East Asian Arch Psychiatry 2016;26:77-82

ORIGINAL ARTICLE

Dr Nurul Azreen Hashim, MD, MPM, Psychological & Behavioural Medicine Unit, Universiti Teknologi Mara, Selangor, Malaysia.
A/Prof. Suthahar Ariaratnam, MBBS, MMed (Psych), Psychological & Behavioural Medicine Unit, Universiti Teknologi Mara, Selangor, Malaysia.
Prof. Mohd Razali Salleh, MPM, FAMM, Psychological & Behavioural Medicine Unit, Universiti Teknologi Mara, Selangor, Malaysia.
Prof. Mas Ayu Said, MBBS, MPH(Epidemiology), PhD, Julius Centre University of Malaya, Department of Social and Preventive Medicine / University of Malaya Centre for Addiction Sciences, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Prof. Ahmad Hatim Sulaiman, MBBS, MPM, PhD, Professor, Department of Psychological Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Address for correspondence: Dr Nurul Azreen Hashim, Faculty of Medicine, Universiti Teknologi Mara, Selangor, Malaysia.
Tel: (60) 0361264800 ext 4713; Fax: (60) 0361264888; Email: azreenhashim@yahoo.com

Submitted: 19 August 2015; Accepted: 28 January 2016

pdf Full Paper in PDF

Introduction

Diabetes mellitus (DM) is a chronic and debilitating disease that affects millions of people globally. Its prevalence is rising in many countries and it is recognised as a global epidemic of the 21st century that is rapidly becoming rampant. According to the International Diabetes Federation, the global prevalence of DM is estimated to increase from 6.6% in 2010 to 7.8% by 2030. This represents an increase in number of diabetics from 285 million to an estimated 438 million people worldwide over 20 years.¹ In Malaysia, a rising trend in the incidence of DM is also seen. The Third National Health and Morbidity Survey in 2006 showed that the overall prevalence of DM (known and newly diagnosed) was 11.6%,² compared with 8.3% in the Second National Health and Morbidity Survey 10 years earlier.³ Diabetes mellitus is viewed as a multidimensional biopsychosocial problem. Its association with depression is well established.^4-7

A meta-analysis of 42 studies worldwide by Anderson et al⁸ demonstrated that 11% of patients with DM fulfilled the criteria for a co-morbid major depressive disorder (MDD) and 31% experienced significant depressive symptoms. The prevalence of depression in patients with DM was significantly higher in women than men. Analysis of the controlled studies in the meta-analysis revealed that the odds of a diabetic patient having depression were twice that of their non-diabetic counterparts.⁸

Nichols and Brown⁹ conducted a large study involving 16,180 type 2 DM patients with the same number of controls matched for age and gender. The prevalence of diagnosed depression was greater in the DM group than the control group (17.6% vs. 11.9%). The associated factors with depression were younger age, female gender, higher body mass index, and presence of cardiovascular disease. Other documented associated factors with depression in DM are smoking status, perceived worsening of health status,¹⁰ more severe DM symptoms,^11,12 poor glycaemic control, diabetic complications,¹³ and a depressive history.¹² A lower level of education¹⁴ and lower income¹⁰ were also found to be implicated in depression.

There is growing evidence that depression and type 2 DM share a common biological pathway, particularly overactivation of innate immunity leading to a cytokine- mediated inflammatory response, and potentially through dysregulation of the hypothalamic-pituitary-adrenal axis. Over time, these pathways can lead to insulin resistance, cardiovascular disease, depression, increased risk of type 2 DM, and increased mortality. Proinflammatory cytokines are neurotoxic and can cause depressive symptoms.¹⁵ There is limited information regarding depression in type 2 DM patients in Malaysia despite extensive evidence of their co- morbidity. In addition, available data mainly focused on prevalence derived from a screening questionnaire, rather than diagnostic interview.^16,17 This study aimed to determine the prevalence of MDD using a diagnostic tool and its association with socio-demographic and clinical factors among patients with type 2 DM in a hospital-based primary care clinic.

Methods

This was a cross-sectional study of patients diagnosed with type 2 DM who attended the General Outpatient Clinic and Family Clinic, hospital-based primary care clinics at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The study was conducted from January to June 2011. Informed and written consent was obtained from all participants. This study was approved by the Ethics Committee of UMMC.

Sample size was calculated using OpenEpi; by con- sidering the population size of 10,000, 80% power of study, frequency of outcome was 11% based on Anderson et al,⁸ and alpha set at 0.05, a sample size of 149 was required. Universal sampling method was used to select patients with type 2 DM who attended the clinic for follow-up of their DM during the study period. Inclusion criteria were patients who had agreed to give informed consent, age ≥ 18 years, and ability to communicate either in Malay or English language. Patients were excluded if they refused to give informed consent, had a physical disability such as being deaf, blind or too ill, and if they were unable to communicate due to factors such as dysphasia or severe dementia. During the recruitment period, patients were identified at the registration counter while they recorded their attendance. Subsequently, their case notes were scrutinised and those eligible for the study were approached to participate. These patients were then interviewed to collect socio-demographic data, their clinical profile, as well as personal and family history of depression.

