Diabetes mellitus is a common childhood illness, and its management is often complicated by mental health challenges. Psychiatric comorbidities are common, including anxiety, depression, and eating disorders. The illness can profoundly affect the developing brain and family functioning and have lifelong consequences. The child mental health provider can provide valuable assistance to support the child and family and assessment and treatment of comorbid mental health problems and to promote positive family functioning and normal developmental progress.
Diabetes mellitus (type 1) has long been identified as one of the most common chronic, lifelong illnesses developing in childhood. In the United States, type 2 diabetes and metabolic syndrome are increasing in children and adolescents at an alarming rate. Type 1 diabetes mellitus (T1DM) has also been called insulin-dependent diabetes mellitus (IDDM) and juvenile onset diabetes mellitus. The hallmark feature of T1DM is the under production or lack of production of insulin by the beta cells of the pancreas. This lack of insulin is felt to be due to the destruction of the beta cells. The hallmark feature of type 2 diabetes is “insulin resistance.” In type 2 diabetes, the pancreatic beta cells still make insulin, but cells become “resistant” to insulin and are unable to take up circulating glucose. Thus, high levels of circulating insulin and glucose are found in type 2 diabetes. Risk factors for type 2 diabetes include being overweight ( Table 1 ). The incidence of overweight children and adolescents (above the 95th percentile for weight) has been increasing during the last few decades, with 17.1% of all children and adolescents being defined as overweight in 2003 and 2004. Risk factors for children and adolescents becoming overweight and who are at risk for metabolic syndrome or type 2 diabetes have included the increased use of atypical antipsychotics, most notably olanzapine and clozapine.
| Type 1 Diabetes Mellitus | Type 2 Diabetes Mellitus | Metabolic Syndrome |
|---|---|---|
| Onset: abrupt; often in childhood Insulin dependent Defect: insulin producing cells of the pancreas | Onset: gradual; originally adult disease, now increasing in childhood Insulin resistant: hallmark feature Associated with obesity, use of atypical antipsychotic medications May be controlled with diet and exercise |
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The incidence of T1DM varies with geography, age, gender, family history, and race. Risk for developing T1DM in childhood seems to increase with distance from the equator. In the United States, the highest incidence of T1DM is found in non-Hispanic white children, 23.6 per 100,000 annually. Childhood-onset T1DM has a bimodal presentation for age of onset, with the first peak between ages 4 and 6 years and the second peak in early adolescence.
Development of childhood-onset IDDM occurs with the destruction of the beta cells in the pancreas. The destruction is most often felt to be mediated by an autoimmune response but can also be seen in association with cystic fibrosis. In addition, there is noted genetic susceptibility as the risk for T1DM increases for first-degree relatives. Thus, for genetically susceptible individuals, it is postulated that environmental exposures (proposed agents including: viral infections, immunizations, diet, vitamin D deficiency and perinatal factors) trigger an immune response, leading to the destruction of the beta cells of the pancreas. There is also an associated increased risk for celiac disease for children with T1DM. Some children and families struggle with the dietary restrictions of T1DM and the gluten-free dietary requirements for celiac disease.
The treatment regimen for T1DM includes close monitoring of blood glucose level by “finger sticks,” monitoring of urine for glycosuria, diet modifications, and multiple injections of insulin per day. Some treatment centers advocate “tight” control, with blood glucose levels monitored as frequently as every 4 hours and decisions on insulin dose made as predicated by the blood glucose level. Other programs may have as “loose” a program as twice a day injections and twice a day monitoring of blood and urine glucose levels. But in the developing child with variable times of exercise, school lunches, birthday parties ensuring healthy blood glucose levels can be a challenge to the child, the family, and the care providers. Often in later adolescence, the individual with T1DM may opt (or be recommended by the treatment provider) to receive treatment from an insulin pump (subcutaneous continuous infusion of insulin). The insulin pump delivers continuous basal insulin with boluses associated with meals. Use of the insulin pump may reduce rates of hypoglycemic events, but controlled trials of pump therapy comparing injection therapy in the pediatric population are currently limited.
There are both long-term complications of chronically high blood glucose levels on the vascular system and serious short-term problems with acute hypoglycemic events ( Box 1 ). The preschool-age child may be more vulnerable to severe hypoglycemic events, and prepubertal children may be more protected from microvascular complications of T1DM. For the person with frequent “sugars running high,” measurement of the glycated hemoglobin levels (A 1c ) will be elevated. The recognized risk of hypoglycemia in younger children has led to the setting of higher HbA 1c target levels compared with the expectation of “stricter” metabolic control for older children and adolescents.
