scholarly journals Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kamal Albarazanji ◽  
Andrea R. Nawrocki ◽  
Bin Gao ◽  
Xiaoli Wang ◽  
Yixin Wang ◽  
...  

AbstractMeal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

Diabetes Care ◽  
2011 ◽  
Vol 34 (3) ◽  
pp. 607-609 ◽  
Author(s):  
R. E. J. Besser ◽  
J. Ludvigsson ◽  
A. G. Jones ◽  
T. J. McDonald ◽  
B. M. Shields ◽  
...  

Diabetes Care ◽  
2012 ◽  
Vol 36 (2) ◽  
pp. 195-201 ◽  
Author(s):  
R. E. J. Besser ◽  
B. M. Shields ◽  
R. Casas ◽  
A. T. Hattersley ◽  
J. Ludvigsson

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
David Hopkins ◽  
Geltrude Mingrone ◽  
Guruprasad P Aithal ◽  
Vijeta Bhambhani ◽  
Guido Costamagna ◽  
...  

Abstract BACKGROUND: The duodenum is a key metabolic signaling center and regulator of metabolic homeostasis. Duodenal mucosal hyperplasia is therefore a potential therapeutic target for metabolic diseases related to insulin-resistance. Previous reports demonstrated that DMR, a minimally invasive, endoscopic mucosal ablative procedure, safely improves hepatic and glycemic parameters. Primary endpoints from REVITA-2, the first randomized, sham-controlled, double-blind, prospective, multicenter study of DMR safety and efficacy in patients with T2D, were met and previously reported. Here we further explore mechanisms underlying the beneficial effects of DMR on hepatic and glucose metabolism by analyzing mixed meal tolerance test (MMTT) data from the REVITA-2 study. Methods: Eligible patients (HbA1c 7.5–10%, BMI ≥ 24 to ≤ 40 kg/m2, on stable treatment with ≥1 oral anti-diabetic medication) received DMR or sham procedure (1:1). Exploratory endpoints included median change in fasting plasma glucose (FPG), MMTT glucose area under the curve (AUC) over 2 hours, and change in MMTT C-peptide and glucagon over 2 hours, from baseline to 12 weeks post-DMR. One-sided P value based on ANCOVA model on ranks without imputation assessed treatment difference at the 0.05 significance level. The modified intent to treat primary analysis population included randomized patients in whom study procedure was attempted. Results: A total of 70 patients (DMR, N = 35; sham, N = 35) were included in the analysis, of which 57% and 54% (DMR, n = 20; sham, n = 19) had baseline FPG ≥ 180 mg/dL. Median MMTT AUC for glucose was significantly reduced post-DMR (-36.38 mg/dL) compared with sham (-4.94 mg/dL; P = 0.009), driven by a significant decrease in FPG (DMR, -41.0 mg/dL; sham, -15.0 mg/dL; P = 0.003) rather than median MMTT postprandial glucose excursion (DMR, -4.63 mg/dL; sham, 5.34 mg/dL; P = 0.209). AUC glucose reductions were more pronounced in patients with baseline FPG ≥ 180 (DMR, -63.03 mg/dL; sham, -20.31 mg/dL; P = 0.007) compared with baseline FPG < 180 (DMR, -26.81 mg/dL; sham, 13.81 mg/dL; P = 0.271). In patients with baseline FPG ≥ 180, postprandial C-peptide excursion was significantly increased (DMR, 0.41 ng/mL; sham, 0.02 ng/mL; P = 0.012) and postprandial glucagon excursion was significantly decreased (DMR, -8.03 pg/mL; sham, 2.13 pg/mL; P = 0.027). Conclusion: DMR markedly improves glucose responses to a mixed meal challenge, primarily driven by a decrease in FPG, suggesting a primary effect on insulin resistance. Increases in C-peptide and reductions in glucagon levels suggest improvement in beta cell function in addition to improvements in hepatic insulin sensitivity, and ratifies the position of the duodenum as both a culprit endocrine organ and therapeutic target for patients with T2D.


2019 ◽  
Vol 20 (3) ◽  
pp. 282-285 ◽  
Author(s):  
Yue Ruan ◽  
Ruben H. Willemsen ◽  
Malgorzata E. Wilinska ◽  
Martin Tauschmann ◽  
David B. Dunger ◽  
...  

2012 ◽  
Vol 22 (2) ◽  
pp. 73-74
Author(s):  
Abu Saleh Md. Moosa ◽  
Shahina Akther

Caffeine containing beverages is widely used and popular world-wide. Studies showed that caffeine acutely decreased insulin sensitivity in young, non-diabetic adults.3-5 This double-blind study was carried out with habitual coffee drinkers who had at least a 6-months history of type II diabetes. The effects of caffeine on fasting glucose & insulin levels and on glucose & insulin response to a mixed-meal tolerance test were studied. The total daily caffeine intake was 375 mg in a divided schedule. Overnight fast and caffeine abstinence baseline fasting blood samples were drawn then after administration of caffeine (250 mg/day) or placebo they consumed a commercial meal that contained 75 gram of carbohydrate for mixed-meal tolerance test. Comparisons of the AUC2h values demonstrated significant caffeine effects for both plasma glucose and plasma insulin (P < 0.05) responses to the mixed-meal tolerance test. Caffeine did not affect the fasting levels of plasma glucose or insulin when compared with placebo. It may be concluded that acute administration of caffeine plus carbohydrate impaired post-prandial glucose metabolism and insulin responses. Such effects could have implication for the management of type II diabetic patients. Medicine Today 2010 Volume 22 Number 02 Page 73-74 DOI: http://dx.doi.org/10.3329/medtoday.v22i2.12437


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3090 ◽  
Author(s):  
Chun Yeh ◽  
Hsien-Hao Huang ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Kong-Han Ser ◽  
...  

Background The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery. Methods A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUC (ΔAUC) were compared between the two groups. Results One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC0′–180′ of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC0′–180′ for hunger and ΔAUC0′–180′ for desire to eat in the GB group, while negatively correlated with ΔAUC0′–180′ for fullness in the SG group. Discussion Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery.


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