Depression and diabetes by Dr Shahjada Selim

Dr Shahjada Selim
Assistant Professor
Department of Endocrinology, BSMMU
DEPRESSION AND DIABETES

Diabetes and depression are rapidly growing
chronic health conditions that have
signiﬁcant negative impact upon the physical,
psychological, social and occupational
functioning, quality of life and often leads to
socio-economic burden.
Background

Worldwide, more than 425 million people are
estimated to have type 2 diabetes and
almost 373 million people have major
depression (IDF Atlas 2017).
Both these disorders are projected to be
among the ﬁve leading causes of disease
burden by 2045 (Mthers CD et al., 2006).

The co-occurrence of type 2 diabetes and
depression has attracted much research
interest. If this association was causal, it
would have profound implications for
prevention and treatment of these disorders.
However, the association between diabetes
and depression seems to be complex, and
does not follow a simple cause-and-e ectﬀ
pattern (Mathers CD et al., 2006).

Epidemiology of depression and diabetes
•In people with diabetes, the prevalence of
clinically relevant depressive symptoms is
31% and that of major depression is 11%
(Anderson et al., 2001).
•People with depressive disorders have a
65% increased risk of developing diabetes
(Campayo et al., 2010).
Lloyd CE et al 2010.

Epidemiology of depression and diabetes
•The prognosis of both diabetes and depression
(in terms of complications, treatment resistance
and mortality) is worse when the two diseases
are comorbid than when they occur separately.
Lloyd CE et al 2010.

Salinero-Fort MA, et al. BMJ Open 2018;8:e020768
Recent Spanish study found 20.03% depression in
T2DM (n=592; 95% CI 18.6% to 21.5%) and was
associated with previous personal history of depression
(OR 6.482; 95% CI 5.138 to 8.178), mental health
status below mean (OR 1.423; 95% CI 1.452 to
2.577), neuropathy (OR 1.951; 95% CI 1.423 to
2.674), fair or poor self-reported health status (OR
1.509; 95% CI 1.209 to 1.882), treatment with OAD
plus insulin (OR 1.802; 95% CI 1.364 to 2.380),
female gender (OR 1.333; 95% CI 1.009 to 1.761) and
blood cholesterol level (OR 1.005; 95% CI 1.002 to
1.009).

Salinero-Fort MA, et al. BMJ Open 2018;8:e020768
The variables inversely associated with depression
were: being in employment (OR 0.595; 95% CI 0.397
to 0.894), moderate physical activity (OR 0.552; 95%
CI 0.408 to 0.746), systolic blood pressure (OR 0.982;
95% CI 0.971 to 0.992) and social support (OR
0.978; 95% CI 0.963 to 0.993).
In patients without depression at baseline, the incidence
of depression after 1 year of follow-up was 1.20%
(95% CI 1.11% to 2.81%).

Rates of depression in diabetes patients from some countries participating in INTERPRET-DD
Catherine L et al 2018: International Prevalence an
Treatment Study (INTERPRET-DD)
INTERPRET-DD was
conducted among 3000
patients in 15 countries —
Argentina, Bangladesh,
China, Germany, India,
Italy, Kenya, Mexico,
Pakistan, Poland, Russia,
Serbia, Thailand, Uganda,
and Ukraine.
Depression affected
almost 30% of type 2
diabetes patients assessed
in Bangladesh, with
Mexico, Russia, and
Poland also scoring
highly.

WHO reports state, in Bangladesh, one in eight
adults has diabetes and 4.6% of the population is
suffering from depression, 15.3–34% of the
diabetic population is affected by depression.
WHO Bulletin 2018

Results: The prevalence of depressive symptoms was 34%
(PHQ-9 score ≥ 5) and 36% (WHO-5 score < 52) with audio
questionnaire delivery method.

Result: Overall, 61.9% participants had depressive symptoms, and the prevalence was
higher among females (70.9%) compared to males (50.6%). One-third (35.7%) of
participants had mild depression and 36.2% had moderate to severe depression. In the
multivariate analysis, factors signiﬁcantly associated with depression were: age 60 years
(OR: 2.1, 95% CI = 1.2–3.6; p 0.006), female gender (OR = 1.9, 95% CI = 1.3–3.0; p
0.002), those having 1–3 complications (OR = 2.3, 95% CI = 1.2–4.3; p = 0.010),
experienced loss of business or crop failure (OR = 2.1, 95% CI = 1.2–3.6; p = 0.006),
major family conﬂicts (OR = 2.2, 95% CI = 1.4–3.5; p 0.001), separation or deaths of
family members or divorce (OR = 2.2, 95% CI = 1.4–3.5; p 0.001), and those who
experienced unavailability of food or medicines (OR = 2.2, 95% CI = 1.0–4.5; p = 0.038).
Patients with diabetes, especially females, those having other
complications, and major life-events should routinely be screened
for symptoms of depression with adequate management of these
conditions.

