Postprandial Phase Research Articles

Glucagon-Like Peptide-1 Receptor Agonists-Use in Clinical Practice.

In the past 2decades, eight glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the management of type 2 diabetes, each with its peculiar molecular structure, pharmacokinetics, and metabolic effects. Along with their marked glucose-lowering actions, which occur both at fasting and in the postprandial phase without an increased risk of hypoglycemia, GLP-1RAs have provided marked reductions in body weight and ancillary improvements in blood pressure and lipid profile. Recent cardiovascular outcome trials have established the benefits of GLP-1RAs on major cardiovascular events and all-cause mortality, independent of glucose control, with minor effects on preventing hospitalization for heart failure. Novel evidence is also emerging on the protection of GLP-1RAs against diabetic kidney disease, mainly preventing the onset of macroalbuminuria. Several mechanisms have been proposed to explain the cardiorenal protective properties of GLP-1RAs, which may be direct or mediated by additional hemodynamic and anti-inflammatory/antioxidant effects. With their favorable cardiometabolic properties and safety profile, GLP-1RAs may offer an ideal pharmacological option for the management of diabetic kidney disease. In this review, we discuss pharmacokinetic properties, glucometabolic effects, and cardioprotective actions of GLP-1RAs, highlighting the available evidence for a kidney protective role and the proposed mechanisms.

Diet and lung disease-Are fruits and vegetables the ideal whole-food intervention?

Diet and lung disease-Are fruits and vegetables the ideal whole-food intervention?

Safety and Feasibility Evaluation of Step Count Informed Meal Boluses in Type 1 Diabetes: A Pilot Study.

Physical activity can cause glucose fluctuations both during and after it is performed, leading to hurdles in optimal insulin dosing in people with type 1 diabetes (T1D). We conducted a pilot clinical trial assessing the safety and feasibility of a physical activity-informed mealtime insulin bolus advisor that adjusts the meal bolus according to previous physical activity, based on step count data collected through an off-the-shelf physical activity tracker. Fifteen adults with T1D, each using a continuous glucose monitor (CGM) and an insulin pump with carbohydrate counting, completed two randomized crossover daily visits. Participants performed a 30 to 45-minute brisk walk before lunch and lunchtime insulin boluses were calculated based on either their standard therapy (ST) or the physical activity-informed bolus method. Post-lunch glycemic excursions were assessed using CGM readings. There was no significant difference between visits in the time spent in hypoglycemia in the post-lunch period (median [IQR] standard: 0 [0]% vs physical activity-informed: 0 [0]%, P = NS). Standard therapy bolus yielded a higher time spent in 70 to 180 mg/dL target range (mean ± standard: 77% ± 27% vs physical activity-informed: 59% ± 31%, P = .03) yet, it was associated with a steeper negative slope in the early postprandial phase (P = .032). Use of step count to adjust mealtime insulin following a walking bout has proved to be safe and feasible in a cohort of 15 T1D subjects. Physical activity-informed insulin dosing of meals eaten soon after a walking bout has a potential of mitigating physical activity related glucose reduction in the early postprandial phase.

Effects of exercise before and/or after a mixed lunch on postprandial metabolic responses in healthy male individuals.

Exercise plays an important role in preventing and treating postprandial dysmetabolism. We investigated the postprandial metabolic responses to a standard lunch when a session of aerobic exercise is performed in the early postprandial phase or divided between the pre- and postprandial period. Nine healthy volunteers consumed a standardised mixed lunch and rested for the following 3h (Con) or performed 40min of cycling at 65% V̇O2max after lunch (CPPEx), or two 20-min sessions, one before (SplitEx1) and the other after lunch (SplitEx2), at the same intensity. At 1-h post-lunch, a significant reduction (P < 0.001) in glycaemia was observed for CPPEx (-25 ± 10%) and SplitEx (-34 ± 7%) compared to Con. Yet, a post-exercise rebound lessened the exercise effect on the glycaemic area under the curve (AUC) at 2 and 3h. At 1h, a significant reduction (P < 0.009) in plasma insulin (SplitEx -53 ± 31%; CCPEx -48 ± 20%) and C-peptide (SplitEx -57 ± 20%; CCPEx -47 ± 24%) was observed compared to Con. Glucose-dependent insulinotropic polypeptide (GIP) increased after the meal, without differences between conditions. Compared with SplitEx1, cortisol response was attenuated during SplitEx2 and CPPEx. At 3 hours, triglyceride AUC was significantly higher (P = 0.039) in SplitEx compared to Con (+ 19 ± 8%). Forty minutes of postprandial exercise or 20min of pre- and postprandial exercise are both effective at attenuating the glycaemic and insulinaemic response to a mixed lunch, while a higher lipaemia was found in the pre- and postprandrial exercise condition.

