Curr Diab Rep (2015) 15:53 DOI 10.1007/s11892-015-0623-4
PEDIATRIC TYPE 2 DIABETES (PS ZEITLER, SECTION EDITOR)
Type 2 Diabetes in Children and Adolescents on Atypical Antipsychotics Pornpoj Pramyothin 1 & Lalita Khaodhiar 2
# Springer Science+Business Media New York 2015
Abstract Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient’s access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.
Keywords Antipsychotics . Children and adolescents . Diabetes . Obesity . Psychosis . Serious mental illness
This article is part of the Topical Collection on Pediatric Type 2 Diabetes * Lalita Khaodhiar [email protected] 1
Division of Nutrition, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2
Center for Nutrition and Weight Management, Boston Medical Center, School of Medicine, Boston University, 88 East Newton Street Robinson Bldg, Suite 4400, Boston, MA 02118, USA
Introduction Children and adolescents affected by severe mental illnesses (SMIs), namely psychotic disorders and bipolar disorder, are particularly at risk of type 2 diabetes (T2D), obesity, and metabolic syndrome. These co-morbidities, in conjunction with cardiovascular disease, result in a significant decrease in life expectancy and an excess in morbidity and mortality in this vulnerable population [1]. Historically, the association between diabetes and psychotic disorders was described even before the advent of antipsychotic drugs [2]. This is likely due to the fact that the risk of T2D in this population is attributable not only to treatment but also to the underlying mental illnesses and lifestyle factors, including poor nutrition [3], sedentary lifestyle [4], smoking [4, 5], and substance abuse [6], that are more prevalent among patients with SMIs. Genetic [7], environmental, and socioeconomic factors such as disparities in access to medical care [8, 9] also likely contribute to this association. With steadily rising trends in prescription of antipsychotic medications, particularly in children and adolescents [10], these drugs are among the most significant risk factors for T2D in this population. Secondgeneration antipsychotics (SGAs) were developed in order to negate the side effects of first-generation antipsychotics (FGAs), particularly anticholinergic effects, sedation, extrapyramidal symptoms, and tardive dyskinesia [11]. However, SGAs have been associated with significant metabolic complications, including T2D, weight gain, and metabolic syndrome [12]. The purpose of this article is to review recent advances in epidemiology, pathophysiology, prevention, and treatment of T2D associated with SMI and antipsychotics, with a special focus on children and adolescents.
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Curr Diab Rep (2015) 15:53
Epidemiology of T2D Associated with SMI and Antipsychotics
Mechanisms of T2D Associated with SMI on Antipsychotics
Overall, the risk of diabetes is increased by 2- to 3-fold with use of antipsychotic medications. In a retrospective cohort study utilizing data from the Tennessee Medicaid program, incidence of diabetes was compared between youth 6–24 years of age who were started on antipsychotics and matched controls. Among patients who were started on antipsychotics, the risk of diabetes was three times that of controls (HR 3.03, 95 % CI 1.73–5.32). This risk was dosedependent, observed early in the first year of treatment, and was elevated for up to 1 year after the antipsychotic drug was discontinued [13•]. Andrade et al. compared the incidence of diabetes in children aged 5–18 years between those who were started on SGAs and those who did not receive any psychotropic medications (
PEDIATRIC TYPE 2 DIABETES (PS ZEITLER, SECTION EDITOR)
Type 2 Diabetes in Children and Adolescents on Atypical Antipsychotics Pornpoj Pramyothin 1 & Lalita Khaodhiar 2
# Springer Science+Business Media New York 2015
Abstract Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient’s access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.
Keywords Antipsychotics . Children and adolescents . Diabetes . Obesity . Psychosis . Serious mental illness
This article is part of the Topical Collection on Pediatric Type 2 Diabetes * Lalita Khaodhiar [email protected] 1
Division of Nutrition, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2
Center for Nutrition and Weight Management, Boston Medical Center, School of Medicine, Boston University, 88 East Newton Street Robinson Bldg, Suite 4400, Boston, MA 02118, USA
Introduction Children and adolescents affected by severe mental illnesses (SMIs), namely psychotic disorders and bipolar disorder, are particularly at risk of type 2 diabetes (T2D), obesity, and metabolic syndrome. These co-morbidities, in conjunction with cardiovascular disease, result in a significant decrease in life expectancy and an excess in morbidity and mortality in this vulnerable population [1]. Historically, the association between diabetes and psychotic disorders was described even before the advent of antipsychotic drugs [2]. This is likely due to the fact that the risk of T2D in this population is attributable not only to treatment but also to the underlying mental illnesses and lifestyle factors, including poor nutrition [3], sedentary lifestyle [4], smoking [4, 5], and substance abuse [6], that are more prevalent among patients with SMIs. Genetic [7], environmental, and socioeconomic factors such as disparities in access to medical care [8, 9] also likely contribute to this association. With steadily rising trends in prescription of antipsychotic medications, particularly in children and adolescents [10], these drugs are among the most significant risk factors for T2D in this population. Secondgeneration antipsychotics (SGAs) were developed in order to negate the side effects of first-generation antipsychotics (FGAs), particularly anticholinergic effects, sedation, extrapyramidal symptoms, and tardive dyskinesia [11]. However, SGAs have been associated with significant metabolic complications, including T2D, weight gain, and metabolic syndrome [12]. The purpose of this article is to review recent advances in epidemiology, pathophysiology, prevention, and treatment of T2D associated with SMI and antipsychotics, with a special focus on children and adolescents.
53
Page 2 of 8
Curr Diab Rep (2015) 15:53
Epidemiology of T2D Associated with SMI and Antipsychotics
Mechanisms of T2D Associated with SMI on Antipsychotics
Overall, the risk of diabetes is increased by 2- to 3-fold with use of antipsychotic medications. In a retrospective cohort study utilizing data from the Tennessee Medicaid program, incidence of diabetes was compared between youth 6–24 years of age who were started on antipsychotics and matched controls. Among patients who were started on antipsychotics, the risk of diabetes was three times that of controls (HR 3.03, 95 % CI 1.73–5.32). This risk was dosedependent, observed early in the first year of treatment, and was elevated for up to 1 year after the antipsychotic drug was discontinued [13•]. Andrade et al. compared the incidence of diabetes in children aged 5–18 years between those who were started on SGAs and those who did not receive any psychotropic medications (
