Association between diabetes and depression: Sex and age differences

Public Health (2006) 120, 696 704 www.elsevierhealth.com/journals/pubh ORIGINAL RESEARCH Association between diabetes and depression: Sex and age differences W. Zhao a,, Y. Chen a, M. Lin a, R.J. Sigal b a Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada, K1 H 8M5 b Department of Medicine, University of Ottawa, Canada Received 17 March 2005; received in revised form 4 February 2006; accepted 5 April 2006 Available online 7 July 2006 KEYWORDS Depression; Diabetes; Cross-sectional study; Age factor; Prevalence; Health survey Summary Objective: To examine the association between diabetes and the prevalence of depression in different sex and age groups by analysing the crosssectional data from the National Population Health Survey, conducted in Canada in 1996 1997. Study design: A total of 53 072 people aged 20 64 years were included in the analysis. Depression was defined as depression scale X5, based on the Composite International Diagnostic Interview Short-Form (CIDI-SF). Respondents who answered the following question affirmatively were considered to have diabetes: do you have diabetes diagnosed by a health professional? Methods: A multiple logistic regression model was used to adjust for potential confounding effects, and a bootstrap procedure was used to take sampling weights and design effects into account. Results: The prevalence of diabetes was much higher in people aged 40 64 years than in people aged 20 39 years (men: 4.7% vs. 0.5%; women: 3.5% vs. 0.8%, respectively). In contrast, people aged 20 39 years had a slightly higher prevalence of depression than those aged 40 64 years (men: 3.1% vs. 2.9%; women: 6.6% vs. 5.4%, respectively). Diabetes was significantly associated with depression in women aged 20 39 years (odds ratio [OR] ¼ 2.52, 95% confidence interval [CI] ¼ 1.19, 5.32), but not in women aged 40 64 years (OR ¼ 1.62, and 95% CI ¼ 0.65, 4.06). The association was not significant in both age groups in men, but it tended to be stronger in the younger age group. Conclusions: The data suggest that diabetes is significantly associated with depression, particularly in young adults. & 2006 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. Corresponding author. Tel.: +1 613 694 6904; fax: +1 613 241 8120. E-mail address: hzhao@cihi.ca (W. Zhao). 0033-3506/$ - see front matter & 2006 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.puhe.2006.04.012

Diabetes and depression: sex and age differences 697 Introduction Diabetes is one of the most prevalent non-communicable diseases globally. In Canada it is a public health problem of potentially enormous proportions. The prevalence of physician-diagnosed diabetes is 4.8% among people aged 20 years and older in Canada. 1 With the conservative assumption that one-third of all cases of diabetes are undiagnosed, the total number of Canadians with diabetes was about 1.7 million in 1998 1999. 1 About 1.4% of adults developed diabetes during the 4-year period between 1994 and 1998. 1 The economic burden of diabetes and its complications in Canada is estimated to be up to $9 billion (US) annually in direct healthcare costs and indirect costs, including lost productivity due to diabetes-related illness and premature death. 1 Psychological illness is responsible for considerable disability worldwide. The World Health Organization Global Burden of Disease Survey estimates that, by the year 2020, major depression will be second only to ischaemic heart disease in the amount of disability experienced by sufferers. Many studies have shown that the risk of depression is higher in individuals with diabetes than in those without diabetes. 2,3 Known to impair overall functioning and quality of life, 4,5 depression has additional importance in diabetes because of its association with poor compliance with diabetes treatment, 4 poor glycaemic control, 6 and an increased risk for micro- and macro-vascular disease complications. 7,8 The presence of concomitant depressive symptoms among people with diabetes is associated with substantially increased health economic burden compared with people with diabetes without depression or depressed people without diabetes. This is because of the increased use of emergency care, outpatient primary care, medical and psychiatric specialty care, medical inpatient care, and higher prescription costs. 