Depression is associated with diabetes, but the underlying causes remain unclear. To better understand depression in diabetes, this study investigated associations between 135 inflammatory and neurological protein biomarkers and depressive symptoms in individuals with diabetes.This cross-sectional study included 430 adults with a known diabetes duration <
1 year from the German Diabetes Study (GDS), in whom biomarkers were measured in serum and depressive symptoms were evaluated at baseline and annually over 5 years using the Center for Epidemiological Studies Depression Scale (CES-D). Based on the information on depressive symptoms from the baseline and follow-up visits (n=305, ≥3 time points), we subdivided the sample into individuals with persistent or recurrent and transient or never depressive symptoms. We assessed the associations of each biomarker with baseline CES-D score (continuous) and persistent/recurrent depressive symptoms using multiple linear and logistic regression models, respectively.After adjustment for covariates, we identified a three-protein signature associated with baseline CES-D score and persistent/recurrent depressive symptoms. CUB domain-containing protein 1 (CDCP1) and NAD-dependent protein deacetylase sirtuin-2 (SIRT2) were positively associated with baseline (β 1.24 (95% CI 0.19 to 2.29)
β 0.89 (95% CI 0.06 to 1.72)), respectively) and persistent/recurrent depressive symptoms (OR 1.58 (95% CI 1.08 to 2.31)
OR 1.32 (95% CI 1.03 to 1.71), respectively), whereas leptin receptor (LEPR) was inversely associated with baseline (β -0.99 (95% CI -1.87 to -0.11)) and persistent/recurrent depressive symptoms (OR 0.70 (95% CI 0.49 to 0.99)). However, results were not significant after adjustment for multiple testing.In conclusion, the three-protein signature identified may provide insights into mechanisms underlying depressive symptoms in diabetes and might open new therapeutic avenues.The trial registration number of the study is NCT01055093.