Child Adolesc Psychiatric Clin N Am

12 (2003) 439 458

Psychological aspects of diabetes mellitus

David Szydlo, MD, PhDa,b,*,
Pieter Joost van Wattum, MD, MAa, Joseph Woolston, MDa
a

Yale Child Study Center, Yale University School of Medicine, 230 South Frontage Road,
New Haven, CT 06520, USA
b
National Center for Children Exposed to Violence, Yale University School of Medicine,
230 South Frontage Road, New Haven, CT 06520, USA

Diabetes mellitus (DM) is a chronic metabolic disorder that hinders the bodys
ability to use carbohydrates adequately while lipid metabolism is altered, which
forces energy production on protein and metabolic compensation. DM affects
various organs and functions, which further impinges on metabolic processes.
DM presents itself in two forms: insulin-dependent (juvenile-onset) or type 1 DM
and non insulin-dependent or type 2 DM. It is estimated that 16 million
Americans have diabetes, but probably only one third to one half have been
diagnosed; 800 000 new cases are identified each year. Recently, new lower
diagnostic criteria [1] have made it possible for patients to be diagnosed earlier.
Thus, another 15 million Americans have met the criteria for impaired glucose
tolerance and are at high risk for developing type 2 DM [2]. Although type 2 DM
usually has an adult onset, in recent years there has been a significant rise in the
number of children diagnosed with type 2 DM in the United States. Reasons for
this increased frequency are believed to be a larger percentage of children who
are overweight (a risk factor for type 2 DM), a family history of diabetes, and a
considerable increase in the use of psychotropic medication in children. This
increase leads to medication-induced side effects, such as weight gain and
hyperglycemia, which subsequently lead to type 2 DM. A study by Reynolds
et al showed that the use of psychotropic medication also could unmask a weight
gain related genetic predisposition for DM [3].
The diagnosis of DM is a significant stressor not only for patients but also for
their environment. Children with DM are sometimes stigmatized by their peers
and relatives who do not understand the illness or are frightened by it. Some

* Corresponding author. Yale Child Study Center, Yale University School of Medicine, 230 South
Frontage Road, New Haven, CT 06520.
E-mail address: david.szydlo@yale.edu (D. Szydlo).
1056-4993/03/$ see front matter D 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S1056-4993(03)00006-3

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children also may need to alter several of their customary routines and are often
scared, especially at the beginning, to participate in activities in which they were
previously actively engaged. Unfortunately, at times they are unintentionally left
out by their friends or teachers who are mistakenly trying to protect them.
Parents, siblings, and other relatives often must modify their behavior around
patients to ensure that adequate control can be achieved. Schools must establish
routines to ensure that patients with this condition follow the indicated medical
procedures, and they frequently must consider risks and be prepared in sports
activities, field trips, and other extracurricular events. It has been documented that
the familys response to the new diagnosis of DM may have a negative effect on
glycemic control [4,5]. Differences have been found in the way patients with type
1 DM and type 2 DM cope with and adapt to their diagnosis [6].

Type 1 diabetes mellitus

The prevalence of type 1 DM is estimated to be 1 to 2 per 1000 in school-aged
children [7], and treatment requires a life-long daily regimen of insulin replacement and dietary control. Daily checking of blood glucose and insulin injections
that are usually given twice per day (with a minimum of once a day) are needed
to maintain adequate glucose control. In the past decade, however, flexible
administration of insulin has become more common through more personalized
daily injection schedules and the introduction of insulin infusion pumps. Pumps
are especially useful for picky eaters, such as toddlers, and for patients with
variable exercise and meal routines.
During ones lifetime, DM can lead to disabling vascular complications, such
as retinopathies and coronary artery disease, and neurologic complications. Psychological and social complications are also seen frequently, not only secondary
to later onset medical complications but also in the early stages of the disease.
Studies found that one third to one half of adolescents with type 1 DM had
psychiatric disorders [8,9]. The prevalence of depression in persons with diabetes
is twofold to threefold higher than in persons without it [10,11]. At least 10% of
adolescent girls with type 1 DM meet criteria for an eating disorder, which is
twice the rate for girls without diabetes [12]. Self-perception also can play a role
in the management of diabetes, particularly in adolescents who struggle with their
changing bodies during puberty. Murphy found that adolescents who have a
negative perception of their bodies, perceive little internal control over health
when ill, and have an external attributional style for negative events were at
greatest risk for poor compliance as indicated by less frequent checking of blood
sugar [13].
Prognosis
Strict diabetes control achieved by intensive diabetes management can prevent
or markedly delay the onset and progression of microvascular and neuropathic

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complications in type 1 DM [14]. Recent data indicate that the favorable

outcomes regarding microvascular complications in intensively treated versus
conventionally treated adolescents persisted for more than 4 years after completion of the study, although HbA1C levels no longer differed between the two
former treatment groups. Current recommendations mandate that youths with
type 1 DM should aim to achieve metabolic control as close to normal as possible
and as early in the course of the disease as possible. Psychiatric illness, as a
complication of or unrelated to DM, can lead to poor metabolic control [15,16].
Early detection and treatment of these illnesses are important.

