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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:  Publisher    
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 (S(I)) (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 S(I)), had higher levels of TNF-α than subjects characterized by high insulin sensitivity (3.8 and 3.3 pg/ml in subjects with an S(I) 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     Date:  2012-1-11
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Pathology (N.C.O.) Pathology and Biochemistry (R.P.T.), University of Vermont College of Medicine, Burlington, Vermont 05405; Department of Medical Biostatistics (P.W.C.), University of Vermont, Burlington, Vermont 05405; Departments of Nutritional Sciences and Medicine and Dalla Lana School of Public Health (A.J.G.H.), University of Toronto, Toronto, Ontario, Canada M5S 3E2; Eli Lilly and Co. (A.F.), A-1030 Vienna, Austria; Department of Medicine (S.M.H.), Baylor College of Medicine, Houston, Texas 77030; and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.
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