Association of antipsychotic drugs on type 2 diabetes mellitus risk in patients with schizophrenia: a population-based cohort and in vitro glucose homeostasis-related gene expression study

• Published in: BMC psychiatry Vol. 24; no. 1; pp. 751 - 13
• Main Authors: Fang, Yi-Jen, Lee, Wan-Yi, Lin, Cheng-Li, Cheah, Yu-Cun, Hsieh, Hui-Hsia, Chen, Chi-Hua, Tsai, Fuu-Jen, Tien, Ni, Lim, Yun-Ping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30-10-2024; BioMed Central; BMC
• Subjects: Adult; Analysis; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Antipsychotic drugs; Antipsychotic medications; Antipsychotics; Cardiovascular disease; Care and treatment; Cell lines; Chronic illnesses; Cohort study; Complications and side effects; Dextrose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes therapy; Diagnosis; Dopamine; Dosage and administration; Drug therapy; Drugs; Female; Gene expression; Gene Expression - drug effects; Gene Expression - genetics; Genes; Genetic aspects; Gluconeogenesis; Glucose; Glucose - metabolism; Glucose homeostasis; Health aspects; Health insurance; Hepatocytes; Homeostasis; Homeostasis - drug effects; Humans; Hyperglycemia; Hyperlipidemia; Hypertension; Incidence; Insulin resistance; Liver; Male; Medical research; Medicine, Experimental; Mental disorders; Middle Aged; Mortality; Patients; Population; Population studies; Psychotropic drugs; Retrospective Studies; Risk Factors; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - epidemiology; Schizophrenia - genetics; Taiwan - epidemiology; Type 2 diabetes; Type 2 diabetes mellitus; Taiwan; Antipsychotic medications; Schizophrenia; Type 2 diabetes mellitus; Glucose homeostasis; Cohort study
• ISSN: 1471-244X; 1471-244X
• DOI: 10.1186/s12888-024-06222-z

Type 2 diabetes mellitus (T2DM) and its related complications are associated with schizophrenia. However, the relationship between antipsychotic medications (APs) and T2DM risk remains unclear. In this population-based, retrospective cohort study across the country, we investigated schizophrenia and the effect of APs on the risk of T2DM, and glucose homeostasis-related gene expression.
We used information from the Longitudinal Health Insurance Database of Taiwan for individuals newly diagnosed with schizophrenia (N = 4,606) and a disease-free control cohort (N = 4,606). The differences in rates of development of T2DM between the two cohorts were assessed using a Cox proportional hazards regression model. The effects of APs on the expression of glucose homeostasis-related genes in liver and muscle cell lines were assessed using quantitative real-time PCR.
After controlling potential associated confounding factors, the risk of T2DM was higher in the case group than that in the control group [adjusted hazard ratio (aHR), 1.80, p < 0.001]. Moreover, the likelihood of T2DM incidence in patients with schizophrenia without AP treatment (aHR, 2.83) was significantly higher than that in non-schizophrenia controls and those treated with APs (aHR ≤ 0.60). In an in vitro model, most APs did not affect the expression of hepatic gluconeogenesis genes but upregulated those beneficial for glucose homeostasis in muscle cells.
This study demonstrates the impact of schizophrenia and APs and the risk of developing T2DM in Asian populations. Unmeasured confounding risk factors for T2DM may not have been included in the study. These findings may help psychiatric practitioners identify patients at risk of developing T2DM.