l “Diabetes is the result of sadness, or long

sorrow” (Thomas Willis)

l “Diabetes is a disease which often shows

itself in families where insanity
prevails” (Henry Maudsley)
Clinical implications of diabetes
mellitus in psychiatry

Presenter: Ravi Philip Rajkumar

Chairperson: Dr. G. Venkatasubramanian
 Definition
l A group of metabolic disorders that
share the common phenotype of
hyperglycemia, either due to decreased
insulin production or reduced insulin
sensitivity.
l “Identifiable causes” account for only
about 5% of cases
(Tattersall et al. 1981)
 How common is the problem?
l 6% of the population in developed
countries, such as the United States
l Less common in some Asian countries
l Very common in India: 2.4 – 2.7% of the
rural and 5.6% – 11.6% of the urban
population
(Sadikot et al., 2004; Ramachandran, 2005)
 Classification
l Type I diabetes mellitus
l Type II diabetes mellitus
l Other specific types – including drug-
induced and genetic
l Gestational diabetes mellitus
 Diagnosis
Symptoms of DM plus random blood
glucose > 200 mg%
OR
Fasting blood glucose > 126 mg%
OR
2-hour postprandial glucose > 200 mg%
during GTT
 Other investigations
l Lipid profile

l Glycosylated haemoglobin (HbA1c) –

measure of glycaemic control
v Normals: 4-6%
v Controlled DM: <7%
v Poorly controlled DM: >8%
 Risk factors for Type II DM
l Age
l Obesity
l Hypertension
l Hypercholesterolaemia
l Family history
l Gestational DM, or having a child with high
birth weight
l Polycystic ovarian disease
 Impact of DM on quality of life
l Treatable but not curable
l Requires lifestyle changes as well as
complex treatment regimens
l Need for strict glycaemic control
l Complications – life-threatening and
disabling
l Complications of treatment
 Complications of DM
l Ischaemic heart disease
l Cerebrovascular accidents
l End-stage renal disease
l Neuropathy – peripheral, autonomic
l Ulcers, limb infections, gangrene
l Diabetic ketoacidosis
l Nonketotic hyperosmolar coma
Factors affecting response to illness
l Patient’s personality and coping skills
l Psychosocial support, especially family
support
l Perception of the “sick role” by patient,
family and society

(Tattersall, 1981; Mechanic, 1961;

Rose et al., 2002)
 DM in psychiatry
1. Psychiatric comorbidities in DM

2. DM in common psychiatric disorders

3. DM and medications in psychiatry

PSYCHIATRIC COMORBIDITY
IN DIABETES MELLITUS
 Psychological “causes”
l DM as a psychosomatic disorder
(Menninger 1935), based on theories of
stress (Cannon 1911)
l The diabetic personality (Dunbar 1943)
l Effects of stress on glycaemic control
(Rose et al. 2002)
l Effects of coping skills and cognitive styles
on outcome (Rose et al. 2002)
 Depression
l Prevalence up to 40% (Peyrot 2003)
l 2-3 fold rate compared to general
population
l Often missed
l Affects all age groups (Garrison et al.
2005, Kilbourne et al. 2005)
 Effects of depression on DM
Effect Cause
Weight gain Increased intake, reduced
activity
Increased vascular risk Comorbid substance use

Hyperglycaemia Hypothalamic-pituitary-
adrenal axis dysfunction
Autonomic instability As part of adrenergic
dysfunction
Source: Lustman and Clouse, 2004 (adapted)
 “The silent killer”
l Overall, depression reduces quality of life,
increases morbidity due to diabetic
complications (De Groot et al. 2001), leads
to more hospitalizations, and increases
mortality by up to 5-fold (Peyrot 2003)
 Effective treatments: evidence
l Fluoxetine and nortryptiline have been
effective in controlled trials. (Lustman and
Clouse 2004)
l Overall, SSRIs have better effects on
glycaemic control (Goodnick et al. 1995)
l CBT effective in a controlled trial (Lustman et
al. 1998)
l Long-term treatment as relapse rates are
higher in DM (Talbot and Nouwen 2000)
 Factors affecting illness
behaviour
l In children: parental overprotection,
rejection, over-anxiety, and individual
temperament
l In adolescents: similar factors, non-
adherence is common
l In adults: personality disorders (for
example, BPD)
 Effect of these factors
l Childhood emotional disorders
l Eating disorders
l Non-adherence to treatment
l Worsening of diabetic control
l Diabetic ketoacidosis
l Illness denial
l Abnormal assumption of “sick role”
(Tattersall, 1983; Ellis et al. 2005)
 Interventions
l Multisystems family therapy: proven
useful in adolescents (Ellis et al. 2005)
l Group therapy: improves quality of life,
illness severity and coping skills (Trento et
al. 2004)
l Community-based approaches: improve
knowledge and quality of life (Delamater et
al. 2001)
 Eating disorders

