In a national sample of men and women aged ≥50 years, we found that elevated depressive (CES-D) symptoms at baseline were associated with a higher risk of developing type 2 diabetes. This association did not vary according to age and sex and was largely independent of known correlates of diabetes and depression and cardiovascular, psychiatric, and other comorbidities. Hypothesized mechanisms through which elevated depressive symptoms might affect incident diabetes involving health behaviors, BMI, and use of antidepressants explained little or nothing of the association. From a public health perspective, the burden of diabetes that could be attributed to elevated depressive symptoms was comparable, although less, to the burden of diabetes that can be attributed to the lack of physical activity.
In accordance with most previous studies and two recent meta-analyses (11
), we found that elevated CES-D symptoms were associated with a higher risk of developing type 2 diabetes. Also, in agreement with previous studies (7
), we found that baseline somatic comorbidities did not confound this association. In addition, we found that baseline psychiatric comorbidities and cognitive impairments similarly did not confound this association. To our knowledge, this article is the first to adjust simultaneously for such a wide array of baseline somatic and psychiatric comorbidities.
Most previous studies have adjusted their models for a single SES indicator (typically, this was education) (4
). We accounted for SES in a more satisfactory way by adjusting not only for education but also for total net household wealth, which has been found to be related to diabetes more strongly than other indicators of SES in our sample (17
). We still found, in accordance with all previous reports, that SES did not fully explain the association between elevated depressive symptoms and incident diabetes. We did demonstrate, however, that SES had the strongest individual confounding effect on the association between baseline depressive symptoms and incident diabetes.
We hypothesized that obesity and unhealthy behaviors would be potential mechanisms linking depression to diabetes. Depression can lead to obesity, which is a major risk factor for diabetes through stimulating increased activity of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system (11
). Moreover, depression is related to unhealthy behaviors such as physical inactivity and smoking (18
), which are also risk factors for diabetes (19
). However, we found that neither BMI, despite being a powerful correlate of incident diabetes, nor health behaviors substantially mediated the association between CES-D and diabetes. These findings are in agreement with most but not all (6
) previous studies, which have shown that neither BMI nor health behaviors fully explained the observed association (3
). We also found that use of antidepressants and other psychotropic medication could not explain the observed association. This is consistent with the findings of most (6
) but not all (14
) previous studies and with our finding that obesity did not mediate the association between depression and diabetes, since use of antidepressants was expected to affect diabetes largely through change in weight (21
). Our findings in relation to use of antidepressants should be treated with some caution, since data on use of antidepressants and other psychotropic medication predate the ELSA baseline data.
Future research on the mechanism of the association between elevated depressive symptoms and incident diabetes should concentrate on factors other than obesity, unhealthy behaviors, and use of antidepressants. It is possible that there are common causes underlying the relationship, such as factors from early life that are risk factors for both depression and diabetes. Low birth weight has been found to be related to diabetes (22
) and possibly with depressive symptoms (23
). Further, low birth weight has been found to modify the association of diabetes or cardiovascular disease with depression in a sample of older adults (24
). Alternatively, there may be biological pathways where depression leads to biological changes, which then result in diabetes (11
). Biological pathways related to glucose homeostasis such as hypothalamic-pituitary-adrenocortical axis dysregulation and sympathetic nervous system stimulation warrant further exploration (21
). Inflammation is another candidate pathway, but was found not to explain the association between depression and diabetes in recent studies (8
The use of a large national sample of community-dwelling men and women aged ≥50 years is a major advantage of our study. The detailed assessment of SES and background psychiatric, cognitive, and physical health problems means that appropriate adjustment was made for a wide range of potential confounding variables. Accounting for both wealth and education diminished the chances of residual confounding because of inadequate adjustment for SES and therefore strengthened previous evidence that SES did not fully explain the association between depressive symptoms and incident diabetes. CES-D measures depressive symptoms experienced in the past week and, therefore, does not account for history of depression. By accounting for baseline psychiatric comorbidities, we showed that elevated baseline depressive symptoms were related to a higher risk of diabetes irrespective of background depressive disorder or other psychiatric disease.
A limitation of our study is the use of self-reported diabetes as the outcome measure. However, comparing baseline self-reported diabetes with objective information about the use of diabetes medication from wave 0 indicated minimal misclassification of cases of diagnosed diabetes. The possibility of undiagnosed diabetes influencing our findings remains. A recent cross-sectional study using data from wave 2 indicated that 18.5% (n
= 36) of all cases of diabetes in the ELSA sample were undiagnosed (25
). Reverse causality is thus a potential issue, since there is the possibility that some depressive symptomatology at baseline may be a result of undetected prevalent cases of diabetes. However, elevated CES-D symptoms remained related to risk of developing diabetes, even after having excluded from analysis all incident cases of diabetes that were diagnosed within the first 12 months after the baseline. Further, there is evidence showing that untreated diabetes is not associated with the incidence of depressive symptoms (10
Missing data and attrition are unavoidable in large cohorts based on a national general population sample such as ELSA. In supplementary analyses, we showed that our findings remained similar in a larger sample that included individuals with missing BMI information. We would expect attrition to have made our results more conservative, since individuals who dropped out from ELSA were less educated, and there is evidence (3
) that the depression-related risk of developing type 2 diabetes is higher among individuals who are less educated irrespective of age, sex, race, health behaviors, BMI, and family history of diabetes.
Our research suggests that elevated depressive symptoms were associated with a higher risk of developing type 2 diabetes in middle-aged and older adults. SES and baseline comorbidities including psychiatric diseases did not fully explain this association. There was little evidence that obesity, unhealthy behaviors, or use of antidepressants substantially mediated this association. Future research should explore the etiology and mechanism of this association. Action to prevent and treat depression might contribute to the fight against diabetes.