The patients were interviewed using the Mini- International Neuropsychiatric Interview (MINI) to diagnose MDD. The MINI is a short structured diagnostic interview designed to diagnose DSM-IV and ICD-10 psychiatric disorders (lifetime and current). It is a relatively brief instrument and is fully structured to allow administration by non-specialised interviewers. For most modules, 2 to 4 screening questions are used to exclude the diagnosis when answered negatively. Positive responses to screening questions are explored by further investigation of other diagnostic criteria. The initial study found its inter- rater reliability to be high with kappa coefficient ranging from 0.88 to 1.0 and for MDD, the test-retest reliability was good with kappa of 0.83.¹⁸ Other studies have also reported excellent inter-rater and test-retest reliability for the English version of MINI¹⁹ and moderate validity of MINI versus Composite International Diagnostic Interview (CIDI)¹⁹ and Structured Clinical Interview for DSM-IV-TR Axis 1 Disorders Patients Edition (SCID-P).²⁰ The MINI has been translated into many different languages including Malay. To date, no cross-cultural validity in Malay has been evaluated. Nonetheless, the Japanese version of MINI has shown good validity and reliability.²¹

Data were analysed using the Statistical Package for the Social Sciences Windows version 17 (SPSS Inc., Chicago [IL], US). The relationship between MDD as a dependent variable and socio-demographic and clinical variables as independent variables was analysed using cross-tabulation analysis. Categorical variables were analysed using Chi-square test and analysis of variance to test for statistical significance of difference. For continuous variables, the data were analysed using either independent sample t test or Mann-Whitney U test based on the result of the normality test. Regression analyses were carried out to study the strength of association between outcome and factors of interest with adjustment for covariates / confounders.

Results

A total of 228 patients were approached to participate in the study and 24 patients failed to participate; 15 patients refused to give consent due to time constraints and 9 patients could not speak and read in the Malay or English language. The remaining 204 patients completed all the questionnaires required for the study.

The mean (± standard deviation) age of the sample was 61.3 ± 10.3 years and most (62.7%) were female. The majority of patients (75.5%) had been diagnosed with type 2 DM when they were aged 40 to 60 years; only 4.9% were diagnosed in the age-group 20 to 30 years. The socio-demographic and clinical profiles of the patients are summarised in Table 1.

Of 204 patients, 32 (15.7%) were diagnosed to have MDD. Univariate analysis of the socio-demographic, clinical, and disease variables revealed 4 variables that were significantly associated with MDD: patient age, age at diagnosis of DM, having secondary education, and having a history of depression (Tables 2 and 3).

Logistic regression analysis showed that 4 factors, including patient age, age at diagnosis of DM, secondary education, and duration of DM were significantly associated with MDD after controlling the confounders (Table 4).

Discussion

In this study, the prevalence of current MDD determined by MINI was 15.7% (n = 32). The prevalence of depression among the general population in Malaysia was much lower, between 10.7% in 1996³ and 11.2% in 2006.²

The prevalence in this study was within the range for uncontrolled studies of between 11% and 19.9%.²² The figure was also comparable with that of 17.9% demonstrated by Nichols et al⁹ in the large population-based controlled study. Nevertheless, their study relied exclusively on a medical record database rather than face-to-face interviews. It was noted that the prevalence of depression in our study was higher compared with figures reported by Anderson et al⁸ and Fisher et al²³ of 11% and 9.9%, respectively. The plausible reason for this is that both studies used different diagnostic instruments to assess MDD.

The prevalence of MDD in this study was indeed lower compared with 3 other cross-sectional studies across Asia^13,24,25 that have identified varying rates of 28%, 19.4% and 23.7%, respectively. These studies used questionnaires based on the DSM-IV criteria such as CIDI and SCID-P. The difference in the prevalence with previous studies could also be due to use of different diagnostic instruments.

In our study, univariate analysis revealed that 4 variables were significantly associated with depression: patient age, age at diagnosis of  DM,  having secondary education, and a history of depression. Multivariate analysis demonstrated that duration of DM was also significantly demonstrated that duration of DM was also significantly associated with MDD.

In this study, the mean age of patients who had MDD was significantly younger (57.8 ± 15.1 years) compared with patients without MDD (62.0 ± 9.0 years). This finding was similar to other studies^9,26 that reported depression to be associated with age < 65 years. Nonetheless, other studies have documented conflicting results and advancing age was associated with depression.^10,13  We theorise that the elderly are more prone to depression due to the presence of multiple medical illnesses and disabilities.