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Shorter-term complications of diabetes include difficulties associated with hypoglycemia, ranging from tremor, confusion, and lethargy to stupor and seizures. Acute hyperglycemia can lead to polyuria, nocturnal enuresis, weight loss, and risk for diabetic ketoacidosis, which can potentially cause coma and death. Thus, diabetes can cause acute life-threatening events in addition to chronic complications. For the developing child and adolescent, effects of hypoglycemic events and hyperglycemia may cause cognition and neurodevelopmental challenges (see next section).
Longer-term complications of diabetes affect all organ systems, with the causal agent being microvascular damage. Most notable potential complications include retinopathy, nephropathy, neuropathy, cardiovascular disease, and impotence. Additional complications can include gastroparesis, menstrual difficulties, necrobiosis lipoidica, and bone changes.
Effect on cognition and neuropsychological difficulties in children and adolescents
Children and adolescent brains continue to develop through pruning, myelinization, and other maturational processes. Childhood cognitive development is well recognized to undergo remarkable changes from barely recognizing letters to abstract thinking. The effect of hypoglycemia and hyperglycemia in the developing child on cognitive functioning and subtle neuropsychological deficits has been the subject of ongoing studies. In 2004, Desrocher and Rovet provided a comprehensive review of the literature, some of the controversies, and a discussion of some of the limitations of past research. Further research since 2004 is described in the next section and in Table 2 .
| Hypoglycemia | Hyperglycemia | |
|---|---|---|
| Long-term |
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| Immediate |
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Hypoglycemia
Earlier age of onset (<5 years) has often been associated with more frequent or more severe bouts of hypoglycemia. This is thought to be secondary to individual lack of hypoglycemia awareness (or lack of verbal skills to express the acute event) and sensitivity to nocturnal hypoglycemic spells. Repeated severe bouts of hypoglycemia (more than 3 episodes) have been associated with deficits in spatial memory, worse cognitive outcome and delayed recall, and smaller gray matter volume in the left superior temporal region. Greater exposure to severe hypoglycemia in childhood has also been associated with greater hippocampal volume, and researchers postulated that this enlargement may reflect a pathologic reaction, leading to gliosis, reactive neurogenesis, or impairment of normal pruning.
A recent small study tried to examine the immediate neuropsychological and neurometabolic effects of a severe hypoglycemic event (with associated seizure) in 3 prepubertal children. Immediate difficulties were noted with selective attention that improved during the subsequent 6 months, and the neuronal integrity in the anterior brain appeared particularly susceptible to acute hypoglycemia.
Hyperglycemia
Longer-term effects of chronic hyperglycemia have been noted to affect overall verbal intelligence, overall brain changes including decreased gray matter volume in the right cuneus and precuneus regions, smaller white volume in the right posterior parietal region, and increased gray matter in the prefrontal region.
Parents and children alike have anecdotally reported knowing when the child is running “high” glucoses by reporting changes in behavior. McDonnell and colleagues studied prepubertal children with T1DM to test the potential association between glucose levels and behaviors. They, indeed, found an association between intercurrent high glycemic levels and increased externalizing behaviors, such as agitation and aggression. A recent study conducted imaging studies during hyperglycemia in children with or without associated diabetic ketoacidosis, and the frontal region was notably affected with elevations of taurine associated with increased risk for cerebral edema.
Summary of Neurocognitive Effects of T1DM
T1DM has significant acute and chronic implications for the developing child and adolescent brain. Severe hypoglycemic episodes for children less than 5 years of age may later predispose the child to significant learning issues. On the other hand, chronically elevated glucose levels may predispose the child to lower verbal intelligence scores. Immediate effects of hypoglycemia may lead to problems with selective attention, whereas the child with “high sugars” may exhibit problematic externalizing behaviors. The child or adolescent and her/his family face the challenge of finding a correct balance.
Psychiatric comorbidity associated with IDDM
Evidence suggests that maladjustment in children negatively affects glycemic control and subsequent metabolic functioning. Recent studies indicate elevated rates of psychiatric disorder between 33% and 42% in adolescents and young adults with diabetes, which are 2 to 3 times higher than those found in the general population. Diagnoses include internalizing and externalizing disorders. A recent study examined the effect of internalizing and externalizing disorders on the risk for readmission to the hospital for diabetes care, demonstrating an increased risk for readmission for adolescents (but not children) with internalizing behaviors and possibly an increased risk among those with externalizing behaviors. Many studies suggest that individuals with comorbid psychiatric disorders are less likely to adhere to treatment regimens, resulting in poorer control of the illness. Thus, disturbed adolescents with diabetes may be at “double jeopardy” for adverse physical and mental health outcomes. An association between mood disorders in the child or adolescent with T1DM and family conflict and very “tight” metabolic control has also been reported, raising the possibility that psychiatric symptoms may either contribute to or result from obsessive preoccupation with the demands of the diabetes treatment regimen. Depression and anxiety are most commonly seen in children and adolescents with diabetes, and early adjustment disorders are more predictive of these diagnoses. Eating disorders are also common, particularly among women, and are discussed in the later section.
