Antipsychotics are medications commonly prescribed to treat mental health conditions such as psychosis (losing touch with reality). They are also prescribed to treat anxiety and irritability in children with autism, a condition that affects the way a person thinks and interacts with the world, improving the lives of both the child and the family. However, adverse effects, including weight gain and insulin resistance (occurs when the body's cells do not respond well to insulin, leading to higher levels of blood sugar in the bloodstream), have been observed in adults using antipsychotics. As a result, there are now concerns about the potential risk of developing type 2 diabetes mellitus (T2DM), a condition that leads to difficulties in managing blood sugar levels, among children and young people taking antipsychotics.
The aim of this study is to evaluate the long-term risk of developing T2DM among children and young people treated with antipsychotics. We will:
1. Examine the cumulative incidence of T2DM among children and young people treated with antipsychotics, and how this is affected by age at treatment initiation, sex, and ethnicity.
2. Determine the risk factors associated with the development of T2DM in children and young people treated with antipsychotics.
3. Evaluate the risk of T2DM according to the type of antipsychotic and duration of use.
Against the background of this information, our overall goal is to develop guidance for clinicians and patients to reduce the risk of developing T2DM among children and young people taking antipsychotics through risk factor modification.
This will be a population-based cohort study that includes children and young people who were aged <18 years and newly prescribed antipsychotics between 1990-2017. Patients who had a diagnosis for T1DM anytime during the study period or had a diagnosis for T2DM before the first antipsychotic prescription will be excluded. The cohort will be followed until 31 December 2022 (or the latest available data). The outcome will be incident T2DM defined by a record of diagnosis or a prescription of antidiabetic drugs other than insulin. We will investigate 1) cumulative incidence of T2DM yearly, stratified by age at treatment initiation, sex, and ethnicity, 2) the risk of T2DM according to the types of antipsychotics and duration of use, and 3) the risk factors associated with the development of T2DM with antipsychotic medication in children and young people. Covariates will be included based on previously published findings of potential risk factors for T2DM, such as age, sex, ethnicity, sociodemographic status, family history of diabetes, body mass index (BMI), disease and medication history. Childhood BMI will be transformed using the Lambda Mu Sigma method. Comorbidities will be measured any time before and on the first antipsychotic prescription (cohort entry). Co-medications will be assessed within the year before and on the cohort entry. In our analysis, we will use the Cox proportional hazard regression models to examine risk factors for T2DM. To analyse duration-response relationship, drug exposure status will be updated monthly and presented as a time-dependent exposure variable in the Cox model. Cumulative duration of use will be defined as the total number of days of use since the cohort entry. The study finding will help clinicians and patients better understand and reduce the potential risk of T2DM in children and young people taking antipsychotics.
Incident type 2 diabetes mellitus (T2DM), defined by a record of diagnosis or a prescription of antidiabetic drugs (other than insulin) after initiation of antipsychotic drugs.
Wallis Lau - Chief Investigator - University College London ( UCL )
Sohee Park - Corresponding Applicant - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record;CPRD GOLD Ethnicity Record