Changes in Ghrelin and Glucagon following a Low Glycemic Load Diet in Women with PCOS.

Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. Secondary analysis of a randomized crossover trial. Thirty women diagnosed with PCOS. Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.

Effects of a whey protein pre-meal on bone turnover in participants with and without type 2 diabetes-A post hoc analysis of a randomised, controlled, crossover trial.

Whey protein may improve bone turnover and have anti-osteoporotic effects. The aim of the present randomised, controlled, crossover trial was to evaluate the effects of a whey protein pre-meal on bone turnover in people with type 2 diabetes and controls. Two groups, matched on sex, age and body mass index, comprising 12 participants with and 12 participants without type 2 diabetes were randomly given a pre-meal of whey protein (20g) or water, which was consumed 15min before a fat-rich meal or a fat-rich meal supplemented with 20g whey protein. During a 360-min period, postprandial responses in bone turnover were examined. Osteocalcin, P-procollagen type 1 amino terminal propeptide (P1NP), C-terminal cross-linked telopeptide of type-I collagen (CTX) and parathyroid hormone (PTH) were lower at baseline and PTH, osteocalcin and P1NP were lower during the entire postprandial phase in participants with type 2 diabetes than in participants without type 2 diabetes. We observed similar postprandial responses in bone turnover markers between persons with and without type 2 diabetes. We observed no effect of the whey protein or the water pre-meal on bone turnover markers. The changes were unrelated to secretion of hormones of the gut-bone axis. Osteocalcin, P1NP, CTX and PTH all decreased following meal ingestion. We observed no convincing effect of a whey protein pre-meal on bone turnover. However, these results confirm that people with type 2 diabetes have low bone turnover and that the decreased bone formation markers are also extend into the postprandial responses.

Botanicals and Food Supplement Combination in Patients with Polygenic Hypercholesterolemia: Evaluation at Fasting and after Oral Fat Load Test

The aim of this study was to evaluate, in hypercholesterolemic patients, the effects on lipid profile both at fasting and after an oral fat load (OFL), of 3 months of treatment with a nutraceutical combination containing monacolin K, Cynara scolymus, Thea sinensis L., Oryza sativa L., Brassica campestris L., folic acid, coenzyme Q10, and Resveratrol compared to placebo. We enrolled 63 Caucasian patients, aged ≥18 of either sex, at low cardiovascular risk (≤ 2%) and randomized them to take the nutraceutical or placebo for 3 months. We evaluated fasting plasma glucose, lipid profile, high sensitivity C-reactive protein and safety parameters at baseline and after 3 months. Patients also underwent an OFL at baseline and at the end of the study. Nutraceutical combination gave a reduction of total cholesterol (TC), triglycerides (Tg), and low-density lipoprotein-cholesterol (LDL-C), both compared to baseline (p < 0.05), and compared to placebo (p < 0.05). High-sensitivity C-reactive protein decreased in the active group both compared to baseline and to placebo (p < 0.05 for both). During the OFL performed at the end of the study, TC, and LDL-C recorded in the group treated with the nutraceutical combination were lower compared to the values recorded during the baseline OFL (p < 0.05), and also compared to values recorded in placebo group (p< 0.01) at every time of OFL. Regarding Tg, the value recorded during the OFL at the end of the study was lower at 6 hours compared to baseline OFL (p < 0.05 vs baseline), and to placebo (p < 0.05). A nutraceutical containing monacolin K, Cynara scolymus, Thea sinensis L., Oryza sativa L., Brassica campestris L., folic acid, coenzyme Q10, and Resveratrol could be helpful in improving lipid profile in hypercholesterolemic patients, both at fasting and in post-prandial phase.

Blackcurrant (Ribes nigrum) lowers sugar-induced postprandial glycaemia independently and in a product with fermented quinoa: a randomised crossover trial.