Adjustment Disorders
From the time of diagnosis, there is an expected pattern of adjustment because both children and families are introduced to a new world filled with challenges, constraints, and uncertainties associated with a lifelong illness. Initial adjustment to the diagnosis of diabetes is characterized by sadness, anxiety, withdrawal, and dependency, and approximately 30% of children develop a clinical adjustment disorder in the 3 months subsequent to diagnosis. Such difficulties often resolve within the first year, but poor adaptation in this initial phase places children at risk of later psychological difficulties.
Depression
Studies have associated a diagnosis of depression with substantially worse glycemic control and more serious retinopathy in patients without psychiatric disorders. Because of the overlap of symptoms such as fatigue, weight loss, and impaired memory common to both mood disorder and poor metabolic control, depression may be under diagnosed in children with diabetes. Therefore, it is useful to reevaluate patients with symptoms of depression after glycemic control has been established. If symptoms persist, a diagnosis of depression may be indicated. Massengale provides a recent review on the salient features of depression in the adolescent with T1DM. A 2003 study reported that there is a 10-fold increase in the incidence of suicide and suicidal ideation in the adolescent with diabetes. In addition to other means, insulin is a potential means for self-injury.
With nearly one-third of diabetic adolescents experiencing comorbid depression and similar numbers reported in the adult population, researchers are looking for links of brain pathology/changes caused by the illness leading to increased risk for depression. McEwen and colleagues propose that the progressive atrophy of the hippocampus is seen in animals with diabetes, which is similar to changes seen in depression.
Psychotherapeutic and psychopharmacologic interventions have been found to be helpful in treating depression. Psychopharmacologic treatment should be accompanied by psychotherapy addressing the pessimistic attitudes that typically accompany depression in adolescents and that can limit the patient’s willingness or ability to do what is necessary to treat the diabetes.
Psychopharmacologic treatment use in conjunction with IDDM may present with unique challenges. Although the initiation of treatment with antidepressants does not usually cause serious problems, patients and parents should be alerted to the possibility of changes in blood glucose control. Tricyclic antidepressants frequently stimulate appetite that can lead to hyperglycemia. Selective serotonin reuptake inhibitors can have appetite-suppressing effects and may also enhance the action of insulin, thereby inducing hypoglycemic episodes. Because lithium carbonate seems to have effects that mimic those of insulin as well as stimulate the secretion of glucagon, either hyper- or hypoglycemia may result from its use. Successful treatment of depression may also bring about changes in eating habits, exercise patterns, and the regularity of insulin injections, thereby causing unforeseen changes in blood glucose control.
Anxiety Disorders
Symptoms of anxiety may also be more common in diabetic children and adolescents. As with other diagnoses, anxiety symptoms may occur in the context of poor glycemic control and must be differentiated from hypo- or hyperglycemic conditions. Self-monitoring of blood glucose concentrations can help the patients and parents discriminate between hypoglycemia and anxiety. It is often useful to help the child discriminate internalizing symptoms of worry or persistent fears associated with anxiety from physical symptoms of palpitations or diaphoresis associated with a hypoglycemic state. Treatment with antianxiety medications may lead to improved glucose control and even to hypoglycemia. Caution is advised when using β-blockers to treat anxiety symptoms, because they can block adrenergic symptoms that are useful in identifying the hypoglycemic state.
Eating Disorders
The coexistence of eating disorders, such as anorexia nervosa and bulimia nervosa, and diabetes has long been recognized in the clinical setting, particularly among female patients. The cause of eating disorders is multifactorial, involving psychological, biologic, genetic, family, social, and environmental factors. Overall, eating disorders that meet DSM-IV diagnostic requirements are more prevalent among adolescents with T1DM than the general population. Subthreshold eating disorder, eating-related disturbances, and misuse of insulin to influence body weight, which pose an increased risk for related medical complications and eating disorders, are common in the female adolescent diabetic population.
