High plasma levels of soluble triggering receptor expressed on Myeloid Cells 2 were associated with depression in patients with newly diagnosed type 2 diabetes mellitus

Aims The hypothesis was that depressed patients compared to non-depressed patients with newly diagnosed type 2 diabetes mellitus (T2DM) had higher levels of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) as a sign of increased microglial activation. The aim was to explore a potential association between depression and sTREM2. Materials and methods Cross-sectional and multicentre study which included adults with serologically verified, newly diagnosed T2DM. Associations with depression and high sTREM2 (>3.38 pg/mL) were assessed using multiple regression analyses. Potential covariations were explored for age, sex, anxiety, soluble neuropilin-1 (sNRP-1), C-peptide, body mass index (BMI), Haemoglobin A1c, physical inactivity, smoking, and prior cardiovascular disease. ELISA techniques were used to analyse sTREM2, sNRP-1, and C-peptide. Results Included were 726 patients (aged 18–94 years, women 38%, depressed 16%, anxious 23%, physically inactive 32%). The prevalence was for high sTREM2 (>3.38 pg/mL) 20%, low sNRP-1 (<225.5 ng/ml) 24%, and high C-peptide (≥1.60 nmol/L) 26%. Associated with depression ( n = 630) were anxiety (adjusted odds ratio (AOR) 10.5, p < 0.001), low sNRP-1 (AOR 3.3, p < 0.001), high sTREM2 (AOR 2.0, p = 0.016), high C-peptide (AOR 1.9, p = 0.024), and physical inactivity (AOR 1.8, p = 0.025). Associated with high sTREM2 ( n = 656) were BMI (per kg/m 2 ) (AOR 1.08, p < 0.001) and depression (AOR 1.8, p = 0.015). Conclusions Depressed patients compared non-depressed patients with newly diagnosed T2DM had higher levels of sTREM2. High sTREM2, high C-peptide, low sNRP-1, physical inactivity, and anxiety, were independently associated with depression. Depression and BMI were independently associated with high sTREM2. The hypothesis was supported.