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Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx

Review

Depression in type 2 diabetes mellitus—A brief review Samreen Siddiqui * Max Super Speciality Hospital, India

A R T I C L E I N F O

A B S T R A C T

Keywords: Depression Type 2 diabetes T2DM

Diabetes mellitus is a chronic disease which has been associated with depression. Depression is more common in adults with type 2 diabetes mellitus (T2DM) as compared to those without. Both micro- and macro vascular diabetic complications are associated with depression and have shown to increase the risk of mood disorder. Further, poor glycemic control in T2DM patients could lead to more complications of diabetes and such patients are more likely to develop depression. More research is needed in this area to determine the exact relationship between depression and T2DM and to unfold the mystery of mechanism behind this. ß 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Contents 1. 2. 3. 4. 5. 6. 7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Depression and type 2 diabetes . . . . . . . . . . . . . . . . . . . . . . Pathophysiology of depression and type 2 diabetes-linked . Depression and diabetic complications. . . . . . . . . . . . . . . . . Depression and glycemic control . . . . . . . . . . . . . . . . . . . . . Depression in non-diabetics . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction Diabetes mellitus is a group of metabolic diseases that leads to a substantial reduction in life expectancy, decreased quality of life, and increased costs of care. The global prevalence of type 2 diabetes mellitus (T2DM) has been estimated to be 6.4% [1]. The World Health Organization has projected that around 300 million people will suffer from diabetes by 2025 [2]. T2DM is much more prevalent as compared to type 1 diabetes. It comprises 90% of people with diabetes around the world [3], and is caused by a combination of resistance to insulin action and an inadequate compensatory insulin secretory response [4]. Depression is a common co-morbid condition in T2DM and it has been estimated that people with T2DM are twice as likely as the general population to suffer from depression [5,6]. Individuals with diabetes and co-morbid depression have been shown to have poor adherence to diabetes medications [7], poor adherence to dietary recommendations [7], poor glycemic control

* Tel.: +91 9582865898. E-mail address: [email protected]

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[8], more diabetes-related complications [9], and a higher risk of mortality than individuals with diabetes who are not depressed [10,11]. American Diabetes Association (ADA) has also recommended the assessment of psychological problems like depression in the patients with diabetes [12]. 2. Depression and type 2 diabetes A relation between depression and T2DM has been indicated in several clinical reports [5,13,14]. However the direction of the relationship is unclear. For example the research by Knol et al. suggests that depression being a consequence of diabetes may also be a risk factor for the onset of diabetes [15]. Individuals with depression, but no diabetes, are at a higher risk for developing diabetes at follow-up. Mezuk et al. reported data showing that depression may be an important risk factor for developing T2DM. Depression was associated with a 60% increased risk of developing T2DM [16]. The reason for this could be that people with elevated depressive symptoms are less attentive toward a healthy lifestyle, therefore increasing their risk for diabetes. Conversely, individuals with no depression, but receive diabetes treatment, are at a higher risk for developing depression at follow-up [17]. A recent

1871-4021/$ – see front matter ß 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.dsx.2013.06.010

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meta-analysis has reported 24% increased risk of incident depression in T2DM patients as compared with non-diabetics [18]. These findings among others [13,19] suggest that there is strong evidence for a bidirectional relationship between diabetes and depression. Golden et al. also found evidence for a bidirectional relationship within the same cohort [14]. Literature reports that patients with diabetes are almost twice as likely to suffer from depression as the general population [20,21], with women at a higher risk with prevalence of 28.2% compared to 18% among males [5,6,22–24]. Several other studies have reported the prevalence rates of depression in T2DM patients between 24 and 30% [5,6,25]. However, recently it has been suggested that although up to 30% of individuals with diabetes report depressive symptoms, only about 10% have major depression [26]. A fact which cannot be ignored is that the published studies differ widely in terms of the methods used to measure depression, which makes any conclusions premature. Rates of depressive symptoms have been found to be higher in those studies where self-report instruments were used compared to diagnostic interviews [5]. Several neuroendocrine and neurotransmitter abnormalities common to both depression and diabetes have been identified which, to some extent can explain the close relationship between these two. One of the findings refer to chronic dysregulations of the hypothalamic–pituitary–adrenal (HPA) axis such as high cortisol levels and reduced insulin sensitivity or an activation of the immune system leading to or fostering chronic inflammatory processes [27]. The risk factors for depression in the patients with T2DM include comorbidity of diabetes-related complications, in particular vascular complications [28,29]. Knowledge of having diabetes [14], longer duration of diabetes [30,31], more demanding regimens, low levels of daily activities [32], smoking [33] and obesity [34,30] have all been postulated as risk factors, but the epidemiological evidence remains limited. Other studies have suggested that an increased level of depression is associated with demographic variables such as low education [6], female sex [13,30,35], or being unmarried [6]. Potential risk factors for depression in people with diabetes often interact with each other and with other factors. For example, the relationship between duration of diabetes and depression may be confounded by the number of complications present. It has been reported that duration of diabetes is associated with the development of depression. Increased duration of the disease is known to significantly increase the risk for developing diabetic complications and health care expenditures, as a result such patients are more prone to develop psychological illnesses [36]. Depression in T2DM has been found to be associated with diminished quality of life [37] and poorer diabetes self-care [38].

