Sibylle de Germay1,2, Cécile Conte3,4,5, Olivier Rascol3,5,6, Jean-Louis Montastruc3,4,7,5,6, Maryse Lapeyre-Mestre3,4,5. 1. Service de Pharmacologie Médicale Et Clinique, Faculté de Médecine, Centre Hospitalier Universitaire, 37 allées Jules-Guesde, Toulouse, France. Sibylle.de-germay@univ-tlse3.fr. 2. UMR 1027 INSERM Pharmacoépidémiologie, Université Paul Sabatier Toulouse III, Toulouse, France. Sibylle.de-germay@univ-tlse3.fr. 3. Service de Pharmacologie Médicale Et Clinique, Faculté de Médecine, Centre Hospitalier Universitaire, 37 allées Jules-Guesde, Toulouse, France. 4. UMR 1027 INSERM Pharmacoépidémiologie, Université Paul Sabatier Toulouse III, Toulouse, France. 5. CIC INSERM 1436, Paris, France. 6. Réseau NS-PARK/FCRIN Et Centre COEN NeuroToul, Toulouse, France. 7. Faculté de Médecine, Centre de PharmacoVigilance, Pharmacoépidémiologie Et D'Informations Sur Le Médicament, Centre Hospitalier Universitaire, Toulouse, France.
Abstract
BACKGROUND: Potential relationships between β-adrenergic drugs and α-synuclein synthesis in Parkinson's disease (PD) have been recently suggested. OBJECTIVE: This study investigated the putative association between β-adrenoceptor drug exposure and PD occurrence. METHODS: A nested case-control study was performed in the Echantillon Généraliste des Bénéficiaires (EGB) (a 1/97th random sample of affiliates to the French Insurance System). Incident PD patients diagnosed between 01/01/2008 and 31/12/2017 (index date) were matched 1:1 to controls by gender, birth year, and insurance scheme. Exposure to any β-agonist and to any β-antagonist was compared between cases and controls within 1-2 years before the index date, and exposure to salbutamol and to propranolol was individualized. The association between PD and β-adrenoceptor drugs was investigated through conditional logistic regression models adjusted for potential confounding factors. Because of a statistical interaction between β-agonists and diabetes, results were stratified according to the presence of diabetes. RESULTS: Among the 2225 incident PD patients identified in the EGB (mean age 75.6 ± 10.2 years, sex ratio 1.04), no significant association was found between PD and β-antagonists (adjusted odds ratio [aOR] 1.05 [95% confidence interval 0.91-1.20]), except for propranolol (aOR 2.11 [1.38-3.23]). For β-agonists, a protective association in non-diabetic patients (aOR 0.75 [0.60-0.93]) and an opposite and significant association in diabetic patients (aOR 1.61 [1.02-2.55]) were observed. Similar results were found with salbutamol. CONCLUSION: This study did not identify an increased risk of PD occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The discordant results observed with β-agonists in patients with or without diabetes deserve further exploration of the influence of diabetic comorbidity on PD occurrence and evolution.
BACKGROUND: Potential relationships between β-adrenergic drugs and α-synuclein synthesis in Parkinson's disease (PD) have been recently suggested. OBJECTIVE: This study investigated the putative association between β-adrenoceptor drug exposure and PD occurrence. METHODS: A nested case-control study was performed in the Echantillon Généraliste des Bénéficiaires (EGB) (a 1/97th random sample of affiliates to the French Insurance System). Incident PDpatients diagnosed between 01/01/2008 and 31/12/2017 (index date) were matched 1:1 to controls by gender, birth year, and insurance scheme. Exposure to any β-agonist and to any β-antagonist was compared between cases and controls within 1-2 years before the index date, and exposure to salbutamol and to propranolol was individualized. The association between PD and β-adrenoceptor drugs was investigated through conditional logistic regression models adjusted for potential confounding factors. Because of a statistical interaction between β-agonists and diabetes, results were stratified according to the presence of diabetes. RESULTS: Among the 2225 incident PDpatients identified in the EGB (mean age 75.6 ± 10.2 years, sex ratio 1.04), no significant association was found between PD and β-antagonists (adjusted odds ratio [aOR] 1.05 [95% confidence interval 0.91-1.20]), except for propranolol (aOR 2.11 [1.38-3.23]). For β-agonists, a protective association in non-diabeticpatients (aOR 0.75 [0.60-0.93]) and an opposite and significant association in diabeticpatients (aOR 1.61 [1.02-2.55]) were observed. Similar results were found with salbutamol. CONCLUSION: This study did not identify an increased risk of PD occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The discordant results observed with β-agonists in patients with or without diabetes deserve further exploration of the influence of diabetic comorbidity on PD occurrence and evolution.
Authors: Joseph R Patterson; Warren D Hirst; Jacob W Howe; Christopher P Russell; Allyson Cole-Strauss; Christopher J Kemp; Megan F Duffy; Jared Lamp; Andrew Umstead; Michael Kubik; Anna C Stoll; Irving E Vega; Kathy Steece-Collier; Yi Chen; Anne C Campbell; Catherine L Nezich; Kelly E Glajch; Caryl E Sortwell Journal: NPJ Parkinsons Dis Date: 2022-05-24