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      Diabetes and the Risk of Developing Parkinson’s Disease in Denmark

      research-article
      , MD 1 , 2 , 3 , , PHD 4 , , PHD 4 , , MD 5 , , MD 6
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson’s disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson’s disease.

          RESEARCH DESIGN AND METHODS

          From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of Parkinson’s disease between 2001 and 2006. We randomly selected 9,651 population control subjects from the Central Population Registry and density matched them by birth year and sex. Pharmacy records comprising all antidiabetes and anti-Parkinson drug prescriptions in Denmark were available. Odds ratios (ORs) were estimated by logistic regression models.

          RESULTS

          Having diabetes, as defined by one or more hospitalizations and/or outpatient visits for the condition, was associated with a 36% increased risk of developing Parkinson’s disease (OR 1.36 [95% CI 1.08–1.71]). Similarly, diabetes defined by the use of any antidiabetes medications was associated with a 35% increased Parkinson’s disease risk (1.35 [1.10–1.65]). When diabetes was defined as the use of oral antidiabetes medications, effect estimates were stronger in women (2.92 [1.34–6.36]), whereas when diabetes was defined as any antidiabetes drug prescription, patients with early-onset Parkinson’s disease were at highest risk (i.e., Parkinson’s disease diagnosed before the age of 60 years; 3.07 [1.65–5.70]).

          CONCLUSIONS

          We found that a diagnosis of, or treatment received for, diabetes was significantly associated with an increased risk of developing Parkinson’s disease, especially younger-onset Parkinson’s disease. Our results suggest a common pathophysiologic pathway between the two diseases. Future studies should take age at Parkinson’s disease onset into account.

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          Most cited references22

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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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            Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease.

            To determine whether history of hypertension, hypercholesterolemia, or diabetes is associated with risk of Parkinson disease (PD). Prospective study among participants in two large cohorts: the Nurses' Health Study (121,046 women) and the Health Professionals Follow-up Study (50,833 men). Mean duration of follow-up was 22.9 years in women, aged 30 to 55 years at baseline, and 12.6 years in men, aged 40 to 75 years at baseline. Relative risks (RRs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. We identified a total of 530 incident cases of PD during the follow-up. Risk of PD was not associated with self-reported history of hypertension (RR = 0.96, 95% CI = 0.80 to 1.15), high cholesterol (RR = 0.98, 95% CI = 0.82 to 1.19), or diabetes (RR = 1.04, 95% CI = 0.74 to 1.46), after adjusting for age and smoking in pack-years. Risk of PD decreased modestly with increasing levels of self-reported total cholesterol (RR for a 50-mg/dL increase in total cholesterol = 0.86, 95% CI = 0.78 to 0.95, p for trend = 0.02), but use of cholesterol-lowering drugs was not associated with PD risk (RR comparing users with nonusers = 0.85, 95% CI = 0.59 to 1.23). Among individuals with PD, systolic blood pressure was similar to noncases up to the time of diagnosis but declined afterward. Results of this large prospective study suggest that Parkinson disease risk is not significantly related to history of hypertension, hypercholesterolemia, or diabetes but may modestly decline with increasing blood cholesterol levels.
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              Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS).

              Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes. The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208). At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5+/-1.3 vs 96.7+/-2.0 nmol/l; p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5+/-2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9+/-1.4 vs 90.1+/-2.4 nmol/l; p<0.0001) and at follow-up (77.1+/-2.8 nmol/l vs 87.2+/-4.5 nmol/l; p=0.048). The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                May 2011
                20 April 2011
                : 34
                : 5
                : 1102-1108
                Affiliations
                [1] 1Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts
                [2] 2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
                [3] 3LBI-ACR and Applied Cancer Research–Institution for Translational Research Vienna (ACR-ITR VIEnna/CEADDP), Vienna, Austria
                [4] 4Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
                [5] 5Department of Neurology, Odense University Hospital, Odense, Denmark
                [6] 6Department of Epidemiology, University of California Los Angeles School of Public Health, Los Angeles, California
                Author notes
                Corresponding author: Eva Schernhammer, eva.schernhammer@ 123456channing.harvard.edu .
                Article
                1333
                10.2337/dc10-1333
                3114482
                21411503
                c7d1acb2-62f0-4a5b-baa8-180c0299826a
                © 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
                : 18 August 2010
                : 4 February 2011
                Categories
                Original Research
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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