Diabetes & Metabolic Syndrome: Clinical Research & Reviews 8 (2014) 6265

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Diabetes & Metabolic Syndrome: Clinical Research &

Reviews
journal homepage: www.elsevier.com/locate/dsx

Review

Depression in type 2 diabetes mellitusA 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: Diabetes mellitus is a chronic disease which has been associated with depression. Depression is more
Depression common in adults with type 2 diabetes mellitus (T2DM) as compared to those without. Both micro- and
Type 2 diabetes macro vascular diabetic complications are associated with depression and have shown to increase the
T2DM 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.
2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
2. Depression and type 2 diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3. Pathophysiology of depression and type 2 diabetes-linked . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
4. Depression and diabetic complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
5. Depression and glycemic control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
6. Depression in non-diabetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

1. Introduction [8], more diabetes-related complications [9], and a higher risk of

mortality than individuals with diabetes who are not depressed
Diabetes mellitus is a group of metabolic diseases that leads to a [10,11]. American Diabetes Association (ADA) has also recom-
substantial reduction in life expectancy, decreased quality of life, mended the assessment of psychological problems like depression
and increased costs of care. The global prevalence of type 2 in the patients with diabetes [12].
diabetes mellitus (T2DM) has been estimated to be 6.4% [1]. The
World Health Organization has projected that around 300 million 2. Depression and type 2 diabetes
people will suffer from diabetes by 2025 [2]. T2DM is much more
prevalent as compared to type 1 diabetes. It comprises 90% of A relation between depression and T2DM has been indicated in
people with diabetes around the world [3], and is caused by a several clinical reports [5,13,14]. However the direction of the
combination of resistance to insulin action and an inadequate relationship is unclear. For example the research by Knol et al.
compensatory insulin secretory response [4]. suggests that depression being a consequence of diabetes may also
Depression is a common co-morbid condition in T2DM and it be a risk factor for the onset of diabetes [15]. Individuals with
has been estimated that people with T2DM are twice as likely as depression, but no diabetes, are at a higher risk for developing
the general population to suffer from depression [5,6]. diabetes at follow-up. Mezuk et al. reported data showing that
Individuals with diabetes and co-morbid depression have been depression may be an important risk factor for developing T2DM.
shown to have poor adherence to diabetes medications [7], poor Depression was associated with a 60% increased risk of developing
adherence to dietary recommendations [7], poor glycemic control 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
* Tel.: +91 9582865898. with no depression, but receive diabetes treatment, are at a
E-mail address: sid_samreen@hotmail.com higher risk for developing depression at follow-up [17]. A recent

1871-4021/$ see front matter 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.dsx.2013.06.010
 S. Siddiqui / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 8 (2014) 6265
meta-analysis has reported 24% increased risk of incident
depression in T2DM patients as compared with non-diabetics
[18]. These ndings 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 [5,6,2224]. 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 conclu-
sions 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 identied
which, to some extent can explain the close relationship between
these two. One of the ndings refer to chronic dysregulations of the
hypothalamicpituitaryadrenal (HPA) axis such as high cortisol
levels and reduced insulin sensitivity or an activation of the
immune system leading to or fostering chronic inammatory
processes [27].
The risk factors for depression in the patients with T2DM
include comorbidity of diabetes-related complications, in particu-
lar 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 signicantly 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].
Fig. 1. Possible pathophysiological pathways linking depression and diabetes.
63
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 nding refer to chronic dysregu-
lations of the hypothalamicpituitaryadrenal (HPA) axis such as
high cortisol levels and reduced insulin sensitivity or an activation
of the immune system leading to or fostering chronic inammato-
ry 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
decit 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].
64 S. Siddiqui / Diabetes & Metabolic Syndrome: Clinical Research & Reviews 8 (2014) 6265
Another study by Yoshida et al., have reported that the presence of
microvascular complications, specically neuropathy, is associ-
ated with depression independent of age, gender, marital status,
social support, pain, perception of general health, diabetes type,
duration of diabetes, glycated hemoglobin and insulin require-
ment [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 claried.
5. Depression and glycemic control
HbA1c (glycated hemoglobin) is accepted as the best measure
of recent glycemic control and is used to guide clinical manage-
ment 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, hypoglyce-
mia 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 preva-
lence 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
1025% for women and from 5% to 12% for men. In any year, 59%
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 pre-
diabetes [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
signicantly greater in subjects with T2DM than in an age- and
sex-matched control subjects. Overall, diabetic subjects have
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 nd
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.
Conict of interest statement
There was no conict of interest involved in this study.
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