Diabetes mellitus (DM) is an increasingly prevalent and complex chronic illness with significant psychosocial and psychiatric ramifications. Stress and psychiatric illness can contribute to the development of the disease itself, via neurohormonal pathways and the side effects of psychiatric medication treatment, and psychiatric symptoms and disorders are prevalent and can have profound effects on the disease course of diabetes.
Thus, there is a pressing need for integration of general medical care and psychiatric care for the diabetic patient in order to improve quality of life and illness outcomes. This chapter will provide a background to appreciate the interplay between mental health and diabetes by distilling the current literature. We review the epidemiology of psychiatric disorders in diabetes, the effects of psychiatric symptoms and disorders on the course of diabetes, psychiatric and neurocognitive comorbidities caused by diabetes, and psychiatric treatment of the diabetic patient. With this summary, we hope to offer the clinician an appreciation for how to recognize and treat psychiatric aspects of diabetes and when a referral for psychiatric or other mental health consultation is likely warranted.
Psychiatric Symptoms and Disorders and the Risk for Diabetes
There is now abundant literature to suggest that psychiatric symptoms and disorders often precede the onset of diabetes and may in fact comprise independent risk factors. Large epidemiological studies have documented that the presence of depressive and anxiety symptoms at a baseline measurement predicts the later onset of metabolic syndrome and diabetes. In a prospective population-based Norwegian study, Engum found that individuals reporting symptoms of depression and anxiety at baseline had increased risk for onset of type 2 diabetes at 10-year follow-up, after controlling for established diabetes risk factors. Interestingly, baseline diabetes was not associated with the presence of depressive or anxiety symptoms at follow-up (see next section).
In a Swedish cohort of approximately 5200 individuals followed for 8–10 years, Eriksson et al.1 found that the presence of distress symptoms at baseline (anxiety, apathy, depression, fatigue, and insomnia) predicted the onset of abnormal glucose tolerance and diabetes for men and abnormal glucose tolerance for women. The potential etiological mechanisms mediating the relationships between depression/anxiety/distress and diabetes are speculative, complex, and involve both neurohormonal and behavioral mechanisms. Depression/anxiety and prolonged stress affect the entire neuroendocrine system via activation of the central sympathetic nervous system and hypothalamus–pituitary–adrenal (HPA) axis. Activation of the HPA axis causes excessive cortisol production that induces insulin resistance, dyslipidemia, visceral obesity, and type 2 diabetes. Also, depression may diminish healthy dietary and physical activity, leading to cardiovascular and diabetes risk.
In addition to depression and anxiety, there is now a growing literature linking other forms of mental illness including schizophrenia, schizoaffective disorder, and bipolar disorder to the risk for diabetes. This relationship has been found to exist independently of the known effects of antipsychotic medications (particularly the second-generation atypical antipsychotics) on weight gain and glucose homeostasis (see below). Patients with schizophrenia, independent of antipsychotic medication use, are two to three times more likely than the general population to have type 2 diabetes. In one hospital-based sample, 50% of bipolar and 26% of schizoaffective disorder patients were found to have type 2 diabetes. In addition to the disorders themselves, newer generation atypical antipsychotic medications, particularly clozapine and olanzapine (and to a lesser degree and more inconsistently, risperidone, quetiapine, ziprasidone, aripiprazole) have been associated with dyslipidemia, insulin resistance, and hyperglycemia.
In general, the risk associated with these medications is proportional to weight gain; however, clozapine and olanzapine may have direct effects on glucose regulation independent of adiposity. A synthesis of the above data would support the notion that primary care patients be regularly screened for chronic distress and psychiatric disorders. Further, patients with significant symptoms should be referred for mental health treatment as indicated but should also be counseled regarding the effects of psychotropic medication, diet, and exercise on diabetes risk and should be monitored regularly for the development of metabolic complications, including dyslipidemia, insulin resistance, and diabetes. For patients treated with secondgeneration antipsychotics, The American Diabetes Association in conjunction with the American Psychiatric Association have published consensus guidelines for the monitoring of patients taking these medications (Table 46.1).