Physiology of psychological complications in type 1 diabetes mellitus

Epinephrine and norepinephrine are hormones that are involved in the stress
response. Despite the fact that both hormones are involved with glucose homeostasis, however, to date there is no evidence that psychological stress leads to
a significant physiologic effect that requires insulin adjustments. Recent studies
[17] have indicated that there may be a link between another neurotransmitter,
gamma-amino butyric acid (GABA), and the development of depression in
patients with type 1 DM. Antibodies against glutamic acid decarboxylase, an
enzyme needed for GABA metabolism, were found in patients with new-onset
type 1 DM [18], which led to lower corticospinal fluid GABA levels. The latter
has been linked to development of depression, whereas pharmacologic treatment
of depression leads to normalization of GABA levels [17].

Type 2 diabetes mellitus

The chronic complications of type 1 DM account for much of its morbidity
and mortality. Diabetes is currently the fourth leading cause of death by disease in
the United States [19]. The genesis of type 2 DM has been linked strongly to
genetic and environmental factors. In studies performed with identical twins, the
concordance rate for type 2 DM has been estimated at 60% to 90% [20]. There
also is an important difference in prevalence among racial and ethnic groups,
which further suggests a genetic basis. In the United States, type 2 DM is almost
twice as common in African Americans as it is in whites, is 2.5 to three times
higher in Hispanic Americans, and is up to five times as high in Native
Americans [21]. More than a decade ago, Leslie showed that having one firstdegree relative with type 2 DM doubles the risk of developing the disease, and
having two relatives with the disease quadruples the risk [22]. Other studies have
reported that offspring whose mothers had type 2 DM while pregnant are more
likely to develop type 2 DM, impaired glucose tolerance, and obesity at an earlier
age than children whose fathers had DM. Although there is still uncertainty as to
the role of genetics versus long-term intrauterine environment in the transmission
of type 2 DM, studies show that exposure of the fetus to the mothers DM confers

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a risk for the disease and for obesity that is above the genetically transmitted
susceptibility [23].
In 1998, the World Health Organization first provided a unified definition for
metabolic syndrome. According to this definition, patients with type 2 DM or
impaired glucose tolerance have the syndrome if they fulfill two of the following
criteria: hypertension, dyslipidemia, obesity/abnormal obesity, and microalbuminuria. Approximately 70% of people with type 2 DM have elements of this syndrome, which has been associated with reduced survival [24]. Likely the result of
the interaction between several genes and the environment, the syndrome points
to the importance of individual, familial, and environmental factors in the genesis
and progression of this disease.
Obesity is probably the highest risk factor for type 2 DM. Children who are
genetically or otherwise predisposed and have a body weight more than 20%
above their ideal body weight, or a body mass index more than 27 kg/m2,
increase their risk not only for type 2 DM but also its development at an earlier
age. Childrens eating habits paired with lack of exercise are associated with
increase obesity, and changes in food intake can alter glucose control significantly in individuals who already have developed the disease. Psychological
factors are related to obesity and to the lifestyle that may impinge on the
development of DM in predisposed individuals. Several studies have addressed
the importance of treating obesity as the most logical frontline approach to the
preclusion of further complication in children with type 2 DM and a preventive
strategy with at-risk children [25 28]. Even if diet, exercise, and behavioral
modification stand for a satisfactory combination and small weight loss results in
improvement of all related comorbidities, however, most programs have had little
long-term success. This is partly because of the adverse effects of diabetic
medication, poor glycemic control, and other diabetes-related complications [29].
The relationship between improved glycemic control and the delay or
prevention of complications has been reported widely [30,31]. Children may
benefit most from tight glycemic control because of their life expectancy; hence,
the need to focus on preventing microvascular complications. Young patients
with diabetes and their families must work together to set and achieve realistic
goals that will ensure high care standards.
Prognosis
Children with type 2 DM must engage in a permanent effort to reach and
maintain blood glucose levels as close to the normal range as possible. Adequate
glycemic control reduces greatly the risk of microvascular and neuropathic
complications. Young patients with DM should be educated and helped, and
their families should be encouraged to follow a comprehensive treatment plan.
Although there is ample information in the current literature regarding the
physical aspects of type 2 DM, there are few indications that psychological
aspects should be part of an all-inclusive management and treatment plan, and
there are not enough reference to psychiatric comorbidity.