Berries rich in anthocyanins have beneficial effects on postprandial glycaemia. We investigated whether blackcurrant (75 g in a portion) independently and in a product with fermented quinoa induced similar effects on the sugar-induced postprandial glucose metabolism as observed before with 150 g of blackcurrant. Twenty-six healthy subjects (twenty-two females and four males) consumed four test products after fasting overnight in a randomised, controlled crossover design. Each test product portion contained 31 g of available carbohydrates and had similar composition of sugar components: 300 ml water with sucrose, glucose and fructose (SW; reference), blackcurrant purée with added sugars (BC), a product consisting of the blackcurrant purée and a product base with fermented quinoa (BCP) and the product base without blackcurrant (PB). Blood samples were collected at 0, 15, 30, 45, 60, 90, 120 and 180 min after eating each test product to analyse the concentrations of glucose, insulin and NEFA. In comparison with the SW, the intake of both the BC and BCP resulted in reduced glucose and insulin concentrations during the first 30 min, a more balanced decline during the first hour and improved glycaemic profile. The BCP induced more efficient effects than the BC due to the product base with fermented quinoa. A rebound of NEFA after the sugar-induced hypoglycaemic response was attenuated at the late postprandial phase by the BC and BCP. In conclusion, we showed that 75 g of blackcurrant and the product with fermented quinoa were able to lower postprandial glycaemia and insulinaemia.

The daytime feeding frequency affects appetite-regulating hormones, amino acids, physical activity, and respiratory quotient, but not energy expenditure, in adult cats fed regimens for 21 days.

The effects of feeding frequency on postprandial response of circulating appetite-regulating hormones, insulin, glucose and amino acids, and on physical activity, energy expenditure, and respiratory quotient were studied in healthy adult cats. Two experiments were designed as a 2 x 3 replicated incomplete Latin square design. Eight cats, with an average body weight (BW) of 4.34 kg ± 0.04 and body condition score (BCS) of 5.4 ± 1.4 (9 point scale), were fed isocaloric amounts of a commercial adult maintenance canned cat food either once (0800 h) or four times daily (0800 h, 1130 h, 1500 h, 1830 h). Study 1 consisted of three 21-d periods. On day 14, two fasted and 11 postprandial blood samples were collected over 24 hours to measure plasma concentrations of ghrelin, GLP-1, GIP, leptin, PYY, insulin and amino acids, and whole blood glucose. Physical activity was monitored from day 15 to 21 of each period. In Study 2 indirect calorimetry was performed on the last day of each period. Body weight was measured weekly and feed intake recorded daily in both experiments. No effect of feeding regimen on BW was detected. Cats eating four times daily had lesser plasma concentrations of GIP and GLP-1 (P<0.05) and tended to have lesser plasma PYY concentrations (P<0.1). Plasma leptin and whole blood glucose concentrations did not differ between regimens (P>0.1). Cats fed once daily had a greater postprandial plasma amino acid response, and greater plasma ghrelin and insulin concentrations (P<0.05). Physical activity was greater in cats fed four times (P<0.05), though energy expenditure was similar between treatments at fasting and in postprandial phases. Finally, cats eating one meal had a lower fasting respiratory quotient (P<0.05). Overall, these data indicate that feeding once a day may be a beneficial feeding management strategy for indoor cats to promote satiation and lean body mass.

Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials

l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD). Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P<0.001; I2: 76.7%, P<0.001), while l-arginine supplementation (daily range: 3-21g) increased fasting FMD by 0.53PP (95% CI: 0.12, 0.93; P=0.012; I2: 91.6%, P<0.001). Effects between treatments were not statistically different (P=0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25PP, 95% CI:-0.31, 2.81, P=0.12; I2: 91.4%, P<0.001), whereas l-arginine supplementation (range: 3-15g) improved FMD during the postprandial phase by 2.02PP (95% CI: 0.92, 3.13, P<0.001; I2: 99.1%, P<0.001). However, treatment effects did not differ significantly (P=0.60). Overall, these results derive from high-quality evidence. Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.

