Curr Psychiatry Rep (2011) 13:26–30
DOI 10.1007/s11920-010-0165-z
Diabetes and Depression
Antonio Campayo & Carlos H. Gómez-Biel &
Antonio Lobo
Published online: 30 October 2010
# Springer Science+Business Media, LLC 2010
Abstract In a context of the potentially epidemic nature of
both diabetes mellitus and depression, and the negative
effects reported in cases of comorbidity, this review
suggests that the association of the two conditions is
multifaceted. Increased risks of prevalent depression and
incident depression among diabetic patients have been
reported in community studies. Even more consistent is the
finding supporting psychosomatic hypotheses regarding the
increased risk of diabetes among depressed patients. A
recent relevant finding is the increased risk of diabetes
reported in depression that is commonly found in the
community, namely nonsevere, persistent, untreated depres-
sion. In view of the negative implications of the comorbid-
ity of depression and diabetes, the suggestion that all
clinically relevant cases of depression found in the
community should be treated seems logical. However,
new studies seem mandatory to document the efficacy of
treatment of depression and the safety of antidepressant use
in cases of comorbidity.
Keywords Mood disorders . Diabetes mellitus . Metabolic
syndrome . Neuroendocrinology . Liaison psychiatry
A. Campayo (*) : C. H. Gómez-Biel : A. Lobo
Hospital Clínico Universitario, Servicio de Psiquiatría (3ª Planta),
Avenida San Juan Bosco 15,
50009 Zaragoza, Spain
e-mail: acampayo.iacs@aragon.es
A. Campayo : A. Lobo
Centro de Investigación Biomédica en Red de Salud Mental
(CIBERsam), Ministry of Science and Innovation,
Madrid, Spain
A. Campayo : A. Lobo
Instituto Aragonés de Ciencias de la Salud (I+CS),
Zaragoza, Spain
Introduction
The relationships between endocrine disturbances and
psychiatric conditions have stirred considerable interest
for several reasons [1]. Historically, several authors have
speculated about the role of hormones and endocrine
disorders in the etiology of psychiatric conditions. Endo-
crine hypotheses persist today in attempts to explain
classical psychiatric disturbances, but more ambitious
research has attempted to document the implicated physio-
pathologic mechanisms. For example, attention has been
devoted to the role of hormones in relation to control and
feedback processes in neural structures [2]. On the other
hand, psychiatric syndromes have been documented con-
sistently in endocrine diseases and may pose a real clinical
challenge for the liaison psychiatrist [3]. The relationship
between diabetes mellitus and depression is one of the main
examples in this field, but this relationship is complex and
multifaceted. In view of predictions about the epidemic
nature of diabetes mellitus and depression during the first
quarter of the 21st century [4, 5], and because of negative
effects reported in cases of comorbidity, the relationships
between these two conditions are a matter of concern [6]. In
this article, we review the intersection of diabetes and
depression, in particular from the perspective of new
contributions to the literature.
Depression in Diabetic Patients
Classical studies in different medical and psychiatric settings
documented a high prevalence of depression in diabetic
patients [1], and this has been a traditional field of clinical
activity for liaison psychiatrists [7]. Recent reviews con-
firmed this classical finding. The prevalence of depression in
Curr Psychiatry Rep (2011) 13:26–30
adult patients diagnosed with type 1 and type 2 diabetes also
has been documented in several recent studies, which were
summarized by Anderson et al. [8] and more recently by Ali
et al. [9]. These studies suggest that the presence of diabetes
almost doubles the risk of comorbid depression. Negative
implications of comorbid depression in patients with
diabetes mellitus might be expected and have been docu-
mented; they include worsened glycemia control [10],
nonadherence to treatment [11], poor metabolic control
[12], and increased risk of vascular complications (eg,
diabetic retinopathy, neuropathy, and macrovascular compli-
cations) [13•]. Furthermore, depression in diabetic patients
tends to persist and has been associated with increased
disability, decreased quality of life [14], more somatic
symptoms [15], increased health care costs, and even
increased mortality risk [12]. Some studies have even
reported an increased risk of dementia [16], although this
subject remains controversial [17].
