| アブストラクト | BACKGROUND: Second-generation antipsychotics contribute to excess cardiometabolic morbidity in people with severe mental illness, but the timing of early glycaemic change and whether it parallels weight gain remain unclear. We aimed to evaluate glycated haemoglobin A(1c) (HbA(1c)) and weight trajectories before and after initiation of antipsychotic treatment. METHODS: We conducted an individual-level interrupted time-series analysis in England using electronic health records (EHR) from the Clinical Practice Research Datalink Aurum database between Jan 1, 2000, and June 7, 2023. Included participants were aged 18-59 years with severe mental illness (SMI) who had at least a second oral second-generation antipsychotic prescription issued within 90 days from their first antipsychotic prescription. Individuals were excluded if they had dementia, type 2 diabetes, or antipsychotic prescriptions before age 18 years. The exposure was the first recorded oral initiation of antipsychotic treatment. We used individual-level, interrupted time-series mixed models with linear splines to estimate rates of change in HbA(1c) and weight in people with SMI before treatment initiation, 0-90 days after initiation, and from 91 days to 2 years after initiation. An additional outcome was time to type 2 diabetes diagnosis or antidiabetic medication prescription. Analyses were stratified by sex, antipsychotic drug, and baseline glycaemic status. People with lived experience contributed to the research question, study approach, interpretation, and dissemination. FINDINGS: Of the 96 849 eligible individuals, 53 558 (55.3%) were male and 43 291 (44.7%) were female. The mean age of participants was 37.2 years (SD 11.1; range 18-59); 62 683 (64.7%) reported their ethnicity as White, 5952 (6.1%) as south Asian, 6736 (7.0%) as Black, 3793 (3.9%) as other or mixed ethnicity, and 17 693 (18.3%) had missing ethnicity. 74 233 (76.6%) individuals had at least one recorded weight measurement and 24 084 (24.9%) had at least one HbA(1c) measurement. In the pre-treatment period, HbA(1c) increased at a rate of 0.01 mmol/mol per week (95% CI 0.00-0.01) and weight at a rate of 0.02 kg (0.02-0.02) per week. In the 0-90 days following antipsychotic treatment initiation, HbA(1c) increased at a rate of 0.12 mmol/mol per week (0.09-0.15) and weight at 0.21 kg (0.20-0.22) per week. From day 91 to 2 years, the rate of increase of HbA(1c) returned to pre-treatment levels (0.01 mmol/mol per week [0.00-0.01]) and weight increased at 0.03 kg (0.02-0.03) per week. Increases were largest for olanzapine (HbA(1c) 0.18 mmol/mol per week [95% CI 0.12-0.25]; weight 0.28 kg [0.27-0.30]) and generally higher among women (HbA(1c) 0.14 mmol/mol [0.09-0.18]; weight 0.22 kg [0.21-0.23]). Quetiapine was associated with weight gain (0.19 kg per week [95% CI 0.18 to 0.21]), but minimal HbA(1c) change (0.02 mmol/mol [-0.03 to 0.08]). Among 918 individuals with baseline prediabetes, 126 (13.7%)developed type 2 diabetes, corresponding to an estimated 2-year cumulative incidence of 19.0%, compared with 152 (1.7%) of 9171 individuals with normal baseline HbA(1c), corresponding to an estimated 2-year cumulative incidence of 3.0%. INTERPRETATION: Antipsychotic treatment initiation was followed by rapid HbA(1c) and weight increases in the first 90 days followed by slower increases up to 2 years. Imperfect concordance between HbA(1c) and weight supports baseline and 12-week monitoring of both outcomes, followed by risk-stratified monitoring and intervention. FUNDING: National Institute for Health and Care Research (NIHR) Three Research Schools Mental Health Programme, NIHR School for Primary Care Research, NIHR Applied Research Collaboration West Midlands, NIHR Dementia and Neurodegeneration Policy Research Unit, UK Research and Innovation, University College London Hospitals NIHR Biomedical Research Centre, and NIHR North Thames Applied Research Collaboration. |
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| ジャーナル名 | The lancet. Psychiatry |
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| Pubmed追加日 | 2026/10/14 |
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| 投稿者 | Bazo-Alvarez, Juan Carlos; Stone, Philip W; Avgerinou, Christina; Quartagno, Matteo; Boman, Magnus; Jordan, Kelvin P; Cooper, Claudia; Hayes, Joseph F; Walters, Kate; Petersen, Irene |
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| 組織名 | Research Department of Primary Care and Population Health, Institute of;Epidemiology and Health Care, University College London, London, UK; Escuela de;Psicologia, Universidad Cesar Vallejo, Trujillo, Peru. Electronic address:;juan.alvarez.16@ucl.ac.uk.;Epidemiology and Health Care, University College London, London, UK.;UCL Innovative Clinical Trials Unit, University College London, London, UK.;Division of Psychiatry, University College London, London, UK; Department of;Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet,;Stockholm, Sweden.;School of Medicine, Keele University, Keele, UK.;Centre for Psychiatry and Mental Health, Wolfson Institute of Population Health,;Queen Mary University of London, London, UK.;Division of Psychiatry, University College London, London, UK.;Epidemiology and Health Care, University College London, London, UK; Department;of Clinical Epidemiology, Aarhus University, Aarhus, Denmark. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42874604/ |
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