Endocrine Abstracts

The prevalence of both type 2 diabetes and depression are increasing globally and previous research has demonstrated evidence that diagnosis with both conditions leads to poorer diabetes control and an increased likelihood of developing treatment resistant depression. However, the relationship between type 2 diabetes and depression is complex with many unanswered questions. The aim of our research is to use longitudinal health records and genetic analyses in 10,000s of individuals to establish a more complete understanding of the relationships between type 2 diabetes and depression. We have used summary statistics from the largest available published Genome Wide Association Studies (GWAS) of depression and type 2 diabetes to perform Mendelian randomisation (MR) to explore causal pathways between type 2diabetes and depression. We have also used data from an unpublished type 2 diabetes GWAS in >2.5 million individuals where they identify 8 clusters of genetic variants that increase an individual’s risk of type 2 diabetes via specific pathways (e.g. via adiposity based pathways). Our initial work indicates there was evidence that a higher genetic liability to depression predicted type 2 diabetes. A doubling of the depression risk was associated with a 1.04 (95%CI: 1.01, 1.08) higher odds of type 2 diabetes. There was also evidence of a bidirectional causal relationship between depression and type 2 diabetes but only when using the larger unpublished set of T2D variants and focusing on specific clusters of variants. This suggested that the association was driven by variants that predominantly acted via obesity and body fat pathways. Initial analyses in the UK Biobank study of 500,000 individuals suggests similar results. Initial work suggests bidirectional causal pathways between depression and type 2 diabetes and indicates the potential importance of adiposity/obesity pathways in this relationship.