Address of the institution at which the work was carried out: Div. Molecular Metabolism and Diabetes, Tohoku Univ. Grad. Sch. Med., Sendai, 980-8575, Japan
Neuropathy is associated with depression independently of health-related quality of life in Japanese patients with diabetes
Article first published online: 1 DEC 2008
© 2008 The Authors. Journal compilation © 2008 Japanese Society of Psychiatry and Neurology
Psychiatry and Clinical Neurosciences
Volume 63, Issue 1, pages 65–72, February 2009
How to Cite
Yoshida, S., Hirai, M., Suzuki, S., Awata, S. and Oka, Y. (2009), Neuropathy is associated with depression independently of health-related quality of life in Japanese patients with diabetes. Psychiatry and Clinical Neurosciences, 63: 65–72. doi: 10.1111/j.1440-1819.2008.01889.x
- Issue published online: 15 JAN 2009
- Article first published online: 1 DEC 2008
- Received 11 February 2008; revised 13 September 2008; accepted 14 September 2008.
- mental health;
- quality of life
Objectives: To identify factors independently associated with depression in Japanese patients with diabetes, after controlling for potential confounding factors.
Methods: Among 197 outpatients with diabetes, 129 (type 1: 24, type 2: 105) completed a questionnaire concerning socio-demographic and health-related variables. Depression screening was done using Zung's Self-Rating Depression Scale test, followed by diagnostic interviews by experienced psychiatrists employing the Diagnostic Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
Results: Forty-seven patients (36.4%) had symptomatological depression. A Self-Rating Depression Scale cut-off score of 40 had good sensitivity (100%) and modest specificity (59%) for detecting major depressive episode, in accordance with the DSM-IV. Diabetic patients suffering from depression were more likely to have neuropathy, retinopathy, body pain, a feeling of poor general health, and lack of social support, than the non-depressed patients. However, age, gender, marital status, diabetes type, insulin requirement, duration of diabetes, hemoglobin A1c (HbA1c) and the presence of nephropathy did not differ between the two groups. In multivariate logistic regression analysis, body pain (OR 3.26, 95% CI 1.31–8.08) and the presence of microvascular complications (OR 2.81, 95% CI 1.13–6.98) were independent factors associated with depression. Specifically, diabetic neuropathy (OR 3.10, 95% CI 1.17–8.22) was associated with depression independently of age, gender, marital status, social supports, quality of life, diabetes type, duration of diabetes, HbA1c, and insulin requirement.
Conclusions: A diabetic complication, specifically neuropathy, was independently associated with depression in patients with diabetes. The present findings indicate the need to find a biological base common to both depression in diabetes and diabetic neuropathy.
DEPRESSION IS MORE common among diabetic patients in western countries. Recent studies have documented a doubling of depression rates in individuals with, as compared to those without, diabetes.1,2 It has been shown that diabetic patients who are depressed have poorer glycemic control,3 are less physically active,4 and more obese.5 Depression appears to be a very important problem in the management of diabetes.
To date, the socio-demographic factors reported to be associated with depression include: female gender,2 younger age,2,6 being unmarried,2,7,8 lower levels of education6,8 and lack of social support.9 Factors concerning health-related quality of life (QOL), such as perception of poor general health10 and body pain,11 were also associated with depression. Poor glycemic control,3,7 types of diabetes treatment,8 duration of diabetes,8 presence of diabetic complications,8,12 diabetic neuropathy13–15 and retinopathy9,16 were similarly associated with depression. However, these reports did not adequately control for potential confounding factors. Are there any factors underlying both depression and diabetes?
The prevalence of major depressive episodes in the Japanese diabetic population according to the Diagnostic Statistical Manual of Mental Disorders 4th edition (DSM-IV),17 has not been investigated. In addition, only a few studies designed to identify factors associated with depression in individuals with diabetes in Asian countries, including Japan, have been reported. We first investigated the prevalence of depression, diagnosed by experienced psychiatrists, to confirm the increased prevalence of major depressive episodes in Japanese diabetic patients. Then we investigated factors possibly associated with depression in diabetic patients using multivariate logistic analysis, after controlling for the potential confounding factors.
All 197 patients who visited the Diabetes and Metabolism Unit, Tohoku University Hospital in November 2003 were recruited. The diagnosis of type 1 or type 2 diabetes had been made in accordance with the criteria of the American Diabetes Association.18 One hundred twenty-nine of the 197 patients (65%) completed a questionnaire concerning socio-demographic and health-related variables. This study was conducted under the guidelines of the ethics committee at the Tohoku University. The procedures were fully explained to each subject before the assessments and written informed consent was obtained from each subject.
Gender, age, marital status, the number of family members, educational level, and social support were assessed as socio-demographic variables. For social support, one item was selected from among the five items used in previous Japanese studies19,20 as the strongest association with depression was found in the present samples. Health-related quality of life was assessed using the subscales for pain and perception of general health in the Japanese version of the Short-Form 36 Health Survey questionnaire.21,22 All scores were dichotomized by the average score of the Japanese general population.
