Depression a causal risk factor for coronary artery disease in diabetes

There appears to be genetic evidence that depression contributes to an increased risk of coronary artery disease (CAD) in patients with diabetes, as shown in the results of a Mendelian randomization study.

In the study, researchers drew data from the largest genome-wide association studies (GWAS) and examined single-nucleotide polymorphisms (SNPs) associated with depression (807,553 individuals), anxiety (83,556 individuals), and neuroticism (329,821 individuals). They extracted summary-level data for CAD from the recently published GWAS of 15,666 diabetic patients (3,968 CAD cases and 11,696 controls).

Analysis applying the inverse-variance weighted (IVW) method showed that genetic liability to depression had a significant association with a higher risk of CAD in patients with diabetes (odds ratio, 1.286, 95 percent confidence interval, 1.018–1.621; p=0.035).

On the other hand, anxiety and neuroticism was not causally associated with CAD.

Results were consistent on sensitivity analyses that included weighted median, maximum likelihood, and the MR-Egger method.

There are several possible mechanisms that could explain the causal effect of depression on CAD. In patients with depression, the secretion of the corticotropin-releasing hormone is high. As a result, glucocorticoids are overproduced, the sensitivity of glucocorticoid receptor is reduced, and the hypothalamic-pituitary-adrenal axis negative feedback mechanism is impaired. There is also evidence showing that behavioural changes (eg, irregular diet and treatment nonadherence) accompanied by depression could worsen blood sugar control and lead to insulin resistance. [Diabetes Care 2008;31:2398-2403]

The findings highlight a need for the provision of mental health treatments in patients with diabetes in order to prevent CAD.