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Indian Journal of Endocrinology

and Metabolism
Wolters Kluwer -- Medknow Publications

Diabetes and psychiatric disorders

Yatan Pal Singh Balhara

Additional article information

Abstract
Interface of diabetes and psychiatry has
fascinated both endocrinologists and mental
health professionals for years. Diabetes and
psychiatric disorders share a bidirectional
association -- both influencing each other in
multiple ways. The current article addresses
different aspects of this interface. The interaction
of diabetes and psychiatric disorders has been
discussed with regard to aetio-pathogenesis,
clinical presentation, and management. In spite of
a multifaceted interaction between the two the
issue remains largely unstudied in India.

Keywords: Diabetes, psychiatric disorders,

psychotropic medications

INTRODUCTION
The interface of diabetes and psychiatry has
fascinated both endocrinologists and mental
health professionals for years. Way back in 17th
century Thomas Willis speculated that diabetes
was caused by “long sorrow and other
depressions.” Sir Henry Maudsley commented
that “Diabetes is a disease which often shows
itself in families in which insanity prevails” in
“The Pathology of Mind” published in 1879.
Insulin coma therapy was used as a psychiatric
treatment within a decade of isolation of insulin.
Over the past few decades this interface has been
studied more extensively with greater scientific
rigor.

Diabetes and psychiatric disorders share a

bidirectional association - both influencing each
other in multiple ways. The current article
addresses different aspects of this interface.
General issues pertaining to the topic would be
described first. Subsequently salient features of
individual psychiatric disorder would be
presented.

Patterns of co-occurrence of diabetes and

psychiatric disorders
Comorbidity of diabetes and psychiatric disorders
can present in different patterns. First, the two can
present as independent conditions with no
apparent direct connection. In such a scenario
both are outcome of independent and parallel
pathogenic pathways. Second, the course of
diabetes can be complicated by emergence of
psychiatric disorders. In such cases diabetes
contributes to the pathogenesis of psychiatric
disorders. Various biological and psychological
factors mediate the emergence of psychiatric
disorders in such context. Third, certain
psychiatric disorders like depression and
schizophrenia act as significant independent risk
factors for development of diabetes. Fourth, there
could be an overlap between the clinical
presentation of hypoglycemic and ketoacidosis
episodes and conditions such as panic attacks.
Fifth, impaired glucose tolerance and diabetes
could emerge as a side effect of the medications
used for psychiatric disorders. Treatment of
psychiatric disorders could influence diabetes
care in other ways also as discussed in subsequent
sections [Box 1].

Box 1
Interaction between diabetes and
psychiatric disorders

Diabetes and psychiatric disorders interact in

other ways as well. Certain substances of abuse
such as tobacco and alcohol can alter the
pharmacokinetics of the oral hypoglycemic
agents. Moreover, the presence of a comorbid
psychiatric disorder like depression could
interfere with the management of diabetes by
influencing treatment adherence. Similarly certain
disorders such as phobia of needles and injections
can present difficulties with investigations and
treatment processes such as blood glucose testing
and insulin injection. Also patients with
psychiatric disorders are less likely to seek
treatment. Such delays would postpone detection
of co-occurring diabetes as well.

Implications of co-occurrence of diabetes

and psychiatric disorders
Co-occurring psychiatric disorders in patients
with diabetes are associated with impaired quality
of life,[1] increased cost of care,[2] poor
treatment adherence,[3] poor glycemia control
(evidenced by elevated HbA1c levels),[4]
increased emergency room visits due to diabetic
ketoacidosis,[5] higher frequency of
hospitalization, and higher rate of absenteeism.[6]
Additionally there is an increase in cost of
medical care. Cost of care for non-mental health
conditions among patients with co-occurring
psychiatric disorders and endocrinal disorders is
twofold or even higher (depending on the
treatment setting) than the population without co-
occurring psychiatric disorders.[7]

Diagnosing psychiatric disorders among

patients with diabetes
One of the biggest challenges in management of
psychiatric disorders among those suffering from
diabetes is the low rates of detection. Up to 45%
of the cases of mental disorder and severe
psychological distress go undetected among
patients being treated for diabetes.[8] This is a
result of both patient and physician-related
factors. Physicians should be aware of the
possible co-morbid psychiatric disorders likely to
be associated with diabetes. As highlighted in the
subsequent sections psychiatric co-morbidity is
not uncommon in those suffering from diabetes.
Consequently these patients should be regularly
screened for common psychiatric disorders. Brief
instruments such as patient health questionnaire
(PHQ) and symptom checklist-90 (SCL-90) are
sensitive, time efficient, and well-validated
screening tools for common psychiatric disorders
like depression and anxiety. Scales such as
Hospital Anxiety and Depression Scale (HADS)
could be used to further quantify the severity of
anxiety and depression in this population. It is
imperative to screen those suffering with diabetes
for emergence of psychiatric disorders and vice
versa. Since there could be some overlap between
the physical features of diabetes and psychiatric
disorders it is important to look for the behavioral
and cognitive features of psychiatric disorders.