Diabetes type (Types 1 and 2), duration of illness (≧10 and <10 years), body mass index (BMI), medical regimen, anti-hypertensive requirements, hypolipidemic requirements, and blood pressure were obtained from the patient's medical record. Fasting plasma glucose concentration, hemoglobin A1c (HbA1c, ≧7 and <7%), and plasma lipid levels (Triglycerides [TG], total cholesterol [TC], high density lipoprotein cholesterol [HDL], and low density lipoprotein cholesterol [LDL]) were also evaluated as variables representing glycemic control status.
Microvascular complications were defined as the presence of at least one of the following: diabetic nephropathy, neuropathy or retinopathy. Diabetic nephropathy was defined as the presence of persistent proteinuria. Diabetic neuropathy was defined as the presence of symmetric neuropathic symptoms in the lower extremities and/or absence of bilateral Achilles tendon reflexes. Diabetic retinopathy, diagnosed by experienced ophthalmologists, was categorized as: simple, preproliferative or proliferative retinopathy, or none.
Assessment of depression
The Zung Self-Rating Depression Scale (SDS)23 was used to screen for depression. Patients scoring 40 or more on the SDS were defined as suffering from depression.24,25 The Japanese version of the SDS has been extensively validated.26 All patients with a score of 40 or more on the SDS were suggested to undergo a psychiatric evaluation using the DSM-IV to diagnose a possible major depressive episode within the following one-month period. Almost the same number of patients with scores under 40 on the SDS had the same interviews as the controls. None of the subjects who were interviewed were taking any psychoactive drugs during the study.
The χ2 test or t-test was used to compare differences in characteristics between diabetic patients with and without depression. Multivariate logistic regression analysis was used to estimate the association between depression and potential predictor variables by calculating odds ratios (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using SPSS for Windows, version 11.5J. A value of P < 0.05 was considered to be statistically significant.
Prevalence of depression and major depressive episode
Forty- seven out of 129 subjects (36.4%) had depression. Thirty-one of the 47 depressed subjects underwent diagnostic interviewing by experienced psychiatrists. Seven (type 1: 3, type 2: 4) of these 31 were diagnosed as having a major depressive episode. None of 34 subjects with SDS scores below 40, who had the same interviews, were diagnosed as having a major depressive episode. (Fig. 1 shows the experimental design.) Thus, the prevalence of a current major depressive episode in adult diabetic patients was estimated to be 7.9%. There is no difference of the prevalence between type 1 and type 2 (P = 0.34). In this study, an SDS cut-off of 40 yielded good sensitivity (100%) and modest specificity (59%) for detecting a major depressive episode in accordance with the DSM-IV.
Comparison of characteristics of diabetic patients with and without depression
The characteristics of patients with and without depression are presented in Table 1. The depressed patients were more likely to lack social support (P < 0.05), have pain (P. 0.01), and feel that their general health was poor (P < 0.01), than patients without depression. The prevalence of microvascular complications, that is, diabetic neuropathy and/or retinopathy, was also higher in the patients with than in those without depression (P < 0.01). In contrast, age, gender, marital status and educational level did not differ between the two groups. There was also no difference in the diabetes type, duration of diabetes, BMI, insulin requirement, blood pressure, anti-hypertensive medication requirement, fasting plasma glucose concentration, HbA1c, plasma lipid levels, hypolipidemic medication requirement or the presence of nephropathy between the depressed and non-depressed patients.
|Variables||SDS < 40||SDS ≧ 40|
|(n = 82)||(n = 47)|
|Age||54.12 ± 10.31||52.72 ± 10.47|
|Number of family members||3.13 ± 1.45||3.32 ± 1.80|
|SF36: pain||76.72 ± 23.80||63.24 ± 27.00**|
|SF36: general health||54.82 ± 18.00||40.93 ± 22.91**|
|∼ junior high school||9||4|
|∼ high school||42||33|
|∼ college (university)||31||10|
|Duration of illness|
|BMI (kg/M2)||24.07 ± 4.69||24.07 ± 3.74|
|Blood pressure (mmHg)||127.6 ± 15.0||126.3 ± 15.8|
|Diastolic||77.4 ± 10.1||75.0 ± 8.8|
|Systolic||146.61 ± 38.20||154.04 ± 66.90|
|Fasting blood glucose (mg/dl)||7.00 ± 1.19||7.12 ± 1.69|
|HbA1c (%)||112.76 ± 59.93||118.57 ± 73.70|
|TG (mg/dl)||193.82 ± 28.90||193.60 ± 35.99|
|TC (mg/dl)||56.40 ± 19.84||52.60 ± 17.25|
|HDL (mg/dl)||113.57 ± 26.10||117.40 ± 30.83|
Tables 2 and 3 show the factors predictably associated with depression in diabetic patients. As shown in Table 2, the subjective feeling of body pain (OR = 3.26, 95% CI = 1.31–8.08) and the presence of microvascular complications (OR = 2.81, 95% CI = 1.13–6.98) were independently associated with depression. In the analysis focused on neuropathy rather than the presence of microvascular complications in general, the presence of diabetic neuropathy (OR = 3.10, 95% CI = 1.17–8.22) was significantly associated with depression (Table 3). This association was independent of age, gender, marital status, social support, pain, a perception of poor general health, diabetes type, duration of diabetes, HbA1c, and insulin requirement. Neither nephropathy nor retinopathy was independently associated with depression.
