Depression and incident diabetic retinopathy: a prospective cohort study

doi:10.1016/j.genhosppsych.2011.05.021

General Hospital Psychiatry

Volume 33, Issue 5, September–October 2011, Pages 429-435

https://doi.org/10.1016/j.genhosppsych.2011.05.021 Get rights and content

Abstract

Objective

This study examined whether depression is associated with a higher incidence of diabetic retinopathy among adults with type 2 diabetes after controlling for sociodemographic factors, health risk behaviors and clinical characteristics.

Method

This study included 2359 patients enrolled in Pathways Epidemiologic Follow-Up Study, a prospective cohort study investigating the impact of depression in primary care patients with type 2 diabetes. The predictor of interest was baseline severity of depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9). The outcome was incident diabetic retinopathy. Risk of diabetic retinopathy was assessed using logistic regression, and time to incident diabetic retinopathy was examined using Cox proportional hazard models.

Results

Over a 5-year follow-up period, severity of depression was associated with an increased risk of incident retinopathy [odds ratio =1.026; 95% confidence interval (CI) 1.002–1.051] as well as time to incident retinopathy (hazard ratio=1.025; 95% CI 1.009–1.041). The risk of incident diabetic retinopathy was estimated to increase by up to 15% for every significant increase in depressive symptoms severity (5-point increase on the PHQ-9 score).

Conclusion

Diabetic patients with comorbid depression have a significantly higher risk of developing diabetic retinopathy. Improving depression treatment in patients with diabetes could contribute to diabetic retinopathy prevention.

Introduction

Depression and diabetes mellitus are two of the most common diseases in the general population and often co-occur. A meta-analysis of 42 studies demonstrated that the prevalence of depression was twice as high among adults with diabetes compared to similar individuals without diabetes [1]. The relationship between depression and diabetes has been described as bidirectional. Depression is associated with a 40% to 60% increased risk of subsequent development of diabetes [2], [3], [4], [5], [6], and diabetes is predictor of future depressive episodes [2], [3], [7], [8], [9].

Comorbid depression and diabetes often result in increased disease burden (higher symptom severity [10], [11], lower adherence to treatment [11], [12], additive functional impairment [11], [13], decreased quality of life [14], [15], [16], [17], [18]) and higher mortality [19]. A meta-analysis of 27 studies found a significant association between depression and numerous diabetes complications (diabetic retinopathy, nephropathy, neuropathy, coronary artery disease, peripheral vascular disease and ischemic heart disease) [20]. These studies were all cross-sectional in design; thus, causality could not be determined. In a large-scale prospective study investigating a population of elderly Mexican Americans with type 2 diabetes, Black and Ray concluded that comorbid depression at baseline was associated with an increased and earlier incidence of macrovascular and microvascular complications and mortality over a 7-year follow-up period [21]. Examining the same cohort of adults with type 2 diabetes from the present study, Lin et al. found that depression was associated with a 25% increase of severe macrovascular complications and a 35% increase of severe microvascular complications. The composite microvascular complication measure included retinopathy, nephropathy, foot ulcers and amputations [22].

While several studies have examined the association between depression and microvascular and macrovascular complications, the literature on the relationship between depression and diabetic retinopathy is scarce. Diabetic retinopathy is one of the most frequent complications in patients with diabetes. In the United States, 40% of individuals with type 2 diabetes and 86% of individuals with type 1 diabetes will develop diabetic retinopathy [23]. It is considered the principal cause of impaired vision in patients between 25 and 74 years old, leading to 12,000 to 24,000 new cases of blindness each year [23], [24]. A few cross-sectional studies have shown an association between depression and retinal microvascular damage [25] or diabetic retinopathy in diabetic patients [26], [27], while other studies failed to do so [28], [29]. One prospective study of 66 children with type 1 diabetes identified depression as a risk factor for subsequent development of diabetic retinopathy [30]. In a longitudinal study of 581 African Americans adults with type 1 diabetes, Roy et al. demonstrated a link between depression and incidence and progression of diabetic retinopathy [31], [32]. However, generalizability of these results is limited by the studies' relatively small samples and the specificity of the populations examined. Larger prospective studies investigating a more general population with type 2 diabetes are needed to better understand the relationship between depression and diabetic retinopathy.

