Document Detail


Circulating levels of TNF-α are associated with impaired glucose tolerance, increased insulin resistance, and ethnicity: the Insulin Resistance Atherosclerosis Study.
MedLine Citation:
PMID:  22238388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Although several epidemiological studies have investigated associations between TNF-α and insulin resistance, results have been inconsistent. We studied the relationship between TNF-α and glucose tolerance status as part of the Insulin Resistance Atherosclerosis Study.
RESEARCH DESIGN AND METHODS: Serum concentrations of TNF-α were measured in 1558 individuals in a triethnic population across a spectrum of glucose tolerance. Insulin sensitivity and insulin secretion were assessed by a frequently sampled iv glucose tolerance test (FSIGT).
RESULTS: Compared with those with normal glucose tolerance, circulating levels of TNF-α were elevated in individuals with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2D) after adjusting for age, gender, ethnicity, clinic site, and body mass index (3.3, 3.5, and 3.7 pg/ml in subjects with normal glucose tolerance, IGT, and T2D, respectively; P<0.05). Age-, sex-, and body mass index-adjusted levels of TNF-α differed by ethnicity, with Hispanics having the highest levels and African-Americans having the lowest (4.1, 3.6, and 3.0 pg/ml in Hispanics, non-Hispanic whites, and African-Americans, respectively; P<0.05). TNF-α was correlated with waist circumference, high-density lipoprotein, triglycerides, plasminogen activator inhibitor-1 and insulin sensitivity index (SI) (r=0.22, -0.30, 0.35, 0.31, and -0.25; P<0.0001); however, correlations varied by ethnicity. After adjusting for demographics and adiposity, individuals characterized by increased insulin resistance (lower SI), had higher levels of TNF-α than subjects characterized by high insulin sensitivity (3.8 and 3.3 pg/ml in subjects with an SI below/above the median at baseline; P<0.0001). No differences were found for acute insulin response.
CONCLUSIONS: We confirm that TNF-α is associated with IGT and T2D in a large, multiethnic population, independent of measures of adiposity. Adjusted values of TNF-α, as well as relationships between TNF-α and variables related to T2D, varied by ethnicity. Increased TNF-α levels were predominantly associated with insulin resistance but not with primary defects in β-cell function.
Authors:
Nels C Olson; Peter W Callas; Anthony J G Hanley; Andreas Festa; Steven M Haffner; Lynne E Wagenknecht; Russell P Tracy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-11
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  97     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-06     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1032-40     Citation Subset:  AIM; IM    
Affiliation:
Department of PathologyUniversity of Vermont College of Medicine, Burlington, VT 05405, USA.
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MeSH Terms
Descriptor/Qualifier:
African Americans
Diabetes Mellitus, Type 2 / blood*,  physiopathology
European Continental Ancestry Group
Female
Glucose Intolerance / blood*,  physiopathology
Glucose Tolerance Test
Hispanic Americans
Humans
Insulin / secretion*
Insulin Resistance / physiology*
Male
Middle Aged
Tumor Necrosis Factor-alpha / blood*
Grant Support
ID/Acronym/Agency:
HL-47887/HL/NHLBI NIH HHS; HL-47889/HL/NHLBI NIH HHS; HL-47890/HL/NHLBI NIH HHS; HL-47892/HL/NHLBI NIH HHS; HL-47902/HL/NHLBI NIH HHS; HL-55208/HL/NHLBI NIH HHS; M01 RR01346/RR/NCRR NIH HHS; M01 RR431/RR/NCRR NIH HHS; R01-HL-58329/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/Tumor Necrosis Factor-alpha
Comments/Corrections

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