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Neuropsychological aspects of type 1 and type 2 diabetes mellitus

A wide range of psychological elements influence the management and
treatment adherence needs of young patients with diabetes. These elements
include individual characteristics and family dynamics. In broad terms they can
be included in the following three groups:
1. Premorbid fundamentals are general attitudes, understanding of healthy and
pathologic phenomena, personal expectations, previous illness experiences,
and health care relationships. For example, children who have had difficult,
tense, stressful experiences with health care providers or have suffered from
painful or complicated illnesses before DM is diagnosed tend to have a
harder time understanding their condition and find it more difficult to relate
to their doctors and nurses.
2. Treatment demands are goals for treatment, flexibility and adaptation to
treatment modification, degree of intrusiveness, and extent of and diversity
of treatment. For many children and adolescents, the strain and burden of
having to adapt to the new necessities imposed by the treatment goals and
requirements negatively affect their motivation, cooperation with the
treatment team, and commitment to their own well-being. This becomes
even more dramatic when the treatment involves numerous modifications
and adjustments.
3. Individual characteristics are personality, family dynamics and functionality, and external stressors, which may positively or negatively affect the
psychological response of the young patient with diabetes. Tension
provoked by external events or situations, such as the death of a relative
or a friend, parental divorce, or relocation, can add to an already complicated management.
Cognitive development
Children with DM have an elevated risk of persistent mild cognitive deficits
[32,33]. Compared to children without diabetes, they perform more poorly on
measures of intelligence, attention, processing speed, long-term memory, and
executive skills. The long-term effects of these findings are not yet clear [34]. In a
study that observed the life span of DM, Ryan et al concluded that DM-related
biomedical and psychosocial risk factors seem to interact with age and produce
somewhat different patterns of neuropsychological dysfunction in children and
adolescents versus adults with diabetes [35]. In children, mild to moderate
hypoglycemic episodes seem to affect the developing nervous system, whereas
psychosocial and psychoeducational disruption interferes with the acquisition of
knowledge. For cognitive and psychosocial reasons, obesity further hinders the
ability to learn. In adults with type 1 DM, cognitive impairments may be
associated independently with chronic hyperglycemia, as indexed by glycosylated hemoglobin levels, the presence of biomedical complications, or repeated

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episodes of moderately severe hypoglycemia. In a recent study, Schoenle et al

[36] concluded that male sex, diagnosis at a young age, metabolic condition at
diagnosis, and long-term metabolic control were more highly correlated to
deterioration of intellectual performance than the experience of severe hypoglycemic attacks. This was corroborated by Austins study [37], in which hypoglycemia episodes were not associated with cognitive decline. Associations
between prospectively documented numbers of severe hypoglycemic episodes
and baseline cognitive ability level were not significant either.
Early detection and the assessment of the metabolic condition at diagnosis and
the psychosocial disruptions seem to be of crucial importance for the clinician
who wants to intervene with the young patient and provide adequate advice in
terms of the possibility of cognitive deficits. Helping the patient with diabetes and
obesity to lose weight also provides benefits in the cognitive sphere because it
may have a positive effect in the learning process per se and in the development
of a stronger psychosocial milieu of the child.

Affective disorders
Depression
The causes underlying the relationship between depression and diabetes are
unclear. Depression may develop because of stress but also may result from the
metabolic effects of diabetes on the brain. Studies suggest that people with
diabetes who have a history of depression are more likely to develop diabetic
complications than persons without depression [38]. Population-based studies of
children and adolescents with type 1 DM have shown that the prevalence of
depression ranges from twofold to threefold higher than that of adolescents
without diabetes [10]. Grey (unpublished data, 2002) and six- to eightfold higher
than preadolescents without diabetes. This rate may vary according to the
duration of illness, and the possibility of becoming depressed increases as
diabetes complications worsen. Depression leads to poorer physical and mental
functioning [39], so children are less likely to follow a required diet or medication
plan. Depression is a common initial response to a new diagnosis of diabetes
[9,40]. Grey et al found that youths with diabetes reported significantly higher
depressive symptomatology than youths without diabetes at the time of the
diabetes diagnosis and then again at the end of the second year [41]. They
characterized this second period of depression as being associated with the end of
the physiologic honeymoon period and the necessity of learning to live with
diabetes. Similarly increased rates of depression and dysthymia were seen in
adolescent girls (aged 13 19) with recently diagnosed type 1 DM [42]. In the
past, several factors, such as loss of self-esteem, adjustment to chronic illness,
and fear of diabetes-related complications, have been suggested to account for the
increased rates of depression in type 1 DM. Although major depression can
compromise the effective management of diabetes, successful treatment of
depression may reverse abnormalities in hypothalamic-pituitary-adrenal axis

