ObjectiveTo determine the mediating role of hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-thyroid axis (HPT) axis in anxiety disorder in patients with diabetes mellitus. MethodsA total of 562 hospitalized patients with anxiety disorder participate in the study. Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), free tetraiodothyronine (FT4), adrenocorticotropic hormone (ACTH) and cortisol (PTC) were measured. Glucose tolerance test (OGTT) was performed, estimating insulin resistance index (HOMA IR) and insulin sensitivity index (WBISI). ResultsOf the participants, 83 (14.8%) had diabetes. In those who were younger than 40 yr., the diabetic patients were more likely to have abnormal FT4 and HPT ( POR=1.067,95%CI:1.041-1.094, P=0.000) and have higher FT4 (OR=1.104,95%CI:1.022-1.193, P=0.012) and PTC (OR=1.001,95%CI:1.000-1.003, P=0.025). Insulin resistance index increased while insulin sensitivity index decreased ( P P