Results: 24.8% non-diabetic and 56.2% diabetic subjects were
found to have depression. Statistically signiﬁcant difference was
found in income, waist-to-hip ratio between diabetic and non-
diabetic subjects (P < 0.001). Diabetic patients show 7-fold greater
odds of having depression in comparison to their non-diabetic
counterpart [OR 7.0, 95% CI (3.4, 14.3)]. Female gender
appeared as signiﬁcant predictor of depression [OR 4.3, 95% CI
Bangladeshi people with diabetes are more likely to
have coexisting depression. The risk of having coexisting
depression is seven times higher in diabetic patients in
comparison to the non-diabetic patients.

Health care utilization is significantly higher among depressed compared with non-
depressed diabetes patients (US 1996 data).
Egede LE. Chichester: Wiley, 2010.

The co-occurrence of type 2 diabetes and
depression has attracted much research interest.
If this association was causal, it would have
profound implications for prevention and
treatment of these disorders.
However, the association between diabetes and
depression seems to be complex, and does not
follow a simple cause-and-e ect pattern.ﬀ
Vos T et al. 2010;Mathers CD et al. 2006

A bidirectional association between depression and
diabetes have been have demonstrated (Mezuk B et al.,
2008; Golden SH et al., 2008), with most prior work
focusing on understanding potential mechanisms by which
diabetes leads to depression and vice versa.
Focusing more on mechanisms common to the
development of both depression and diabetes lead to
treatment and preventative strategies to address these two
major public health burdens simultaneously.
Mechanisms and Pathogenesis Underlying the Association
Between Diabetes and Depression

Summary of shared pathogenic mechanisms in the depression–diabetes association
covered at the International Conference on Depression and Diabetes.
Richard I.G. Holt et al. Dia Care 2014;37:2067-2077 ©2014 by American Diabetes Association

Depression and diabetes complications
•A prospective association has been documented
between prior depressive symptoms and the onset
of coronary artery disease in people with diabetes
(Orchard et al., 2003).
•A prospective association has been found between
depression and the onset of retinopathy in children
with diabetes (Kovacs et al., 1995).

Depression and diabetes complications
•Depressive symptoms are more common in
diabetes patients with macro- and micro-
vascular problems, such as erectile
dysfunction and diabetic foot disease,
although the causal direction of the
relationship is unclear (Thomas et al., 2004)

ght restrictions may apply.
Zhang, X. et al. Am. J. Epidemiol. 2005 161:652-660; doi:10.1093/aje/kwi089
Survival functions in a diabetic population stratified by Centers for Epidemiologic Studies
Depression (CES-D) Scale score, NHANES I Epidemiologic Follow-up Study, 1982-1992
Copyright restrictions may apply.
Zhang, X. et al. Am. J. Epidemiol. 2005 161:652-660; doi:10.1093/aje/kwi089
Survival functions in a nondiabetic population stratified by Centers for Epidemiologic Studies
Depression (CES-D) Scale score, NHANES I Epidemiologic Follow-up Study, 1982-1992
A strong association has been found between depressive symptoms (as assessed by
the Center for Epidemiological Studies - Depression Scale, CES-D) and increased
mortality in people with diabetes, but not in those without diabetes, after adjusting for
socio-demographic and lifestyle factors.
Population with Diabetes Population without Diabetes
Zhang et al., Am. J. Epidemiol. 2005

Association between duration of DM and
depression
Diabetes mellitus like any other chronic illness
adds signiﬁcant stress to the life of the
individuals suffering from it. Some studies
reported that duration of T2DM of 2–4 years
signiﬁcantly increases the risk of depression
(Khullar et al., 2016).
Some even reported that only one year is enough
to increase the risk of depression in a T2DM
patient (Guruprasad et al., 2012).

