.2014 Jan 29;9(1):e87095.

doi: 10.1371/journal.pone.0087095. eCollection 2014.

Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study

Chin-Chou Huang¹, Chia-Min Chung², Hsin-Bang Leu³, Liang-Yu Lin⁴, Chun-Chih Chiu⁵, Chien-Yi Hsu⁵, Chia-Hung Chiang⁶, Po-Hsun Huang⁷, Tzeng-Ji Chen⁸, Shing-Jong Lin⁹, Jaw-Wen Chen¹, Wan-Leong Chan¹⁰

Affiliations

¹ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
² Environment-Omics-Disease Research Centre, China Medical University Hospital, Taichung, Taiwan, R.O.C ; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
³ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁴ Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁵ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁶ Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Zhudong Veterans Hospital, HsinChu, Taiwan, R.O.C.
⁷ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁸ Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁹ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
¹⁰ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.

PMID:24489845
PMCID: PMC3906115
DOI: 10.1371/journal.pone.0087095

Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study

Chin-Chou Huang et al. PLoS One.2014.

.2014 Jan 29;9(1):e87095.

doi: 10.1371/journal.pone.0087095. eCollection 2014.

Authors

Affiliations

¹ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
² Environment-Omics-Disease Research Centre, China Medical University Hospital, Taichung, Taiwan, R.O.C ; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
³ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁴ Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁵ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁶ Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Zhudong Veterans Hospital, HsinChu, Taiwan, R.O.C.
⁷ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁸ Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, R.O.C.
⁹ Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C ; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
¹⁰ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C ; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.

PMID:24489845
PMCID: PMC3906115
DOI: 10.1371/journal.pone.0087095

Abstract

Objectives: Possible association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.

Methods: Data were collected from Taiwan's National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74 ± 14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.

Results: Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50-2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10-1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06-1.46, p=0.008), hypertension (HR, 1.30; 95% CI, 1.07-1.59, p=0.01), previous stroke history (HR, 1.79; 95% CI, 1.28-2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07-1.63, p=0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04-4.52, p=0.039).

Conclusion: Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.

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Conflict of interest statement

Competing Interests:The authors have declared that no competing interests exist.

Figures

**Figure 1. Kaplan-Meier estimates of survival free of Alzheimer’s disease (AD) events in subjects categorized by diabetes mellitus (DM).**
The event-free survival rates were significantly different in two groups (p<0.001 by log rank test).

**Figure 2. The trend of the incidence of Alzheimer’s disease (AD) according to the duration of diabetes mellitus (DM).**

See this image and copyright information in PMC

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References

1. Roberts JS, Tersegno SM (2010) Estimating and disclosing the risk of developing Alzheimer’s disease: challenges, controversies and future directions. Future Neurol 5: 501–517. - PMC - PubMed
1. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM (2013) Monetary costs of dementia in the United States. N Engl J Med 368: 1326–1334. - PMC - PubMed
1. Maiorini AF, Gaunt MJ, Jacobsen TM, McKay AE, Waldman LD, et al. (2002) Potential novel targets for Alzheimer pharmacotherapy: I. secretases. J Clin Pharm Ther 27: 169–183. - PubMed
1. Thies W, Bleiler L (2011) 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 7: 208–244. - PubMed
1. Wolfson C, Wolfson DB, Asgharian M, M’Lan CE, Ostbye T, et al. (2001) Clinical Progression of Dementia Study Group (2001) A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 344: 1111–1116. - PubMed

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Grants and funding

The present study was partly supported by research grants V99B1-011, V99C1-125, V100B-004, V100B-013, and V102B-024 from Taipei Veterans General Hospital, Taipei, Taiwan; CI-97-13 and CI-98-16 from the Yen Tjing Ling Medical Foundation, Taipei, Taiwan; NSC 100-2314-B-075-055, NSC 102-2314-B-075-022-MY3, and UST-UCSD International Center of Excellence in Advanced Bio-engineering NSC-99-2911-I-009-101-A2 from the National Science Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study

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Diabetes mellitus and the risk of Alzheimer's disease: a nationwide population-based study

Authors

Affiliations

Abstract

Conflict of interest statement

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