The Pathways Study was a prospective population-based cohort study investigating the impact of depression in primary care patients with diabetes [33]. The current study proposes to utilize the Pathways Epidemiologic Follow-Up Study to assess the relationship between depression and subsequent risk of diabetic retinopathy over a 5-year period. We hypothesized that the presence of depression would be associated with a higher incidence of diabetic retinopathy among adults with type 2 diabetes.

Section snippets

Study design: Pathways Epidemiologic Study

The Pathways Study was designed by a multidisciplinary team in the Department of Psychiatry and Behavioral Sciences at the University of Washington and the Group Health Research Institute. Group Health is an integrated health care system based on a mixed-model prepaid health plan structure. It comprises 30 primary care clinics serving approximately 523,000 patients in western Washington State. The study protocol was reviewed and approved by institutional review boards at the University of

Results

Fig. 1 illustrates the Pathways Epidemiologic and Follow-Up Study sample recruitment. For the Pathways Study, of the 9064 subjects initially identified as eligible, 1223 were noneligible because of death, disenrollment, erroneous diagnosis of diabetes or cognitive impairment. Of the 7841 eligible subjects, 4839 subjects returned the baseline questionnaire of which 216 were excluded because of a diagnosis of type 1 diabetes, resulting in a total cohort of 4623 subjects with type 2 diabetes. For

Discussion

In this prospective population-based cohort study of adults with type 2 diabetes, we found that baseline depressive symptom severity score is associated with a greater risk of diabetic retinopathy. Over a 5-year follow-up period, the risk of incident diabetic retinopathy was estimated to be up to 3% higher for each 1-point increase in depression severity based on the PHQ-9 score. The results based on survival analysis were also consistent with an approximately 3% increase in risk of retinopathy

Acknowledgments

This work was supported by grants from the National Institute of Mental Health (NRSA-T32/MH20021-12, PI: Katon; K24MH069741-07, PI: Katon; RO1MH073686-04, PI: Von Korff).

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Cited by (43)

