OP45 PREDICTORS OF THE EFFECTIVENESS OF INCRETIN-BASED THERAPY: RESPONSIVENESS OF C-PEPTIDE TO MIXED MEAL TOLERANCE TEST AND GLUCAGON LOADING TEST IN JAPANESE TYPE 2 DIABETES

2014 ◽  
Vol 106 ◽  
pp. S23
Author(s):  
E. Nara ◽  
T. Kitamoto ◽  
Y. Matsuzawa ◽  
J. Saito ◽  
M. Omura ◽  
...  
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.


2013 ◽  
Vol 60 (9) ◽  
pp. 1077-1084 ◽  
Author(s):  
Wei-Cheng Lian ◽  
Jiunn-Diann Lin ◽  
Jin-Biou Chang ◽  
Chun-Hsien Hsu ◽  
Chun Pei ◽  
...  

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242360
Author(s):  
Morgan Obura ◽  
Joline W. J. Beulens ◽  
Roderick Slieker ◽  
Anitra D. M. Koopman ◽  
Trynke Hoekstra ◽  
...  

Aim Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D. Methods The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders. Results At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1–3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18–1.92) for subgroup 2 and 1.88 (-0.08–3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose. Conclusions Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.


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 ◽  
...  

2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Suzan Wopereis ◽  
Johanna H. M. Stroeve ◽  
Annette Stafleu ◽  
Gertruud C. M. Bakker ◽  
Jacobus Burggraaf ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document