Psychiatric disorders could be diagnosed using

two of the most commonly used nosological
systems. These are the International Statistical
Classification of Diseases and Related Health
Conditions- 10 (ICD-10) of World Health
Organization (WHO) and Diagnostic and
Statistical Manual of Mental Disorders-IV (DSM-
IV) of American Psychiatric Association (APA).
In spite of certain dissimilarities, there is a
substantial overlap between these two manuals.
ICD-10, the more widely used of the two, makes
use of the alpha-neumaric coding system for
different psychiatric disorders. Psychiatric
disorders are coded in chapter F of ICD-10. The
chapter is further divided into 10 categories from
00-09 with each housing a particular group of
psychiatric diagnoses [Table 1]. There is a brief
primary care version of ICD-10 that is aimed at
assisting the primary care physicians in
diagnosing psychiatric disorders.

Table 1
List of categories of psychiatric
disorders (mental and behavioral
disorders) in ICD-10

Some of the psychiatric disorders of particular

relevance with regard to diabetes include
delirium, substance use disorders, depression,
anxiety, psychotic illness like schizophrenia,
eating disorders.

The subsequent section presents an overview of

these psychiatric conditions in the context of
diabetes.

Delirium
Delirium in diabetes could be a manifestation of
hypoglycemic episodes[9] or diabetic
ketoacidosis. Delirium represents the severe end
of the spectrum of clinical manifestation of these
phases. Patients with diabetes suffering from co-
morbid psychiatric disorders are more likely to
experience hypoglycemic delirium. Because of
use of overlapping terminology in the literature it
is difficult to estimate the exact prevalence of
delirium in diabetes based on current nosological
systems. However, episodes of hypoglycemia[10]
and diabetic ketoacidosis[11] are not uncommon
in diabetes and consequently delirium is also not
an infrequent occurrence. Delirium is associated
with various adverse outcomes including
increased hospital stay, increased cognitive and
functional deterioration, morbidity and mortality.
[12,13]

Delirium in diabetes could present as hypoactive

or hyperactive delirium. The patient is excited,
talking irrelevantly and moving around aimlessly
in hyperactive delirium. On the contrary,
calmness and reduced psychomotor activity
predominates the clinical picture in hypoactive
variety. Additionally, disorientation, confusion,
and altered sensorium are shared by both these
forms. Other clinical features of delirium include
perceptual disturbances such as hallucinations,
sleep-wake cycle disturbances and thought
disturbance. The usual course is waxing and
waning interspersed with lucid intervals.

Early identification is crucial to the outcome of

delirium. The main stay of treatment is correction
of the underlying cause with supportive care.
Low-dose dopaminergic antagonists (also known
as typical antipsychotics) could be used for
control of behavioral disturbance. It is
recommended to use high potency medications
such as haloperidol. Since the clinical picture can
vary rapidly it is important to assess the patient at
frequent intervals and modify the treatment plan
accordingly [Box 2].

Box 2
Delirium in diabetes: salient features

Substance abuse: tobacco

Tobacco can be used in smoking (cigarettes, biri,
hooka, cigar) and smokeless forms (gutkha,
tobacco powder, khaini, snuff). The prevalence of
smoking among those having diabetes has been
found to be comparable to that of the general
population in studies from western settings.[14]

Cigarette smoking is an independent, modifiable

risk factor for development of diabetes. It is
associated with increased risk of diabetes in a
dose-response manner.[15,16] Although evidence
is less compelling but smokeless tobacco use has
also been associated with increased risk of
development of type 2 diabetes.[17]

Cigarette smoking increases this risk for diabetic

nephropathy, retinopathy, and neuropathy
(strongest association in type 1 diabetes) as well
as that of macrovascular complications, coronary
heart disease (CHD), stroke, and peripheral
vascular disease (strongest association in type 2
diabetes).[18] Severe periodontal conditions and
oral symptoms are more common among those
diabetics who chew gutkha.[19]

The proposed hypotheses on the role of smoking

in causation of diabetes include smoking-induced
hyperglycemia, hyperinsulinemia, and elevated
blood pressure;[20] smoking induced impaired
endothelial function;[21] pro-diabetogenic action
of components of tobacco smoke (e.g., cadmium).
[22]

In diabetes care, smoking cessation is of utmost

importance to facilitate glycemia control and limit
the development of diabetic complications.
However smoking (tobacco) cessation is a
challenging job, more so in those having diabetes.
[23] Early smoking cessation reduces the risk of
development of type 2 diabetes to the nonsmoker
level.[24] Smoking cessation is an effective
intervention in the early course of microvascular
and macrovascular complications. Smoking
cessation also reduces the risk of coronary heart
disease and mortality among these patients.[25]

Every patient should be offered advice on

quitting. There are various pharmacological and
nonpharmacological interventions for tobacco
use. The medications available for use in India
include nicotine replacement therapy (NRT) in
form of gums, vareniclnie, bupropion, clonidine,
and nortryptiline [Table 2]. These medications
should be used under clinical supervision because
of certain uncommon but potentially severe side
effects such as seizures with bupropion and
suicidal behavior with varenicline.

