Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study
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OBJECTIVE: Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. METHOD: The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained from the Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. RESULTS: Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. CONCLUSIONS: Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics. Early detection and effective treatment of diabetes should be an integral part of multidisciplinary management of schizophrenia regardless of antipsychotic drug exposure.
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In schizophrenia, APs add significantly to the risk of metabolic dysregulation, with clozapine and olanzapine carrying the greatest metabolic liability.
“In SCZ, APs add significantly to this risk of metabolic dysregulation, with clozapine and olanzapine carrying the greatest metabolic liability98,99.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [98]
The first-line treatment section (page not provided) reports significantly higher diabetes rates with antipsychotic treatment and a nearly fourfold increase after starting clozapine. It also reports increased diabetes risk with olanzapine, but does not establish that olanzapine and clozapine have the greatest metabolic liability. The study measures diabetes risk, not metabolic dysregulation broadly. (LLM, conf=0.88)
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- Authors
- Rajkumar, A. P., Horsdal, H. T., Wimberley, T., Cohen, D., Mors, O., Børglum, A. D., & Gasse, C.
- Affiliations
- King's College London (GB)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2017-07-01
- Volume
- 174
- Issue
- 7
- Pages
- 686-694
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2579288121
- Cited by
- 137
- References
- 53
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 13 · 2021: 15 · 2020: 12 · 2019: 23 · 2018: 12 · 2017: 10
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (acceptedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Aarhus Universitet
- Aarhus Universitetshospital
- National Institute for Health and Care Research (CL-2015-17-008)
- King's College London
- European Commission (279227)
- Lundbeckfonden (R155-2014-1724)
- Sundhedsstyrelsen
- H. Lundbeck A/S
- Menzies Centre for Australian Studies, King's College London, University of London
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- schizophrenia, diabetes mellitus, antipsychotic drugs, typical antipsychotics, atypical antipsychotics, type 2 diabetes, youth, cardiovascular risk
- MeSH terms
- Adult, Denmark, Diabetes Mellitus, Female, Humans, Male, Registries, Risk Factors, Schizophrenia, Antipsychotic Agents, Cohort Studies, Proportional Hazards Models, Early Diagnosis, Young Adult, Early Medical Intervention
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