Plasma Metabolomic Markers of Insulin Resistance and Diabetes and Rate of Incident Parkinson’s Disease

Article type: Research Article

Authors: Molsberry, Samantha^{a; *} | Bjornevik, Kjetil^b | Hughes, Katherine C.^b | Zhang, Zhongli Joel^b | Jeanfavre, Sarah^c | Clish, Clary^c | Healy, Brian^d | Schwarzschild, Michael^e | Ascherio, Alberto^{e; f; g}

Affiliations: [a] Population Health Sciences Program, Harvard University, Cambridge, MA, USA | [b] Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA | [c] Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA | [d] Partners Multiple Sclerosis Center, Brigham and Women’s Hospital, Boston, MA, USA | [e] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA | [f] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA | [g] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Samantha Molsberry, PhD, Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Tel.: 617 432 1841; E-mail: sam306@mail.harvard.edu.

Abstract: Background:Although there is evidence of shared dysregulated pathways between diabetes and Parkinson’s disease, epidemiologic research on an association between the two diseases has produced inconsistent results. Objective:We aimed to assess whether known metabolomic markers of insulin resistance and diabetes are also associated with Parkinson’s disease development. Methods:We conducted a nested case-control study among Nurses’ Health Study and Health Professionals Follow-up Study participants who had provided blood samples up to twenty years prior to Parkinson’s diagnosis. Cases were matched to risk-set sampled controls by age, sex, fasting status, and time of blood collection. Participants provided covariate information via regularly collected cohort questionnaires. We used conditional logistic regression models to assess whether plasma levels of branched chain amino acids, acylcarnitines, glutamate, or glutamine were associated with incident development of Parkinson’s disease. Results:A total of 349 case-control pairs were included in this analysis. In the primary analyses, none of the metabolites of interest were associated with Parkinson’s disease development. In investigations of the association between each metabolite and Parkinson’s disease at different time intervals prior to diagnosis, some metabolites showed marginally significant association but, after correction for multiple testing, only C18 : 2 acylcarnitine was significantly associated with Parkinson’s disease among subjects for whom blood was collected less than 60 months prior to case diagnosis. Conclusions:Plasma levels of diabetes-related metabolites did not contribute to predict risk of Parkinson’s disease. Further investigation of the relationship between pre-diagnostic levels of diabetes-related metabolites and Parkinson’s disease in other populations is needed to confirm these findings.

Keywords: Parkinson’s disease, diabetes mellitus, metabolomics, epidemiology

DOI: 10.3233/JPD-191896

Journal: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1011-1021, 2020