Considering the frequency of eating disorders based on DSM-IV criteria, some studies indicate that subjects with diabetes mellitus were 2.4 times more likely to have an eating disorder than controls and 1.9 times more likely to have a subthreshold eating disorder. Smith and colleagues compared adolescent women with diagnoses of scoliosis and IDDM with a normal control group for an increased risk of eating disorders. Of the adolescents with T1DM, 27.5% were found to have either bulimia or binge-eating disorder based on DSM-IV criteria. Although many patients may not meet strict DSM-IV criteria for anorexia nervosa or bulimia, as indicated by refusal to maintain body weight at or above minimally normal weight for age and height and recurrent inappropriate compensatory behavior to prevent weight gain, respectively, deliberate insulin omission was cited as the most common weight loss behavior after dieting. Data suggest that between 15% and 39% of young women with diabetes manipulate their insulin to control their weight, with clinically relevant changes in eating attitudes in boys and girls occurring after their first year of treatment for diabetes. Although some diabetic patients tend to be slightly more overweight than controls, it is the rapid weight gain of rehydration and the anabolic effect of insulin that may be responsible for the rapid weight gain, particularly after diagnosis. Although these changes in eating attitudes were associated with significant changes in body weight, girls were more likely to experience changes in body dissatisfaction, preoccupation with food, body image, and body shape. In relation to bulimia, rather than purging, many diabetic women reduce their dose of insulin to achieve a similar calorie-voiding effect. The availability of this method of weight control, together with dietary restrictions imposed by the diabetes regimen, may explain why many diabetic patients may report less dieting to lose weight, even though they report more binge eating.
Such eating disorders or disturbances in adolescents with T1DM pose a particular health risk in that they are associated with impaired metabolic control and about a 3-fold increase in the risk of diabetic retinopathy. For the clinician, these findings emphasize the importance of considering an eating disorder, or at least disturbed eating, as a cause of poor control of hemoglobin HbA 1c control in young women with diabetes.
Psychiatric comorbidity associated with IDDM
Evidence suggests that maladjustment in children negatively affects glycemic control and subsequent metabolic functioning. Recent studies indicate elevated rates of psychiatric disorder between 33% and 42% in adolescents and young adults with diabetes, which are 2 to 3 times higher than those found in the general population. Diagnoses include internalizing and externalizing disorders. A recent study examined the effect of internalizing and externalizing disorders on the risk for readmission to the hospital for diabetes care, demonstrating an increased risk for readmission for adolescents (but not children) with internalizing behaviors and possibly an increased risk among those with externalizing behaviors. Many studies suggest that individuals with comorbid psychiatric disorders are less likely to adhere to treatment regimens, resulting in poorer control of the illness. Thus, disturbed adolescents with diabetes may be at “double jeopardy” for adverse physical and mental health outcomes. An association between mood disorders in the child or adolescent with T1DM and family conflict and very “tight” metabolic control has also been reported, raising the possibility that psychiatric symptoms may either contribute to or result from obsessive preoccupation with the demands of the diabetes treatment regimen. Depression and anxiety are most commonly seen in children and adolescents with diabetes, and early adjustment disorders are more predictive of these diagnoses. Eating disorders are also common, particularly among women, and are discussed in the later section.
Adjustment Disorders
From the time of diagnosis, there is an expected pattern of adjustment because both children and families are introduced to a new world filled with challenges, constraints, and uncertainties associated with a lifelong illness. Initial adjustment to the diagnosis of diabetes is characterized by sadness, anxiety, withdrawal, and dependency, and approximately 30% of children develop a clinical adjustment disorder in the 3 months subsequent to diagnosis. Such difficulties often resolve within the first year, but poor adaptation in this initial phase places children at risk of later psychological difficulties.
Depression
Studies have associated a diagnosis of depression with substantially worse glycemic control and more serious retinopathy in patients without psychiatric disorders. Because of the overlap of symptoms such as fatigue, weight loss, and impaired memory common to both mood disorder and poor metabolic control, depression may be under diagnosed in children with diabetes. Therefore, it is useful to reevaluate patients with symptoms of depression after glycemic control has been established. If symptoms persist, a diagnosis of depression may be indicated. Massengale provides a recent review on the salient features of depression in the adolescent with T1DM. A 2003 study reported that there is a 10-fold increase in the incidence of suicide and suicidal ideation in the adolescent with diabetes. In addition to other means, insulin is a potential means for self-injury.