Longitudinal bidirectional associations between diabetic retinopathy and diagnosed depression: Results from a Danish nationwide registry-based cohort study
2023, Journal of Diabetes and its Complications
Diabetic retinopathy (DR) is a feared complication and a leading course of visual impairment, but the connection between DR and depression including the direction has never been studied in a nationwide cohort. We aimed to assess, whether the associations between DR and diagnosed depression are bidirectional.
We performed a national register-based cohort study of individuals with type 2 diabetes, who attended diabetic eye screening between January 2013 and June 2022. Level of DR was extracted from the Danish Registry of Diabetic Retinopathy. The severity of DR was assessed according to the International Clinical Diabetic Retinopathy severity scale. Diagnosed depression was ascertained by physician diagnostic codes of unipolar depression (F32), recurrent depression (F33) or dysthymia (F34.1) from the Danish National Patient Register. We estimated presence of diagnosed depression according to DR level at index date and risk of diagnosed depression during follow-up using multivariable logistic and Cox regression, respectively. Secondly, we assessed whether diagnosed depression at index date could predict incident DR.
We included 240,893 individuals with type 2 diabetes with baseline rates of diagnosed depression ranging from 5.2 to 6.0 % for DR level 1–4. At index date, individuals with type 2 diabetes and DR were less likely to have a history of diagnosed depression (multivariable adjusted OR, 0.77 [95 % CI 0.73–0.82]). In 226,523 individuals with type 2 diabetes followed for 1,159,755 person-years, 1.7 % developed at least one episode of diagnosed depression.
In a model adjusted for age and sex, individuals with DR at index date had an increased risk of incident diagnosed depression compared to those without DR (HR 1.25 [95 % CI 1.16–1.36]). Adjusting for marital status, use of glucose-, lipid- and blood pressure lowering medication, HbA1c, diabetic neuropathy and Charlson comorbidity index waived the above risk (multivariable adjusted HR 1.02 [95 % CI 0.93–1.12]).
Furthermore a previous history of diagnosed depression was not associated with increased risk of incident DR (multivariable adjusted HR 0.89 [95 % CI 0.77–1.03]).
In this nationwide cohort study, individuals with DR at first screening were 23 % less likely to have a history of depression, but our data did not support a bidirectional association between DR and depression. Selection bias may have occurred as diagnosed depression is a known barrier for attending DR-screening.
Associations of concomitant retinopathy and depression with mortality in a nationally representative population
2023, Journal of Affective Disorders
To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes.
Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models.
Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27–1.71), CVD-specific (1.87; 1.45–2.41), and other-specific (1.43; 1.14–1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02–1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (P_interaction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15–2.45) and CVD-specific mortality (P_interaction = 0.042; RERI 2.65; 95 % CI −0.12–5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91–4.28), CVD-specific (4.70; 2.57–8.62), and other-specific mortality risks (2.18; 1.14–4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants.
The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.
The burden of suicidal ideation among persons with type II diabetes: A scoping review
2017, Journal of Psychosomatic Research
Citation Excerpt :
A large body of research finds the relationship between diabetes and depression is bidirectional, where depression is associated with decreased metabolic control and diabetes may increase depressive symptoms [8]. Studies have also shown that depressive illness in those with diabetes is associated with increased risk for medical complications, disability, and mortality [9–12]. One lesser-known correlate of depression is suicidal ideation, or thoughts of self-harm, which can lead to suicide attempts.
Diabetes is a major global health concern. People with diabetes have worse mental health outcomes than those without diabetes. Researchers have recently sought to examine the relationship between diabetes and suicidal ideation. The aim of this study is to determine the burden of suicidal ideation among adults with type II diabetes from existing literature.
We conducted a scoping review of published literature in PubMed, PsycINFO, CINAHL, Web of Science, and Google Scholar published before March 2017. To identify relevant literature, search terms included suicidal ideation and type II diabetes. The search was limited to English language peer-reviewed journal articles. The main outcome of interest was suicidal ideation captured on a validated scale in a population with type II diabetes.
This review resulted in 10 relevant studies, which reported the prevalence of suicidal ideation ranging from 2.5–51.4% with a median prevalence of 18.6% among adults with diabetes. Across the five studies reporting the associated risks, all but one study found a significant risk for persons with diabetes to endorse suicidal ideation and only three studies adjusted for depression.
This review demonstrates the need for future studies to investigate potential mechanistic pathways of suicidality among persons with diabetes.
Interaction Between Depression, Obesity, and Type 2 Diabetes: A Complex Picture
2017, Archives of Medical Research
Citation Excerpt :
The Pathways Epidemiologic Follow-Up Study is a prospective cohort study aiming to determine the impact of depression in patients with T2D in primary care. Results showed that severity of depression was associated with increased risk of retinopathy (OR 1.03, 95% CI 1.002–1.051) (56). In addition, an association between depression and incident diabetic foot ulcers (adjusted HR 2.00, 95% CI 1.24–3.25) has been reported (57).
Depression plays an important role in the pathogenesis and treatment of obesity and type 2 diabetes (T2D). However, its relevance is frequently unrecognized by clinicians and researchers. The purpose of this review is to present a critical analysis of the evidence linking depression and metabolic disorders and to highlight the practical implications of this complex relationship. Evidence obtained from epidemiological, basic, clinical and controlled studies demonstrate that the association goes beyond a random phenomenon. Epidemiological studies have rendered controversial results due to the lack of control of the confounding variables and the bidirectional relationship that exists between the outcomes and the conditions that modulate the association (i.e. socioeconomic status). Animal and human studies have been useful to define the anatomic substrates and physiologic processes that participate in the association, but, the evidence is preliminary in many areas (i.e gene × environmental interactions). Controlled studies have shown the strong impact that treatment of depression has on body weight and the large effect that has the correction of excess body weight on the depression-related symptoms. Practical implications of the depression-obesity duet include the training of the health providers to assess and treat these conditions in a concomitant manner, the need for translational medicine projects and the application the systems biology approach to fill the existing gaps of knowledge.
Assessment of patient-reported outcomes in retinal diseases: a systematic review
2017, Survey of Ophthalmology
Advances in the understanding of the genetic, molecular, and cellular biology of retinal diseases have led to the development of new treatments. These expanding treatment options demand appropriate outcome measures for studies of treatment benefit including patient-reported outcomes (PROs). A plethora of PRO instruments assess impacts of retinal diseases from the patients' perspectives. We review all the studies that implemented PRO assessment in retinal diseases and also discuss quality assessment of the PRO instruments. We also include qualitative studies that explored quality of life impact on people with retinal diseases. Most studies used PRO instruments not specifically developed for retinal diseases (non–disease specific), nor have they undergone comprehensive validation in this disease group. A few retina-specific PRO instruments are available, but they suffer from limited content coverage of quality of life. Finally, we discuss the need for a new comprehensive and technologically advanced PRO instrument to assess quality of life impacts in retinal diseases.
Female sex, young age, northern German residence, hypoglycemia and disabling diabetes complications are associated with depressed mood in the WHO-5 questionnaire – A multicenter DPV study among 17,563 adult patients with type 2 diabetes
2017, Journal of Affective Disorders
Like other mental illnesses, depression is a culturally sensitive topic. Hence, findings cannot be transferred between countries. We investigated the frequency of depressed mood and its association with diabetes-related factors in a large type 2 diabetes (T2D) cohort from real-life care in Germany.
17,563 adults (median [IQR]: 64.5[55.9–71.1] years) from the multicenter diabetes follow-up registry, DPV (diabetes prospective follow-up), were investigated. All had completed the WHO-5 questionnaire, a screening tool for depression. Logistic regression was applied to study the association of demographic and diabetes-related factors with depressed mood (SAS 9.4). P<0.05 was considered significant.
Using a WHO-5 cut-off of <13, 27.4% of patients were at risk for depressed mood. A clinical depression diagnosis was recognized in 8.4%. Female sex (OR: 1.5[95%-CI: 1.4–1.6]), young age (1.2[1.1–1.4]), longer diabetes duration (1.2[1.1–1.3]), and living in Northern Germany (1.3[1.2–1.4]) were each associated with increased odds for depressed mood. After adjusting for these confounders, worse glycemic control (1.4[1.3–1.5]), insulin use (1.3[1.2–1.4]), myocardial infarction (1.3[1.2–1.5]), stroke (1.8[1.5–2.0]), retinopathy (1.4[1.3–1.6]), renal failure (1.4[1.2–1.8]), diabetic foot syndrome (1.3[1.2–1.4]), severe hypoglycemia (1.5[1.2–1.9]), two or more inpatient admissions (2.1[1.8–2.4]), and longer duration of hospital stay (1-<14 days: 1.3[1.2–2.3]; >14 days: 2.1[1.9–2.3]) were related to depressed mood.
Due to the cross-sectional design, no causality can be drawn.
In T2D, depressed mood is not uncommon. However, in routine care a clinical depression might be missed and regular screening is advisable. Besides the well-known associations with depressed mood, northern German residence and mainly life-compromising diabetes comorbidities were identified as related factors.

