| Circulating levels of TNF-α are associated with impaired glucose tolerance, increased insulin resistance, and ethnicity: the Insulin Resistance Atherosclerosis Study. | |
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MedLine Citation:
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PMID: 22238388 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-11 |
Journal Detail:
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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:
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Created Date: 2012-03-06 Completed Date: 2012-07-06 Revised Date: 2013-04-15 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1032-40 Citation Subset: AIM; IM |
Affiliation:
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Department of PathologyUniversity of Vermont College of Medicine, Burlington, VT 05405, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Insulin; 0/Tumor Necrosis Factor-alpha |
| Comments/Corrections | |
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