l Commoner than in the general population

(Jones et al. 2000)
l 14 / 51 women in a recent study (Barziv
and Davis 2005)
l Linked to Axis II issues – BPD, OCPD
l Atypical behaviours – non-compliance
rather than binging, purging…
l Antidepressants (fluoxetine) and CBT may
help
 Anxiety disorders
l Injection phobia
l Fear of hypoglycaemia
l Hypochondriasis
l Panic attacks vs hypoglycaemia
(Tattersall, 1981)

BT and group therapy may be useful.

 Sexual disorders
l ED in 32% of type I DM and 46% type II
DM in men
l In women - ↓ libido, vaginal discomfort,
dryness
l Causes: organic (neuropathy, vascular)
and psychological (marital discord,
previous sexual difficulties)
(Vickers and Wright 2004)
 Sexual disorders: treatment
l Evaluate for organic causes
l Rule out drug-induced causes
l Brief sex therapies may be useful in ED
(Bohannon et al. 1982)
l Consider sildenafil (Vickers and Wright
2004) or alprostadil
 Cognitive disorders
l Vascular dementia – second commonest
dementia, preventable
l DM is a risk factor (Gregg and Brown
2003), but does treating it reduce
dementia risk? (Cochrane Review 2002)
l Vascular depression (Alexopoulos, 1997)
l Cognitive deficits after hypoglycaemia
(Selam 1998, Langan 1991)
 Others
l Mental retardation: syndromal; may
interefere with management, but not
severely (Tattersall 1983)
l Childhood emotional disorders:
internalizing disorders associated with
more hospitalizations, less so for
externalizing disorders (Garrison et al.
2005)
 DIABETES MELLITUS IN
PSYCHIATRIC DISORDERS
 Schizophrenia
l Common comorbidity (Bushe and Holt
2004)
l Documented even in pre-neuroleptic era
(Freeman 1946)
l Prevalence of 18% (Sernyak et al. 2003) to
21% (Subramaniam et al. 2003)
l IGT even more common (31%;
Subramaniam et al. 2003)
l Contributes to morbidity and mortality;
should be treated (Marder et al. 2004)
Theories of DM in schizophrenia
l Genetic linkage – 17% DM (type II) in
families of patients with schizophrenia
(Lamberti et al. 2004)
l Nutritional and substance use factors
(Brown et al. 1999)
l Lower socioeconomic status (Dixon et al.
2000)
l Neurobiology – serotonin, NPY
l Neuroleptics (Newcomer et al. 2002)
 Tardive dyskinesia
l DM may be a risk factor for TD (Ganzini et
al. 1991)
l Possibly related to dopaminergic
mechanisms, hyperglycaemia,
hyperinsulinaemia (Schultz et al. 1999)
l Higher AIMS scores in schizophrenia with
DM (Andreasen et al. 1999)
l Risk may not be significant when atypicals
are used (Levy et al. 2004)
 Guidelines (Marden et al. 2004)
l Baseline fasting blood glucose (“fasting
blood sugar”, FBS) for all patients.
l Monitoring of FBS and glycosylated
haemoglobin (HbA1c) 4-monthly in any
patient with risk factors for diabetes.
l Education of patients and caregivers
regarding the symptoms of diabetes.
 Bipolar disorder
l May affect as many as 9.9% of
hospitalized bipolars (Cassidy et al. 1999)