Thour et al’s study found that duration of T2DM has
a strong association with depression and that the
risk of depression nearly doubles after 3 years of
diagnosis of diabetes. This ﬁnding was backed by
studies done by Guruprasad et al. (2012), Das et
al. (2013), Iype et al. (2009), Kulkarni et al. (2014),
Jain et al. (2015) and Khullar et al. (2016), all of
whom found statistically signiﬁcant association
between duration of diabetes and depression in
subjects (p < 0.05).
Association between duration of diabetes mellitus and depression

Association between glycemic control and
depression
Khullar et al. (2016) from Punjab reported that
subjects with higher blood glucose level (>125
mg/dl) were at increased risk of having
depression. Almost similar ﬁnding was observed
by Mathew et al. (2013). Singh et al. (2014), Iype
et al. (2009) and Das et al. (2013) found that
depression was strongly associated with poor
glycemic control in T2 diabetic patients, they
reported a signiﬁcant association of HbA1C with
depression.

Association between glycemic control and depression
Mathew et al. (2012) observed that after adjusting
for age and sex, presence of depression
increased HbA1c by an average of 0.94% and
this increase was statistically signiﬁcant (P =
0.022). Poongothai et al’s found a signiﬁcant
association between depression and glucose
intolerance (even in prediabetes).

Impact of Depression on Diabetes Control
Depressive symptoms have been shown to be associated
with worsened blood glucose levels and diabetes
complications such as coronary heart disease.
There is increasing evidence that significant additional
functional, fiscal, and psychological costs are associated
with depression in patients with diabetes.
Several studies have documented decreased adherence to
diet, exercise, and medication regimens associated with
depression among adults with diabetes.
Lustman PJ et al 2000; deGroot M et al 2001; Clouse RE et al 2003
Egede L et al 2009;

Impact of Depression and Diabetes
Medical costs associated with moderate to severe levels of
depression have also been found to be 51-86% higher than
among patients reporting low levels of depression.
Patients with diabetes and depression have been found to
have 4.5 times higher medical expenditures than patients
with diabetes alone. Patients with comorbid depression also
have higher ambulatory care use and fill more prescriptions.
Ciechanowski PS et al 2006; Egede LE et al 2002

Health care expenditures are significantly higher in depressed than in non-depressed
diabetes patients (US 1996 data). From Egede LE. Medical costs of depression and
diabetes. In: Depression and Diabetes.
Katon W et al. Chichester: Wiley, 2010.

Comorbid depression has also been shown to have a significant
impact on functional disability. Data from the National Health
Interview Study have shown that individuals with diabetes and
comorbid depression are 7.15 times more likely to experience
functional disability (i.e., impairment in work or social
activities) compared to peers with either condition
alone. Simon et al. found that > 50% of patients diagnosed with
both conditions in a health maintenance organization
population reported unemployment.
Egede LE et al 2007; Simon GE et al 2005

People with both depression and diabetes have a greater decrement in self-reported
health than those with depression and any other chronic disease
Moussavi et al., Lancet 2007

Finally, comorbid depression and diabetes have been found to
increase the risk of early mortality 2.3 times compared to
nondepressed patients with diabetes.
Zhang et al. reported a 54% increased risk of early mortality
among patients reporting elevated depression scores.
As Lin et al. have recently documented, causes of mortality in
this vulnerable population extend beyond cardiovascular
disease to the full range of diseases and disorders.
Katon WJ et al 2005; Zhang X et al 2007; Lin E 2007

The depression-diabetes link: biological factors
•Depression is a phenotype for a range of stress-related
disorders which lead to an activation of the
hypothalamic-pituitary-adrenal axis, a dysregulation of
the autonomic nervous system and a release of pro-
inflammatory cytokines, ultimately resulting in insulin
resistance.
•Metabolic programming at the genetic level and
undernutrition (in utero and childhood) may predispose
to both diabetes and depression.
Ismail K 2010; Lustman PJ et al 2010

Problem Impact
• Depression and diabetes
symptoms overlap
• Depression symptoms mimic
diabetes symptoms
• Patient and clinician may be unaware of
depression, and may primarily attribute changed
status to worsening diabetes self-care
• Depression may be
associated with onset or
amplification of physical
symptoms
• Patient may not sense he/she is fully understood
or supported by his/her clinician during health care
visits when physical or lab results do not
correspond to subjective complaints
• Depression is commonly
associated with difficulties
with diabetes self-
management and treatment
adherence
• Patient may feel resigned about the ability to make
changes, e.g. “I know what I am supposed to do
and what I am not supposed to do, but I still do the
wrong things and I don’t know why!”
• Clinician may feel discouraged about the ability of
the patient to make relevant changes in his/her
care
Practical problems arising from depression-diabetes comorbidity - I
Hellman R et all, 2010.

