Cytokine profiling of young overweight and obese female African American adults with prediabetes

Abstract

Approximately 5–10% of subjects with prediabetes become diabetic every year. Inflammation is involved in the development of obesity-related type 2 diabetes (T2D). However, to date, the relationship between inflammation and prediabetes, defined by hemoglobin A1c (HbA1c) ≥ 5.7 and < 6.5%, remains largely unexplored, especially in African Americans. Therefore, in this study we examined a comprehensive panel of 13 cytokines involved in the inflammatory response in overweight/obese subjects with prediabetes. A total of 21 otherwise healthy, overweight/obese, young adult African American females with prediabetes, together with 20 matched overweight/obese controls, were selected for this study. Plasma cytokines were assessed by multiplex cytokine profiling. Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p < 0.05). Plasma concentrations of all the other cytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the prediabetic group, but failed to reach statistical significances. Upon merging both groups, HbA1c was found to be positively correlated with IFN- γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. This study demonstrates elevated levels of various pro-inflammatory cytokines in overweight/obese young subjects with prediabetes, which place them at higher risk of developing T2D and cardiovascular diseases. Our data also call for further investigations in animal models and population cohorts to establish the roles of a variety of pro-inflammatory cytokines in the early development of obesity-related T2D.

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

“…To this regard, it is important to take into account that DM and prediabetes are considered pro-inflammatory states (Lucas et al, 2013;Nwose et al, 2014) that could be favoring the onset of ED by oxidative stress and by impaired regulation of calcium metabolism (Haubner et al, 2007;Patel et al, 2013;Piarulli et al, 2013;Tousoulis et al, 2013). An interesting but scarcely studied mechanism, probably associated with the onset of ED in the prediabetic patient, could be linked to toll like-receptors.…”

“…Interestingly, the levels of these same markers were associated with the glucose levels in the prediabetic patient. Additionally, determination of interleukin-5 (IL-5), IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) associated with inflammatory processes revealed significantly higher values in prediabetic patients (Lucas et al, 2013). Likewise, cytokines such as interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL12p70, and IL-13 showed an increase in their levels, although not statistically significant.…”

“…Although diabetes and prediabetes are considered pro-inflammatory states (Lucas et al, 2013;Nwose et al, 2014), the role of TLR9 has been especially studied in type 1 diabetes. For example, in 2007, using biobreeding of diabetes-resistant rats (BBDR) that were later on infected with the parvovirus, Kilham rat virus (KRV), 25% of total animals infected with KRV developed DM1 (Zipris et al, 2007).…”

Cytokine Profile in Pregnant Women With Metabolic Disorders

“…В результате проведенного исследования мы вы-явили крайне низкое содержание IL-10 на фоне повышенных концентраций GM-CSF, IFNγ, IL-6 и TNFα в крови беременных с ГСД и ожире-нием. Схожие результаты были получены и в дру-гих исследованиях при обследовании больных с метаболическим синдромом [3], женщин с из-быточной массой тела и нарушением толерант-ности к глюкозе [11] и больных с ожирением [8]. Дополнительно к описанным выше негативным эффектам цитокинов IL-6 и TNFα следует ука-зать на связь повышенного уровня GM-CSF в крови и активации дендритных клеток с патоло-гическим ремоделированием сосудов и высоким риском развития заболеваний сердечно-сосуди-стой системы у лиц с инсулинорезистентностью и ожирением [14].…”

Endothelial Function in Pre-diabetes, Diabetes and Diabetic Cardiomyopathy: A Review

“…These results confirmed those coming from Rasmussen et al [23] demonstrating no increasing in adhesion molecules VCAM-1 and E-selectin expression on activated endothelial cells in patients suffering from diabetes and pre-diabetes. Nevertheless, Lucas et al [24] recently demonstrated the higher concentrations of serum cytokines [IL-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF)] in pre-diabetic patients as compared to matched controls. The combination of systemic inflammatory condition and high blood glucose levels is the mixture for the atherosclerosis development: apart from the increase in adhesion molecules concentrations, pre-diabetes and inflammatory condition are associates to plasma asymmetrical dimethyl-l-arginine (ADMA) thus to the development of early endothelial dysfunction in such individuals [25][26][27].…”