A recently published World Health Organization (WHO) World Health Survey about the impact of depression on quality of life in different chronic diseases (arthritis, asthma, angina and diabetes) showed that quality of life was most impaired in patients with diabetes and depression [39]. For women with type 2 diabetes, negative moods have been reported to impact their day-to-day living and overall quality of life [40]. And they have been reported to have poorer glycemic control and quality of life than men with diabetes [41]. Depression in T2DM decreases compliance with medications and healthy lifestyle measures, increase health care expenditures, and above all increase the risk of cardiovascular mortality [42]. 3. Pathophysiology of depression and type 2 diabetes-linked The reason for this timely relationship between depression and diabetes manifestation is unclear. It could be that people with elevated depressive symptoms are less attentive toward a healthy lifestyle, therefore increasing their risk for type 2 diabetes. Alternative explanations for this finding refer to chronic dysregulations of the hypothalamic–pituitary–adrenal (HPA) axis such as high cortisol levels and reduced insulin sensitivity or an activation of the immune system leading to or fostering chronic inflammatory processes [27] (see Fig. 1). A second explanation for the close relationship between depression and diabetes comes from the observation that depressed patients with diabetes also report a high amount of diabetes-related distress [43]. It might be that in vulnerable patients a high amount of diabetes-related distress or a deficit in coping with diabetes-related problems could result in elevated depression symptoms. A third explanation stems from study results indicating that blood glucose is itself a potent regulator for mood states. In particular, hypoglycemia or severe hyperglycemia is able to induce negative emotional states in patients with diabetes [44]. 4. Depression and diabetic complications Poorly controlled diabetes leads to a number of co-morbid complications. These include diabetic retinopathy, nephropathy, neuropathy, cardiac heart diseases and peripheral vascular disease. Association between depression and various long-term diabetic complications have been reported in several studies [43,45,46]. The prevalence of depression in T2DM patients appears to increase with the number of diabetic complications [47]. Two recent reviews have reported that depressed mood is positively associated with the presence of diabetic complications and it has been investigated that the prevalence of depression is higher among T2DM subjects with retinopathy, neuropathy, nephropathy and peripheral vascular disease (PVD) [28,48].

Fig. 1. Possible pathophysiological pathways linking depression and diabetes.

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Another study by Yoshida et al., have reported that the presence of microvascular complications, specifically neuropathy, is associated with depression independent of age, gender, marital status, social support, pain, perception of general health, diabetes type, duration of diabetes, glycated hemoglobin and insulin requirement [49]. Reason for this association could be the increase in the burden of the disease due to complications which can lead to depressive symptoms. Conversely, it has been reported that functional impairment in individuals with T2DM may also increase prevalence of depression [43]. However, the underlying mechanisms explaining this association are still unclear and needed to be clarified. 5. Depression and glycemic control HbA1c (glycated hemoglobin) is accepted as the best measure of recent glycemic control and is used to guide clinical management and according to the American Diabetes Association (ADA) guidelines, patients with diabetes should maintain low levels of HbA1c [12]. An explanation for the relationship of depression and T2DM stems from the study results indicating that blood glucose is itself a potent regulator for mood states. In particular, hypoglycemia or severe hyperglycemia is able to induce negative emotional states in patients with diabetes [50]. Clinical reports [40,44,51] have indicated that depression is associated with higher GHb, i.e., with hyperglycemia. Depressed adults with T2DM have poor glycemic control as compared to those without any mood disorder. The presence of depression in a patient with diabetes has been suggested as one of the possible causes of an inadequate metabolic control, especially for those patients who cannot achieve an adequate glycemic control despite intensive medical recommendations. Besides the elevated prevalence of depression in diabetes, several authors observed an impact of depression on glycemic control of diabetes. Skaff et al., evaluating 206 showed that a daily negative mood correlated positively with the fasting glucose level of the next morning in men with T2DM [53]. In addition, Eren (2003) reported that the number of depressive episodes correlated positively with HbA1c levels. Another longitudinal study investigated the correlation between depression and A1C levels in T2DM patients with and without depression [8]. The authors observed that type 2 diabetic patients with depression exhibited higher HbA1c levels compared to patients without depression in all time points evaluated. 6. Depression in non-diabetics Lifetime prevalence of depression in the general population is 10–25% for women and from 5% to 12% for men. In any year, 5–9% of women will have this disorder and from 2% to 3% of men will have it [54,55]. Individuals with depression experience reduced functioning and decreased quality of life [56,57], as well as higher health care utilization and costs, and disability [58]. Furthermore, depression is more prevalent in patients with chronic illness in general [59] and diabetes in particular, and it is associated with poor adherence to medical regimens in patients with comorbid medical illness [5,38]. The prevalence of type 2 diabetes is approximately 13%, and an additional 30% of individuals have prediabetes [60]. Few studies have been done so far which have included a control group for comparing the prevalence of depression in T2DM patients and in the general population. All those which have been done reported the prevalence rates to be twice in adults with T2DM as compared to those without [7,19,25,26]. The prevalence of diagnosed depression has been found to be significantly greater in subjects with T2DM than in an age- and sex-matched control subjects. Overall, diabetic subjects have

