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

G. Daniele, R. Guardado Mendoza, D. Winnier, T. V. Fiorentino, Z. Pengou, J. Cornell, F. Andreozzi, C. Jenkinson, Eugenio Cersosimo, M. Federici, Devjit Tripathy, F. Folli

Research output: Contribution to journalArticle

121 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalActa Diabetologica
Volume51
Issue number1
DOIs
StatePublished - Feb 2014

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Chemokine CX3CL1
Osteopontin
Adiponectin
Hyperglycemia
Type 2 Diabetes Mellitus
Insulin Resistance
Interleukin-6
Glucose
Cytokines
Glucose Clamp Technique
Inflammation
Adipose Tissue
Fasting
Photon Absorptiometry
Glucose Tolerance Test
Obesity
Insulin

Keywords

  • Adiponectin
  • Disposition index
  • Euglycemic hyperinsulinemic clamp
  • Fractalkine
  • Glucose metabolism
  • IL-6
  • Inflammation
  • MCP-1
  • Osteopontin
  • TNF-α
  • Type 2 diabetes mellitus
  • Whole-body insulin sensitivity

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Daniele, G.; Guardado Mendoza, R.; Winnier, D.; Fiorentino, T. V.; Pengou, Z.; Cornell, J.; Andreozzi, F.; Jenkinson, C.; Cersosimo, Eugenio; Federici, M.; Tripathy, Devjit; Folli, F.

In: Acta Diabetologica, Vol. 51, No. 1, 02.2014, p. 123-131.

Research output: Contribution to journalArticle

Daniele, G, Guardado Mendoza, R, Winnier, D, Fiorentino, TV, Pengou, Z, Cornell, J, Andreozzi, F, Jenkinson, C, Cersosimo, E, Federici, M, Tripathy, D & Folli, F 2014, '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 Diabetologica, vol. 51, no. 1, pp. 123-131. https://doi.org/10.1007/s00592-013-0543-1
Daniele, G. ; Guardado Mendoza, R. ; Winnier, D. ; Fiorentino, T. V. ; Pengou, Z. ; Cornell, J. ; Andreozzi, F. ; Jenkinson, C. ; Cersosimo, Eugenio ; Federici, M. ; Tripathy, Devjit ; Folli, F. / 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. In: Acta Diabetologica. 2014 ; Vol. 51, No. 1. pp. 123-131.
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T1 - 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

AU - Daniele, G.

AU - Guardado Mendoza, R.

AU - Winnier, D.

AU - Fiorentino, T. V.

AU - Pengou, Z.

AU - Cornell, J.

AU - Andreozzi, F.

AU - Jenkinson, C.

AU - Cersosimo, Eugenio

AU - Federici, M.

AU - Tripathy, Devjit

AU - Folli, F.

PY - 2014/2

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N2 - 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.

AB - 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.

KW - Adiponectin

KW - Disposition index

KW - Euglycemic hyperinsulinemic clamp

KW - Fractalkine

KW - Glucose metabolism

KW - IL-6

KW - Inflammation

KW - MCP-1

KW - Osteopontin

KW - TNF-α

KW - Type 2 diabetes mellitus

KW - Whole-body insulin sensitivity

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