Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia

Zhuo, Chuanjun; Xu, Yong; Wang, Haibo; Zhou, Chuanhua; Liu, Jian; Yu, Xiaocui; Shao, Hailin; Tian, Hongjun; Fang, Tao; Li, Qianchen; Chen, Jiayue; Xu, Shaoyuan; Ma, Xiaoyan; Yang, Wenjun; Yao, Cong; Li, Bo; Yang, Anqu; Chen, Yuhui; Huang, Gongyong; Lin, Chongguang

doi:10.1016/j.jad.2021.08.023

Cited by 11 publications

(8 citation statements)

References 87 publications

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“…To date, no drugs have been approved specifically for prediabetes, meaning that doctors are limited to prescribing diabetes drugs or other medications "off label" to treat the condition. Metformin is the most commonly used drug (44). However, metformin is not always prescribed for prediabetes, even if a patient meets the prediabetes criteria.…”

Section: Discussionmentioning

confidence: 99%

Worldwide trends in prediabetes from 1985 to 2022: A bibliometric analysis using bibliometrix R-tool

Zhao

Li²

2023

Front. Public Health

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BackgroundPrediabetes is a widespread condition that represents the state between normal serum glucose and diabetes. Older individuals and individuals with obesity experience a higher rate of prediabetes. Prediabetes is not only a risk factor for type 2 diabetes mellitus (t2dm) but is also closely related to microvascular and macrovascular complications. Despite its importance, a bibliometric analysis of prediabetes is missing. The purpose of this study is to provide a comprehensive and visually appealing overview of prediabetes research.MethodsFirst, the Web of Science (WOS) database was searched to collect all articles related to prediabetes that were published from 1985 to 2022. Second, R language was used to analyze the year of publication, author, country/region, institution, keywords, and citations. Finally, network analysis was conducted using the R package bibliometrix to evaluate the hotspots and development trends of prediabetes.ResultsA total of 9,714 research articles published from 1985 to 2022 were retrieved from WOS. The number of articles showed sustained growth. Rathmann W was the most prolific author with 71 articles. Diabetes Care was the journal that published the highest number of articles on prediabetes (234 articles), and Harvard University (290 articles) was the most active institution in this field. The United States contributed the most articles (2,962 articles), followed by China (893 articles). The top five clusters of the keyword co-appearance network were “prediabetes”, “diabetes mellitus”, “glucose”, “insulin exercise”, and “oxidative stress”. The top three clusters of the reference co-citation network were “Knowler. WC 2002”, “Tabak AG 2012”, and “Matthews DR1985”.ConclusionsThe combined use of WOS and the R package bibliometrix enabled a robust bibliometric analysis of prediabetes papers, including evaluation of emerging trends, hotspots, and collaboration. This study also allowed us to validate our methodology, which can be used to better understand the field of prediabetes and promote international collaboration.

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Section: Discussionmentioning

confidence: 99%

Worldwide trends in prediabetes from 1985 to 2022: A bibliometric analysis using bibliometrix R-tool

Zhao

Li²

2023

Front. Public Health

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“…Previous studies reported that the prevalence of prediabetes in patients with schizophrenia ranged from 4.0% to 67% in other countries [16][17][18][19][20]. No large study has been conducted to investigate the prevalence of prediabetes in patients with schizophrenia in China.…”

Section: Discussionmentioning

confidence: 99%

“…A study of 145 schizophrenia patients receiving clozapine or olanzapine with a body mass index (BMI) ≥ 27 kg/m 2 showed that the prevalence of prediabetes was 69.7% [19]. Another study of 230 schizophrenia patients receiving clozapine revealed that the prevalence of prediabetes was up to 73.91%, and prediabetes was signi cantly associated with a poor response to clozapine [20].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and associated factors of prediabetes in Chinese inpatients with schizophrenia

et al. 2023

Preprint

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Background: Numerous studies have demonstrated a high prevalence of type 2 diabetes (T2DM) in patients with schizophrenia. Prediabetes is associated with an increased risk of developing T2DM. However, little is known about prediabetes in patients with schizophrenia. This study was conducted to investigate the prevalence and associated factors of prediabetes among adult inpatients with schizophrenia in a large psychiatric hospital in China. Methods: This retrospective observational study included adult inpatients with schizophrenia who were discharged from the Affiliated Brain Hospital of Guangzhou Medical University in 2019. Data were obtained from electronic records of this hospital. Prediabetes was defined as fasting blood glucose (FBG) 5.6–6.9 mmol/L or glycosylated hemoglobin (HbA1c) of 5.7%–6.4%. Binary logistic regression analysis was used to estimate the factors associated with prediabetes. Results: A total of 1,725 inpatients with schizophrenia were included. The prevalence of prediabetes was 21.5%. The patients with prediabetes were older and had a longer duration of schizophrenia, fewer years of education, a higher prevalence of hypertension, a higher BMI, and higher levels of TG, TC and LDL-C than patients with normal glucose regulation. Binary logistic regression analysis revealed that hypertension, age, BMI, and TG were significantly associated with prediabetes. Conclusion: The prevalence of prediabetes was 21.5% in our study, which suggests that prediabetes is prevalent among schizophrenia inpatients in China. In addition, hypertension, age, BMI, and TG may be potential risk factors for prediabetes in patients with schizophrenia.

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“…Most recently, we performed a clinical study to evaluate clozapine-induced prediabetes/diabetes in the treatment of schizophrenia patients with the early-treatment resistance (E-TR) subtype. Notably, of 230 schizophrenia patients with the E-TR subtype, 170 and 6 patients developed clozapine-induced prediabetes and diabetes, respectively, accounting for 76.52% of the studied subjects [ 23 ]. Collectively, these previous studies, including ours, have demonstrated that the incidence of clozapine-induced prediabetes/diabetes and other metabolic side effects is considerably high.…”

Section: Side Effects Of Antipsychotic Drugsmentioning

confidence: 99%

Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy

Zhuo

Hou

et al. 2022

Transl Psychiatry

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Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

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Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia

Cited by 11 publications

References 87 publications

Worldwide trends in prediabetes from 1985 to 2022: A bibliometric analysis using bibliometrix R-tool

Worldwide trends in prediabetes from 1985 to 2022: A bibliometric analysis using bibliometrix R-tool

Prevalence and associated factors of prediabetes in Chinese inpatients with schizophrenia

Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy

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