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.

IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals

“…Furthermore, IL-6 regulates/stimulates production of cell adhesion molecules, chemotactic mediators, and acute phase protein, and mediates the release of other cytokines that amplify the inflammatory response (35)(36)(37). Similar to our result, other studies have shown that T2DM individuals have higher circulating IL-6 levels when compared to non-diabetic controls (38)(39)(40)(41)(42)(43). The increased levels of IL-6 and other inflammatory markers (IL-1β, CRP) emerge as early predictors of T2DM, preceding its clinical onset (44).…”

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood

“…A recent report assessing suitable biomarkers for evaluation of inflammation suggested that potentially patterns or clusters, as opposed to single inflammatory variables, may be more robust as biomarkers of inflammation (46) . In line with this report, a number of research groups have utilised inflammatory scores encompassing a range of inflammatory and antiinflammatory markers to assess sub-clinical inflammation and relating this to insulin sensitivity, which could be used to stratify cohorts based on inflammatory phenotype (114)(115)(116) . An increase in the inflammatory score was associated with an increase in IR, with a high inflammatory score associated with increased BMI, waist circumference and higher blood pressure (115) .…”

An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells

“…Overall, our data placed the upregulation of α-cell mass at a stage where β-cells exhibit normal or even enhanced function, which suggests that the upregulation of α-cell mass could be a primary driving force for hyperglycemia in animal models and human type 2 diabetes patients. The underlying mechanism could be an enrichment of some cytokines and microRNAs in subjects that have obesity, insulin resistance or type 2 diabetes (Daniele et al, 2014;Guardado-Mendoza et al, 2013;Poy et al, 2009), which selectively preserve the upregulation of α-cell mass (Ellingsgaard et al, 2008;Poy et al, 2009). Consistent with this idea, most patients with glucagon-secreting pancreatic neuroendocrine tumors are diabetic (Eldor et al, 2011).…”