Adding vitamin D may lessen the risk of developing new-onset diabetes in patients taking atypical antipsychotics, according to a study published in Scientific Reports

Atypical antipsychotics are used to treat various psychiatric disorders, including schizophrenia, bipolar disorder, depression, and sleep disorders. Antipsychotic-induced hyperglycemia is often associated with use of these agents. It frequently results in new-onset diabetes mellitus, and can sometimes result in life-threatening diabetic ketoacidosis, coma, or even death. 

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Researchers from Kyoto University set out to establish the molecular mechanism underlying the hyperglycemia induced by antipsychotics. They first examined the Food and Drug Administration (FDA)’s Adverse Event Reporting (FAERS) system for atypical antipsychotic usage and diabetes-related adverse events. Quetiapine and olanzapine had a strong association (odds ratio [OR] >20) with diabetes mellitus, and an intermediate association (OR between 5-20) was seen for risperidone, aripiprazole, and ziprasidone. A low association (OR <5) was seen for clozapine. They then examined potential antidotes that reduced the hyperglycemia risk of atypical antipsychotics, focusing on quetiapine due to the high OR. 

They found that a combination with vitamin D analogues significantly reduced the occurrence of quetiapine-induced adverse events relating to diabetes mellitus in FAERS. Mice models further validated that the insulin resistance caused by quetiapine was mitigated by cholecalciferol supplementation. 

Additional analysis on the signaling pathway and gene expression predicted quetiapine-induced downregulation of phosphatidylinositol 3-kinase (Pik3r1). A reduced expression of Pik3r1 mRNA was reversed by cholecalciferol supplementation in skeletal muscle and researchers also found that insulin-stimulated glucose uptake in C2C12 myotube was inhibited in the presence of quetiapine but reversed by concomitant calcitriol. 

Based on the study findings, coadministration of vitamin D may prevent antipsychotic-induced hyperglycemia and insulin resistance seen from upregulation of PI3K function. 

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