3,4 The mental health of young individuals with diabetes is of particular concern. A meta-analysis including 20 controlled studies found that the risk of depression in the diabetic groups was two-fold higher than that in the non-diabetic comparison groups. 2 This relative risk of depression is greater than found in most other chronic diseases. 3 The results from previous studies suggest that younger age was associated with depression, 9 and the primary age of risk for major depression was age 25 40 years in the general population. 10 A controlled prospective study found that type 1 diabetes mellitus was associated with more protracted depressions and a higher recurrence rate among young women, compared with depressed psychiatric patients without diabetes. 11 Patients with type 1 diabetes aged 16 25 years were found to be more socially isolated than a healthy comparison group. 12 Young diabetic women with depression had higher ambulatory care use and filled more prescriptions than their counterparts without depression. 3 However, only 27% of them monitored blood glucose reasonably well, and only 8% of them had a glycated haemoglobin concentration within the optimal range. 13 Treatment of depression in people with diabetes resulted in improvements in self-efficacy, self-care behaviours, glycaemic control, patient satisfaction, and quality of life. 14 The effect of sex and age on the association between depression and diabetes has not been previously reported. Monitoring the psychological status of young people with diabetes may help to identify diabetic patients at risk for psychiatric disorder, and facilitate prevention or treatment efforts. 11 Identifying the sex and age difference in the association between diabetes and depression may be useful for developing targeted intervention strategies for depression control and prevention in people with diabetes. We therefore explored the associations between gender, age, depression and diabetes in a national cross-sectional survey. Methods This analysis was based on cross-sectional data from the Canadian National Population Health Survey (NPHS), conducted by Statistics Canada (Ottawa, Ontario) in 1996 1997. The target population of NPHS was household residents 12 years of age or more in all provinces, excluding people living in Indian Reserves, Canadian Forces Bases, and some remote areas of Quebec and Ontario. The 1996 1997 NPHS was collected mainly by telephone. The NPHS used a multi-stage stratified sampling design to draw a representative sample of 95 466 households, and 78 751 households participated in the survey, with a national response rate of 82%. In all provinces, except Quebec, the Labor Force Survey design was used to draw the sample. In Quebec, the Enquête Sociale et de Sante conducted by Santé Quebec in 1992 1993, with a two stage design similar to that of the Labor Force Survey, was used. In each household, all members were asked to complete a short general questionnaire, and one person was randomly selected for a more in depth interview. The survey included

698 questions related to the determinants of health, health status and use of health services. 15 This analysis was based on data from of 53 072 people aged 20 64 years. Depression was assessed by the depression scale from the Composite International Diagnostic Interview (CIDI) Short-Form (CIDI-SF). 15 The CIDI is a structured diagnostic instrument that was designed to produce diagnoses according to the definitions and criteria of both DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) and the Diagnostic Criteria for research of ICD-10. 15 The CIDI-SF is a subset of items from CIDI that measures major depressive symptoms during the previous 12 months. A complete copy of the CIDI-SF questions and scoring instructions is available from the World Health Organization website www.who.int/msa/ cidi/index.htm). Depression was considered to be present when depression scale score was greater than or equal to 5. Respondents who answered affirmatively to the question do you have diabetes diagnosed by a health professional? were considered to have diabetes. The association between diabetes and depression was examined separately in study participants aged 20 39 and 40 64 years. We categorized the participants according to other potential risk factors for depression in the study, which were similar to a previous report by Chen et al. 16 Self-reported body weight and height were used to calculate body mass index (BMI): BMI ¼ weight (kg)/height (m 2 ). BMI values were categorized into the four groups:o20, 20.0 24.9, 25.0 29.9, and X30.0 kg/m 2. Participants in the low education