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445

function, improve insulin sensitivity and glycemic control [43], and improve
emotional well-being and compliance to therapy.
In a recent study, Grey et al found that significant depressive symptoms
emerged as a major obstacle to achieving recommendations for strict diabetes
control [44]. Other studies have demonstrated that depressed children with
diabetes have poorer metabolic control [15,45], poorer quality of life [46], and
lower feelings of self-worth [47,48]. Adults with diabetes and depression have
been described as having similar difficulties in diabetes management; consequently, children and adults with depression and type 1 DM are at increased risk
for microvascular and neuropathic complications [14].
In a study, Goldston [49] showed that suicidal ideation among adolescents
with diabetes was higher than expected, but suicide attempts were comparable
with rates reported for the general population. Suicidal thoughts were strongly
linked to noncompliance with medical treatment, which was associated with
psychiatric disorder and with not living in a two-parent home.
Bipolar disorder
No data exist concerning the prevalence of bipolar disorder in children with
DM; however, the prevalence and incidence of bipolar disorder in children and
adolescents has been documented [50,51]. Mania and depression can lead to
noncompliance with diabetes management and subsequently to poor metabolic
control with possible fatal ketoacidosis.
Anxiety disorders
Anxiety and stress can affect blood glucose levels significantly. Panic attacks
may resemble hypoglycemic episodes, whereas hypoglycemic attacks may look
like anxiety states. Given that children respond in various ways to the same
circumstances, the glucose response of one child with diabetes may differ from
another childs response. Monitoring blood glucose more frequently during
periods of stress is good practice.
The prevalence of anxiety disorders in children with type 1 or type 2 DM is
unknown. In a study that compared a group of 68 newly diagnosed children with
IDDM and 40 healthy peers, Grey et al found no differences in anxiety scores
between the two groups [52]. A 10-year follow-up study by Kovacs found
anxiety to be the second most prevalent psychiatric disorder after depression in
children with type 1 DM 10 years after onset of diabetes [9]. In that study,
47.6% of the children met criteria for a psychiatric disorder 10 years after diagnosis of type 1 DM, which indicated that children diagnosed with type 1 DM
are more prone to develop anxiety or other psychiatric disorders than are children
without diabetes.
It has become easier to measure short-term and long-term effects of emotional
factors on blood glucose level. One study found that children judged to have a
Type A personality structure had an increased blood sugar elevation in
response to stress. Children with a calmer disposition had a smaller glucose rise

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when stressed [53]. Several studies found a relationship between hemoglobin

A1c, a measure of metabolic control, and anxiety [54,55]. Although no differences in anxiety scores were found between children with type 1 DM and
children without diabetes, a 1997 study suggested that patients with a psychiatric
history were found to have a higher average glycosylated hemoglobin [56].
Expressed emotion studies have shown that children whose relatives made more
critical comments had significantly poorer glucose control. Emotional overinvolvement between family members was not correlated with poor diabetic
control, however [57]. These findings indicate that anxiety disorders can have an
impact on metabolic control.
Psychotic disorders
To date, there are no reports on the comorbidity of DM and psychotic
disorders. It is assumed that the prevalence of psychotic disorders in patients
with DM is similar to that in persons without DM. Poor management of diabetes
can lead to delirium because of its fluctuating course often not immediately
recognized or because of presenting perceptual disturbances misdiagnosed as
psychosis. As in mania, delirium and psychosis can lead to (further) noncompliance with diabetes management.
Eating disorders
The prevalence of eating disorders is up to twofold higher in adolescent girls
with type 1 DM than in girls without diabetes [12] and causes serious problems
for glycemic control with a risk for fatal ketoacidosis. According to a study by
Takii et al [58], bulimic patients with type 1 DM showed significantly more
severe disturbances related to eating disorders, depression, anxiety, and poorer
psychological functioning than type 1 DM patients with binge-eating disorder;
they also showed poorer glycemic control. Eating disturbances and psychological sense of control are significant correlates of metabolic control in DM in
general. In a recent study, Surgenor [59] found that interpersonal relationships,
eating disturbance in the form of bulimia, and food preoccupation best
predicted level of metabolic control. Given the relation between obesity and
t ype 2 DM, binge-eating disorder and bulimia nervosa have been studied in
the adolescent population. A study conducted by Crow showed that bingeeating disorder and other psychopathologies were common in adolescents with
type 2 DM and that even if glycosylated hemoglobin levels were similar in
patients with and without binge-eating disorder, the presence of the disorder
was associated with greater obesity [60]. Psychological factors are also
involved in the degree of metabolic control in children with type 2 DM. In
an interesting comparative study, Weglage showed that internalizing problems,
such as depressive mood, anxiety, physical complaints, or social isolation, were
elevated in the two clinical groups he studied (persons with phenylketonuria
and diabetes), whereas externalizing problems were not. Researchers did not