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1.5 times greater prevalence than non-diabetic subjects found. However, after adjusting for age, sex, presence of cardiovascular disease, and body weight, diagnosed depression prevalence in diabetic subjects declined to 15.0% [24]. 7. Conclusion Depression is a commonly associated condition with T2DM. Above studies suggest that depression is almost twice more common in patients with type 2 diabetes as compared to the general population. It can be concluded from this review that there is a need for the assessment of depression among the patients with T2DM, which is also recommended by the ADA guidelines [12]. Large epidemiological studies worldwide would help to find out the incidence of depression in T2DM at large. Further, it would also help to identify co-relation of co-morbid complications of diabetes with depression. Conflict of interest statement There was no conflict of interest involved in this study. References [1] Diabetes Facts. World Diabetes Foundation. Source: IDF, Diabetes Atlas. 4th ed. Available from: http://www.worlddiabetesfoundation.org/composite-35.htm. [2] 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 Journal of Medical Research 2010;132:195–200. [3] Diabetes Basics: American Diabetes Association [Internet, accessed 22.06.12]. Available from: http://www.diabetes.org/diabetes-basics/type-2/. [4] Diagnosis and Classification of Diabetes Mellitus Diabetes Care, vol. 31, Suppl. 1. January 2008 by the American Diabetes Association. [5] Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of co-morbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069–78. [6] Ali S, Stone MA, Peters JL, Davies MJ, Khunti K. The prevalence of co-morbid depression in adults with type 2 diabetes: a systematic review and metaanalysis. Diabetic Medicine 2006;23:1165–73. [7] Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Archives of Internal Medicine 2000;160:3278–85. [8] Richardson LK, Egede LE, Mueller M, Echols CL, Gebregziabher M. Longitudinal effects of depression on glycemic control in veterans with type 2 diabetes. General Hospital Psychiatry 2008;30:509–14. [9] Simon GE, Katon WJ, Lin EH, Ludman E, VonKorff M, Ciechanowski P, et al. Diabetes complications and depression as predictors of health service costs. General Hospital Psychiatry 2005;27:344–51. [10] Egede LE, Nietert PJ, Zheng D. Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 2005;28:1339–45. [11] Katon W, Fan MY, Unutzer J, Taylor J, Pincus H, Schoenbaum M. Depression and diabetes: a potentially lethal combination. Journal of General Internal Medicine 2008;23:1571–5. [12] American Diabetes Association. Standards of medical care in diabetes 2012. Diabetes Care 2012;35(January (Suppl. 1)):S67–74. [13] Knol MJ, Twisk JW, Beekman AT, Heine RJ, Snoek FJ, Pouwer F. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 2006;49:837–45. [14] Golden SH, Lazo M, Carnethon M, Bertoni AG, Schreiner PJ, Diez Roux AV, et al. Examining a bidirectional association between depressive symptoms and diabetes. JAMA 2008;299:2751–9. [15] Knol M, Heerdink E, Egberts A, Geerlings MI, Gorter KJ, Numans ME, et al. Depressive symptoms in subjects with diagnosed and undiagnosed type 2 diabetes. Psychosomatic Medicine 2007;69:300–5. [16] Mezuk B, Eaton W, Albrecht S, Golden SH. Depression and type 2 diabetes over the lifespan: a meta-analysis. Diabetes Care 2008;31:2383–90. [17] Lin EH, Heckbert SR, Rutter CM, Katon WJ, Ciechanowski P, Ludman EJ, et al. Depression and advanced complications of diabetes: a prospective cohort study. Diabetes Care 2010;33:264–9. [18] Nouwen A, Winkley K, Twisk J, Lloyd CE, Peyrot M, Ismail K, et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 2010;53:2480–6. [19] Chandola T, Brunner E, Marmot M. Chronic stress at work and the metabolic syndrome: prospective study. British Medical Journal 2006;332: 521–5. [20] Trento M, Raballo M, Trevisan M, Sicuro J, Passera P, Cirio L, et al. A crosssectional survey of depression, anxiety, and cognitive function in patients with type 2 diabetes. Acta Diabetologica 2012;49:199–203.

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Please cite this article in press as: Siddiqui S. Depression in type 2 diabetes mellitus—A brief review. Diab Met Syndr: Clin Res Rev (2013), http://dx.doi.org/10.1016/j.dsx.2013.06.010

Depression in type 2 diabetes mellitus--a brief review.

Diabetes mellitus is a chronic disease which has been associated with depression. Depression is more common in adults with type 2 diabetes mellitus (T...
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