category had not proceeded beyond secondary school, and the high education category included particpants who had been admitted to college or university, as well as those with a postsecondary school certificate or diploma. Participants were classified into low-, middle-, and highincome groups based on total household income adjusted for number of household members (appendix A). A positive history of allergy was defined by an affirmative response to either of the following questions: do you have any food allergies diagnosed by a health professional? or do you have other allergies diagnosed by a health professional? A regular alcohol drinker was defined as a person who reported drinking alcoholic beverages at least once a month. Daily smokers were respondents smoking cigarettes every day at the time of survey, former smokers were those smoking cigarettes daily in the past but not smoking at the time of survey; otherwise, participants were classified as non- or occasional smokers. A regular exerciser was defined as a person who engaged in physical activities that lasted more than 15 min at least 12 times a month. Other variables included in the analysis were region (eastern, central and western Canada), immigrant status (yes, no), marital status (married/common-law/partner, single, widow/divorced/separated), household size (1, 2, 3, or X4 people), and number of bedrooms (o3, X3). The associations between diabetes and depression in different age groups were examined for men and women separately and jointly. We calculated the prevalence of depression according to various factors. Multiple logistic regression models were used to evaluate the association between diabetes and the prevalence of depression before and after controlling the potential confounders. Potential interactions of diabetes with other factors were tested at an alpha level of 0.1 in a multiplicative scale. We calculated the unadjusted and adjusted odds ratios for depression associated with diabetes and corresponding 95% confidence intervals by sex and age groups. The NPHS used a complex survey design. A design effect is defined as the ratio of the estimated variance taking into account the nature of the survey design to a comparable estimate of variance based on a simple random sample of the target population. 16 In the present study, the Rao Wu bootstrap method was used for variance estimation to take both the population weights and design effects into consideration, as described in detail elsewhere. 16 Statistical analyses were carried out with SAS V8. Results W. Zhao et al. The prevalence of diabetes is presented in Table 1. Diabetes was found to be higher in people aged 40 64 years than in people aged 20 39 years (men: 4.7% vs. 0.5%; women: 3.5% vs. 0.8%, respectively). In contrast, people aged 20 39 years had a slightly higher prevalence of depression than those aged 40 64 yeas of age (men: 3.1% vs. 2.9%; women: 6.6 vs. 5.4, respectively) (Fig. 1). The prevalence of diabetes and depression by the potential confounders for the relation between diabetes and depression is also shown in Table 1. Participants with BMI X 30 kg/m 2 had a higher prevalence of diabetes than participants with lower BMI; participants with BMIo20 kg/m 2 or X30 kg/m 2 had higher prevalence of depression than others in both sexes. Participants with low educational level, smaller number of bedrooms (o3) and low income had a higher prevalence of both diabetes and depression than those with high educational level,

Diabetes and depression: sex and age differences 699 Table 1 Prevalences (%) of diabetes and depression, by potential risk factors, among individuals aged 20 64 years based on cross-sectional observations from 1996 to 1997 National Population Health Survey, Canada. Men Women N Diabetes Depression N Diabetes Depression Case Case Case Case N % N % N % N % Age (years) 20 39 12 991 89 0.5 448 3.1 14 399 142 0.8 1049 6.6 40 64 12 386 595 4.7 367 2.9 13 296 539 3.5 779 5.4 Region Eastern 1145 29 3.4 34 3.0 1330 35 2.7 69 5.8 Central 14 358 406 2.5 445 2.8 15 906 382 2.1 1013 5.5 Western 9874 249 2.4 336 3.6 10 459 264 2.0 746 7.2 BMI (kg/m 2 ) o2 0 615 12 3.2 40 8.9 3190 17 0.3 252 7.0 20 24.9 8881 148 1.5 304 1.2 12 133 143 0.9 742 5.5 25 29.9 11 602 280 2.5 331 1.3 6645 211 3.1 446 6.5 X30 3965 235 5.7 139 2.7 3316 241 6.6 283 7.7 Unknown 314 9 2.1 1 0.2 2411 69 2.5 105 3.0 Physical activity Regular exercise 14 227 348 2.8 466 3.0 17059 367 2.0 1046 6.0 Not regular 10 524 301 2.2 346 3.3 10 250 301 2.3 778 6.4 Unknown 