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Cited by 216Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance.

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Cavaghan, M K, Ehrmann, D A, Byrne, M M, Polonsky, K S·1997·Journal of Clinical Investigation
DOI 10.1172/jci119562PMC PMC508219
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Abstract

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM).Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion.We sought to determine the role of ␤ cell function in mediating improved glucose tolerance.Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone ( n ϭ 14) or placebo ( n ϭ 7) in a randomized, double-blind design.Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (S I ) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and ␤ cell glucose-sensing ability during an oscillatory glucose infusion.Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% ( P ϭ 0.03) and 39% ( P ϭ 0.003), respectively.S I increased from 1.3 Ϯ 0.3 to 2.6 Ϯ 0.4 ϫ 10 Ϫ 5 min Ϫ 1 pM Ϫ 1 ( P ϭ 0.005).Average insulin secretion rates adjusted for S I over the glucose interval 5-11 mmol/liter were increased by 52% ( P ϭ 0.02), and the ability of the ␤ cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% ( P ϭ 0.04).No significant changes in these parameters were demonstrated in the placebo group.In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced ␤ cell response to glucose characteristic of subjects with IGT.This appears to be an important factor in the observed improvement in glucose tolerance.( J. Clin.Invest.1997.100: 530-537.)Key words: thiazoles • insulin resistance • insulin secretion • non-insulin-dependent diabetes mellitus • glucose intolerance Methods SubjectsThe study design was that of a double blind, placebo-controlled clinical trial in which two subjects were assigned to treatment with troglitazone for every one subject treated with placebo.Randomization was performed by Parke-Davis Pharmaceutical Research Division, Warner Lambert Co. (Ann Arbor, MI), who kindly provided the study medication and placebo.The groups were well matched for age, degree of obesity, and extent of glucose intolerance (for all compari-

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  • Subjects at high risk of developing Type 2 diabetes, including first-degree relatives, women with a history of gestational diabetes or polycystic ovarian disease, older subjects, and subjects with impaired glucose tolerance, have diminished beta-cell function, manifest as a reduced first-phase insulin response to intravenous glucose relative to insulin sensitivity, even when many still have NGT.

    “Based on the concept of a feedback loop, it has become evident that subjects who are at high risk of developing Type 2 diabetes have diminished beta-cell function at a time when many of them still have NGT.”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [105]

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Authors
Cavaghan, M. K., Ehrmann, D. A., Byrne, M. M., & Polonsky, K. S.
Affiliations
University of Chicago (US)
ORCID
Byrne, M M
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1997-08-01
Volume
100
Issue
3
Pages
530-537
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci119562
PMC
PMC508219
OpenAlex
W2085390992
Cited by
216
References
63
Citations by year
2026: 4 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 3 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 2 · 2012: 5
FWCI
10.73
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k08dk002315-02)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-31842, DK 20595, DK-02315)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
troglitazone, impaired glucose tolerance, beta-cell function, insulin secretion, insulin sensitivity, insulin resistance, type 2 diabetes, glucose tolerance, thiazolidinediones, oral glucose tolerance test, insulin sensitivity index, insulin secretion rate, type 2 diabetes prevention, insulin sensitizers
MeSH terms
Troglitazone, Administration, Oral, Adult, Animals, Chromans, Double-Blind Method, Female, Glucose, Glucose Tolerance Test, Guinea Pigs, Humans, Hypoglycemic Agents, Islets of Langerhans, Male, Middle Aged, Thiazoles, Treatment Outcome, Glucose Intolerance, Thiazolidinediones

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