With nearly one-third of diabetic adolescents experiencing comorbid depression and similar numbers reported in the adult population, researchers are looking for links of brain pathology/changes caused by the illness leading to increased risk for depression. McEwen and colleagues propose that the progressive atrophy of the hippocampus is seen in animals with diabetes, which is similar to changes seen in depression.
Psychotherapeutic and psychopharmacologic interventions have been found to be helpful in treating depression. Psychopharmacologic treatment should be accompanied by psychotherapy addressing the pessimistic attitudes that typically accompany depression in adolescents and that can limit the patient’s willingness or ability to do what is necessary to treat the diabetes.
Psychopharmacologic treatment use in conjunction with IDDM may present with unique challenges. Although the initiation of treatment with antidepressants does not usually cause serious problems, patients and parents should be alerted to the possibility of changes in blood glucose control. Tricyclic antidepressants frequently stimulate appetite that can lead to hyperglycemia. Selective serotonin reuptake inhibitors can have appetite-suppressing effects and may also enhance the action of insulin, thereby inducing hypoglycemic episodes. Because lithium carbonate seems to have effects that mimic those of insulin as well as stimulate the secretion of glucagon, either hyper- or hypoglycemia may result from its use. Successful treatment of depression may also bring about changes in eating habits, exercise patterns, and the regularity of insulin injections, thereby causing unforeseen changes in blood glucose control.
Anxiety Disorders
Symptoms of anxiety may also be more common in diabetic children and adolescents. As with other diagnoses, anxiety symptoms may occur in the context of poor glycemic control and must be differentiated from hypo- or hyperglycemic conditions. Self-monitoring of blood glucose concentrations can help the patients and parents discriminate between hypoglycemia and anxiety. It is often useful to help the child discriminate internalizing symptoms of worry or persistent fears associated with anxiety from physical symptoms of palpitations or diaphoresis associated with a hypoglycemic state. Treatment with antianxiety medications may lead to improved glucose control and even to hypoglycemia. Caution is advised when using β-blockers to treat anxiety symptoms, because they can block adrenergic symptoms that are useful in identifying the hypoglycemic state.
Eating Disorders
The coexistence of eating disorders, such as anorexia nervosa and bulimia nervosa, and diabetes has long been recognized in the clinical setting, particularly among female patients. The cause of eating disorders is multifactorial, involving psychological, biologic, genetic, family, social, and environmental factors. Overall, eating disorders that meet DSM-IV diagnostic requirements are more prevalent among adolescents with T1DM than the general population. Subthreshold eating disorder, eating-related disturbances, and misuse of insulin to influence body weight, which pose an increased risk for related medical complications and eating disorders, are common in the female adolescent diabetic population.
Considering the frequency of eating disorders based on DSM-IV criteria, some studies indicate that subjects with diabetes mellitus were 2.4 times more likely to have an eating disorder than controls and 1.9 times more likely to have a subthreshold eating disorder. Smith and colleagues compared adolescent women with diagnoses of scoliosis and IDDM with a normal control group for an increased risk of eating disorders. Of the adolescents with T1DM, 27.5% were found to have either bulimia or binge-eating disorder based on DSM-IV criteria. Although many patients may not meet strict DSM-IV criteria for anorexia nervosa or bulimia, as indicated by refusal to maintain body weight at or above minimally normal weight for age and height and recurrent inappropriate compensatory behavior to prevent weight gain, respectively, deliberate insulin omission was cited as the most common weight loss behavior after dieting. Data suggest that between 15% and 39% of young women with diabetes manipulate their insulin to control their weight, with clinically relevant changes in eating attitudes in boys and girls occurring after their first year of treatment for diabetes. Although some diabetic patients tend to be slightly more overweight than controls, it is the rapid weight gain of rehydration and the anabolic effect of insulin that may be responsible for the rapid weight gain, particularly after diagnosis. Although these changes in eating attitudes were associated with significant changes in body weight, girls were more likely to experience changes in body dissatisfaction, preoccupation with food, body image, and body shape. In relation to bulimia, rather than purging, many diabetic women reduce their dose of insulin to achieve a similar calorie-voiding effect. The availability of this method of weight control, together with dietary restrictions imposed by the diabetes regimen, may explain why many diabetic patients may report less dieting to lose weight, even though they report more binge eating.
Such eating disorders or disturbances in adolescents with T1DM pose a particular health risk in that they are associated with impaired metabolic control and about a 3-fold increase in the risk of diabetic retinopathy. For the clinician, these findings emphasize the importance of considering an eating disorder, or at least disturbed eating, as a cause of poor control of hemoglobin HbA 1c control in young women with diabetes.
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