Type 2 diabetes (T2DM) is promoted by systemic and low-grade inflammation in adipose tissue(AT). Group 1 innate lymphoid cells (ILC1s) regulate inflammatory processes and exacerbate metabolic dysfunction, but their significance in T2DM pathogenesis remains unknown. Here, a total of 41 newly-diagnosed T2DM subjects (age 43.4±1.9 year, BMI 29.3±1.1 kg/m2) and 43 matched non-T2DM subjects (age 42.5±1.0 year, BMI 28.3±1.2 kg/m2) were recruited and peripheral blood mononuclear cells (PBMCs) and visceral AT were obtained for measurement of ILC1s by flow cytometry. The results showed that the rates of circulating ILC1s were dramatically increased in T2DM subjects relative to non-T2DM patients (2.44%±0.47% vs. 0.56%±0.14%, p<0.001). Compared with those in the lowest circulating ILC1s tertile, subjects in the highest tertile had significantly higher HbA1c, fasting blood glucose (FBG) and Homeostasis model assessment of insulin resistance (HOMA-IR). Further correlation analysis revealed a positive correlation between the rates of circulating and adipose ILC1s (r=0.536, p=0.007). Remarkably, adipose ILC1s were significantly increased in T2DM subjects (1.70%±0.58% vs. 0.23%±0.17%, p=0.024). adipose ILC1s were positively associated with HbA1c (r=0.583, p=0.003) and FBG (r=0.494, p=0.014) after adjustment of age and BMI. In linear regression analysis, adipose ILC1s were the major determinants (β=0.629, p=0.004) of the variations of HbA1c. This study for the first time provided direct human evidence that ILC1s abnormalities are critically involved in the development of diabetes, suggesting their potential role as a therapeutic target in the treatment of T2DM.
F. Liu: None. Y. Bi: None. H. Wang: None.
