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Association Between Antipsychotic Treatment and Advanced Diabetes Complications Among Schizophrenia Patients With Type 2 Diabetes Mellitus.

ABSTRACT: Antipsychotic drug use is an established risk factor for the development of type 2 diabetes mellitus. However, the effect of antipsychotic drug on the progression of diabetes complications remains unclear. This study aimed to explore the association between antipsychotic treatment and advanced diabetes outcome among schizophrenia patients with type 2 diabetes.The authors conducted a retrospective cohort study using Taiwan's universal health insurance database. A total of 17 629 schizophrenia patients with newly-diagnosed diabetes were enrolled. The mean duration of follow-up, after excluding the first 6-month observation period, was 4.8 years, ranged from 1 month to 11.5 years. Antipsychotic treatment patterns within a 6-month time window were classified into none, irregular use, and regular use. Antipsychotics were further categorized into the high, intermediate, and low metabolic risks. The status of exposure was treated as time-dependent variables. The outcomes measures included any advanced diabetes complications, macrovascular and microvascular complications, and all-cause mortality.Compared to no antipsychotic treatment in the past 6 months, regular antipsychotic use was associated with a lower risk of any advanced diabetes complications (adjusted hazard ratio, aHR = 0.81, 95% CI = 0.69-0.95), macrovascular complications (aHR = 0.80, 95% CI = 0.66-0.97), and all-cause mortality (aHR = 0.73, 95% CI = 0.62-0.85). The hazard ratios for advanced diabetes complications with regular use of antipsychotics with a high, intermediate, and low metabolic risk were 0.69 (95% CI = 0.53-0.91), 0.82 (95% CI = 0.68-0.99), and 0.85 (95% CI = 0.70-1.02), respectively.Regular antipsychotic treatment in the past 6 months was associated with reduced risks of any diabetes complications, compared to no antipsychotic treatment.

SUBMITTER: Wu CS

PROVIDER: S-EPMC4838103 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Association Between Antipsychotic Treatment and Advanced Diabetes Complications Among Schizophrenia Patients With Type 2 Diabetes Mellitus.

Wu Chi-Shin CS Gau Susan Shur-Fen SS

Schizophrenia bulletin 20151231 3

<h4>Objective</h4>Antipsychotic drug use is an established risk factor for the development of type 2 diabetes mellitus. However, the effect of antipsychotic drug on the progression of diabetes complications remains unclear. This study aimed to explore the association between antipsychotic treatment and advanced diabetes outcome among schizophrenia patients with type 2 diabetes.<h4>Methods</h4>The authors conducted a retrospective cohort study using Taiwan's universal health insurance database. A ...[more]

PMID: 26721264

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Project description:BackgroundSchizophrenia (SCZ) and type 2 diabetes mellitus (T2D) are both complex diseases. Accumulated studies indicate that schizophrenia patients are prone to present the type 2 diabetes symptoms, but the potential mechanisms behind their association remain unknown. Here we explored the pathogenetic association between SCZ and T2D based on pathway analysis and protein-protein interaction.ResultsWith sets of prioritized susceptibility genes for SCZ and T2D, we identified significant pathways (with adjusted p-value < 0.05) specific for SCZ or T2D and for both diseases based on pathway enrichment analysis. We also constructed a network to explore the crosstalk among those significant pathways. Our results revealed that some pathways are shared by both SCZ and T2D diseases through a number of susceptibility genes. With 382 unique susceptibility proteins for SCZ and T2D, we further built a protein-protein interaction network by extracting their nearest interacting neighbours. Among 2,104 retrieved proteins, 364 of them were found simultaneously interacted with susceptibility proteins of both SCZ and T2D, and proposed as new candidate risk factors for both diseases. Literature mining supported the potential association of partial new candidate proteins with both SCZ and T2D. Moreover, some proteins were hub proteins with high connectivity and interacted with multiple proteins involved in both diseases, implying their pleiotropic effects for the pathogenic association. Some of these hub proteins are the components of our identified enriched pathways, including calcium signaling, g-secretase mediated ErbB4 signaling, adipocytokine signaling, insulin signaling, AKT signaling and type II diabetes mellitus pathways. Through the integration of multiple lines of information, we proposed that those signaling pathways, which contain susceptibility genes for both diseases, could be the key pathways to bridge SCZ and T2D. AKT could be one of the important shared components and may play a pivotal role to link both of the pathogenetic processes.ConclusionsOur study is the first network and pathway-based systematic analysis for SCZ and T2D, and provides the general pathway-based view of pathogenetic association between two diseases. Moreover, we identified a set of candidate genes potentially contributing to the linkage between these two diseases. This research offers new insights into the potential mechanisms underlying the co-occurrence of SCZ and T2D, and thus, could facilitate the inference of novel hypotheses for the co-morbidity of the two diseases. Some etiological factors that exert pleiotropic effects shared by the significant pathways of two diseases may have important implications for the diseases and could be therapeutic intervention targets.

Project description:BackgroundThe relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association between SUA levels and the prevalence of non-alcoholic fatty liver disease (NAFLD), diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 2,809 participants (1,784 males and 1,025 females) were included in this cross-sectional study. Clinical characteristics and the prevalence of each of the four diseases were analyzed based on gender-specific quartiles of SUA levels. The Pearson correlation analysis and linear-regression analysis were used to access the correlation between SUA levels and clinical characteristics. Furthermore, a binary logistic regression analysis was carried out to determine whether SUA was an independent risk factor for each of the four complications.ResultsSUA levels were positively correlated to BMI, BUN, Scr and TG, but negatively associated with eGFR, HDL, FBG, 2h-PG and HbA1c% for the patients with T2DM. The prevalence of NAFLD and DN, but not DR or DPN, were increased with SUA levels from the first to the fourth quartile. Binary logistic regression further disclosed that SUA was an independent risk factor for NAFLD (ORs Male = 1.002, ∗ P = 0.0013; ORs Female = 1.002, ∗ P = 0.015) and DN (ORs Male = 1.006, ∗ P < 0.001; ORs Female = 1.005, ∗ P < 0.001), but not for DR and DPN. After adjustment for the confounders, SUA levels were significantly associated with NAFLD within the 3rd (ORs = 1.829, P = 0.004) and 4th quartile (ORs = 2.064, P = 0.001) for women, but not independently associated with SUA for man. On the other hand, our results revealed increased prevalence of DN for SUA quartile 2 (ORs = 3.643, P = 0.039), quartile 3 (ORs = 3.967, P = 0.024) and quartile 4 (ORs = 9.133, P < 0.001) in men; however, SUA quartiles were significantly associated with DN only for quartile 4 (ORs = 4.083, P = 0.042) in women.ConclusionFor patients with T2DM, elevated SUA concentration is an independent risk factor for the prevalence of NAFLD and DN after adjustment for other indicators, but not DR or DPN.

Dataset Information

Association Between Antipsychotic Treatment and Advanced Diabetes Complications Among Schizophrenia Patients With Type 2 Diabetes Mellitus.

Publications

Association Between Antipsychotic Treatment and Advanced Diabetes Complications Among Schizophrenia Patients With Type 2 Diabetes Mellitus.

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