Acute-phase glycoprotein profile responses to different oral macronutrient challenges: Influence of sex, functional hyperandrogenism and obesity

Acute-phase glycoprotein 1H-NMR spectroscopy profiles serve as surrogate markers of chronic inflammation in metabolic disorders such as obesity, diabetes and polycystic ovary syndrome (PCOS). The latter is associated with increased height-to-width (H/W) ratios of GlycA and GlycB after fasting, but not to glycoprotein areas, regardless of obesity. We studied the responses to separate glucose, lipid and protein oral challenges of five glycoprotein variables (GlycA, GlycB, and GlycF areas and the GlycA and GlycB H/W ratios) in 17 women with PCOS, 17 control women, and 19 healthy men. Glucose and protein ingestion resulted into decreases in all glycoprotein variables, whereas lipid ingestion increased GlycA, GlycF and induced minimal changes in GlycB and GlycB H/W. We found no effects of obesity or group of subjects on postprandial glycoprotein variables regardless of the macronutrient being ingested. However, a statistically significant interaction indicated that obesity blunted the decrease in some of these variables in control women and men, whereas obese women with PCOS showed larger changes when compared with their non-obese counterparts. In conclusion, acute-phase glycoprotein profiles indicate an anti-inflammatory response during postprandial phase that is less pronounced after lipid ingestion, and is counteracted by the chronic inflammatory background associated with obesity and PCOS.

Gastric Motility in Parkinson's Disease is Altered Depending on the Digestive Phase and Does Not Correlate with Patient-Reported Motor Fluctuations.

Background:Altered gastric motility is a frequent non-motor symptom of Parkinson’s disease (PD). It has been hypothesized that disturbed gastric motility contributes to motor fluctuations in PD due to an erratic gastro-duodenal transport and an unpredictable absorption of drugs.Objective:We investigated whether patient-reported fluctuations are associated with parameters of gastric motility visualized by real-time magnetic resonance imaging (MRI) of the stomach.Methods:We analyzed real-time MRI-scans of the stomach after an overnight fasting period in 16 PD patients and 20 controls. MRI was performed 1) in the fasting state, 2) directly after a test meal, and 3) 4 hours postprandially. Gastric motility indices were calculated and compared between groups.Results:MRI showed an attenuated gastric motility in PD patients compared to controls. The difference was most obvious in the early postprandial phase. Gastric motility was not associated with patient-reported motor fluctuations. Using an iron-containing capsule we were able to retrace retention of drugs in the stomach.Conclusion:The results of this study stress the importance of considering the phase of digestion when investigating gastric motility in PD. Despite theoretical considerations, we did not find robust evidence for an association between MRI parameters of gastric motility and patient-reported motor fluctuations. For future studies that aim to investigate gastric motility in PD by MRI, we suggest multiple short-time MRIs to better track the whole gastro-duodenal phase in PD. Such an approach would also allow to retrace the retention of drugs in the stomach as shown by our approach using an iron-containing capsule.

Effects of Acute Cocoa Supplementation on Postprandial Apolipoproteins, Lipoprotein Subclasses, and Inflammatory Biomarkers in Adults with Type 2 Diabetes after a High-Fat Meal.

Dyslipidemia and inflammation exacerbate postprandial metabolic stress in people with diabetes. Acute dietary supplementation with polyphenols shows promise in improving postprandial metabolic stress in type 2 diabetes (T2D). Cocoa is a rich source of dietary polyphenols with demonstrated cardioprotective effects in adults without diabetes. To date, the acute effects of cocoa on postprandial lipids and inflammation have received little attention in the presence of T2D. This report expands on our earlier observation that polyphenol-rich cocoa, given as a beverage with a fast-food-style, high-fat breakfast, increased postprandial high-density lipoprotein-cholesterol (HDL-C) in adults with T2D. We now test whether polyphenol-rich cocoa modulated postprandial apolipoproteins (Apo-A1, B), non-esterified fatty acids, nuclear magnetic resonance (NMR)-derived lipoprotein subclass profiles, and select biomarkers of inflammation following the same dietary challenge. We found that cocoa decreased NMR-derived concentrations of total very low-density lipoprotein and chylomicron particles and increased the concentration of total HDL particles over the 6-hour postprandial phase. Serum interleukin-18 was decreased by cocoa vs. placebo. Thus, polyphenol-rich cocoa may alleviate postprandial dyslipidemia and inflammation following a high-fat dietary challenge in adults with T2D. The study was registered at clinicaltrials.gov as NCT01886989.

Toward a Fully Automated Artificial Pancreas System Using a Bioinspired Reinforcement Learning Design: In Silico Validation.