Depression was also found to be significantly associated with younger age at the time of diagnosis of DM. The mean age at diagnosis of depressed patients was 46.2 ± 13.0 years, while that for non-depressed patients was 51.2 ± 8.8 years. To the best of our knowledge, no such association has been previously documented in Malaysia. We hypothesise that being diagnosed with type 2 DM at a younger age may increase the risk of depression due to perceived negative impact of illness on normal daily life such as work and family as well as perceived threat of DM to general well-being.²⁶

This study also showed that having secondary education was significantly associated with depression and concurs with another study²⁶ among individuals with DM in the US that found a high school education level to be an independent factor of MDD. The supporting evidence proposed that as the number of years of formal education increased, the corresponding odds of having an affective disorder also increased, at the rate of 16% per year of education.²⁷ The same trend was found in another study from Pakistan wherein depression in type 2 DM was associated with having schooling for more than 5 years.¹⁶

The only clinical factor to demonstrate a significant association with depression was a history of depression. This finding was consistent with a study that investigated factors associated with MDD during a 5-year follow-up of patients with DM.¹² The risk of MDD among diabetics was increased in the presence of a history of depression. A reason proposed by Lustman et al²⁸ was that MDD in DM is usually noted to be a chronic and highly recurrent disorder, whereby 70% of patients with DM and MDD relapse with a mean of approximately 4 episodes over a 5-year period.

Our study revealed an unexpected negative finding that DM complications were not associated with MDD. On the contrary, many studies have affirmed that DM complications are associated with depression.^29-34 The plausible explanation for this difference is that the cross- sectional design of this study was unable to demonstrate the association. Moreover, the prevalence of MDD in this study did not reflect the true prevalence due to the non- randomisation sampling method. It is also possible there was poor detection and documentation of DM complications in the case notes as well as recall bias or under-reporting by the patients.

Limitations

The design of this study was cross-sectional, thus it could not demonstrate a cause-and-effect relationship. The prevalence of MDD from this study did not reflect the true prevalence due to the non-randomisation sampling method. The study sample of 204 patients was relatively small compared with previous studies.^7,8,22 This underpowered study led to no association of important clinical features with MDD, whereas other studies with larger sample size demonstrated positive findings and association of DM complications with depression.^29,32-34 We also did not include a group of healthy subjects as controls. Finally, other confounding factors such as stressful life events, co-morbid psychiatric illnesses, and level of social support were not controlled.

Conclusions and Recommendations

A prospective study would be a better study design to determine the risk factors for depression in patients with type 2 DM. The future study should include a control group, who are non-diabetic persons matched for age and gender. Finally, in order to enable the findings to be generalised, a multi-centre study would have been better in recruiting samples that are representative of the Malaysian population. It is hoped that the results of this study will help health care providers plan appropriate services for these patients.

Acknowledgements

We would like to thank all the patients who participated in this study and thus made this study a success. Our appreciation also goes to the staff and doctors in the General Outpatient Clinic and Family Clinic, UMMC for their assistance. Finally, we would like to thank the Head of Department of Primary Care Medicine, Head of Department of Psychological Medicine of UMMC, and Ethics Committee of UMMC for their cooperation and permission to conduct the study.

Declaration

The authors have no conflicts of interest to declare.

