ABSTRACT
BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.
Subject(s)
3-Hydroxybutyric Acid , Aortic Aneurysm , Aortic Dissection , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Aortic Dissection/genetics , Aortic Dissection/epidemiology , Aortic Dissection/etiology , 3-Hydroxybutyric Acid/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Risk Factors , Aortic Aneurysm/genetics , Aortic Aneurysm/epidemiology , Aortic Aneurysm/etiology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Risk Assessment , Protective Factors , Phenotype , Biomarkers/blood , Mediation AnalysisABSTRACT
INTRODUCTION: There is still insufficient appreciation whether neuropsychological rehabilitation and psychotherapy are effective in attenuating depression following traumatic brain injury (TBI). This knowledge gap was addressed in the present systematic review and meta-analysis of the literature. EVIDENCE ACQUISITION: We conducted electronic database (Medline, PsychINFO, Scopus) searches (time frame: January 1st, 2005 to December 31st, 2015) for clinical studies that had tested neuropsychological rehabilitation and psychotherapy in adult TBI survivors with depression. The studies were to have experimental or quasi-experimental study design, and to include survivors from non-military TBI. Quantitative assessment of qualifying studies was done using the random effects model. We calculated the pooled size effect using standardized mean difference (SMD) as the main effect measure. EVIDENCE SYNTHESIS: We identified three studies, totaling 231 participants, which tested cognitive behavioral therapy or mindfulness-based cognitive therapy as interventions to attenuate post-TBI depression. The analysis revealed a small and non-significant decrease in depression symptoms due to intervention (SMD=-0.23 [95% CI: -050, 0.03; z=1.73, P=0.08]). Testing for publication bias was not feasible due to low number of identified studies. CONCLUSIONS: Current evidence indicates only a small therapeutic effect of psychotherapy in attenuating post-TBI depression.