Table 46.1 Consensus guidelines for monitoring patients taking second-generation antipsychotic medications (SGAs)*
Baseline 4 weeks 8 weeks 12 weeks Quarterly Annually Every 5 years
Personal/family history X X
Weight (BMI) X X X X X
Waist circumference X X
Blood pressure X X X
Fasting plasma glucose X X X
Fasting lipid profile X X X
*More frequent assessments may be warranted based on clinical status
Epidemiology of Psychiatric Disorders in Patients Who Have Diabetes
It has long been recognized that depression and other forms of pathological distress are more common in patients with diabetes compared to individuals without the illness. Early studies focused on psychopathology in children with type 1 diabetes from clinical populations, documenting higher rates of psychopathology, particularly depression, compared to nondiabetic children. Psychiatric disorders were generally found in 20–50% of patients. However, these studies were limited due to use of nonstandardized diagnostic instruments, the confounding of somatic depressive symptoms with those of diabetes, and the rates which tended to be inflated due to over-selection for patients in specialty clinics with increased diabetes illness severity and complications. Since the late 1980s, studies employing representative samples of persons with both type 1 and type 2 diabetes and nondiabetic comparisons, using standardized psychiatric diagnostic instruments, have appeared in the literature.
A sampling of such epidemiological studies from the USA and Europe is presented in Table 46.2. The Epidemiological Catchment Area Study (ECA) is the first such study (USA; N = 2552) comparing rates of psychiatric disorders in individuals with diabetes (as well as arthritis, heart disease, hypertension, or chronic lung disease) to rates in persons with no medical illness.11 Findings from the ECA were largely reflective of subsequent studies. Individuals with history of diabetes were found to have a prevalence of 26% lifetime and 16% current anxiety disorders, 14% lifetime, and 10% current depressive disorders, both twice the rate of these disorders in medically healthy participants. Substance use disorders (22% lifetime and 6% current) were not significantly more frequent than the nonmedical population (17% lifetime and 6% current). Studies from the UK and Germany reflect a similar pattern for increased rates of overall psychiatric illness, particularly depression, anxiety, and their combination in patients with diabetes compared to the general population. It is important to note that subclinical depressive and anxiety symptoms are also prevalent in patients with diabetes and may have considerable association with illness burden, particularly physical symptoms and disability. For example, in a clinic population of patients with type 1 and type 2 diabetes screened with the Hospital Anxiety and Depression Scale, 28% reported moderate-to-severe anxiety and/or depressive symptoms, which were associated with increased physical symptom burden.14 Similarly, in a study of 581 African-American patients with diabetes, 27% reported significant depressive symptoms (Beck Depression Inventory [BDI] score > 14). Those with BDI scores >14 had more proliferative retinopathy and were more likely to be on disability.
Table 46.2 Population-based prevalence rates of psychiatric disorders in diabetic compared to nondiabetic individuals, the USA, the UK, and Germany
Differential Diagnosis of Psychiatric and Neuropsychiatric Symptoms in Diabetes
There are a number of important differential diagnostic considerations regarding psychopathology in diabetes, which are outlined in Table 46.3 and discussed in more detail throughout this chapter. First, patients should be assessed for prior history of psychiatric disorder, including mood (depression and mania), anxiety, psychotic, and substance use disorders. The presence of premorbid psychopathology is a predictor of recurrence of these illnesses during the course of diabetes. Second, when applicable, the neuroendocrine effects of atypical antipsychotic medications and other psychotropic medications should be considered in terms of their effect on diabetes management. Third, the acute and chronic/recurrent neuropsychiatric effects of hyper- and hypoglycemia must be considered regarding their effects on mood and cognition. Fourth, cognitive impairment is prevalent in diabetes and should always be considered as an etiological factor in neuropsychiatric symptomatology. Fifth, common medical complications, comorbidities, and their treatments in diabetes, particularly cardiovascular, cerebrovascular, and renal disease, may cause or exacerbate neuropsychiatric symptoms, including more extreme manifestations such as delirium.
Table 46.3 Differential diagnostic considerations for psychiatric and neuropsychiatric symptoms in diabetes
• Premorbid history of psychiatric disorder, including mood (depression and mania), anxiety, psychotic, and substance use disorders
• Acute and chronic neuropsychiatric effects of hyperglycemia
• Acute and chronic neuropsychiatric effects of hypoglycemia
• Neuroendocrine adverse effects of psychotropic drugs, particularly second-generation antipsychotics, mood stabilizers, and tricyclic antidepressants
• Neurocognitive impairment secondary to microvascular ischemic disease
• Neuropsychiatric complications of common medical comorbidities and their treatments (e.g., cardiovascular, cerebrovascular, and renal disease)
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