l Associated with a more severe course and

more hospitalizations
 Theories
l Genetic (less robust than schizophrenia)
l Neuroendocrine - ↑ cortisol (Hudson et al.
1984)
l Vascular lesions due to DM in the brain
l Role of medications – lithium, valproate,
atypicals
 Management
l No clear guidelines
l Monitoring when on neuroleptics
l Weight-neutral medications –
carbamazepine, lamotrigine
l Metformin – beneficial in both DM type II
and PCOD
DIABETES MELLITUS AND
MEDICATIONS
 NEUROLEPTICS
l Most propensity for atypicals
l Highest effect for clozapine and
olanzapine, followed by risperidone
l Lesser for injectable typicals (Newcomer
et al. 2002)
l 36.6% of patients on clozapine develop
DM over 5 years (Henderson et al. 1999)
l The former two can also cause sudden
ketoacidosis (Goldstein et al. 1999)
 Mechanisms
l Direct: impaired glucose transport,
increased insulin resistance, impaired beta
cell function (serotonergic?
dopaminergic?)

l Indirect: weight gain via leptins, NPY,

serotonergic or histaminergic mechanisms
 Order of risk
Drug Weight gain Diabetes Lipid
abnormalities
Clozapine +++ + +
Olanzapine +++ + +
Risperidone ++ ± ±
Quetiapine ++ ± ±
Aripiprazole* ± - -
Ziprasidone* ± - -

* Limited data. (Source: Consensus Statement 2004)

 Assesments recommended
l Family / personal history of diabetes and
related conditions
l Weight monitoring and BMI
l Waist circumference
l Blood pressure
l Fasting plasma glucose (FBS)
l Lipid profile
(Consensus Statement 2004)
 Monitoring
l FBS: 1 month after treatment, and at least
annually therafter
l Weight: monthly
l Lipid profile: at least five-yearly
l HbA1c: every 3-6 months to assess
control
l Awareness: patient and family education
about symptoms of decompensation
 MOOD STABILIZERS
l Valproate: causes weight gain,
associated with PCOD

l Lithium: causes weight gain and

hypothyroidism

l Carbamazepine, lamotrigine,
topiramate: no effect
 ANTIDEPRESSANTS
l MAO inhibitors: can cause hypoglycaemia

l Tricyclics: cause hyperglycaemia, weight

gain and increased appetite

l SSRIs: anorectic effect, improve glycaemic

control – sertraline preferred, then
fluoxetine
(Goodnick et al. 1995)
 ANTIDEPRESSANTS
l Duloxetine
• Newer antidepressant
• Can cause weight loss
• Less sexual dysfunction
• No effect on glycaemic status
• Effective in pain due to diabetic
neuropathy
(Smith 2006; Lott and Baker 2003)
 MISCELLANEOUS
l Gabapentin: effective in neuropathic pain,
superior to and better tolerated than
amitryptiline (Dallocchio et al. 2000); may
have a role in bipolar disorder

l Metformin: effective in type II DM and

PCOD; may have antidepressant effects
(Rasgon et al. 2002)
 DRUG INTERACTIONS
l Dynamic: effects of atypicals, propranolol,
valproate, lithium, TCAs as mentioned
earlier

l Kinetic: few documented; tricyclics may

increase glimepiride levels.
EFFECTS OF DM ON DRUGS
l Dynamic: as discussed earlier

l Kinetic: reduced absorption (autonomic

gastropathy, diarrhoea); impaired
elimination (renal failure)
CONCLUSIONS
 Clinical practice: 1. Evaluation
l High index of suspicion
l Search for risk factors
l Baseline investigations – 2-hr. PPBS has
maximum specificity
l Others – FBS, lipid profile, weight
monitoring, ECG
l Psychoeducation and monitoring at follow-
up
 Clinical practice: 2. Preferred
agents
l To be preferred: l To be avoided:
v Carbamazepine v Atypicals, especially
v Lamotrigine olanzapine/clozapine
v Typicals v Valproate

v Aripiprazole, v Lithium
ziprasidone v Propranolol
v SSRIs v Tricyclics
v Duloxetine
 Clinical practice: 3. Other
interventions
l Psychological: CBT / BT packages
(thesis, Dr. Paulomi, 1998) group therapy,
family therapy, other individual therapies
l Social: patient support groups, education,
community based approaches
l Alternative: yoga therapy – proven
efficacy in depression and diabetes
mellitus
THANK
YOU!