Biomarkers of inflammation as determinants of depressive symptoms and response to depression treatment in patients with type 1 and type 2 diabetes

• Applicants: Dr. Dominic Ehrmann, Ph.D.; Professor Dr. Christian Herder; Professor Dr. Norbert Hermanns, Ph.D.
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491985376

Depression is one of the most frequent mental comorbidities in both patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). The high prevalence of depressive disorders in patients with diabetes represents a clinically relevant problem because it is linked with poorer long-term prognosis and higher mortality. Inflammation has been proposed as an important pathomechanism in patients with the double burden of diabetes and depression. However, the majority of studies on the relationship between inflammation, depression and diabetes (i) have a cross-sectional design, (ii) do not consider the impact of diabetes type, (iii) are limited to very few inflammation-related biomarkers and (iv) do not assess to what extent response to depression treatment is modulated by immune activation in patients with diabetes. Based on our previous work investigating the impact of step-care interventions for depression in patients with T1D and T2D and characterising the relationship between biomarkers of inflammation and the risk of diabetic complications, we now plan to combine data from 3 intervention studies (DIAMOS, ECCE-HOMO, DDCT; total n=789 including 514 patients with T1D, 275 patients with T2D; total follow-up time 2,700 patients-years) to test the following hypotheses:(1) A state-of-the-art multimarker assay (measuring 92 proteins) allows the identification of novel biomarkers and pathways of inflammation that are associated with depressive symptoms in T1D and T2D (cross-sectional analysis). (2) Changes of the levels of these biomarkers will be related to changes in depressive symptoms during the follow-up (longitudinal analysis). (3) Biomarkers of inflammation that predict response to an intervention targeting depressive symptoms and diabetes distress can be identified and differ between T1D and T2D (longitudinal analysis). (4) Stable patterns/clusters of associations between biomarkers of inflammation and depression subtypes can be identified (cross-sectional analysis). (5) Factors mediating the association between depression and inflammation, e.g. coping and self-management (cross-sectional and longitudinal analysis), can be identified.This project will be the first longitudinal study including both patients with T1D and T2D as well as a comprehensive assessment of systemic inflammation to clarify the question to what extent inflammation may mediate the risk of depression in patients with diabetes and if findings are specific for T1D and T2D or shared between both diabetes types. Depending on the results, we believe that the outcome of the project will enable us to design more effective intervention studies for diabetes patients with depression by including immunomodulating components and/or identifying non-responders to step-care approaches with the possibility of early treatment intensification.

• DFG Programme: Research Grants