The automation of insulin treatment is the most challenge aspect of glucose management for type 1 diabetes owing to unexpected exogenous events (e.g., meal intake). In this article, we propose a novel reinforcement learning (RL) based artificial intelligence (AI) algorithm for a fully automated artificial pancreas (AP) system. A bioinspired RL designing method was developed for automated insulin infusion. This method has reward functions that imply the temporal homeostatic objective and discount factors that reflect an individual specific pharmacological characteristic. The proposed method was applied to a training method using an RL algorithm and was evaluated in virtual patients from the FDA approved UVA/Padova simulator with unannounced meal intakes. For a single-meal experiment with preprandial fasting, the trained policy demonstrated fully automated regulation in both the basal and postprandial phases. In the in silico trial with a variation of insulin sensitivity and dawn phenomenon, the policy achieved a mean glucose of 124.72 mg/dL and percentage time in the normal range of 89.56%. The layer-wise relevance propagation provides interpretable information on AI-driven decision for robustness to sensor noise, automated postprandial regulation, and insulin stacking avoidance. The AP algorithm based on the bioinspired RL approach enables fully automated blood glucose control with unannounced meal intake. The proposed framework can be extended to other drug-based treatments for systems with significant uncertainties.

Effect of Fat and Fasting on Post-Prandial Relative Bioavailability of Vitamin E

Abstract Objectives We hypothesized that meal fat co-administered with fat-soluble α-tocopherol (vitamin E) facilitates vitamin E absorption and increases relative bioavailability in the immediate post-prandial phase, when compared with non-fat meals. We tested this hypothesis using deuterated oral α-tocopherol co-administered with breakfast containing meal fat (40% group) and without meal fat (0% group) in hospitalized healthy women. We also evaluated the role of subsequent meals in modulating the vitamin E relative bioavailability by fasting patients for 12 h following a breakfast meal with 0% fat (0% fat-fasting group). We compared area under the curve (AUC) for oral d3-α-tocopherols %enrichment at 0–4 h, 0–12 h and 0–24 h. Methods Custom-synthesized deuterated d3-α-tocopherol was co-administered with breakfast meal with and without fat, with subsequent serial sampling. Enrolled subjects were healthy women hospitalized for 5–6 days at the NIH Clinical Research Center. Results The AUC0–4 h for 40% fat group was more than twice 0% fat group (6.4 ± 1.8 vs 2.3 ± 0.7). This difference was erased following ingestion of meals containing 30% fat at 4 h and 8 h post-dosing, with AUC0–12 h for 40% and 0% fat groups (96.8 ± 10.2 vs 107.4 ± 8.) and AUC0–24 h (254 ± 16.3 vs 301.8 ± 19.7). To evaluate the effect of fasting, we compared 0% fat group with 0% fat-fast groups. At 4 h and 8 h post-dosing, the 0% fat group received meals with 30% fat, while 0% fat-fast group remained in fasting state. We therefore predicted and found significantly higher AUC0–12 h in the 0% fat group compared with the 0% fat-fast (107.4 ± 8.1 vs 41.1 ± 5.2 P &amp;lt; 0.001). Following meal consumption by 0% fat-fast group 12 h post-dosing, AUC0–24 h between 0% fat and 0% fat-fast groups narrowed but remained significantly different (301.8 ± 19.7 vs 207.4 ± 10.6, P &amp;lt; 0.002) respectively. Conclusions Findings demonstrate the effect of meal fat in facilitating vitamin E absorption in the immediate post-prandial state, resulting in increased relative bioavailability. Conversely, fasting decreases vitamin E relative bioavailability. Funding Sources NIDDK Intramural Program.

Suppression of Oral Sweet Sensations during Consumption of Sweet Food in Humans: Effects on Gastric Emptying Rate, Glycemic Response, Appetite, Food Satisfaction and Desire for Basic Tastes.

Suppression of oral sweet sensation (OSS) acutely reduces intake of sweet-tasting food due to lower liking. However, little is known about other physiological responses during both the prandial and postprandial phase. Here, we explored the effects of Gymnema sylvestre (GS)-based suppression of OSS of several types of sweet-tasting food (muffin, sweet yogurt, banana) on gastric emptying, blood glucose (BG), plasma insulin (PI), appetite indices (hunger, fullness and prospective consumption), satisfaction and desire for tastes. Fifteen healthy subjects (22 ± 3 years, 9 women) took part in the study. Subjects rinsed their mouth with either GS solution or distilled water before eating the sweet-tasting food. Subjects felt decreased sweet taste intensity and reduced taste liking associated with GS rinsing after consuming each food, compared with rinsing with distilled water (p < 0.05). Gastric emptying, BG, PI and appetite indices during and after the prandial phase did not significantly change with GS rinsing compared to rinsing with distilled water (p > 0.05). Higher desire for sweet taste as well as lower satisfaction (p < 0.05) in the postprandial phase were observed with GS rinsing. These results suggest that the suppression of OSS does not affect gastric emptying, glycemic response and appetite during and after consumption of sweet-tasting food.

