title: The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus.
abstract: A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (n = 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m(2), HbA(1c) = 7.7 ± 0.3%) and normal glucose-tolerant (NGT) subjects (n = 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m(2), HbA(1c) = 5.6 ± 0.1%) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function [disposition index (DI)] was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine [TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin] values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8; p < 0.001). IS positively correlated with fasting plasma glucose (r = 0.638, p < 0.001), 1-h plasma glucose (r = 0.483, p = 0.005), 2-h plasma glucose (r = 0.611, p < 0.001) and HbA1c (r = 0.469, p = 0.007). IS was inversely correlated with insulin sensitivity (r = -0.478, p = 0.006) and DI (r = -0.523, p = 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (M/I < 4). A state of subclinical inflammation defined and quantifiable by inflammatory score including TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin is associated with both hyperglycemia and whole-body insulin resistance in T2DM.
authors.affiliation: Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
authors.forename: G
authors.initials: G
authors.lastname: Daniele
authors.forename: R
authors.initials: R
authors.lastname: Guardado Mendoza
authors.forename: D
authors.initials: D
authors.lastname: Winnier
authors.forename: T V
authors.initials: TV
authors.lastname: Fiorentino
authors.forename: Z
authors.initials: Z
authors.lastname: Pengou
authors.forename: J
authors.initials: J
authors.lastname: Cornell
authors.forename: F
authors.initials: F
authors.lastname: Andreozzi
authors.forename: C
authors.initials: C
authors.lastname: Jenkinson
authors.forename: E
authors.initials: E
authors.lastname: Cersosimo
authors.forename: M
authors.initials: M
authors.lastname: Federici
authors.forename: D
authors.initials: D
authors.lastname: Tripathy
authors.forename: F
authors.initials: F
authors.lastname: Folli
mesh_terms: D052242:Adiponectin / Q000097:blood*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D012107:Research Design; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin