Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp

Abstract The primary objective of this study was to evaluate insulin sensitivity in healthy subjects treated with olanzapine or risperidone. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d), risperidone (4 mg/d), or placebo for approximately 3 wk. Insulin sensitivity was assessed pre- and posttreatment using a 2-step, hyperinsulinemic, euglycemic clamp. Glucose and insulin responses were also assessed by a mixed meal tolerance test. Of the 64 subjects randomized, 22, 14, and 19 in the olanzapine, risperidone, and placebo groups, respectively, completed the study procedures. There were no significant within-group changes in the glucose disposal rate or the insulin sensitivity index for the active therapy groups. Further, the results of the mixed meal tolerance test did not demonstrate clinically significant changes in integrated glucose metabolism during treatment with these medications. In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone.

Download Full-text

The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Māori and Pacific ancestry

10.1101/2021.02.27.21252567 ◽

2021 ◽

Author(s):

Hannah J. Burden ◽

Shannon Adams ◽

Braydon Kulatea ◽

Morag Wright-McNaughton ◽

Danielle Sword ◽

...

Keyword(s):

Blood Glucose ◽

Insulin Sensitivity ◽

Insulin Release ◽

Plasma Insulin ◽

Tolerance Test ◽

Sensitivity Index ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp ◽

Significant Difference

AbstractAimThe minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased body mass index (BMI), but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Māori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes.MethodsA mixed meal tolerance test was completed by 172 men (56 with the A allele) of Māori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation.ResultsThe A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins GLP-1 or GIP. Consistent with this point, following an intravenous infusion of a glucose bolus, participants with an A allele had higher early (p<0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p>0.05) in insulin sensitivity index or glucose disposal during hyperinsulinemic-euglycemic clamp.Conclusion/interpretationrs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase maximal ability for β-cells to release insulin to reduce the risk of type 2 diabetes.

Download Full-text

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

Scientific Reports ◽

10.1038/s41598-021-91027-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kamal Albarazanji ◽

Andrea R. Nawrocki ◽

Bin Gao ◽

Xiaoli Wang ◽

Yixin Wang ◽

...

Keyword(s):

Gastric Emptying ◽

Glucose Homeostasis ◽

Plasma Glucose ◽

Nonhuman Primates ◽

Surrogate Marker ◽

Tolerance Test ◽

Mixed Meal ◽

C Peptide ◽

Meal Tolerance Test ◽

Mixed Meal Tolerance Test

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.

Download Full-text

AMENDED ID 107. Mycoprotein reduces endogenous glucose production when consumed with a mixed-meal tolerance test

10.26226/morressier.60b65c8a85c68bde00a35766 ◽

2021 ◽

Author(s):

Grainne Whelehan ◽

Sam West ◽

Tim Finnigan ◽

Francis Stephens

Keyword(s):

Glucose Production ◽

Tolerance Test ◽

Endogenous Glucose Production ◽

Mixed Meal ◽

Meal Tolerance Test ◽

Mixed Meal Tolerance Test ◽

Endogenous Glucose

Download Full-text

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

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(14)70251-7 ◽

2014 ◽

Vol 106 ◽

pp. S23

Author(s):

E. Nara ◽

T. Kitamoto ◽

Y. Matsuzawa ◽

J. Saito ◽

M. Omura ◽

...

Keyword(s):

Type 2 Diabetes ◽

Tolerance Test ◽

Loading Test ◽

Mixed Meal ◽

C Peptide ◽

Meal Tolerance Test ◽

Mixed Meal Tolerance Test

Download Full-text

Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after gastric bypass surgery: association with plasma amino acid concentrations

Surgery for Obesity and Related Diseases ◽

10.1016/j.soard.2018.05.010 ◽

2018 ◽

Vol 14 (8) ◽

pp. 1106-1117 ◽

Cited By ~ 2

Author(s):

Merel van den Broek ◽

Loek J.M. de Heide ◽

Marloes Emous ◽

Ragnhild B. Wijma ◽

Nic J.G.M. Veeger ◽

...