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Psychiatric–Medical ComorbidityDepression and incident diabetic retinopathy: a prospective cohort study

Abstract

Objective

Method

Results

Conclusion

Introduction

Section snippets

Study design: Pathways Epidemiologic Study

Results

Discussion

Acknowledgments

Biol Psychiatry

Biol Psychiatry

Psychosomatics

Gen Hosp Psychiatry

Diabetes Res Clin Pract

J Diabetes Complications

Lancet

Am J Geriatr Psychiatry

Gen Hosp Psychiatry

Am J Cardiol

Trends Immunol

J Affect Disord

The prevalence of comorbid depression in adults with diabetes: a meta-analysis

Diabetes Care

Examining a bidirectional association between depressive symptoms and diabetes

JAMA

Depression and type 2 diabetes over the lifespan: a meta-analysis

Diabetes Care

Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis

Diabetologia

Independent factors associated with major depressive disorder in a national sample of individuals with diabetes

Diabetes Care

Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis

Diabetologia

Relationship of depression and diabetes self-care, medication adherence, and preventive care

Diabetes Care

Potentially modifiable factors associated with disability among people with diabetes

Psychosom Med

Correlates of health-related quality of life in type 2 diabetes

Diabetologia

Diabetes, depression, and quality of life: a population study

Diabetes Care

The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature review

Diabetes/Metab Res Rev

Psychiatric–Medical Comorbidity
Depression and incident diabetic retinopathy: a prospective cohort study