References

1. International Diabetes Federation. Diabetes atlas, 4th edition. Available from: http://www.diabetesatlas.org/component/attachments/?task=download&id=75. Accessed 30 Dec 2015.
2. Institute of Public Health. The Third National Health and Morbidity Survey (NHMS III) 2006. Vol 1. Kuala Lumpur: Ministry of Health Malaysia; 2008.
3. Institute of Public Health. The Second National Health and Morbidity Survey 1996 (NHMS II). Kuala Lumpur: Ministry of Health Malaysia; 1999.
4. Talbot F, Nouwen A. A review of the relationship between depression and diabetes in adults: is there a link? Diabetes Care 2000;23:1556-62.
5. Wasserman LI, Trifonova EA. Diabetes mellitus as a model of psychosomatic and somatopsychic interrelationships. Span J Psychol 2006;9:75-85.
6. Lustman PJ, Clouse RE. Depression in diabetes: the chicken or the egg? Psychosom Med 2007;69:297-9.
7. Egede LE, Ellis C. Diabetes and depression: global perspectives. Diabetes Res Clin Pract 2010;87:302-12.
8. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069-78.
9. Nichols GA, Brown JB. Unadjusted and adjusted prevalence of diagnosed depression in type 2 diabetes. Diabetes Care 2003;26:744-9.
10. Zhang X, Norris SL, Gregg EW, Cheng YJ, Beckles G, Kahn HS. Depressive symptoms and mortality among persons with and without diabetes. Am J Epidemiol 2005;161:652-60.
11. 1 Ludman EJ, Katon W, Russo J, Von Korff M, Simon G, Ciechanowski P, et al. Depression and diabetes symptom burden. Gen Hosp Psychiatry 2004;26:430-6.
12. Katon W, Russo J, Lin EH, Heckbert SR, Ciechanowski P, Ludman EJ, et al. Depression and diabetes: factors associated with major depression at 5-year follow-up. Psychosomatics 2009;50:570-9.
13. Raval A, Dhanaraj E, Bhansali A, Grover S, Tiwari P. Prevalence & determinants of depression in type 2 diabetes patients in a tertiary care centre. Indian J Med Res 2010;132:195-200.
14. Mezuk B, Eaton WW, Golden SH, Ding Y. The influence of educational attainment on depression and risk of type 2 diabetes. Am J Public Health 2008;98:1480-5.
15. Moulton CD, Pickup JC, Ismail K. The link between depression and diabetes: the search for shared mechanisms. Lancet Diabetes Endocrinol 2015;3:461-71.
16. Khuwaja AK, Lalani S, Dhanani R, Azam IS, Rafique G, White F. Anxiety and depression among outpatients with type 2 diabetes: a multi-centre study of prevalence and associated factors. Diabetol Metab Syndr 2010;2:72.
17. Kaur G, Tee GH, Ariaratnam S, Krishnapillai AS, China K. Depression, anxiety and stress symptoms among diabetics in Malaysia: a cross- sectional study in an urban primary care setting. BMC Fam Pract 2013;14:69.
18. Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Sheehan KH, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry 2007;12:224-31.
19. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini International Neuropsychiatry Interview (M.I.N.I): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59:22-33.
20. Sheehan DV, Lecrubier Y, Sheehan KH, Janavs J, Weiller E, Keskiner A, et al. The validity of the Mini International Neuropsychiatric Interview (MINI) according to the SCID-P and its reliability. Eur Psychiatry 1997;12:232-41.
21. Otsubo T, Tanaka K, Koda R, Shinoda J, Sano N, Tanaka S, et al. Reliability and validity of Japanese version of the Mini-International Neuropsychiatric Interview. Psychiatry Clin Neurosci 2005;59:517- 26.
22. Gavard JA, Lustman PJ, Clouse RE. Prevalence of depression in adults with diabetes. An epidemiological evaluation. Diabetes Care 1998;16:1167-78.
23. Fisher L, Skaff MM, Mullan JT, Arean P, Mohr D, Masharani U, et al. Clinical depression versus distress among patients with type 2 diabetes. Diabetes Care 2007;30:542-8.
24. Larijani B, Bayat MK, Gorgani MK, Bandarian F, Akhondzadeh S, Sadjadi SA. Association between depression and diabetes. Ger J Psychiatry 2004;7:62-5.
25. Agbir TM, Audu MD, Adebowale TO, Goar SG. Depression among medical outpatients with diabetes: a cross-sectional study at Jos University Teaching Hospital, Jos, Nigeria. Ann Afr Med 2010;9:5-10.
26. Egede LE, Zheng D. Independent factors associated with major depressive disorder in a national sample of individuals with diabetes. Diabetes Care 2003;26:104-11.
27. Thomas J, Jones G, Scarinci I, Brantley P. A descriptive and comparative study of the prevalence of depressive and anxiety disorders in low-income adults with type 2 diabetes and other chronic illnesses. Diabetes Care 2003;26:2311-7.
28. Lustman PJ, Clouse RE, Griffith LS, Carney RM, Freedland KE. Screening for depression in diabetes using the Beck Depression Inventory. Psychosom Med 1997;59:24-31.
29. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-12.
30. Lin EH, Katon W, Von Korff M, Rutter C, Simon GE, Oliver M, et al. Relationship of depression and diabetes self-care, medication adherence and preventive care. Diabetes Care 2004;27:2154-60.
31. Golden SH. A review of the evidence for a neuroendocrine link between stress, depression and diabetes mellitus. Curr Diabetes Rev 2007;3:252-9.
32. Lustman PJ, Penckofer SM, Clouse RE. Recent advances in understanding depression in adults with diabetes. Curr Diab Rep 2007;7:114-22.
33. Fisher EB, Thorpe CT, Devellis BM, Devellis RF. Healthy coping, negative emotions, and diabetes management: a systematic review and appraisal. Diabetes Educ 2007;33:1080-103.
34. Lin EH, Rutter CM, Katon W, Heckbert SR, Ciechanowski P, Oliver MM, et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care 2010;33:264-9.