A potential limitation to studies regarding the association
of diabetes and depression relates to the lack of an adequate
control group or to the use of self-report questionnaires to
document depression. Significantly different results might
be reported using questionnaires rather than formal inter-
views. For example, Anderson et al. [8] found a prevalence
of 11.4% of depression among diabetics based on formal
psychiatric criteria, but a prevalence of 31.0% based on
self-report scales. We previously argued that the use of
formal psychiatric interviews would be preferable to
diagnose treatable depression [18]. Furthermore, most
earlier studies on the association of diabetes and depression
did not control for other chronic diseases and disabilities.
With such bases, we conducted a large population-based
study in individuals 55 years of age and older, controlling
for these factors and using a formal psychiatric interview
[18]. We found a prevalence of depression of 14.4% in
cases of diabetes (virtually all of them type 2 diabetes), and
diabetes was associated with a 47% increased risk of
prevalent depression. The presence of comorbid medical
diseases seemed to lessen the effect of diabetes on the risk
of prevalent depression.
In a prospective way, we further tested in the same study
the hypothesis that diabetes increases the risk of depression.
Several studies had previously reported an increased risk,
but these studies either did not use a prospective,
population-based design or did not use formal psychiatric
criteria. We found a 40% increased risk of incident
depression among diabetics, and the presence of comorbid
medical diseases seemed to increase this risk. In a recent
systematic review and meta-analysis of 11 studies meeting
inclusion criteria, Nouwen et al. [19•] confirmed the
association of diabetes and increased risk of developing
depression, although the increase was more modest than in
our study (24% increased risk).
27
The chronic psychosocial stressors of having a chronic
medical condition have been considered to explain the
presence of depression in patients with type 1 and type 2
diabetes [12]. However, we suggested that the coexistence
of multiple comorbid conditions and the related disabilities
might largely account for the increased risk of depression
among diabetic patients [18]. In their systematic review,
Nouwen et al. [19•] concluded that the mechanisms
underlying this relationship are still unclear.
Depression and Incident Diabetes
The possibility that depression may eventually lead to
diabetes had been mentioned in the psychosomatic litera-
ture going back to British physician Thomas Willis but was
never convincingly demonstrated [20]. More recently, this
hypothesis has been tested in empiric, longitudinal studies
and was first supported by Eaton et al. [21•] in the
Baltimore Epidemiologic Catchment Area study. Knol et
al. [22] identified nine longitudinal studies related to this
hypothesis. They concluded that depressed individuals have
a 37% increased risk of developing type 2 diabetes.
However, the variety of methods used to measure depres-
sion and diabetes in these studies precludes a firm
conclusion. We previously made the observation that most
of these studies used rather weak methods to document
depression [23], such as the Center for Epidemiologic
Studies Depression Scale and other self-reports or general
physicians’ diagnoses.
Golden et al. [24] were the first authors to document the
bidirectional association between diabetes and depression.
However, the association between depression and incident
type 2 diabetes was “modest” and “partially explained by
lifestyles” [24]. Furthermore, as these authors also used the
Center for Epidemiologic Studies Depression Scale to
document depression, their study does not provide enough
information on a relevant clinical subject such as treatable
depression [25]. Treatable depression should be docu-
mented by formal psychiatric interview. The recent study
by Mezuk et al. [26] may be relevant in this respect because
they also documented an increased risk of incident diabetes
in cases of major depression detected in the community by
means of a diagnostic interview, the Diagnostic Interview
Schedule. However, most cases of depression in the general
population may be not major depression. For example, we
have shown that about two thirds of clinical cases detected
in a population sample of older adults were not major
depression [27]. In view of this, we recently tested the
hypothesis that clinically significant depression—not limit-
ed to major depressive disorder—increases the risk of
diabetes mellitus in the general population. In addition, we
examined the effect of characteristics of depression that
28
were frequently observed in previous community studies.
We concluded that clinically significant depression is
associated with a 65% increased risk of diabetes mellitus.
The estimated rate of diabetes mellitus attributable to
depression was about 7%. We also concluded that charac-
teristics of depression frequently found in the community,
namely nonsevere depression, persistent depression, and
untreated depression, may play a role in the development of
diabetes in a predominantly older adult population [28].
