Cellular pathways of inflammation in prediabetes.

OBJECTIVES

Prediabetes is a major international problem that confers an increased risk for T2DM and CVD. There is scantly data on the role of cellular inflammatory pathways in prediabetes. We investigated the relationship between prediabetes and cellular biomarkers of inflammation.

METHODS

This study included patients with prediabetes (n=47) and controls (n=55). Fasting blood samples were obtained for circulating biomarkers and monocyte isolation. Also subcutaneous adipose tissue biopsies were performed in a subgroup.

RESULTS

Circulating biomarkers of inflammation were increased with prediabetes even following age adjustment. In monocytes there was a significant increase in TLR2 and its downstream signaling pathways including NFkB and P38 MAPkinase activity. In adipose tissue NLRP-3 inflammasome activity quantified by caspase1 was significantly increased whilst there was a trend to significance for IL-1beta. Also mast cells in AT were significantly increased.

CONCLUSIONS

In patients with prediabetes we present novel data supporting increased cellular pathways of inflammation in both monocytes and adipose tissue further underscoring the pro-inflammatory state of prediabetes as an important potential mechanism for the increase risk for T2DM and CVD.