Hellman R et al 2010.
Problem Impact
• Individuals with depression may attempt
to regulate emotions with food or
substances
• A clinician not understanding the underlying
depressive symptoms and patient’s desperation
to regulate emotional pain may come across as
judgmental because of the stigma and
associated response to these behaviors
• Stressors that interfere with self-
management strategies and worsen
diabetes status may also precipitate or
exacerbate depression
• Patient and clinician may attribute poor
diabetes outcomes to a decrease in self-
management because of a busy lifestyle but
may not appreciate the insidious development
of depression and its consequences
• Depression may reduce the ability of
affected individuals to trust others or to
be satisfied with health care
• Depression is commonly associated with
changes in health care seeking patterns
and follow-through with appointments
• Patient may be reluctant to make
appointments, show up for appointments, seek
support of health care providers or collaborate
with health care providers during
appointments
Practical problems arising from depression-diabetes comorbidity - II

Problem Impact
• Depression may be
associated with poor
blood glucose control
irrespective of
behavioral actions
• This may lead to hopelessness, guilt, loss of empowerment,
or a decreased sense of control of illness and may influence
the motivation of the patient to engage in further clinical
treatment recommendations
• Unsuspecting clinicians may unwittingly blame the patient for
a situation the patient now has little control over
• Depression is
commonly associated
with difficulty
organizing tasks
• What might have been easily understood in the past may
need to be written, repeated and checked for
comprehension while the patient is depressed
• Depression leads to a
more pessimistic view
of the future
• Clinicians may need to help depressed patients break down
tasks into manageable action steps that may have shorter-
term pay-off (e.g., reduction of physical symptoms)
• Depression is
commonly associated
with anxiety
• Clinicians need to consider presence of anxiety which
heightens a patient’s uncertainty around decision-making
and increases a general sense of dread about the likelihood
of success
Practical problems arising from depression-diabetes comorbidity - III
Hellman R et al 2010.

Management of
Depression in DM

Psychosocial Issues: ADA Recommendations
 Psychosocial care should be integrated with a collaborative,
patient-centered approach and provided to all people with
diabetes, with the goals of optimizing health outcomes and
health-related quality of life (QOL). A
 Psychosocial screening and follow-up may include, but are
not limited to, attitudes about diabetes, expectations for
medical management and outcomes, affect or mood, general
and diabetes-related QOL, available resources (financial,
social, and emotional), and psychiatric history. E
Lifestyle Management:
Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S38-S50

 Providers should consider assessment for symptoms of diabetes
distress, depression, anxiety, disordered eating, and cognitive
capacities using patient-appropriate standardized and validated
tools at the initial visit, at periodic intervals, and when there is
a change in disease, treatment, or life circumstance. Including
caregivers and family members in this assessment is
recommended. B
 Consider screening older adults (aged ≥65 years) with
diabetes for cognitive impairment and depression. B
Psychosocial Issues: ADA Recommendations

Referral for Psychosocial Care:Referral for Psychosocial Care: ADA Recommendations

Depression care in patients with diabetes: Step 1
Katon W et al 2010.
Screen for:
• Depression with the Patient Health Questionnaire - 9 (PHQ-9)
• Helplessness/”giving up” or sense of being overwhelmed
about disease self-management
• Comorbid panic attacks and post-traumatic stress disorder
• Inability to differentiate anxiety symptoms from diabetes
symptoms (e.g., hypoglycemia)
• Associated eating concerns
• Emotional eating in response to sadness/loneliness/anger
• Binge eating/purging
• Night eating

Improve self-management:
• Explore “loss of control” of disease self-management
• Explore understanding of bidirectional link between stress
and suboptimal disease self- management and outcomes
• Define depression and how it overlaps with and is distinct
from “stress”
• Review symptoms of depression and how these symptoms
overlap with or mimic diabetes symptoms
• Discuss depression-related medical symptom amplification
• Break down tasks in self-management of diabetes,
depression, other illnesses
• Help patient prioritize order of importance of specific tasks
Katon W et al 2010.

