Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS)
Introduction
Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of depression than people without diabetes [1], and, furthermore, the mortality risk significantly increases with comorbid depression [2]. Hence, an evaluation of depression is very important in diabetes care.
Severe hypoglycemia is known to significantly increase the risk of cardiovascular disease and all-cause death in patients with T2DM [3], [4]. Depression is an independent risk factor for severe hypoglycemia in patients with T2DM [5]. Therefore, the increased risk of death by comorbid depression in patients with T2DM may be mediated by severe hypoglycemia. However, it has not been clarified whether the excess mortality caused by depression is independent of severe hypoglycemia in diabetic patients.
A meta-analysis of 22 observational prospective studies showed that the risk of death increased in those with subthreshold depression defined by a self-report scale [6]. Moreover, a significant relationship was reported between depressive symptoms and mortality even in depressive symptoms with a lower degree of severity than the cutoff value in depression screening [7], [8]. Therefore, regardless of the diagnostic criteria for depression, evaluation of how the risk of death varies with the degree of the depressive symptoms is important. However, previous research in T2DM has not shown sufficient data on the risk of death according to severity of depressive symptoms in patients with diabetes. These previous studies only evaluated the relationship between mortality and depression as a categorical variable or only assessed whether the depressive symptom score and mortality risk had a significant linear correlation [9], [10], [11], [12].
Hence, we aimed to evaluate whether the association between depressive symptoms and all-cause mortality is independent of severe hypoglycemia and to determine variations in the relationships between the degree of depressive symptoms and all-cause mortality after consideration of severe hypoglycemia in patients with T2DM.
Section snippets
Study population
This analysis is part of the Japan Diabetes Complications Study (JDCS), a multicenter prospective study of the incidence of and risk factors for diabetic complications and mortality among Japanese patients with T2DM. The JDCS was originally planned as a randomized lifestyle intervention study, and half of the participants received structured counseling. Details have been published elsewhere [13].
Participants in this study were between 40 and 70 years old and already had been diagnosed with T2DM
Results
Clinical characteristics of the 1060 patients with T2DM are shown in Table 1. The average CES-D score was 12.5 points (SD: 8.2, min: 0, max: 48) and prevalences of retinopathy, peripheral neuropathy, overt nephropathy, coronary artery disease, and stroke at baseline were 42.6%, 24.1%, 7.6%, 4.2%, and 2.7%, respectively. Therapeutic regimens for T2DM were diet only in 16.6%, oral hypoglycemic agents in 50.9%, and insulin in 32.5% of patients. The frequency of severe hypoglycemia during this
Discussion
In the current study, the severity of depressive symptoms was significantly associated with all-cause mortality after adjustment for potential confounders including severe hypoglycemia. Severe depressive symptoms may be a risk factor for death independent of severe hypoglycemia in T2DM. Additionally, the risk of death increased slowly at the lower level of total CES-D scores and increased acceleratingly at higher levels in patients with T2DM.
A meta-analysis revealed that the relative risk of
Conclusions
This study demonstrated that the severity of depressive symptoms was significantly associated with all-cause mortality in patients with T2DM independent of severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in our study population. Further research is needed to clarify whether mild depressive symptoms are significantly associated with mortality in patients with T2DM.
Conflicts of interest
The authors declare that there is no duality of interest associated with this manuscript.
Funding
This study was supported by grants from the Ministry of Health, Labor and Welfare. The sponsor had no role in the design and conduct of the study.
Author contributions
S.M., S.T., K.F., O.H., M.H., J.N., Y.A., Y.O., N.Y., and H.S. contributed to the conception and design of the study, acquisition, analysis and interpretation of data, and drafting and editing the manuscript. All of the authors approved the final version of the manuscript. H.S. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgements
We sincerely thank the late Professor Nobuhiro Yamada, who was a former director of the JDCS and always provided warm spiritual support to us all. We also thank all the patients, staff, and the diabetologists all over Japan for their long-standing collaboration in this study.
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