Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson's disease

Aim: To determine gastric emptying, blood pressure, mesenteric artery blood flow, and blood glucose responses to oral glucose in Parkinson's disease. methods: Twenty-one subjects (13 M, 8 F; age 64.2 ± 1.6 years) with mild to moderate Parkinson's disease (Hoehn and Yahr score 1.4 ± 0.1, duration of known disease 6.3 ± 0.9 years) consumed a 75 g glucose drink, labelled with 20 MBq (99m)Tc-calcium phytate. Gastric emptying was quantified with scintigraphy, blood pressure and heart rate with an automated device, superior mesenteric artery blood flow by Doppler ultrasonography and blood glucose by glucometer for 180 min. Autonomic nerve function was evaluated with cardiovascular reflex tests and upper gastrointestinal symptoms by questionnaire. Results: The mean gastric half-emptying time was 106 ± 9.1 min, gastric emptying was abnormally delayed in 3 subjects (14%). Systolic and diastolic blood pressure fell (P < 0.001) and mesenteric blood flow and blood glucose (P < 0.001 for both) increased, following the drink. Three subjects (14%) had definite autonomic neuropathy and 8 (38%) had postprandial hypotension. There were no significant relationships between changes in blood pressure, heart rate or mesenteric artery blood flow with gastric emptying. Gastric emptying was related to the score for autonomic nerve function (R = 0.55, P < 0.01). There was an inverse relationship between the blood glucose at t = 30 min (R = -0.52, P < 0.05), while the blood glucose at t = 180 min was related directly (R = 0.49, P < 0.05), with gastric emptying. Conclusion: In mild to moderate Parkinson's disease, gastric emptying is related to autonomic dysfunction and a determinant of the glycaemic response to oral glucose.Laurence G Trahair, Thomas E Kimber, Katerina Flabouris, Michael Horowitz, Karen L Jone

Vitamin D3 replacement enhances antigen-specific immunity in older adults

This article has been accepted for publication in Immunotherapy Advances Published by Oxford University Press

Comparative effects of small intestinal glucose on blood pressure, heart rate, and noradrenaline responses in obese and healthy subjects

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m² ) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m² ) received intraduodenal infusions of glucose at 1 or 3 kcal/min, or saline, for 60 min (t = 0-60 min), followed by intraduodenal saline (t = 60-120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery.Laurence G. Trahair, Tongzhi Wu, Christine Feinle-Bisset, Chinmay S. Marathe, Christopher K. Rayner, Michael Horowi and Karen L. Jone

Effect of gastric distension with concurrent small intestinal saline or glucose infusion on incretin hormone secretion in healthy individuals - a randomised, controlled, cross-over study.

Aims There is increasing interest in the use of intragastric balloons as a weight loss procedure, however, the underlying mechanism(s) remain unclear. In rodents, gastric distension has recently been shown to stimulate the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) substantially, but the effect of gastric distension on GLP-1 and the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), in humans is not known. We conducted a randomized, controlled, crossover study to evaluate the effect of gastric distension, induced using a gastric 'barostat' on incretin hormones in healthy individuals Materials and methods Eight healthy participants (2 female, 6 male, mean age 69.3±1.2 years, and body mass index 23.5±0.8 kg/m²) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. Results Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P=1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P=1.00 for saline infusion and P=0.99 for glucose infusion). Conclusion We conclude that gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans. This article is protected by copyright. All rights reserved.Ryan J. Jalleh, Laurence G. Trahair, Tongzhi Wu, Scott Standfield, Christine Feinle-Bisset, Christopher K. Rayner, Michael Horowitz, Karen L. Jone

Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Background: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children’s Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children’s general and cancer-related health-related quality of life (HRQoL) and parents’ emotional well-being. Methods: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1–213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children’s HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL

Acute Administration of the GLP-1 Receptor Agonist Lixisenatide Diminishes Postprandial Insulin Secretion in Healthy Subjects But Not in Type 2 Diabetes, Associated with Slowing of Gastric Emptying

Published online 22 April 2022Introduction: It is uncertain whether lixisenatide has postprandial insulinotropic effects when its effect on slowing gastric emptying is considered, in healthy subjects and type 2 diabetes mellitus (T2DM). We evaluated the effects of single administration of 10 lg sc lixisenatide on glycaemia, insulin secretion and gastric emptying (GE), measured using the ‘gold standard’ technique of scintigraphy following an oral glucose load (75 g glucose). Methods: Fifteen healthy subjects (nine men, six women; age 67.2 ± 2.3 years) and 15 patients with T2DM (nine men, six women; age 61.9 ± 2.3 years) had measurements of GE, plasma glucose, insulin and C-peptide for 180 min after a radiolabeled 75 g glucose drink on two separate days. All subjects received lixisenatide (10 lg sc) or placebo in a randomised, double-blind, crossover fashion 30 min before the drink. Insulin secretory response (ISR) was determined using the C-peptide deconvolution method. Results: GE was markedly slowed by lixisenatide compared with placebo in both healthy subjects (1.45 ± 0.10 kcal/min for placebo vs. 0.60 ± 0.14 kcal/min for lixisenatide) and diabetes (1.57 ± 0.06 kcal/min for placebo vs. 0.75 ± 0.13 kcal/min for lixisenatide) (both P\0.001) with no difference between the two groups (P = 0.42). There was a moderate to strong inverse correlation between the early insulin secretory response calculated at 60 min and gastric retention at 60 min with lixisenatide treatment in healthy subjects (r = - 0.8, P = 0.0003) and a trend in type 2 diabetes (r = - 0.4, P = NS), compared with no relationships in the placebo arms (r = - 0.02, P = NS, healthy subjects) and (r = - 0.16, P = NS, type 2 diabetes). Conclusion: The marked slowing of GE of glucose induced by lixisenatide is associated with attenuation in the rise of postprandial glucose in both healthy subjects and diabetes and early insulin secretory response in healthy subjects.Chinmay S. Marathe . Hung Pham . Tongzhi Wu . Laurence G. Trahair . Rachael S. Rigda . Madeline D. M. Buttfield . Seva Hatzinikolas . Kylie Lange . Christopher K. Rayner . Andrea Mari . Michael Horowitz . Karen L. Jone