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Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson's disease

Authors
 Seong Ho Jeong  ;  Seok Jong Chung  ;  Han Soo Yoo  ;  Namki Hong  ;  Jin Ho Jung  ;  Kyoungwon Baik  ;  Yang Hyun Lee  ;  Young H Sohn  ;  Phil Hyu Lee 
Citation
 BRAIN, Vol.144(4) : 1127-1137, 2021-05 
Journal Title
BRAIN
ISSN
 0006-8950 
Issue Date
2021-05
Keywords
DPP4 inhibitors ; Parkinson’s disease ; dopamine transporter imaging ; prognosis
Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1. In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson's disease. We classified 697 drug naive patients with de novo Parkinson's disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson's disease being treated with (n = 54) or without DPP4 inhibitors (n = 85), and non-diabetic patients with Parkinson's disease (n = 558). Diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had a higher baseline dopamine transporter availability in the anterior (2.56 ± 0.74 versus 2.10 ± 0.50; P = 0.016), posterior (1.83 ± 0.69 versus 1.40 ± 0.50; P < 0.001), and ventral putamina (1.72 ± 0.58 versus 1.35 ± 0.37; P = 0.001) than that in diabetic patients with Parkinson's disease without DPP4 inhibitors. Additionally, diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had higher dopamine transporter availability in the posterior putamen than that in non-diabetic patients with Parkinson's disease (1.83 ± 0.69 versus 1.43 ± 0.59; P < 0.001). After adjusting for age, sex, disease duration, and vascular risk factors, linear regression models showed that a prior treatment of DPP4 inhibitors remained independently and significantly associated with dopamine transporter availability in the anterior (β = -0.186, P = 0.012; β = -0.207, P = 0.003), posterior (β = -0.336, P < 0.001; β = -0.286, P < 0.001), and ventral putamina (β = -0.204, P = 0.005; β = -0.250, P < 0.001). A linear mixed model revealed that the diabetic group with Parkinson's disease being treated with DPP4 inhibitors had a slower longitudinal increase in levodopa-equivalent dose than the other groups (P = 0.003). Survival analyses showed that the rate of levodopa-induced dyskinesia was significantly lower in the diabetic group with a prior treatment with DPP4 inhibitors than the diabetic group without DPP4 inhibitors (hazard ratio = 0.194, P = 0.037). These findings suggest that DPP4 inhibitors may confer beneficial effects on the baseline nigrostriatal dopamine degeneration and long-term motor outcomes in diabetic patients with Parkinson's disease and may extend its role into non-diabetic patients with Parkinson's disease.
Full Text
https://academic.oup.com/brain/article/144/4/1127/6250906
DOI
10.1093/brain/awab015
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Baik, Kyoungwon(백경원) ORCID logo https://orcid.org/0000-0001-7215-375X
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Yang Hyun(이양현)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
Jung, Jin Ho(정진호)
Hong, Nam Ki(홍남기) ORCID logo https://orcid.org/0000-0002-8246-1956
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/183971
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