Hormones, glycaemia and innate immunity: correlates of NK cell dysfunction in type 2 diabetes

Abstract Objectives Type 2 diabetes mellitus (T2DM) is linked to impaired natural killer (NK) cell function and altered sex hormone homeostasis. We examined the associations of HbA 1c , sex hormones and NK-cell subsets with peripheral blood mononuclear cell (PBMC) cytotoxicity. Methods In this cross-sectional study, 58 patients with T2DM and 62 metabolically healthy controls were enrolled. PBMC cytotoxicity (specific lysis of K-562-GFP target cells, an NK cell-associated readout) was measured by flow cytometry. Serum estradiol, testosterone and HbA 1c were measured, and NK-cell subsets were quantified by flow cytometry. In an exploratory sub-cohort of 16 patients undergoing bariatric surgery, omental adipose tissue (OAT)-derived immune cells were compared with paired PBMCs. Results There was a reduction in PBMC cytotoxicity for men with T2DM compared to control men and for women compared to men with T2DM. Multiple regression analysis showed that the cortisol level and PBMC cytotoxicity were inversely correlated (adjusted R 2 =0.218), while the testosterone level and percentage of CD56 + CD16 + NK-cells were positively correlated (adjusted R2=0.218). The OAT-derived cells proved to be more cytotoxic than matched PBMCs (p=0.0005). Conclusions These are theory generating associations. The cross-sectional design and limited number of children in the OAT sub-cohort and the lack of surgical control group in the non-diabetic population limit the ability to make causal inferences and need to be confirmed in future prospective studies.