Assessments of plasma acyl-ghrelin levels in Parkinson’s disease patients treated with deep brain stimulation

Gastrointestinal dysfunction is the most common non-motor symptom in Parkinson’s disease (PD) with rates rising as the disease progresses. Deep brain stimulation of subthalamic nucleus (STN DBS) improves motor functions in advanced PD. However, the effect of STN DBS on ghrelin concentration and consequently on motility disturbances as well as body weight is unclear. The objective of this study was to assess acyl-ghrelin levels in comparison to weight in advanced PD patients treated with STN DBS.Plasma concentrations of acyl-ghrelin was measured in 29 PD patients in the fasting state and at 30, 60, 120, and 180 min after a standard meal preoperatively and 3 months after surgery. The level of acyl-ghrelin in PD patients were compared with 30 age and sex-matched healthy controls.We reported that mean plasma acyl-ghrelin levels were decreased in PD patients before STN DBS in fasting (p = 0.0003) and in 30 min postprandial phase (p = 0.04) compared with healthy controls. The plasma acyl-ghrelin levels after STN DBS increased in pre-prandial and postprandial phase in PD patients at the investigated time points. Body weight gained on average 2.33 kg during the first 3 months after surgery. There was no correlation between the acyl-ghrelin plasma levels and BMI.After STN DBS in fasting and postprandial phase plasma acyl-ghrelin levels were increased. The results showed that STN DBS therapy elicited a modification of ghrelin levels, increasing its concentration in pre- and postprandial state. In addition, body weight was increased during 3 months after surgery.

Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description.

Insulin autoimmune syndrome (IAS), also named Hirata’s disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.

Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion

The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking. To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy. This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018. Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings. Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion). Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected. The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies.

Assessment of gastric acidity by short-duration intragastric pH-monitoring with standardised breakfast in functional and some other dyspepsias

IntroductionPreliminary assessment of gastric secretion in the treatment of organic and functional dyspepsia may offer advantages over the empirical administration of proton pump inhibitors suggested by most clinical guidelines.AimTo develop a simplified pH-metric test with standardised meal, and on its basis to perform an assessment of the functional state of gastric secretion in the most common dyspepsias.Material and methodsSerum pepsinogen 1 and 2 were used for reference. Intragastric pH-monitoring was performed during 45 min in basal phase and 135 min after provocative breakfast (507 kcal, 100 mg caffeine). Consecutive adults enrolled in the study were divided into groups: 1 – “Non-dyspeptic” – 30 persons; 2 – “Duodenal peptic ulcer” – 13; 3 – “GERD” – 82; and 4 – “Functional dyspepsia” – 125 patients.ResultsThere was a moderate association between concentration of pepsinogen-1 and parameters of pH-monitoring. The best correlation coefficients were for the nadir pH in basal conditions and the time of acid neutralisation > 3.5 after the meal – r = –0.534 and r = –0.541, respectively (p < 0.0001). Using these two parameters we considered discriminants for four patterns of acidity. Proposed criteria of Hipo-anacidity included an absence of active secretion of hydrochloric acid in basal (pHmin > 5) and postprandial phases, with the achievement of stable pH < 3.5 after 80 min from meal time. They showed sensitivity 88.9% and specificity 100%. In cases of a detected pattern of hyperacidity, these parameters were 80% and 66.67%, respectively. According to the prevalence of hyperacidic cases, the groups were ranked in the following order: duodenal ulcer (76.9%) – GERD (51.1%) – functional dyspepsia (40.8%) – non-dyspeptic (19.0%).ConclusionsAcid production is increased among patients with functional dyspepsia. There is a small number of patients with functional dyspepsia (12.1%) with hypochlorhydria due to atrophic gastritis. The latter was independently associated with age > 50 years (OR = 20.139), symptoms of postprandial distress-syndrome (OR = 9.821), and signs of atrophy (OR = 5.914) after conventional endoscopy.