Document Detail


The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS).
MedLine Citation:
PMID:  23052060     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time.
METHODS: We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline.
RESULTS: MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (β = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (β = -0.016 [95% CI -0.041, 0.0083] for CRP; β = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (β = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (β = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI.
CONCLUSIONS/INTERPRETATION: We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.
Authors:
C C Lee; C Lorenzo; S M Haffner; L E Wagenknecht; A Festa; M O Goodarzi; D Stefanovski; N C Olson; J M Norris; M J Rewers; A J Hanley
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-10
Journal Detail:
Title:  Diabetologia     Volume:  56     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-18     Completed Date:  2013-05-28     Revised Date:  2014-04-10    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  112-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Atherosclerosis / epidemiology,  etiology*
Body Mass Index
Cohort Studies
Diabetic Angiopathies / blood,  epidemiology,  immunology,  metabolism
Female
Fibrinogen / analysis
Follow-Up Studies
Humans
Hypoglycemic Agents / blood,  pharmacokinetics*
Inflammation Mediators / blood
Insulin / blood,  pharmacokinetics*
Insulin Resistance*
Leptin / blood
Male
Metabolic Clearance Rate
Middle Aged
Overweight / blood,  immunology,  metabolism,  physiopathology*
Plasminogen Activator Inhibitor 1 / blood*
Prediabetic State / epidemiology,  etiology*
Prospective Studies
Risk Factors
United States / epidemiology
Grant Support
ID/Acronym/Agency:
DK-29867/DK/NIDDK NIH HHS; M01-RR-43/RR/NCRR NIH HHS; P30 DK048520/DK/NIDDK NIH HHS; R01 DK029867/DK/NIDDK NIH HHS; R01 HL058329/HL/NHLBI NIH HHS; R01-58329//PHS HHS; U01 HL047892/HL/NHLBI NIH HHS; U01-HL47892/HL/NHLBI NIH HHS; U01-HL47902/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Inflammation Mediators; 0/Insulin; 0/Leptin; 0/Plasminogen Activator Inhibitor 1; 0/SERPINE1 protein, human; 9001-32-5/Fibrinogen

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