626 35 3.7 3 0.3 386 13 3.4 4 0.3 Smoking Non-/ occasional smoker 11 232 234 1.8 229 2.0 14 303 340 1.9 671 4.0 Former smoker 6398 287 3.8 195 1.9 6145 191 2.8 403 6.2 Daily smoker 7655 159 2.6 390 5.5 7162 148 1.9 754 10.2 Unknown 92 4 3.4 1 2.6 85 2 2.2 0 0.0 Drinking Regular drinker 17 808 341 2.1 541 2.9 13 557 167 0.8 934 6.2 Not regular drinker 7296 335 3.7 273 3.6 13 905 510 3.4 890 6.0 Unknown 273 8 1.6 1 0.1 233 4 0.6 4 0.8 Allergy Any allergy yes 5302 134 1.8 240 3.6 8708 269 2.2 767 8.7 No or unknown 20 075 550 2.8 575 2.9 18 987 412 2.0 1061 4.9 Educational level Secondary or lower 9488 320 3.3 309 2.8 10 113 332 3.0 649 6.5 Postsecondary or higher 15 659 358 2.2 503 3.2 17 391 341 1.5 1169 5.8 Unknown 230 6 1.5 3 0.9 191 8 3.4 10 4.1 Size of household 1 person 5048 153 3.2 314 7.6 4514 181 3.6 393 7.9 2 people 7504 294 3.9 199 3.1 9106 248 2.3 580 6.1 3 people 4788 119 2.3 120 2.3 5517 124 2.3 394 6.9 X4 people 8037 118 1.7 182 2.0 8558 128 1.4 461 5.0 Number of bedrooms o3 7635 240 3.3 373 5.3 8482 272 2.6 710 6.8 X3 17 236 431 2.3 432 2.2 18 614 398 1.9 1097 5.8 Unknown 506 13 2.6 10 1.6 599 11 1.4 21 2.3 Income Low 2337 90 3.5 181 6.8 3836 153 3.7 459 11.6 Middle 5187 147 2.4 211 3.5 6161 176 2.6 445 6.2 High 12 851 316 2.5 311 2.5 12 131 221 1.3 643 4.9 Not stated 5002 131 2.4 112 1.6 5567 131 2.1 281 4.5 Marital status Married 16 086 482 3.0 335 2.2 17 411 412 2.1 855 4.7 Single 6809 101 1.2 311 3.7 5731 88 1.4 487 7.1

700 W. Zhao et al. Table 1 (continued ) Men Women N Diabetes Depression N Diabetes Depression Case Case Case Case N % N % N % N % Widow, divorced or 2434 101 3.8 167 8.9 4476 181 3.4 482 11.3 separated Not stated 48 0 0.0 2 3.0 77 0 0.0 4 2.8 Immigrant Yes 3919 124 3.2 114 2.0 4311 112 2.7 209 4.0 No 21 331 559 2.4 698 3.3 23273 565 2.0 1614 6.5 Unknown 127 1 0.5 3 1.8 111 4 2.3 5 3.3 Prevalence of depression (%) 25 20 15 10 5 0 20-39 40-64 20-39 40-64 20-39 40-64 Male Female Total Figure 1 The prevalence of depression in subgroups. Blank, diabetes; black, non-diabetes. larger number of bedrooms (X3) and middle or high income. A higher prevalence of depression in people with diabetes compared with those without is shown in Table 2. The difference in the prevalence of depression between diabetic and non-diabetic individuals was more evident in younger groups for both sexes. The prevalence of depression tended to be higher in women than in men in all age groups except for the category of younger diabetic patients, which had a limited sample size. Table 2 shows that diabetes was positively associated with depression, and the association was stronger among younger adults than among older adults: the odds ratio was 4.19 (95% CI 0.99, 17.70) in people aged 20 39 years and 2.07 (95% CI 1.08, 3.97) in people aged 40 64 years, respectively. This age difference was seen in both sexes: the odds ratios were 8.30 (95% CI 0.72, 95.17) for the younger group and 2.67 (95% CI: 0.90, 7.94) for the older group in men, and in women they were 2.52 (95% CI 1.19, 5.32) and 1.62 (95% CI: 0.65, 4.06), respectively. Discussion In most studies investigating the association between diabetes and depression, age is usually adjusted for, and the modifying effect of age is not examined. 9,17 In this paper, we have focused on the sex and age differences in the association between diabetes and depression. On the basis of cross-sectional data from the NPHS in 1996 1997, our analyses suggest that diabetes was significantly associated with the prevalence of depression in young women, and the association tended to be stronger among younger adults than among older adults. A meta-analysis including 20 controlled studies found that the presence of diabetes doubled the odds of depression. 2 The results of a 5-year follow-up study that included patients with type 1 and type 2 diabetes strongly suggested that the course of depression in people with diabetes was perhaps worse than the course of depression among medically well individuals. 18 The lifetime prevalence of major depression among adults with type 1 diabetes mellitus and type 2 diabetes mellitus ranges between 14.4% and 32.5%. 6,19 Although some studies that were limited to type 2 diabetes mellitus have shown a positive relationship between type 2 diabetes mellitus and depression, 18,19 individuals with type 1 diabetes mellitus have long been viewed as particularly prone to depression. 11 A 10-year follow-up study 10 identified an effect of type 1 diabetes mellitus on lower perceived competence in young adults, which could represent early signs of what may become more clear-cut presentations of self-esteem problems, as well as depressive symptoms and illnesses, later in adulthood. On e study reported that major depressive disorder (MDD) was the most prevalent psychiatric morbidity among young people with childhood-onset type 1 diabetes mellitus, with a

