Low Glucose Concentrations Induce a Similar Inflammatory Response in Monocytes from Type 2 Diabetic Patients and Healthy Subjects

Abstract

This study aims to assess the proinflammatory interleukin 1β (IL-1β) and anti-inflammatory IL-10 production by monocytes from 38 patients with type 2 diabetes and 31 controls in different glucose concentrations. Monocytes were incubated in low (2.5 mmol/L)-, normal (5.0 mmol/L)-, and high (20 mmol/L)-glucose conditions in the presence and absence of lipopolysaccharide (LPS). Monocytes from both patients and controls only produced a significant increase in IL-1β in low-glucose conditions (p < 0.01), and this phenomenon was amplified in the presence of LPS, while it was not seen in normal- or high-glucose conditions, not even in the presence of LPS stimulation. There was no increase in IL-10 production by monocytes from either diabetic patients or controls using whatever glucose concentrations, except when treated with LPS in normal-glucose conditions. These findings seem to suggest that low-glucose conditions induce an inflammatory response in monocytes in all individuals, as an intrinsic capacity of this cell line. On the other hand, monocytes only retain their anti-inflammatory ability in response to known inflammatory stimuli such as LPS, under normal-glucose concentrations. In conclusion, human monocytes express an inflammatory pattern in low-glucose conditions in vitro. This response could contribute to explaining the higher cardiovascular risk induced by hypoglycemia in diabetic patients.

Figure 1

IL-1β released by monocytes obtained from diabetic patients (n = 38) and control subjects (n = 31). (a) Basal conditions. (b) After stimulation with LPS (1 μg/mL). Dot plots show individual absolute values measured in the culture medium at different glucose concentrations: glucose 2.5 mmol/L, 5.0 mmol/L, and 20 mmol/L. Graphs are completed with box plots, where the ends of the box represent the 25th and 75th quantiles, respectively, while the horizontal line within the box represents the median value; whiskers extend the distances computed as 1st quartile − 1.5 × interquartile range and 3rd quartile + 1.5 × interquartile range. Following a significant two-way ANOVA, comparisons between glucose concentrations have been evaluated as paired data (see Table 2 for detailed statistics). No significant differences were detected with one-way ANOVA between controls and diabetic patients at each glucose concentration.