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447

find significant correlations between psychological characteristics and biochemical control, IQ, and socioeconomic status. Their study strongly supports a
psychological perspective for the development of behavioral and emotional
problems in these patients [61].

Treatment
Despite current beliefs about the differences in treatment approaches to type 1
and type 2 DM, there are more similarities than commonly believed. Notwithstanding the obvious differences, this heterogeneous group of diseases, which
have in common the development of microvascular and macrovascular complications, have many other commonalities that are reflected in the range of
treatment interventions. Examples of these are behavioral and emotional topics
associated to compliance, aspects related to diet, medication, and exercise, and
treatment goals.
Although management and treatment are used indistinctly throughout the
literature, they refer to different aspects of intervention, perhaps the clearest
difference being that management refers to the joint responsibility by the patient,
his or her family, the medical and psychiatric staff, and the self-help groups to
achieve metabolic stability. To accomplish this goal, medical, psychological, and
social interventions foster the growth of individual and family strengths in
multigoal, multidiscipline, and comprehensive programs.
The management goals for DM can be summarized as (1) symptom elimination, (2) prevention of acute metabolic and systemic complications, (3) prevention, suspension, or reduction of microvascular and neuropathic complications,
(4) decreasing the morbidity and mortality rates from macrovascular disease, and
(5) supporting psychological development and adaptation. The following clinical
vignettes exemplify these points.
Case examples
A 15-year-old girl with type 1 DM who lost her father in a car accident
8 months ago presents to the office. She always has maintained good metabolic
control. Since the death of her father, however, her visits to the office have
increased because of an inability to maintain metabolic control. When asked how
she is coping with the death of her father, the patient expresses sadness, decreased
appetite, trouble sleeping, anhedonia, and trouble concentrating. A child and adolescent psychiatrist is consulted and the patient is diagnosed with major depressive disorder. Weekly individual psychotherapy is started, and after 6 months the
patients mood is improved, as is her metabolic control.
A 17-year-old girl with type 2 DM presents to the office with her parents.
Although slightly overweight, she always has been focused on her diet and has
maintained a stable weight. As a result of breaking up with her boyfriend she
started gaining weight, although she maintains keeping to her diet. Her mother

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verifies that she has followed her diet at least at home and reports that she has
been failing at school. Her father describes his daughter having crying episodes
and being irritable and sad. When asked, the patient confirms the sadness and
reveals blaming herself and her diabetes for the separation. She feels hopeless
and is willing to take medication to feel better. In further discussions the
patient agrees to see a therapist to address her feelings and is referred to a
child and adolescent psychotherapist. Four months after therapy began, she
again took control of her diet outside home. She also was able to engage her
friends in a more supportive way and improve her social support system. She
decided to continued therapy to understand better her relationship to her
diabetes and expand her psychosocial environment, thus preventing future
periods of lack of control.
A 13-year-old girl with type 1 DM presents to the office. She always has been
compliant with her treatment. Her parents report, however, that after an episode
of severe ketoacidosis, she has become overly concerned about her diabetes and
glucose control to the extent that it impairs her daily life. She is focused on her
diet and refuses to participate in any sports for fear of losing control. The patient
is referred to a child and adolescent psychiatrist, who decides to refer her for
cognitive behavioral psychotherapy. After 3 months of therapy the patients
anxiety has resolved; she is no longer excessively focused on her diet and has
decided to rejoin her sports team.

Psychopharmacologic treatment of children and adolescents with

diabetes mellitus
Only a few psychotropic medications are approved by the Food and Drug
Administration for treatment of psychiatric disorders in children and adolescents.
Currently, several large multicenter trials are investigating the effectiveness of
these medications in this population. No studies are currently available concerning
the treatment of psychiatric disorders in children with comorbid type 1 DM. In the
case of type 2 DM, pharmacotherapy must be considered in the three basic conditions: depression, anxious states, and eating disorders or eating complications.
The following recommendations are based on current psychopharmacology
practice in child and adolescent psychiatry. Possible interactions with current
medications should be considered before initiating psychopharmacotherapy in
children with DM.