Diabetes and depression: sex and age differences 701 Table 2 Unadjusted and adjusted odds ratios and 95% confidence interval for the prevalence of depression associated with diabetes by sex and age among people aged 20 64 years based on cross-sectional observations from 1996 1997 National Population Health Survey, Canada. Age (years) Unadjusted OR 95% CI Adjusted OR* 95% CI Men 20 39 9.66 0.76, 122.41 8.30 0.72, 95.17 40 64 2.28 0.94, 5.54 2.67 0.90, 7.94 Women 20 39 2.33 1.12, 4.85 2.52 1.19, 5.32 40 64 1.76 0.78, 3.94 1.62 0.65, 4.06 Total 20 39 4.30 1.43, 12.91 4.19 0.99, 17.70 40 64 1.87 1.04, 3.37 2.07 1.08, 3.97 OR, odds ratio; *, adjusted for region, BMI, physical activity, smoking status, drinking status, allergy, educational level, size of household, number of bedroom, income, marital status and immigrant status. cumulative probability of 27.5% the tenth year after diagnosis. 11 The prevalence of depression in children and adolescents with diabetes is two to three times that of peers without diabetes. 7,20 The reasons for the stronger association between diabetes and depression in people aged 20 39 years, compared with older age groups, are unclear; however, there are several possible explanations. Different types of diabetes may have different associations with depression. The mean age of onset for type 1 diabetes mellitus was 17.3 years, and type 2 diabetes mellitus is most common in adults over the age of 40 years. 18 Younger adults were more likely to have adolescence-onset diabetes. The prevalence of depression among adolescents with diabetes is three times higher than that among peers without diabetes. 20 The following reasons may explain the significantly higher odds ratio in this particular population. First, for adolescents, the challenge of diabetes, such as, fear of diabetes-related complications and helplessness in avoiding them, is combined with the developmental task of adapting to puberty and a changing body image, peer-group pressure, autonomy from the parents and identity formation. 21 This combination of challenges may increase their risk for a depression episode. Second, the treatment for type 1 diabetes mellitus requires individuals to adhere to a complex set of treatment regimens, including daily multiple insulin injection, monitoring blood glucose value, adherence to specific dietary guidelines and attending regular medical exams. This heavy burden of treatment may increase risk for depression. Third, a number of risk factors have been identified to increase the likelihood of depression during adolescence, including female gender, family dysfunction and stressful experience. One stressful experience that may increase risk for depression in adolescents is diabetes. 21 The history of depressive episode or stressful experience in adolescence is a risk factor for depression or recurrence of depression in young adults with diabetes. 21 In addition, the higher odds ratio in young adults may result from a variety of inherent differences between type 1 diabetes mellitus and type 2 diabetes mellitus, including type of treatment, the influence of the disease on physical and psychological functioning and the quality of life resulting from the disease. For example, patients with type 2 diabetes who are treated with diet only or oral agents may be less likely to have depression. 22 Our data showed that the percentage of patients taking insulin was 48.9% in people aged 20 39 years and 29.7% in people aged 40 64 years, respectively. Early adulthood is the developmental period during which individuals assume a greater degree of independent functioning and take on adult roles; a chronic illness such as type 1 diabetes mellitus could impede these aspects of life-cycle development. 10 It is also possible that type 1 diabetes mellitus places patients at risk for a depressive disorder through a biological mechanism linking the metabolic change of diabetes to changes in brain structure and function. 23 The cross-sectional design of the present study did not permit us to determine the temporal relation between onset of depression and onset of diabetes. However, previously published studies have found that the typical temporal sequence may

