Subclinical inflammation and depressive symptoms in patients with type 1 and type 2 diabetes

Depression is a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Depression and diabetes are linked by a bidirectional relationship, but the underlying mechanisms are still incompletely understood. Experimental, observational and intervention studies showed that inflammatory processes contribute to the development of depression in animal models and humans. Given the high risk of morbidity and mortality in patients with the double burden of diabetes and depression, this review provides an overview of epidemiological studies that addressed the relationship between biomarkers of inflammation and depressive symptoms or depression in diabetes patients. In patients with T1D, there is some evidence that higher levels of high-sensitivity C-reactive protein (hsCRP), IL-6, IL-1 receptor antagonist (IL-1RA) and sICAM-1 may be related to depressive symptoms or (for hsCRP) lower treatment response. For T2D, hsCRP, IL-1RA, CCL2 and adiponectin or its isoforms were associated with depressive symptoms in at least two studies, whereas positive associations of IL-1, IL-6 and IL-18 with depressive symptoms or depression were reported from single cohorts. However, the number of studies is too low for any meaningful meta-analysis. Prospective life course studies including both patients with T1D and T2D, a comprehensive assessment of systemic inflammation and repeated assessment of depressive symptoms should represent a future research priority to clarify to what extent subclinical inflammation affects the risk of depression in patients with diabetes. A better understanding of the role of inflammatory processes may help to identify subtypes of depression with partly different pathogenesis, which could have consequences with respect to therapeutic options including immunomodulation.