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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

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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/m2, HbA1c = 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/m2, HbA1c = 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.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

IS:

Inflammatory score

DEXA:

Dual-energy X-ray absorptiometry

FPG:

Fasting plasma glucose

OGTT:

Oral Glucose Tolerance Test

PG:

Plasma glucose

1 h PG:

1-Hour plasma glucose

2 h PG:

2-Hour plasma glucose

FRK:

Fractalkine

MCP-1:

Monocyte chemoattractant protein-1

TNF-α:

Tumor necrosis factor-α

IL-6:

Interleukin-6

IL-1β:

Interleukin-1β

OPN:

Osteopontin

IR:

Insulin resistance

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Acknowledgments

This work was presented in part in abstract form at the Endocrine Society Meeting, 2013, in San Francisco, CA, USA. G. D. was supported in part by a fellowship from Fo.Ri.SID, Italy.

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None.

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Authors and Affiliations

  1. Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    G. Daniele, R. Guardado Mendoza, D. Winnier, T. V. Fiorentino, Z. Pengou, F. Andreozzi, C. Jenkinson, E. Cersosimo, D. Tripathy & F. Folli

  2. Division of Health Sciences, Department of Medicine and Nutrition, Campus Leòn, University of Guanajuato, Leòn, Mexico

    R. Guardado Mendoza

  3. Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy

    T. V. Fiorentino & F. Andreozzi

  4. Department of Epidemiology and Biostatistic, University of Texas Health Science Center, San Antonio, TX, USA

    J. Cornell

  5. Department of Internal Medicine, University of Tor Vergata, Rome, Italy

    M. Federici

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  1. G. Daniele
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  2. R. Guardado Mendoza
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  10. M. Federici
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  12. F. Folli
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Correspondence to F. Folli.

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Communicated by Antonio Secchi.

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Daniele, G., Guardado Mendoza, R., Winnier, D. et al. 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. Acta Diabetol 51, 123–131 (2014). https://doi.org/10.1007/s00592-013-0543-1

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