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Article: Influence of antipsychotic medications on hyperlipidemia risk in patients with schizophrenia: evidence from a population-based cohort study and

Wu, Tien-Yuan / Tien, Ni / Lin, Cheng-Li / Cheah, Yu-Cun / Hsu, Chung Y / Tsai, Fuu-Jen / Fang, Yi-Jen / Lim, Yun-Ping

2023 Volume 10, Page(s) 1137977

Abstract: Introduction: Schizophrenia increases the risk of mortality and cardiovascular disease (CVD) risk. However, the correlation between antipsychotics (APs) and CVD remains controversial. Hyperlipidemia is a significant risk factor for CVD.: Methods: We ... ...

Abstract	Introduction: Schizophrenia increases the risk of mortality and cardiovascular disease (CVD) risk. However, the correlation between antipsychotics (APs) and CVD remains controversial. Hyperlipidemia is a significant risk factor for CVD. Methods: We conducted a nationwide population-based retrospective cohort study to investigate the effects of APs on the risk of hyperlipidemia and lipid homeostasis gene expression. We used data from the Longitudinal Health Insurance Database of Taiwan on new-onset schizophrenia patients and a comparison cohort without schizophrenia. We used a Cox proportional hazards regression model to analyze the differences in hyperlipidemia development between the two cohorts. Furthermore, we examined the effects of APs on the hepatic expression of lipid homeostasis-related genes. Results: After adjusting for potential interrelated confounding factors, the case group ( Discussion: Patients with schizophrenia had a higher risk of hyperlipidemia than controls; however, compared with non-treated patients, AP users had a lower risk of hyperlipidemia. Early diagnosis and management of hyperlipidemia may help prevent CVD.
Language	English
Publishing date	2023-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1137977
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Article ; Online: Association between Gout, Urate-Lowering Therapy, and Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study.

Fang, Yi-Jen / Chung, Yun-Lung / Lin, Cheng-Li / Lim, Yun-Ping

BioMed research international

2020 Volume 2020, Page(s) 6358954

Abstract: Gout is the most prevalent inflammatory arthritis in adults. Although the link between gout and type 2 diabetes mellitus (T2DM) has been documented, our understanding of the association between urate-lowering therapy (ULT) among gout patients and T2DM ... ...

Abstract	Gout is the most prevalent inflammatory arthritis in adults. Although the link between gout and type 2 diabetes mellitus (T2DM) has been documented, our understanding of the association between urate-lowering therapy (ULT) among gout patients and T2DM development remains poor. We included 69,326 patients with new-onset gout in 2000-2011. Each case was matched randomly with 1 patient without gout during the study period, and 69,326 patients were recognized as the comparison cohort. A Cox proportional hazard regression model was used to analyze differences in the risk of T2DM development between patients with and without gout after considering related comorbidities. After adjusting for potential confounders, the case group had a higher risk of T2DM than the control cohort (adjusted hazard ratio (aHR) = 1.30, 95%confidence interval (CI) = 1.24-1.38;
MeSH term(s)	Aged ; Comorbidity ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/metabolism ; Female ; Gout/complications ; Gout/drug therapy ; Gout/metabolism ; Gout Suppressants/therapeutic use ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Uric Acid/metabolism
Chemical Substances	Gout Suppressants ; Uric Acid (268B43MJ25)
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2020/6358954
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Article ; Online: Association between Gout, Urate-Lowering Therapy, and Risk of Developing Type 2 Diabetes Mellitus

Yi-Jen Fang / Yun-Lung Chung / Cheng-Li Lin / Yun-Ping Lim

BioMed Research International, Vol

A Nationwide Population-Based Retrospective Cohort Study

2020 Volume 2020

Abstract	Gout is the most prevalent inflammatory arthritis in adults. Although the link between gout and type 2 diabetes mellitus (T2DM) has been documented, our understanding of the association between urate-lowering therapy (ULT) among gout patients and T2DM development remains poor. We included 69,326 patients with new-onset gout in 2000-2011. Each case was matched randomly with 1 patient without gout during the study period, and 69,326 patients were recognized as the comparison cohort. A Cox proportional hazard regression model was used to analyze differences in the risk of T2DM development between patients with and without gout after considering related comorbidities. After adjusting for potential confounders, the case group had a higher risk of T2DM than the control cohort (adjusted hazard ratio aHR=1.30, 95%confidence interval CI=1.24-1.38; P<0.001). Gout patients without appropriate ULT had significantly higher risk of T2DM development than the control cohort (aHR=1.39; 95%CI=1.30-1.48; P<0.001). Among gout patients, those receiving ULT excluding probenecid (aHR=0.80; 95%CI=0.64-1.00), all had significantly lower risk of T2DM than gout patients without ULT (all aHR<0.90; all P<0.001). In this study, we found that gout increased the risk of T2DM; however, patients with any ULT exhibited a lower risk of T2DM than gout patients without any ULT (all aHR<0.90, P<0.001; excluding probenecid).
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Impact of Inflammatory Bowel Disease (IBD) and IBD Medications on Risk of Hyperlipidemia and in vitro Hepatic Lipogenic-Related Gene Expression