A recent editorial in the American Journal of Psychiatry
[21•] underlines the relevance of these findings, which had
been anticipated by Eaton et al. [29]. Particularly relevant
were the findings that compared with nonpersistent or
treated depression, persistent depression and, notably,
untreated depression were associated with a higher inci-
dence of diabetes. Globally considered, the findings in all
these studies may imply that treating all forms of clinically
significant depression could influence the incidence of
diabetes at the population level, particularly because in our
study, treatment with antidepressants was not associated
with an increased risk of diabetes mellitus [28]. Therefore,
these findings may have important public health implica-
tions. However, the benefits of this potential treatment
should be balanced with the potential risks of using
antidepressants. A case-control study by Andersohn et al.
[30] provided data to suggest a modest association between
antidepressant use and the incidence of diabetes. Although
our results do not support this association, the limited
power of the calculations preclude a firmer conclusion.
It is unclear in present studies what mediates the
association between depression and incident type 2 diabetes
[31]. Functional disability [32] or behavioral habits such as
current smoking or alcohol risk consumption have been
considered in some reports [24] but did not increase the risk
of type 2 diabetes in our predictive models. Behavioral
habits related to an increased body mass index also have
been considered because depressed individuals are more
likely to be physically inactive [33] and less likely to comply
with dietary and weight loss recommendations [34]. Biolog-
ical mechanisms should be considered. Depression has been
associated with physiologic abnormalities, including activa-
tion of the hypothalamic-pituitary-adrenal and sympathoa-
drenal systems [35], and with proinflammatory cytokines
[36], which can induce insulin resistance and contribute to
diabetes risk. However, the detailed study of these mediators
would require that diabetes be scored on a continuous scale
(eg, using blood glucose levels rather than using a binary
standard) [23].
One important hypothesis may arise from previous
reports about depression leading to development of the
metabolic syndrome [37]. The metabolic syndrome has
been reported in late-onset depression [38] and in persistent
depression [37]. Because the metabolic syndrome is
Curr Psychiatry Rep (2011) 13:26–30
considered to be an important risk factor for type 2 diabetes
[39], a feedback loop of depression, the metabolic
syndrome, and diabetes may be hypothesized. This hypoth-
esis would also be supported by the bidirectional associa-
tion of depression and diabetes reported by Golden et al.
[24], by previous research [18], and more recently by two
meta-analyses conducted by Mezuk et al. [40•] and
Nouwen et al. [19•], which found 15% and 24% increased
risks of depression, respectively, in diabetic patients.
Conclusions
The recent literature confirms the considerable preva-
lence of depression among diabetic patients. However,
the association of physical and psychiatric morbidity is
multifaceted. First, there is evidence that diabetes leads
to incident depression, as suggested in epidemiologic,
longitudinal studies. Second, and of more interest, might
be the finding that depression leads to diabetes. This is a
more consistent finding that supports the psychosomatic
hypothesis formulated in the previous century by authors
such as Thomas Willis. Third, recent studies suggest that
not only major depression, but also mild or nonsevere
depression, such as is observed in the community, is
associated with an increased risk of diabetes. Fourth, the
comorbidity of depression and diabetes is associated with
increased morbidity, increased mortality, and higher
medical costs. In relation to the documented mortality,
it may be especially relevant given the findings of an
increased risk of clinically significant microvascular and
macrovascular complications in depressed diabetic
patients [13•]. Fifth, this epidemiologic and clinical type
of evidence suggests that treatment of depression might be
important to prevent the development of diabetes and to
prevent clinical, potentially severe complications among
diabetic patients. However, new studies seem mandatory
to document the efficacy of psychosocial or biological
treatments of depression. The association of antidepres-
sants and incident diabetes has been suggested in studies
of long-term treatment but has not been confirmed in other
studies, including our own.
Although the clinical and public health implications of
the clinical and epidemiologic findings seem apparent, the
mechanisms to explain the bidirectional association of
diabetes and depression need to be elucidated. Severe
obesity, lack of physical activity, and poor self-care all have
been documented in depressed patients. Chronic stress
associated with hypercortisolemia certainly has been sug-
gested. We also speculate now that a metabolic syndrome
induced by these factors in depressed patients may be the
mediating mechanism. Finally, we cannot exclude the
possibility that depression observed in diabetic patients is
Curr Psychiatry Rep (2011) 13:26–30
qualitatively different than depression observed among
primarily psychiatric depressed patients.
Disclosure Dr. Lobo has served as a consultant for Janssen
Pharmaceutica and has had travel/accommodations expenses covered
for attendance at a meeting by Eli Lilly and Company. Drs. Campayo
and Gómez-Biel reported no potential conflicts of interest relevant to
this article.
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