In this population-based study of patients with type 2 diabetes, we found that compared with no depression, major depression and minor depression were associated with slightly higher average HbA1c levels during follow-up after adjustment for demographic characteristics. However, these associations were attenuated and became non-significant after adjustment for clinical characteristics including diabetes duration and treatment and cardiovascular disease. There was no difference by depression status in average SBP or LDL cholesterol level during follow-up.
The strengths of our study include the population-based design, the careful assessment of depression status at study enrollment, the availability of detailed information on patient characteristics that may be related both to depression and to risk factor control measures, and access to automated data on all measurements of HbA1c and LDL cholesterol conducted at Group Health during follow-up. We did not find strong evidence of differential risk factor measurement across the depression groups, possibly because all individuals under study were members of the same health plan. Regarding study power, the width of the confidence intervals in Table provides an indication of the differences in risk factor levels detectable with this sample size. Considering the estimates adjusted for demographic and clinical characteristics, the study was able to exclude a difference between those with major depression vs. no depression greater than 0.24% for HbA1c, greater than 1.1 mmHg for SBP, and greater than 4.4 mg/dl for LDL cholesterol. Thus, this study had adequate power to detect clinically important differences in risk factor control.
Limitations of this study include the assessment of depression at only one point in time, the possible misclassification of depression status by the PHQ-9, the possibility of unknown or unmeasured confounding factors, and the study of only three risk factors: glycemia, blood pressure, and lipid levels. Further, the study included only patients enrolled at Group Health and only those who gave permission to use medical information during follow-up. These patients may have received medical care that differs from care available in other settings, and those who gave permission may have differed from those who declined permission in unmeasured ways. Finally, the association between diabetes and depression is thought to be bidirectional,11
with diabetes increasing risks of depressive illness as well as depression increasing the risk of diabetes onset. Therefore, it is possible that declines in health prior to study enrollment led to differences in depression status at enrollment, so that the observed differences represent a continuation of a process that began prior to our study of these individuals.
Few studies have examined the association of depression with long-term risk factor control in individuals with diabetes. A small study of 110 African-American patients with diabetes reported no association of depression with glycemic, blood pressure, or lipid control over a 3-year period.12
A recent study in US veterans with type 2 diabetes reported a slightly higher average adjusted HbA1c
(+0.13%, 95% CI 0.03–0.22) in patients with depression compared with those without depression during an average 4.1 years’ follow-up.13
In that study, diabetes and depression diagnoses and cardiovascular co-morbidity were all identified using International Classification of Diseases, 9th revision (ICD-9) codes only. The prevalence of depression in the VA study was only 6%, compared with 12% with major depression and 20% with either major or minor depression in our study. This difference in depression prevalence is consistent with the finding that physicians make an accurate diagnosis in only 40% to 50% of patients with comorbid major depression and diabetes.7
In the VA study, adjustment for clinical characteristics had relatively little effect on the strength of the association between depression and glycemic control, while in our study, which included medical record review to assess cardiovascular co-morbidity, adjustment for these characteristics attenuated the association. These findings suggest that careful measurement of confounding factors is critical in studies of patients with co-morbid diabetes and depression, and that after thorough adjustment for confounding, an association of depression with long-term glycemic control is weak or absent.
Depression in individuals with diabetes is associated with higher mortality,1–4
higher risk of major complications,1,5
and less favorable functional outcomes.14
Prior publications suggest that compared with patients without depression, patients with comorbid diabetes and depression have poorer self-reported diabetes self-management15
and specifically report a lower frequency of checking blood glucose levels, less physical activity, a less healthy diet, and lower adherence to oral hypoglycemic, antihypertensive, and lipid-lowering medications.6
However, no or few differences have been found between depressed and nondepressed patients with diabetes on physician-ordered tests such as number of HbA1c
or lipid panels drawn per year or the percent of patients receiving an annual retinal exam.6
Because depressed patients with diabetes have a significantly higher number of primary care visits per year,16
physicians may have more opportunity to order tests and specialist examinations and to increase treatment intensity. Such increased attention could potentially improve risk factor control.
The findings of no association of depression with long-term risk factor control in the present study, and the relatively weak association of depression with HbA1c
in the study by Richardson et al., are surprising. These results suggest that an adverse effect of depression on outcomes in patients with diabetes may not be mediated in large part by poorer control of these risk factors and that biologic factors need further study. In studies of both community respondents and those with cardiovascular disease, depression has been associated with adverse biologic effects,17
including dysregulation of the hypothalamic-pituitary axis, increases in platelet adhesiveness18
and other pro-inflammatory markers19,20
such as interleukin-6 and C-reactive protein, and abnormalities in the autonomic nervous system such as decreased heart rate variability.21
Further study is needed in patients with diabetes of the biologic sequelae of depression and their relationship with adverse outcomes.