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      Diabetes and Risk of Parkinson’s Disease : A systematic review and meta-analysis

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          Abstract

          OBJECTIVE

          Diabetes has been associated with chronic neurodegeneration. We performed a systematic review and meta-analysis to assess the relationship between pre-existing diabetes and Parkinson’s disease (PD).

          RESEARCH DESIGN AND METHODS

          Original articles in English published up to 10 May 2011 were searched for in electronic databases (PubMed, Embase, and Scopus) and by reviewing references of eligible articles. Prospective cohort and case-control studies providing risk and precision estimates relating to pre-existing diabetes and PD were considered eligible.

          RESULTS

          Nine studies/1,947 citations (cohort, N = 4; case-control, N = 5) fulfilled inclusion criteria for meta-analysis. In prospective studies, the onset of diabetes before onset of PD was found to be a risk factor for future PD (relative risk [RR] = 1.37 [95%CI 1.21–1.55]; P < 0.0001). This association was confirmed by secondary analyses based on estimates derived after the exclusion of participants who had vascular disease at baseline and/or who developed vascular disease during follow-up (RR = 1.34 [1.14–1.58]; P < 0.001) and by sensitivity analyses addressing the association with diabetes at baseline or during follow-up. However, the association found for case-control studies was not significant (odds ratio [OR] 0.75 [95%CI 0.50–1.11]; P = 0.835). Sensitivity analysis based on estimates adjusted for BMI confirmed the lack of a relationship between PD and diabetes (OR 0.56 [0.28–1.15]; P = 0.089).

          CONCLUSIONS

          Although data from cohort studies suggest that diabetes is a risk factor for PD, there is no conclusive evidence on this association. Further prospective studies focused on putative pathogenic pathways and taking a broad range of confounders into account is required to clarify this relationship.

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          Most cited references31

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          Type 2 diabetes and the risk of Parkinson's disease.

          To evaluate whether type 2 diabetes at baseline is a risk factor for Parkinson's disease. We prospectively followed 51,552 Finnish men and women 25-74 years of age without a history of Parkinson's disease at baseline. History of diabetes and other study parameters were determined at baseline using standardized measurements. Ascertainment of the Parkinson's disease status was based on the nationwide Social Insurance Institution's drug register data. Hazard ratios of incident Parkinson's disease associated with the history of type 2 diabetes were estimated. During a mean follow-up period of 18.0 years, 324 men and 309 women developed incident Parkinson's disease. Age- and study year-adjusted hazard ratios of incident Parkinson's disease among subjects with type 2 diabetes, compared with those without it, were 1.80 (95% CI 1.03-3.15) in men, 1.93 (1.05-3.53) in women, and 1.85 (1.23-2.80) in men and women combined (adjusted also for sex). Further adjustment for BMI, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, alcohol drinking, and coffee and tea consumption affected the results only slightly. The multivariate adjusted association between type 2 diabetes and the risk of Parkinson's disease was also confirmed in stratified subgroup analysis. These data suggest that type 2 diabetes is associated with an increased risk of Parkinson's disease. Surveillance bias might account for higher rates in diabetes. The mechanism behind this association between diabetes and Parkinson's disease is not known.
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            Peripheral inflammatory biomarkers and risk of Parkinson's disease.

            Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson's disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson's disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993-2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson's disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend = 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-alpha receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson's disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation.
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              Diabetes and Risk of Parkinson’s Disease

              OBJECTIVE To investigate the relationship between diabetes and future risk of Parkinson’s disease (PD) among older U.S. adults. RESEARCH DESIGN AND METHODS A prospective study of self-reported diabetes in 1995 and 1996 in relation to PD diagnosed after 1995 among 288,662 participants of the National Institutes of Health-AARP Diet and Health Study. Multivariate odds ratio (OR) and 95% CI were derived from logistic regression models. RESULTS A total of 1,565 participants with PD diagnosed after 1995 were included in the analysis. After adjustment for potential confounders, PD risk was ∼40% higher (OR = 1.41 [95% CI 1.20–1.66]) among diabetic patients than among participants without diabetes. Further analysis showed that the risk elevation was largely limited to individuals who had diabetes for more than 10 years at the time of baseline survey (1.75 [1.36–2.25]). The association with diabetes was seen for both participants with PD diagnosed between 1995 and 1999 and participants with PD diagnosed after 2000. In addition, similar results were obtained after excluding participants with stroke, heart disease, cancers, or poor or fair health status and in subgroup analyses by age, sex, smoking status, and coffee consumption. CONCLUSIONS This large study showed that diabetes was associated with a higher future risk of PD and the nature of this association warrants further investigation.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                December 2011
                14 November 2011
                : 34
                : 12
                : 2614-2623
                Affiliations
                [1] 1Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
                [2] 2Parkinson Institute–Istituti Clinici di Perfezionamento, Milano, Italy
                [3] 3Dietetic and Clinical Nutrition Unit, Trento Hospital, Trento, Italy
                [4] 4Biometry and Clinical Epidemiology Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
                Author notes
                Corresponding author: Emanuele Cereda, e.cereda@ 123456smatteo.pv.it .
                Article
                1584
                10.2337/dc11-1584
                3220864
                22110170
                43b3ecdc-57e8-4adb-8947-5a06b8f77639
                © 2011 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 22 August 2011
                : 20 September 2011
                Categories
                Reviews/Commentaries/ADA Statements
                Meta-Analysis

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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