702 differ between type 1 and type 2 diabetes mellitus. In a cohort study of adults with diabetes, the mean age of type 2 diabetes mellitus onset was 37.3 years, and the mean age of depression onset in patients with type 2 diabetes was 28.6 years. 18 It is possible that depression may lead to lack of exercise and poor dietary habits, which in turn increase risk of diabetes. A prospective populationbased study showed that major depressive disorder predicted the onset of type 2 diabetes. 17 In patients with type 1 diabetes mellitus, the mean age of diabetes onset was 17.3 years and the mean age of depression onset was 22.1 years. 18 No study has shown whether the onset of diabetes in childhood or adolescence contributes to the risk for onset of depression. 17 Some studies have observed that a surplus of hormones antagonizing insulin action is present during severe depression, including epinephrine, growth hormone and cortisol. 24,25 In a 5-year follow-up study, poor metabolic control (mean glycated haemoglobin 11.2%) was reported in the psychiatrically ill group of people with diabetes at both the baseline and follow-up evaluations, compared with a mean glycated haemoglobin of 9.0% in patients with diabetes without documented psychiatric illness. It was suspected that depression and diabetes may interact at basic biologic levels, perhaps in some reciprocal fashion. 18 Although some studies indicate that depression may occur secondary to the hardship of advancing diabetes, 2 a 5-year follow-up study found no significant differences at baseline and at followup in the prevalence of diabetes complication between depressed and non-depressed patients (nephropathy, retinopathy and neuropathy; each p40:2). 18 However, it did not rule out the possibility that depression may be more closely related to other unmeasured indices of advancing disease (e.g. changes in cerebral vasculature or specific limitations in function (e.g. blindness or erectile dysfunction). 18 In addition, the present study did not find an association between diabetes and depression in men; however, owing to the relatively small sample size and the consequently limited statistical power of the present study, studies with large sample size are needed to further investigate this association in men. The comorbidity of diabetes and depression among young people aged 20 39 years is a serious problem. Depression alone carries significant potential for disability, but, when combined with diabetes, the comorbidity carries the potential for serious long-term consequences. Many investigators have found that people with type 1 and type 2 diabetes with depression have significantly worse glycaemic control than people with no history of any psychiatric illness. 6,21 Prolonged poor glycaemic control results in more rapid onset and progression of retinopathy, neuropathy and nephropathy, which have been linked with decreases in quality of life 26,27 and increased mortality. 28 Conclusion This analysis, based on cross-sectional data from the Canadian National Population Health Survey in 1996 1997, suggests that diabetes is positively associated with the prevalence of depression, and the association is stronger among young adults than among older adults. The age difference is important for several reasons. Depression in young people with diabetes is associated with a significant increase in suicide and suicidal ideation. 29 The recurrence and course of depression may be more severe than that in older groups. 11 Young people with diabetes and depression are likely to have other comorbid conditions, such as eating disorders, adjustment disorders or anxiety disorders. 11 An eating disorder may be life-threatening for people with diabetes, and early treatment may be particularly beneficial for young people with diabetes. 11 Therefore, young people with diabetes should be monitored for psychological status. Prevention, early diagnosis and early treatment of depression for them, are extremely important. Acknowledgements This research was supported by a grant from the Canadian Institutes of Health Research and the Canadian Diabetes Association. Yue Chen is a Canadian Institutes of Health Research Investigator Award recipient. Ronald J. Sigal was a Canadian Institutes of Health Research new Investigator Award recipient, and currently holds the OHRI Research Chair in Lifestyle Research. Appendix A. The classification of income (Table A1) W. Zhao et al.

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