Antidepressant agents
Although depression is two to three times more prevalent in adolescents with
DM than in children without diabetes, optimal approaches to management have
not been evaluated critically. Even in children without diabetes, the effectiveness
of drug therapy for depression has not been studied extensively. Only a few

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449

studies exist that established the effectiveness of antidepressant pharmacotherapy

in children and adolescents. Keller et al, Wagner et al, and Emslie et al found
that paroxetine, citalopram, and fluoxetine were effective in the treatment of
childhood depression [62 64]. In an earlier study, Emslie [65] concluded after a
literature review of selective serotonin reuptake inhibitors (SSRIs) and tricyclic
antidepressants that SSRIs should be first-line treatment in children and
adolescents because tricyclics have questionable efficacy and definite safety
issues. An added benefit from treatment with SSRIs may include improved
metabolic control through weight loss; however, this also warrants close
monitoring of metabolic control. Weight loss also may be expected with the
use of venlafaxine, a second-line treatment option for depression. Silbutramine, a
noradrenaline and serotonin reuptake inhibitor, also has been used with the
added effect of promoting weight loss and subsequent glycemic control.
Buproprion, an antidepressant used in children without diabetes who have
depression has a 0.4% risk of seizures and is not recommended in children
with type 1 DM because of their increased risk for seizures secondary to episodic
severe hypoglycemia.
Case example
A 17-year-old boy with type 1 DM comes to the clinic. He has had difficulty
maintaining metabolic control for more than a year. His mother reports that her
efforts to help him maintain control are refused. He is oppositional at home and is
failing at school, and his mother reveals that she thinks her son blames her for the
divorce from his father 1 year ago. When asked, the patient reveals feeling sad
and irritable, having trouble sleeping, and missing his father, who has moved out
of state. When offered referral to a therapist, he refuses. He is willing, however, to
take medication to help make him feel better. A trial of SSRIs is started, and a
month after initiation the patient presents to the office with improved mood and
metabolic control.

Anxiolytic agents
As with depression, specific medications and therapies have been shown to
work with states of anxiety in children. It is important to embark on the right
pharmacologic treatment if anxiety is severe. When dealing with stress and mild
to moderate anxiety, other forms of intervention also may be effective without
increasing the unwanted side effects of medical treatment.
Pharmacologic treatment studies of anxiolytic medication in children with DM
are not currently available. Lustman described improved metabolic control in
adults treated with alprazolam regardless of the presence of a diagnosis of anxiety
[66]. Because of their abuse potential, however, benzodiazapines should be
avoided in adolescent patients, and younger children may present with a
paradoxical response when treated with these medications. SSRIs are frequently

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used in the treatment of childhood-onset anxiety and should be considered as a

first-line treatment.

Antipsychotic agents
The number of antipsychotic prescriptions for children has risen significantly in
the past decade. Antipsychotic agents used not only for psychosis but also for
impulsivity and aggression in children and for bipolar disorder and management
of delirium. Patients with DM who need treatment of antipsychotic symptoms
should be monitored closely because the use of the typical and the newer, atypical
antipsychotic medications can cause weight gain. The latter can subsequently
hamper metabolic control. Despite evidence of greater weight gain with atypical
than typical antipsychotic agents, atypicals are considered first-line treatment
because of their safer cardiac side effect profile and lower risk for extrapyramidal
symptoms and tardive dyskinesia, for which type 1 DM patients may be at greater
risk [67]. The choice of antipsychotic medication must be considered carefully for
each individual patient, especially persons with poor metabolic control, because a
single dose of antipsychotic medication may cause hyperglycemia [68 70].
Among the atypical antipsychotic agents, clozapine and olanzapine have been
shown to cause the most weight gain (in excess of 25 30 pounds); the weight gain
is less so with risperidone and quetiapine. Patients on ziprasidone on average do
not gain a significant amount of weight, and they may even lose a significant
amount of weight when switched from other atypical antipsychotic agent [71]
(PJ van Wattum, unpublished data, 2002). Rigorous weight management programs have been shown to be effective for losing weight gained through
antipsychotic medication use [72,73]. These programs are challenging for patients
who are trying to stay in good metabolic control, however. Prevention of weight
gain is a key factor in patients with type1 DM in need of antipsychotic medication.
Because obesity can be an important obstacle to the management of type 2 DM,
weight gain caused by antipsychotic medication is an important consideration
with children at risk for developing type 2 DM, and careful evaluation and
choice are important. When antipsychotic medication is needed with type 2 DM
patients or children with high risk factors, comprehensive programs should include weight control efforts and psychotherapy.
Despite warnings for a risk of sudden death with the use of ziprasidone
because of an extended QTc interval, to date no such cases have been reported.
All atypical medications can lead to an extended QTc-interval, whereas a
combination of antipsychotic agents and SSRIs may increase this risk. It is
recommended to perform a baseline electrocardiogram in all patients who need
antipsychotic medication, with at least one follow-up EKG after initiation of
treatment. Because antipsychotic medication also can lead to increased cholesterol levels and patients with DM, obese children, and patients with impaired
glucose tolerance are at risk for cardiac complications, monitoring of cholesterol
levels and triglycerides should be considered.

