Type 2 diabetes (T2D) has been associated with depressive symptoms, but the causal direction of this association and the underlying mechanisms, such as increased glucose levels, remain unclear. We used instrumental-variable regression with a genetic instrument (Mendelian randomization) to examine a causal role of increased glucose concentrations in the development of depressive symptoms.

Data were from the population-based Cardiovascular Risk in Young Finns Study (n = 1217). Depressive symptoms were assessed in 2012 using a modified Beck Depression Inventory (BDI-I). Fasting glucose was measured concurrently with depressive symptoms. A genetic risk score for fasting glucose (with 35 single nucleotide polymorphisms) was used as an instrumental variable for glucose.

Glucose was not associated with depressive symptoms in the standard linear regression (B = −0.04, 95% CI [−0.12, 0.04], p = .34), but the instrumental-variable regression showed an inverse association between glucose and depressive symptoms (B = −0.43, 95% CI [−0.79, −0.07], p = .020). The difference between the estimates of standard linear regression and instrumental-variable regression was significant (p = .026)

Our results suggest that the association between T2D and depressive symptoms is unlikely to be caused by increased glucose concentrations. It seems possible that T2D might be linked to depressive symptoms due to low glucose levels.