Table 2
Pharmacotherapies for management of
tobacco dependence

It is important to ask each patient for his/her

tobacco use status and advice against tobacco.
This is of special importance among adolescents
with diabetes as most of them initiate tobacco use
after being diagnosed with diabetes.[26] Box 3
presents an outline of the plan of action for a
physician for helping a diabetic quit tobacco use.

Box 3
Recommendation for prevention and
treatment of tobacco use

The clinicians must be prepared for the possible

weight gain and increased risk of type 2 diabetes
following smoking cessations.[27] However,
these effects are either transitory or could be
easily managed with life style modifications and
behavioral interventions.[28] Hence, when
smokers quit, they should be advised on weight
management and be monitored for diabetes in the
years soon after quitting. Additionally since
tobacco smoke is an inducer of various isoforms
of the cytochrome P450 system, it is
recommended to monitor the possible change in
dose requirement of various oral hypoglycemic
agents that are metabolized by the enzyme
system.

Substance abuse: alcohol

Prevalence of alcohol use in diabetic population
has been reported to be around 50--60% in
epidemiological surveys and treatment seeking
population.[29,30] The relation between alcohol
consumption and diabetes remains controversial.
While consumption in higher amounts is
associated with an increased risk of type 2
diabetes, consumption in low to moderate
amounts has been found to be protective in some
studies.[31] Glucose intolerance can develop in
alcoholics due to alcohol induced acute
pancreatitits as well.

One of the commonest and serious concerns

associated with use of alcohol in diabetes is
emergence of hypoglycemia. It could be alcohol-
induced fasting hypoglycemia, potentiation of
drug-induced hypoglycemia, or reactive
hypoglycemia in susceptible individuals.
Additionally alcohol consumption may impair
individual's ability to recognize emergence of
such episode and intervene appropriately. Heavy
alcohol consumption can precipitate diabetic
ketoacidosis. Being a cause of peripheral
neuropathy and retinopathy independently, co-
occurring diabetes and alcohol use can have
synergistic effect for these complications.[32] It
has been seen that alcohol consumption is
inversely associated with adherence to diabetes
self-care behaviors.

Concomitant use of chlorpropamide (a

sulfonylurea agent) and alcohol could lead to
disulfiram-ethanol type of reaction. It is
characterized by facial flushing, warmth,
headache, nausea, vomiting, sweating, or thirst
within minutes of consuming alcohol. Also,
alcohol consumption may lead to excessive
weight gain and elevated glucose levels. Alcohol
can also alter the metabolism of oral
hypoglycemic agents. Metformin is
contraindicated in those actively using alcohol for
the fear of lactic acidosis. Additionally alcohol
induced hepatopathy requires a dose reduction for
oral hypoglycemics metabolized in liver.

Similar to tobacco use all patients with diabetes

should be screened for alcohol use [Box 4]. Those
who have not yet started should be advised to
continue to be sober. Those with problematic
alcohol use should be advised to practice
abstinence or at least use in moderation. Brief
screening tools available to identify individuals
with problem drinking. One such tool is a CAGE
questionnaire which is an acronym for four
simple questions aimed at screening problem
drinking.

Box 4
Recommendations with regard to
alcohol use among diabetics

Diabetics having problem drinking (binge

drinking, alcohol abuse, or alcohol dependence)
should be offered individualized comprehensive
interventions. Some of the commonly used
medications in management of alcohol
dependence include disulfiram, acamprosate,
naltrexone, and topiramate. Table 3 provides a
brief overview of these medications.

Table 3
Pharmacotherapies for management of
alcohol dependence

Additionally, such individuals can be offered

nonpharmacological interventions such as brief
intervention, motivation enhancement therapy,
self-help group such as alcohol anonymous and
relapse prevention.

Mood disorders
Mood disorders include depressive disorders,
dysthymia, and bipolar affective disorders
(BPAD). Co-occurrence of diabetes and
depression has been established in clinical as well
as general population studies.[33] This co-
occurrence is associated with increased
impairment as well as mortality.[34] Risk of
developing depression is 50-100% higher among
patients with diabetes compared to that among the
general population.[35] The prevalence of
diabetes among BPAD patients has been found to
be increased (in hospital based studies) or equal
(in epidemiological surveys) to that observed in
the general population.[36,37]

Emergence of depression in diabetes is associated

with increased complications, mortality rates, and
healthcare costs.[38–40]

Depression and diabetes share a bidirectional

causal association. Depression has been
postulated to play a causal role in emergence of
diabetes. A recent metaanalysis has reported that
depressed individuals have a 60% increased risk
of developing diabetes.[41] A specific association
has been found between risk of developing
diabetes and nonsevere depression, persistent
depression, and untreated depression.[42]

Similarly, diabetes has been recognized as a

“depressogenic” condition.[43] Biochemical
changes (including neuro-endocrinal changes
such as hypercortisolemia, leptin activity in
limbic system, altered glucose transportation,
proinflamatory cytokines) associated with