Ni Tien / Tien-Yuan Wu / Cheng-Li Lin / Chia-Jui Wu / Chung-Y Hsu / Yi-Jen Fang / Yun-Ping Lim

Frontiers in Medicine, Vol

A Population-Based Cohort Study

2022 Volume 9

Abstract: Patients with inflammatory bowel disease (IBD) present a higher risk of developing cardiovascular diseases (CVDs) due to chronic inflammation, which plays an essential role in atherogenesis. Hyperlipidemia is another risk factor for CVDs; however, the ... ...

Abstract	Patients with inflammatory bowel disease (IBD) present a higher risk of developing cardiovascular diseases (CVDs) due to chronic inflammation, which plays an essential role in atherogenesis. Hyperlipidemia is another risk factor for CVDs; however, the association between IBD, IBD medications, and hyperlipidemia remains controversial. We conducted a nationwide, population-based, retrospective, cohort study to examine the effect of IBD and IBD medications on the risk of developing hyperlipidemia. The effects of IBD medications on the expression of lipogenesis-related hepatic genes were also evaluated. We obtained data from the Longitudinal Health Insurance Database of Taiwan from patients with new-onset IBD and a comparison cohort of patients without IBD. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing hyperlipidemia between the two cohorts. We also examined the influence of IBD medications on the expression of lipogenesis-related hepatic genes. After adjusting for comorbidities and confounding factors, the case group (N = 14,524) had a higher risk for hyperlipidemia than the control group (N = 14,524) [adjusted hazards ratio (aHR), 2.18]. Patients with IBD that did not receive IBD medications exhibited a significantly higher risk of hyperlipidemia (aHR, 2.20). In those treated with IBD medications, the risk of developing hyperlipidemia was significantly lowered than those without such medications (all aHR ≤ 0.45). Gene expression analysis indicated that IBD medications downregulated the expression of lipogenesis-related genes. Screening blood lipids in IBD patients is needed to explore the specific role and impact of IBD medications in the development of CVD.
Keywords	inflammatory bowel disease (IBD) ; IBD medications ; hyperlipidemia ; Longitudinal Health Insurance Database (LHID) ; lipogenesis ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Impact of Inflammatory Bowel Disease (IBD) and IBD Medications on Risk of Hyperlipidemia and

Tien, Ni / Wu, Tien-Yuan / Lin, Cheng-Li / Wu, Chia-Jui / Hsu, Chung-Y / Fang, Yi-Jen / Lim, Yun-Ping

Frontiers in medicine

2022 Volume 9, Page(s) 910623

Abstract	Patients with inflammatory bowel disease (IBD) present a higher risk of developing cardiovascular diseases (CVDs) due to chronic inflammation, which plays an essential role in atherogenesis. Hyperlipidemia is another risk factor for CVDs; however, the association between IBD, IBD medications, and hyperlipidemia remains controversial. We conducted a nationwide, population-based, retrospective, cohort study to examine the effect of IBD and IBD medications on the risk of developing hyperlipidemia. The effects of IBD medications on the expression of lipogenesis-related hepatic genes were also evaluated. We obtained data from the Longitudinal Health Insurance Database of Taiwan from patients with new-onset IBD and a comparison cohort of patients without IBD. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing hyperlipidemia between the two cohorts. We also examined the influence of IBD medications on the expression of lipogenesis-related hepatic genes. After adjusting for comorbidities and confounding factors, the case group (
Language	English
Publishing date	2022-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.910623
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Article: Association of epilepsy, anti-epileptic drugs (AEDs), and type 2 diabetes mellitus (T2DM): a population-based cohort retrospective study, impact of AEDs on T2DM-related molecular pathway, and via peroxisome proliferator-activated receptor γ transactivation.

Tien, Ni / Wu, Tien-Yuan / Lin, Cheng-Li / Chu, Fang-Yi / Wang, Charles C N / Hsu, Chung Y / Tsai, Fuu-Jen / Fang, Yi-Jen / Lim, Yun-Ping

Frontiers in endocrinology

2023 Volume 14, Page(s) 1156952

Abstract: Introduction: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains ... ...

