OPLS-DA was used to separate samples at pre- and post-exercise during the water-only trial in one of the studies (PMID: 26561314), and of 590 metabolites, 26 (all but one from the lipid pathway) had a VIP > 2 and were selected for the panel. A second OPLS-DA based on the 26 metabolites was performed to separate pre- and post-exercise samples, and this model performed as well as the one with 590 metabolites (Q2Y = 0.923, 0.925 respectively); this model also showed a complete separation using OPLS-DA plots between pre- and post-exercise samples for the other two studies. A latent variable t1 (a linear combination of the 26 metabolites), was generated and the metabolite data at each time point were projected to t1 with the relative distance on t1 and area under the curve (AUC) determined from the three databases. Acute carbohydrate compared to water-only ingestion was linked to a 28-47% reduction in AUCs following exercise depending on the carbohydrate source and recovery time period. These data support that a panel of 26 metabolites can be used to represent global metabolite increases induced by prolonged, intensive exercise. This select panel includes metabolites primarily from the lipid super pathway, and exercise-induced increases are sensitive to the moderating effect of acute carbohydrate ingestion.

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer.

To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival.

Efficacy and safety assessment of acute sports-related traumatic soft tissue injuries using a new ibuprofen medicated plaster: results from a randomized controlled clinical trial

ABSTRACTObjective: To investigate the efficacy and safety of a recently developed ibuprofen medicated plaster in the treatment of acute sports impact injuries/contusions.Methods: In this double-blind, multi-center, placebo-controlled, parallel group, phase 3 study (EudraCT Number: 2012–003257-2) patients (n = 132; ages 18 to 60 years) diagnosed with acute sports-related traumatic blunt soft tissue injury/contusion to the upper or lower limbs were randomized to receive either ibuprofen 200 mg plaster (n = 64) or placebo plaster (n = 68). Plasters were administered once daily for five consecutive days. The primary assessment was the area under the curve (AUC) of the visual analogue scale (VAS) of pain on movement (POM) over 0 to 72 h (VAS0-72).Results: The ibuprofen medicated plaster was associated with a reduction in pain on movement (POM) based on lower VAS AUC0-72h (2399.4 mm*h) compared with placebo (4078.9 mm*h) (least squares mean difference: – 1679.5 mm*h; P < 0.0001). The reduction in AUC of POM was also significantly greater for the ibuprofen medicated plaster compared with placebo at 12, 48, 24, and 120 h (P < 0.0001). Algometry/tenderness measurements found that the ibuprofen medicated plaster was associated with greater reduction in tenderness/pain than placebo at each timepoint (P values <0.0001). Seven patients experienced drug-related adverse events (n = 1 [1.6%] for the ibuprofen plaster, and n = 6 [8.8%] for placebo). All drug-related AEs were administration site reactions and were mild in intensity.Conclusions: The results of this study indicate that ibuprofen medicated plaster results in rapid and clinically relevant reduction of pain in patients suffering from blunt musculoskeletal injuries or recurrent pain. The ibuprofen medicated plaster was well tolerated.

Impact of a Basal-Bolus Insulin Regimen on Metabolic Control and Risk of Hypoglycemia in Patients With Diabetes Undergoing Peritoneal Dialysis.

Clinical interventional studies in diabetes mellitus usually exclude patients undergoing peritoneal dialysis (PD). This study evaluates the impact of an educational program and a basal-bolus insulin regimen on the blood glucose level control and risk of hypoglycemia in this population. A before-and-after study was conducted in type 1 and type 2 DM patients undergoing PD at the Renal Therapy Services (RTS) clinic network, Bogota, Colombia. An intervention was instituted consisting of a three-month educational program and a basal-bolus detemir (Levemir, NovoNordisk) and aspart (Novorapid, NovoNordisk) insulin regimen. Prior to the intervention and at the end of treatment were conducted measures of HbA1c levels and continuous glucose monitoring (CGM). Forty-seven patients were recruited. Mean HbA1c level decreased from 8.41% ± 0.83 to 7.68% ± 1.32 (mean difference -0.739, 95% CI -0.419, -1.059; P < .0001). Of subjects, 52% achieved HbA1c levels <7.5% at the end of study. Mean blood glucose level reduced from 194.0 ± 42.5 to 172.9 ± 31.8 mg/dl ( P = .0015) measured by CGM. Significant differences were not observed in incidence of overall ( P = .7739), diurnal ( P = .3701), or nocturnal ( P = .5724) hypoglycemia episodes nor in area under the curve (AUC) <54 mg/dl ( P = .9528), but a reduction in AUC >180 ( P < .01) and AUC >250 ( P = .01) was evidenced for total, diurnal, and nocturnal episodes. An intervention consisting of an educational program and a basal-bolus insulin regimen in type 1 and type 2 diabetes mellitus patients undergoing PD caused a decrease in HbA1c levels, and mean blood glucose levels as measured from CGM with no significant increases in hypoglycemia episodes.