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Case example
A 9-year-old girl with type 1 DM presents to the office complaining of hearing
voices. She has a family history significant for schizophrenia. Psychiatric
assessment confirms a diagnosis of psychotic disorder not otherwise specified,
and she is started on a low dose of risperidone. The side effects of the antipsychotic
medicationparticularly weight gain, glucose intolerance, and hypercholesterolemiaare discussed with the patient and her parents. Subsequently a nutritionist is
consulted to help the patient control her weight, and her parents sign her up for
lacrosse. The patient is able to adhere to her diet and becomes an avid lacrosse
player. The risperidone successfully treated her psychosis, and weight gain was
prevented through dietary restrictions and increased exercise.

Mood stabilizers
Lithium is the only mood stabilizer approved by the Food and Drug
Administration for children 12 years and older. Clinical practice, however,
indicates that for children, lithium and valproic acid, an anticonvulsant medication approved for the treatment of mania in adults, are approximately prescribed
with equal frequency. Both medications require regular blood drug level control
and warrant caution when used in children with DM. Lithium use can result in
decreased urinary concentration, which may result in severe dehydration when
combined with osmotic diuresis from hyperglycemia in type 1 DM. This may
lead to not only toxic lithium levels but also a further increase in blood glucose
levels [74]. Thyroid function monitoring is necessary during lithium therapy
because of the increased risk of hypothyroidism in type 1 DM, and drug
interactions also should be monitored closely. Use of lithium and valproic acid
can lead to a significant increase in appetite and weight gain, which may lead to
worsening of diabetic control for both types of diabetes. Carbamazepine and
topiramate are other anticonvulsant drugs used for the treatment of bipolar
disorder in children and for aggressive and impulsive behavior. No impact on
glucose regulation has been reported with those medications, and they seem to be
appropriate alternatives for lithium in children with mania and DM. Topiramate
tends to lead to weight loss and cognitive dulling and should be avoided in
children with type 1 DM. The use of lamotrigine, an anticonvulsant agent used in
the treatment of mania in adults, should be avoided because of the increased risk
for Stevens-Johnson syndrome in children.

Stimulants
Stimulants are widely used for treatment of attention deficit hyperactivity
disorder. Because decreased appetite and weight loss can be prominent side
effects with the use of stimulants, careful monitoring is required in children with
type 1 DM. Alternative and effective pharmacotherapies with less impact on

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metabolism can be clonidine or guanfacine in twice or three times per day dosing
schedules. Bupropion should not be used for treatment of attention deficit
hyperactivity disorder because of the increased vulnerability for seizures in
children with type 1 DM.
Case example
An 8-year-old boy with type I DM presents with symptoms of hyperactivity
and trouble concentrating, as reported by his parents. The boys teachers confirm
the reported symptomatology and he is diagnosed with attention deficit hyperactivity disorder, combined type. A trial of methylphenidate (Ritalin) is initiated,
and his symptoms improve significantly. After several weeks the school reports
that his grades have improved; however, his parents report weight loss because of
decreased appetite, which leads to difficulty maintaining metabolic control. The
methylphenidate is discontinued and the patient is started on guanfacine. The
patients appetite returns, and an initial complaint of sedation disappears after
several days. The patient is successfully stabilized on 1 mg twice per day at 8 AM
and 4 PM.

Weight-reducing medication
Obesity, particularly truncal obesity, has been correlated closely to the
prevalence of diabetes and cardiovascular disease. Because obesity is probably
the most important modifiable risk factor for type 2 DM, weight-reducing drugs
have been used in its management, particularly with children at risk for developing
the disease. Several drugs used for patients with diabetes for allied conditions
produce weight gain as a side effect. A combination of diet, exercise, and lifestyle
modification is necessary to achieve certain success in weight control. Pharmacotherapy has been used specifically with the aim of achieving weight reduction.
Silbutramine has been reported by several researchers as contributing to weight
reduction and glycemic control [75]. Keating reviewed three 2-year studies in
which orlistat, a nonsystematically acting gastric and pancreatic lipase inhibitor,
showed more improvement in glucose tolerance than placebo in a trial that
involved obese patients with type 2 DM [76 78]. Patients on orlistat also had
significantly greater reductions in glycosylated hemoglobin and fasting plasma
glucose levels. Metformin and acarbose have been used with some success in
patients with type 2 DM [79], although the former had never been formally studied
in children until a trial reported this year in which Jones et al [80] showed that it is
safe and effective for the treatment of type 2 DM in children.