|Independent variables||OR||95% CI||p|
|SF 36: pain|
|SF 36: general health|
|Type of diabetes|
|Duration of diabetes (years)|
|Independent variables||OR||95% CI||P|
|SF 36: pain|
|SF 36: general health|
|Type of diabetes|
|Duration of diabetes (years)|
The prevalence of a DSM-IV major depressive episode in adult diabetic patients was estimate to be 7.9%, that is, higher than that of the general Japanese population (1%; DSM-III)27 or working population (4%; ICD-10).28 The prevalence range for current depression, diagnosed by structured diagnostic interviews of diabetic patients, was reported to be 11.0–19.9% in uncontrolled studies.29 The prevalence determined in this study was lower than those reported previously. It might partially be explained by the fact that 16 out of 47 depressive patients who seemed to have severed depressive symptoms refused to be psychiatrically interviewed. However, our result confirmed an increased prevalence of a major depressive episode in diabetic patients as compared to the general population not only in Western countries but also in Japan.
Our findings on the characteristics of patients with and without depression are partially consistent with the results of earlier studies on the relationship between diabetes and depression. Relationships between lack of social support,9 perception of poor general health10 or body pain11 and depression in diabetic patients have been reported previously. Similarly, the presence of microvascular complications,8,12 specifically neuropathy13–15 and retinopathy,9,16 are related to depression. However, our results do not support a relationship between depression and the following factors; female gender,2 younger age,2,6 being unmarried,2,7 lower levels of education,6,8 poor glycemic control,3,7 types of diabetes treatment8 and duration of diabetes.8 The discrepancies across studies might be attributable, at least in part, to differences in patient characteristics. The patients in our study had essentially adequate glycemic control (HbA1c: 7.0 ± 1.4, FBS: 149 ± 50) at the start of the study and most had attained a high level of education. Thus, glycemic control status and educational level appear not to be related to depression.
In multivariate logistic regression analysis, the presence of microvascular complications, specifically neuropathy, was associated with depression independently of age, gender, marital status, social support, pain, perception of general health, diabetes type, duration of diabetes, HbA1c, and insulin requirement. Diabetic complications decreased health-related QOL, which is associated with increased risk of psychological impairment.30,31 One of the subscales for health-related QOL, body pain, was also reported to be strongly associated with depression.11,13 It was also suggested that individuals with inadequate support are most at risk of becoming depressed when disability related to illness increased.31 Thus, several previous reports suggested depression in diabetic patients to be secondarily induced by decreased health-related QOL and/or inadequate social support. However, our results demonstrate that depression is not necessarily secondarily induced by pre-existing factors because a diabetic complication, specifically neuropathy, was independently associated with depression regardless of health-related QOL and/or social support.
There is a possibility that diabetic microvascular impairment induces both neuropathy32 and so-called vascular depression33 in diabetic patients. However, it seems unlikely that depression in diabetic patients would be vascular in origin because neither nephropathy nor retinopathy was independently associated with depression in this study.
The present findings indicate the need to find a biological base common to both depression in diabetes and diabetic neuropathy.
However, there are limitations to interpreting the results of this study. First, because this analysis is based on cross-sectional data, causality can not be determined. Prospective studies are needed. Second, this study has sample size limitation. Future studies enrolling adequate samples of diabetic patients are required.
Diagnostic interviews, conducted by experienced psychiatrists, demonstrated a higher prevalence of current major depressive episodes (7.9%) in Japanese diabetic patients than in the general population. Multivariate logistic regression analyses demonstrated neuropathy to be an independent factor associated with depression in diabetic patients.
This work was supported by a Grant-in-Aid for Research on the Human Genome, Tissue Engineering (H17-genome-003) from the Ministry of Health, Labour and Welfare of Japan to Y. O.
- 17American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association, Washington, DC, 1994.
- 18The expert committee on the diagnosis and classification of diabetes mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–1197.
- 19The physical, psychological and social background factors of elderly depression in the community (in Japanese). Jpn. J. Geriatr. Psychiatry 1996; 7: 397–407., , .
- 26A study on a self-rating depression scale. Psychiatr. Neurol. Jpn. 1978; 75: 673–679., .
- 27Psychiatric epidemiologic research in an area of Kofu city: The prevalence of mild psychiatric disorder using JCM diagnosis (in Japanese). Nippon Iji Shinpou 1992; 3618: 47–50., .
- 30Psychologic stress and glycemic control: A comparison of patients with and without proliferative diabetic retinopathy. Psychosom. Med. 1985; 47: 327–381., , .