Pharmacodynamics, pharmacokinetics, safety and tolerability of the novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist RG7697 after single subcutaneous administration in healthy subjects.

To evaluate the pharmacodynamics, pharmacokinetics and safety of single subcutaneous (s.c.) injection of ascending doses of RG7697, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist, in healthy subjects. A total of 51 healthy volunteers were enrolled in this double-blind, placebo-controlled study investigating RG7697 doses ranging from 0.03 to 5 mg. Adverse events (AEs) were monitored and drug concentrations, fasting glycaemic variables, vital signs, ECG, antibody formation and routine laboratory variables were assessed. A meal tolerance test (MTT) was performed at the same time on day -1 (baseline) and day 1. RG7697 was generally well tolerated in healthy participants after s.c. injections up to 3.6 mg. Tolerability was limited by gastrointestinal AEs (nausea and vomiting) at the highest dose. There was a small dose-dependent increase in heart rate. No episodes of hypoglycaemia occurred. RG7697 concentrations peaked at 2 to 4 hours post-dose with a half-life of 19 to 25 hours. During MTT, RG7697 at doses ≥1.8 mg, reduced glucose maximum plasma concentration (Cmax ; -46%) without affecting overall glucose area under the curve (AUC). Its effect on insulin was more pronounced, with reductions in both Cmax (-64%) and AUC (-51%). Pharmacodynamic variables were well correlated to RG7697 average plasma concentration during MTT, with IC50 (average concentration required for 50% reduction) values of 49 and 24.5 ng/mL for glucose and insulin, respectively. Single s.c. injections of RG7697 up to 3.6 mg were generally well tolerated. Evidence of glycaemic effect and pharmacokinetic profiles consistent with once-daily dosing render this drug candidate suitable to be further tested in multiple-dose clinical trials in patients with type 2 diabetes.

Effects of Lactobacillus casei Shirota intake on caries risk in children

Background/purposeYakult is a well-known probiotic beverage consisting of a single live bacterial species, Lactobacillus casei Shirota. However, the potential cariogenic/cariostatic effects of Yakult intake among children have not been studied yet. Hence, this study aimed to investigate the clinical effects of short-term Yakult intake on oral biofilm acidogenicity, cariogenic bacterial counts, and caries risk in children. Materials and methodsEighteen children, 7–11 years of age, consumed standard Yakult daily for 7 days. Prior to and after intervention, functional oral biofilm acidogenicity characterized by the Stephan curve, Lactobacillus and Streptococcus mutans counts, and caries risk were determined. ResultsProbiotic intervention demonstrated significant increase in minimum pH from 4.88 to 5.14 (P=0.02), 18.2% reduction in area under the Stephen curve [area under the curve (AUC)], and 29.3% decrease in pH recovery time, although these two differences were not statistically significant. No difference was observed in S. mutans and Lactobacillus counts or caries risk after intervention (all P>0.05). However, on subgroup analysis using “reduction of AUC” to separate “responders” from the “nonresponders”, the significant cariostatic effects on oral biofilm acidogenicity, among “responders”, were revealed by an increase in minimum pH (P=0.005) and a reduction in pH recovery time (P=0.003). ConclusionThere may be a potential cariostatic effect of short-term Yakult intake in reducing functional biofilm acidogenicity in children with certain oral biofilm and risk profile. Further studies may be needed to validate this probiotic effect. Quality risk assessment may be critical prior to prescribing/recommending Yakult as an adjunct caries-preventive treatment for children.