Keyword(s):

Gastric Bypass ◽

Amino Acid ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Gastrointestinal Hormones ◽

Tolerance Test ◽

Mixed Meal ◽

Meal Tolerance Test ◽

Mixed Meal Tolerance Test ◽

Amino Acid Concentrations

Download Full-text

Comparison of the rapid insulin sensitivity test (RIST), the insulin tolerance test (ITT), and the hyperinsulinemic euglycemic clamp (HIEC) to measure insulin action in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-102 ◽

2002 ◽

Vol 80 (8) ◽

pp. 811-818 ◽

Cited By ~ 27

Author(s):

Maria A.G Reid ◽

Martin G Latour ◽

Dallas J Legare ◽

Na Rong ◽

W Wayne Lautt

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Insulin Action ◽

Initial Response ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Sensitivity Test ◽

Euglycemic Clamp ◽

Hyperinsulinemic Euglycemic Clamp ◽

Insulin Tolerance

The objective was to compare the ability of the rapid insulin sensitivity test (RIST), the hyperinsulinemic euglycemic clamp (HIEC), and the insulin tolerance test (ITT) to detect hepatic insulin sensitizing substance (HISS) dependent insulin action. HISS action was augmented by feeding and inhibited by fasting, blockade of hepatic nitric oxide synthase, or blockade of hepatic muscarinic cholinergic receptors. A significant correlation was found between the RIST index and ITT nadir (r2 = 0.84) but not between the glucose infusion rate of the HIEC and RIST index. There was, however, a relationship between the RIST index and the initial response during the HIEC. Use of the HIEC resulted in HISS-dependent insulin resistance in both conscious and anesthetized animals. We concluded that since the RIST and ITT were comparable in quantifying both HISS-dependent and HISS-independent insulin action, the RIST was validated against this standard. The observation that the HIEC is capable of detecting HISS action in the first rising slope of the test but not at the end of the test and that HISS release is fully blocked after the conclusion of the HIEC raises concerns about the use of the commonly used HIEC.Key words: HISS, insulin resistance, insulin sensitivity tests.

Download Full-text

Myocardial Fat Accumulation Is Independent of Measures of Insulin Sensitivity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1139 ◽

2015 ◽

Vol 100 (8) ◽

pp. 3060-3068 ◽

Cited By ~ 10

Author(s):

Ranganath Muniyappa ◽

Radwa Noureldin ◽

Ronald Ouwerkerk ◽

Elizabeth Y. Liu ◽

Ritu Madan ◽

...

Keyword(s):

Insulin Sensitivity ◽

Serum Triglyceride ◽

Tolerance Test ◽

Cross Sectional Study ◽

Glucose Disposal ◽

Sensitivity Index ◽

Cross Sectional ◽

Peripheral Insulin Sensitivity ◽

Cardiac Steatosis ◽

Myocardial Steatosis

Background: Myocardial steatosis, an independent predictor of diastolic dysfunction, is frequently present in type 2 diabetes mellitus. High free fatty acid flux, hyperglycemia, and hyperinsulinemia may play a role in myocardial steatosis. There are no prior studies examining the relationship between insulin sensitivity (antilipolytic and glucose disposal actions of insulin) and cardiac steatosis. Objective: Using a cross-sectional study design of individuals with and without metabolic syndrome (MetSyn), we examined the relationships between cardiac steatosis and the sensitivity of the antilipolytic and glucose disposal actions of insulin. Methods: Pericardial fat (PF) volume, intramyocardial and hepatic fat (MF and HF) content, visceral fat (VF) and sc fat content were assessed by magnetic resonance imaging in 77 subjects (49 without MetSyn and 28 with MetSyn). In a subset of the larger cohort (n = 52), peripheral insulin sensitivity index (SI) and adipocyte insulin sensitivity (Adipo-SI) were determined from an insulin-modified frequently sampled iv glucose tolerance test. The Quantitative Insulin Sensitivity Check Index was used as a surrogate for hepatic insulin sensitivity. Results: Individuals with the MetSyn had significantly higher body mass index, total body fat, and MF, PF, HF, and VF content. HF and VF, but not MF, were negatively correlated with the Quantitative Insulin Sensitivity Check Index, Adipo-SI, and SI. Stepwise regression revealed that waist circumference and serum triglyceride levels independently predicted MF and PF, respectively. Adipo-SI and serum triglyceride levels independently predict HF. Conclusion: Myocardial steatosis is unrelated to hepatic, adipocyte, or peripheral insulin sensitivity. Although it is frequently observed in insulin-resistant subjects, further studies are necessary to identify and delineate pathogenic mechanisms that differentially affect cardiac and hepatic steatosis.

Download Full-text