Abstract	Introduction: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains controversial. We aimed to conduct a nationwide, population-based, retrospective, cohort study to evaluate this relationship. Methods: We extracted data from the Taiwan Longitudinal Generation Tracking Database of patients with new-onset epilepsy and compared it with that of a comparison cohort of patients without epilepsy. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing T2DM between the two cohorts. Next-generation RNA sequencing was used to characterize T2DM-related molecularchanges induced by AEDs and the T2DM-associated pathways they alter. The potential of AEDs to induce peroxisome proliferator-activated receptor γ (PPARγ) transactivation was also evaluated. Results: After adjusting for comorbidities and confounding factors, the case group (N = 14,089) had a higher risk for T2DM than the control group (N = 14,089) [adjusted hazards ratio (aHR), 1.27]. Patients with epilepsy not treated with AEDs exhibited a significantly higher risk of T2DM (aHR, 1.70) than non-epileptic controls. In those treated with AEDs, the risk of developing T2DM was significantly lower than in those not treated (all aHR ≤ 0.60). However, an increase in the defined daily dose of phenytoin (PHE), but not of valproate (VPA), increased the risk of T2DM development (aHR, 2.28). Functional enrichment analysis of differentially expressed genes showed that compared to PHE, VPA induced multiple beneficial genes associated with glucose homeostasis. Among AEDs, VPA induced the specific transactivation of PPARγ. Discussion: Our study shows epilepsy increases the risk of T2DM development, however, some AEDs such as VPA might yield a protective effect against it. Thus, screening blood glucose levels in patients with epilepsy is required to explore the specific role and impact of AEDs in the development of T2DM. Future in depth research on the possibility to repurpose VPA for the treatment of T2DM, will offer valuable insight regarding the relationship between epilepsy and T2DM.
MeSH term(s)	Humans ; Anticonvulsants/adverse effects ; Retrospective Studies ; PPAR gamma/genetics ; Cohort Studies ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Transcriptional Activation ; Epilepsy/complications ; Epilepsy/drug therapy ; Epilepsy/epidemiology
Chemical Substances	Anticonvulsants ; PPAR gamma
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1156952
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Population-Based Cohort Study on the Association of Hyperthyroidism With the Risk of Hyperlipidemia and the Effects of Anti-thyroid Drugs on Hepatic Gene Expression.

Wu, Tien-Yuan / Wang, Chung-Hsing / Tien, Ni / Lin, Cheng-Li / Chu, Fang-Yi / Chang, Hsiao-Yun / Lim, Yun-Ping

Frontiers in medicine

2020 Volume 7, Page(s) 228

Abstract: There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a ... ...

Abstract	There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a retrospective cohort study using Longitudinal Health Insurance Database (LHID) from Taiwan, R.O.C. We also evaluate the influence of 6-
Language	English
Publishing date	2020-05-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2020.00228
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Article ; Online: Association between Depression, Antidepression Medications, and the Risk of Developing Type 2 Diabetes Mellitus

Yi-Jen Fang / Tien-Yuan Wu / Jung-Nien Lai / Cheng-Li Lin / Ni Tien / Yun-Ping Lim

BioMed Research International, Vol

A Nationwide Population-Based Retrospective Cohort Study in Taiwan

2021 Volume 2021

Abstract: The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population-based retrospective cohort study using ...

Abstract	The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population-based retrospective cohort study using the Longitudinal Health Insurance Database 2000 available in Taiwan. This large, observational study included 46,201 patients with depression and a 1 : 1 age- and sex-matched nondepression cohort enrolled between January 1, 2000, and December 31, 2013, and the newly diagnosed T2DM incidence rates were determined. We estimated the effects of depression on T2DM and the cumulative incidence curves by Cox proportional regression hazard models and Kaplan-Meier methods, respectively. We found that 47.97% of the patients with depression did not receive ADM. Among patients with depression who received ADM, 29.71%, 6.29%, 0.05%, 9.65%, and 6.32% received selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), heterocyclic antidepressants, and other medications, respectively. Patients without ADM treatment had a 39% higher risk of developing T2DM. However, those who received ADM treatment had a significantly lower risk of T2DM development in every treatment category. Depressive disorder treated with ADMs, especially with long-term use, was associated with an 11–48% decrease in the risk of T2DM in all ADM groups; however, heterocyclic antidepressant treatment for shorter periods (<80 days) was not significantly associated with a decreased risk of T2DM. The incidence of T2DM in Taiwan was found to be associated with an a priori history of depression and was inversely correlated with ADM treatment.
Keywords	Medicine ; R
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Population-Based Cohort Study on the Association of Hyperthyroidism With the Risk of Hyperlipidemia and the Effects of Anti-thyroid Drugs on Hepatic Gene Expression

Tien-Yuan Wu / Chung-Hsing Wang / Ni Tien / Cheng-Li Lin / Fang-Yi Chu / Hsiao-Yun Chang / Yun-Ping Lim

