Diabetes and Risk of Parkinson's Disease: An Updated Meta-Analysis of Case-Control Studies

Abstract

BackgroundWhether diabetes increases the risk of Parkinson's disease (PD) is still inconclusive. The objective of this updated meta-analysis is to synthesize evidence from case-control studies that evaluated the association between diabetes and the risk of PD.MethodsSeven databases were searched to identify case-control studies that evaluated the association between diabetes and PD. The methodological quality of included studies was assessed using Newcastle-Ottawa scale. All data were analyzed using Review Manager 5.1 software. Subgroup analyses were also adopted, according to stratification on gender, geographic location, source of the control group, smoking, anti-diabetes drug prescription and duration of DM.ResultsFourteen studies fulfilled inclusion criteria for meta-analysis, yielding a total of 21395 PD patients and 84579 control subjects. Individuals with diabetes were found to have a negative association with future PD (OR 0.75; 95% CI 0.58–0.98) in spite of significant heterogeneity. In subgroup analyses, the negative correlation was still found in studies from North America, non-PD control groups from general population, never smoking individuals, and DM ascertainment based on questionnaire or self-report. Stratification of gender and DM duration showed no significant association. No association was also found in European and Asian individuals, hospital-based controls, ever smoking subjects, DM assessment by medical record or physician diagnosis, and insulin prescription for DM.ConclusionEvidence from case-control studies suggested that diabetic individuals may have a decreased incidence of PD despite significant heterogeneity. More researches are warranted to clarify an understanding of the association between diabetes and risk of PD.

Network-based metaanalysis identifies HNF4A and PTBP1 as longitudinally dynamic biomarkers for Parkinson’s disease

“…HNF4A is a master metabolic regulatory factor responsible for the activation of the hepatic gluconeogenesis (16) and has been implicated in diabetes, inflammation, and lipid metabolism (17)(18)(19)(20)(21). In this context, diabetes has been associated with PD in numerous epidemiological studies (22)(23)(24)(25). Although the exact mechanism by which both diseases coexist is not clearly understood, a recent review suggests that dysregulation in common molecular processes including the insulin signaling pathway, inflammation, ER stress, and mitochondrial dysfunction may lead to both diseases (26).…”

Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model

“…Insulin de--sensitisation may be one mechanism that underlies both conditions. The analysis of clinical data showed that an 8-30 % of PD patients were diabetic or glucose intolerant, a significantly higher percentage compared to age matched controls (Cereda et al, 2011;Hu, Jousilahti, Bidel, Antikainen, & Tuomilehto, 2007;Lu et al, 2014;Miyake et al, 2010;Schernhammer, Hansen, Rugbjerg, Wermuth, & Ritz, 2011). In preclinical studies, systemic administration of drugs for T2DM, such as insulin (Freiherr et al, 2013), rosiglitazone (Schintu et al, 2009), and metformin (Patil, Jain, Ghumatkar, Tambe, & Sathaye, 2014), significantly attenuate neuropathology, including the loss of SNpc neurons and the striatal dopaminergic fibers, microglial activation, or the expression of pro--inflammatory cytokines, in PD animal models.…”

Current Understanding on the Beneficial Role of Nutrition in Parkinson’s Disease –An Overview

“…Specifically, patients with diabetes mellitus often develop neurodegenerative diseases such as PD and Alzheimer's disease [76]. Recent findings suggest that the metabolic syndrome may increase particularly when the metabolic syndrome develops in midlife [77].…”