| Steroid-induced insulin resistance and impaired glucose tolerance are both associated with a progressive decline of incretin effect in first-degree relatives of patients with type 2 diabetes. | |
| | |
MedLine Citation:
|
PMID: 22286551 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
AIMS/HYPOTHESIS: The aim of this study was to evaluate the separate impact of insulin resistance and impaired glucose tolerance (IGT) on the incretin effect. METHODS: Twenty-one healthy glucose-tolerant first-degree relatives of patients with type 2 diabetes underwent a 75 g OGTT, an isoglycaemic i.v. glucose test and a mixed meal to evaluate the incretin effect before and after treatment with dexamethasone to increase insulin resistance. Beta cell glucose sensitivity, beta cell index and fasting proinsulin were measured as indices of beta cell function. RESULTS: After dexamethasone, ten individuals had increased insulin resistance but normal glucose tolerance (NGT), while 11 individuals with an equal increase in insulin resistance developed IGT. In the NGT and IGT groups, the incretin effects were 71 ± 3.2% and 67 ± 4.6% (p = 0.4) before treatment, but decreased significantly in both groups to 58 ± 5.2% and 32 ± 8.8% (p < 0.05 between groups) after treatment. Dexamethasone increased total glucagon-like peptide-1 and glucose-dependent insulinotropic peptide responses to the OGTT. The impaired incretin effect in NGT was observed in the absence of reductions in beta cell glucose sensitivity and beta cell index during i.v. glucose, corrected for insulin resistance, but in parallel with increased proinsulin/C-peptide ratio. CONCLUSION/INTERPRETATION: Insulin resistance and IGT, representing two stages in the path towards diabetes, are associated with differential reductions in the incretin effect seen before the development of IGT and overt type 2 diabetes. The reduction is unrelated to secretion of incretin hormones, but is related to insulin resistance and subtle beta cell defects, and is further aggravated on development of IGT. TRIAL REGISTRATION: ClinicalTrials.gov NCT00784745. FUNDING: This study was supported by a grant from the Novo Nordisk Foundation. |
| | |
Authors:
|
D H Jensen; K Aaboe; J E Henriksen; A Vølund; J J Holst; S Madsbad; T Krarup |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-29 |
Journal Detail:
|
Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-30 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Endocrinology, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark, David_hebbelstrup_Jensen@hotmail.com. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sources and distribution of hexabromocyclododecanes (HBCDs) in Japanese river sediment.
Next Document: Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 di...