Frontiers in Medicine, Vol

2020 Volume 7

Abstract	There have been no reports on the association of hyperthyroidism with hyperlipidemia in patients undergoing treatment especially in Asia. To determine the association between hyperthyroidism and the risk of hyperlipidemia in patients, we conducted a retrospective cohort study using Longitudinal Health Insurance Database (LHID) from Taiwan, R.O.C. We also evaluate the influence of 6-n-propyl-2-thiouracil (PTU) and methimazole (MMI) on hepatic genes to explain changes in blood lipid levels in a hepatic cell line model. The cohort study involved 13,667 patients with hyperthyroidism, and the corresponding comparison cohort had four times as many patients. Using Kaplan-Meier analysis method, the results showed that, compared to patients without hyperthyroidism, the overall incidence of hyperlipidemia was significantly higher in the hyperthyroidism patients (18.7 vs. 11.8 cases/1,000 persons-years; adjusted HR 1.5; 95% CI, 1.41–1.59). With only PTU or MMI/carbimazole (CBM) treatment, patients with hyperthyroidism showed a 1.78-fold (95% CI, 1.50–2.11) and 1.43-fold (95% CI, 1.27–1.60) higher risk of hyperlipidemia than those without hyperthyroidism, respectively. Additionally, hyperthyroidism patients that received surgery only or surgery with I131 therapy tended to have a higher risk of hyperlipidemia. Although PTU and MMI treatment decreased the expression levels of genes responsible for circulating remnant lipoproteins, they increased the levels of lipogenic gene expression in hepatic cells. Thus, treatment of hyperthyroid patients with anti-thyroid drugs (ATDs), I131, or surgery is likely to induce hyperlipidemia. ATDs downregulate the expression of genes involved in lipoproteins clearance; increases lipogenic genes expression, which may partly contribute to abnormal blood lipid profiles.
Keywords	hyperthyroidism ; anti-thyroid drugs (ATDs) ; hyperlipidemia ; Longitudinal Health Insurance Database (LHID) ; retrospective cohort study ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Influences of antidepressant medications on the risk of developing hyperlipidemia in patients with depression by a population-based cohort study and on in vitro hepatic lipogenic-related gene expression.

Tien, Ni / Wu, Tien-Yuan / Lai, Jung-Nien / Lin, Cheng-Li / Hsiao, Yu-Chi / Khaw, Jie-Yee / Lim, Yun-Ping

Journal of affective disorders

2021 Volume 295, Page(s) 271–283

Abstract: Background: Depression increases the risk of cardiovascular disease (CVD). The association between antidepressant medications (ADMs) and CVD remains controversial. Hyperlipidemia is a risk factor for CVD. We conducted a nationwide population-based ... ...

Abstract	Background: Depression increases the risk of cardiovascular disease (CVD). The association between antidepressant medications (ADMs) and CVD remains controversial. Hyperlipidemia is a risk factor for CVD. We conducted a nationwide population-based retrospective cohort study to examine depression and ADM use on the risk of developing hyperlipidemia. The effects of ADMs on the expression of lipogenesis-related hepatic genes were also evaluated. Methods: We obtained data from the Longitudinal Health Insurance Database of Taiwan on patients with new-onset depression and a comparison cohort without depression. A Cox proportional hazards regression model was used to analyze the differences in the risk of developing hyperlipidemia between these two cohorts. We also examined the influence of ADMs on the expression of lipogenesis-related hepatic genes. Results: After adjustment for comorbidities and confounding factors, the case group (N = 38,322) had a higher risk for hyperlipidemia than that of the control cohort (N = 38,322) [adjusted hazards ratio (aHR) =1.16]. Patients with depression who did not receive ADM therapy exhibited a significantly higher risk of hyperlipidemia (aHR = 1.61). However, in patients with depression treated with ADMs, the risk of developing hyperlipidemia was significantly lowered compared to the patients without ADMs (all aHR < 0.81). Gene expression analysis indicated that ADMs downregulated the expression of lipogenesis-related hepatic genes. Limitations: Unmeasured confounding risk factors for hyperlipidemia might not have been included in the study. Conclusions: ADMs reduced hyperlipidemia risk in patients with depression, partly by downregulating the expression of lipogenesis-related genes and improving the patients' lipid profiles. Early diagnosis and management of hyperlipidemia would further facilitate the prevention of CVD.
MeSH term(s)	Antidepressive Agents ; Cohort Studies ; Comorbidity ; Depression/epidemiology ; Depression/genetics ; Gene Expression ; Humans ; Hyperlipidemias/epidemiology ; Hyperlipidemias/genetics ; Incidence ; Lipogenesis/genetics ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Taiwan/epidemiology
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2021-08-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2021.08.041
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