Psychotherapy and counseling

Psychosocial issues play a major role in the management of children with type
1 and type 2 DM [54]. Coping with and adapting to the new diagnosis has been

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453

studied extensively in children with type 1 DM [6,8,47,52,81,82], and inadequate

coping was found to have a negative effect on metabolic control. Training in
coping strategies, including social problem solving, cognitive behavior modification, and conflict resolution, in six small group sessions and monthly followup was proven successful after 1-year follow-up [83]. Greco showed that peer
group intervention aimed at increasing peer support could have a positive effect
on self-perception in patients with type 1 DM and fewer diabetes-related conflicts
as reported by parents [84]. Although limited in number, these studies show that
behavioral therapy can be effective for treatment of children with DM. The
crucial element seems to be helping young patients learn how to identify
problems early, thus recounting a wide range of potential solutions. Psychotherapy and counseling also can help patients develop various strategies to cope with
the extra pressures of having diabetes and implement support groups.
In a review of the literature, Curry showed that cognitive behavior therapy
(CBT) as a treatment modality for depression in adolescents without diabetes is
more efficacious than a waiting-list condition or a non-CBT alternative psychotherapy at the end of acute intervention, with no long-term follow-up superiority
of CBT over other psychotherapies. CBT also is associated with more rapid
remission of symptoms than family or supportive therapy. Interpersonal psychotherapy has been demonstrated to be more efficacious than a waiting-list
condition [85]. It is likely that similar effectiveness of these treatments will be
found in children with depression and comorbid type 1 DM. Psychotherapy and
antidepressant medications to treat comorbidity of type 2 DM and depression
have been shown to have positive effects on mood and glycemic control [39].
Future studies are needed to assess the efficacy of these treatments in children
with DM and comorbid psychiatric disorders.
Weight reduction has been suggested as a rational option in the management
of obese patients with type 2 DM as opposed to medication aimed at improving
glycemic control, because the latter often leads to weight gain, which has a
detrimental effect on these patients [86]. In a 1999 study, Greenway [87]
suggested that an 800 kcal/day diet induced twice the weight loss produced by
weight loss medication. Weight reduction counseling is even more important as a
preventive measure not only with obese, at-risk children but also with children
who already have developed type 2 DM. Counselors can provide age-appropriate
nutritional information with practical examples with which children can experiment and easy explanations about how the body works and how it reacts to
different conditions, such as exercise. Education and diet, used in conjunction
with exercise, form the basis of all therapeutic regimens for type 2 diabetes.
Integral approaches aimed at reducing risk factors have tended to be more
encouraging in children than in adults with type 2 DM. Weight reduction should
be considered a key objective with these children. Attempting to achieve
prolonged weight loss through behavioral change and fostering an environment
that facilitates physical activity and the choice of adequate food are the key to
successfully reducing insulin resistance by weight loss. Continuous patient
education (which often can be achieved in groups), monitoring the childs

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progress, and individual and family support are key elements of any psychological intervention.
Case example
A group of 13 overweight children (ages 9 13), some with type 2 DM and
some at risk of developing it, were seen for a period of 3 months. During that time
they followed a program that included medical check-ups, patient and family
education, diet and exercise counseling, and bi-monthly individual psychotherapeutic sessions [88]. The aim of the clinical trial was to use a multimodal
approach to help children who previously had difficulties controlling their weight
to reduce their weight and keep it under control. At the end of the 3 months, all but
2 patients (1 who did not attend the individual psychotherapy sessions and 1 who
left the group after the first month) lowered their weight. 5 children chose to
remain in therapy (CBT) once weekly, and all 11 children were actively engaged in
sports activities. At the 6-month follow-up, 6 children had lost additional weight
and the other 5 had maintained their original weight loss. At 1 year follow-up, two
families asked for further educational material and another family asked for further
diet counseling. Only 5 of the 11 children were still actively exercising, and none
of them was receiving individual psychotherapy. The 3 children who received
further education or counseling and the children who were exercising had gained
control over their weight. The rest had either gained weight or were able to
maintain a brittle weight control with many ups and downs. Further data analysis
is required, but this clinical trial seems to indicate that comprehensive, multimodal
approaches to reducing and controlling weight are more effective in helping obese
and diabetic children than monomodal interventions.

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