Association between pro- and anti-inflammatory cytokines and depressive symptoms in patients with diabetes-potential differences by diabetes type and depression scores

Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 +/- 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 +/- 8 years). Subclinical depression was examined using three questionnaires (Center for Epidemiologic Studies Depression [CES-D], Patient Health Questionnaire-9 [PHQ-9], 5-item World Health Organization Well-Being Index [WHO-5]). In T1D, levels of interleukin-1 receptor antagonist (IL-1RA) were positively associated with two depression scores (CES-D, PHQ-9), and high-sensitivity C-reactive protein (hsCRP) was positively associated with depression for one score (WHO-5) after adjustment for age, sex, body mass index, diabetes duration, metabolic variables, medication and comorbidities (P = 0.008-0.042). In T2D, IL-18 and IL-1RA were positively associated with depression for two scores (IL-18: PHQ-9, WHO-5; IL-1RA: CES-D, WHO-5), hsCRP was associated with one depression score (PHQ-9), and adiponectin showed an inverse association with one depression score (PHQ-9) after adjustment (P = 0.006-0.048). No associations were found for IL-6 and CC-chemokine ligand 2 (CCL2). In conclusion, we observed associations between hsCRP, IL-1RA and depressive symptoms in patients with diabetes. In T2D, there was additional evidence for associations of IL-18 and (inversely) adiponectin with depressive symptoms. The strength of the associations appeared to depend on diabetes type and the method used to asssess depressive symptoms.