Depression: ADA RecommendationsDepression: ADA Recommendations
 Providers should consider annual screening of all patients with
diabetes, especially those with a self-reported history of
depression, for depressive symptoms with age-appropriate
depression screening measures, recognizing that further
evaluation will be necessary for individuals who have a
positive screen. B
 Beginning at diagnosis of complications or when there are
significant changes in medical status, consider assessment for
depression. B
Comprehensive Medical Evaluation and Assessment of Comorbidities:

Depression: ADA Recommendations
 Referrals for treatment of depression should be
made to mental health providers with experience
using cognitive behavioral therapy, interpersonal
therapy, or other evidence-based treatment
approaches in conjunction with collaborative care
with the patient’s diabetes treatment team. A
Comprehensive Medical Evaluation and Assessment of Comorbidities:

Efficacy trials of psychotherapies for depression in diabetes
Katon W et al 2010.
Study Interventions Outcome
Lustman et
al., 1998
Cognitive-behavioural therapy (CBT)
plus diabetes education vs. diabetes
education alone
Improvement in depression as well
as glycemic control in CBT vs.
control group
Huang et
al., 2002
Antidiabetics + diabetic education +
psychological treatment + relaxation
and music treatment vs. antidiabetics
only
as glycemic control in treatment vs.
control group
Li et al.,
2003
Antidiabetics + diabetic education +
psychological treatment vs.
antidiabetics only
control group
Lu et al.,
2005
Diabetes and cerebrovascular
accident education +
electromyographic treatment +
psychological treatment vs. usual care
control group
Simson et
al., 2008
Individual supportive psychotherapy
vs. usual care
as glycemic control in supportive
psychotherapy vs. control group

Efficacy trials of medications for depression in diabetes
Study Interventions Outcome
Lustman et
al., 1997
Glucometertraining +
nortriptyline vs. placebo
Improvement in depression but not in glycemic
control with nortryptiline vs. placebo
Lustman et
al., 2000
Fluoxetine vs. placebo Improvement in depression but not in glycemic
control with fluoxetine vs. placebo
Paile-
Hyvärinen et
al., 2003
Paroxetine vs. placebo After initial improvement in paroxetine group at 3
months, no significant improvement for both
outcomes at the end of follow-up
Xue et al.,
2004
Paroxetine vs. placebo Improvement in depression but not in glycemic
control with paroxetine vs. placebo
Gülseren et
al., 2005
Fluoxetine vs.
paroxetine
Both groups improved significantly in depression
but not in glycemic control
Paile-
Hyvärinen et
al., 2007
Paroxetine vs. placebo No significant improvement in depressive
outcomes and glycemic control
Katon W et al 2010.

Support:
• Consider adjunctive brief psychotherapy for:
emotional eating (cognitive-behavioural therapy),
breaking down problems (problem-solving therapy),
improving treatment adherence (motivational
interviewing)
Katon W et al 2010.

Consider medication:
• Comorbid depression and anxiety: SSRI or SNRI
• Sexual dysfunction: use bupropion or, if already
responding to SSRI, add buspirone
• Significant neuropathy: choose bupropion, venlafaxine or
duloxetine due to effectiveness in treating neuropathic pain
Katon W et al 2010.

Public health and prevention: future
research needs and recommendations

Preventing
comorbid
depression
and diabetes
Identify and implement best practice into routine health care for
integrated health services for comorbid depression and diabetes
in different types of service and in different countries
Expand economic studies of depression–diabetes comorbidity
to non-U.S. countries
Incorporate non-health care–related costs into cost-
effectiveness analyses
Preventing
diabetes in
depression
Develop studies to understand the effect of depression and
antidepressants on diabetes preventive interventions
Determine if prevention or treatment of depression can reduce
type 2 diabetes incidence
Validate diabetes risk engines in individuals with depression
Public health and prevention: future research needs and recommendations
Diabetes Care 2014

Preventing
depression in
diabetes
Conduct future depression intervention studies in individuals
with diabetes in primary and subspecialty care settings
• Evaluate effectiveness
• Target health care providers as intervention focus
Conduct health services studies to determine the optimal way of
delivering depression interventions, including the use of
nonprofessional workers (e.g., peer support) and new
technologies
Primary
prevention of
depression
and diabetes
Develop and test in randomized trials population-based
interventions to reduce etiological factors associated with
comorbid diabetes and depression, within and across cultures and
countries
Public health and prevention: future research needs and recommendations
Diabetes Care 2014

Take Home Message
Prevalence and impact of depression in people
with diabetes have significant adverse effects
on morbidity and mortality when both
conditions are present.
Conventional treatments for depression have
been shown to be effective in treating
depression in people with diabetes.

Take Home Message
Challenges remain for providers and patients to
be more aware of depressive symptoms.
The inclusion of established depression
screening protocols in diabetes clinical
management pathways would increase provider
awareness, screening, and psychological referral.

Take Home Message
A multidisciplinary approach of the diabetic
patient would help improve the outcomes of
disease, decrease the number of DALYs and
even mortality.

Depression and diabetes by Dr Shahjada Selim

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