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

Chin Chou Huang, Chia Min Chung, Hsin Bang Leu, Liang Yu Lin, Chun Chih Chiu, Chien Yi Hsu, Chia Hung Chiang, Po Hsun Huang, Tzeng Ji Chen, Shing Jong Lin, Jaw Wen Chen, Wan Leong Chan

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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.

Original languageEnglish
Article numbere87095
JournalPLoS One
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 29 2014
Externally publishedYes

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Alzheimer disease
Medical problems
diabetes mellitus
Hazards
Diabetes Mellitus
Alzheimer Disease
confidence interval
Confidence Intervals
Population
hypoglycemic agents
stroke
Hypoglycemic Agents
hypertension
Stroke
Health insurance
Hypertension
health insurance
Propensity Score
therapeutics
Urbanization

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Diabetes mellitus and the risk of Alzheimer's disease : A nationwide population-based study. / Huang, Chin Chou; Chung, Chia Min; Leu, Hsin Bang; Lin, Liang Yu; Chiu, Chun Chih; Hsu, Chien Yi; Chiang, Chia Hung; Huang, Po Hsun; Chen, Tzeng Ji; Lin, Shing Jong; Chen, Jaw Wen; Chan, Wan Leong.

In: PLoS One, Vol. 9, No. 1, e87095, 29.01.2014.

Research output: Contribution to journalArticle

Huang, CC, Chung, CM, Leu, HB, Lin, LY, Chiu, CC, Hsu, CY, Chiang, CH, Huang, PH, Chen, TJ, Lin, SJ, Chen, JW & Chan, WL 2014, 'Diabetes mellitus and the risk of Alzheimer's disease: A nationwide population-based study', PLoS One, vol. 9, no. 1, e87095. https://doi.org/10.1371/journal.pone.0087095
Huang, Chin Chou ; Chung, Chia Min ; Leu, Hsin Bang ; Lin, Liang Yu ; Chiu, Chun Chih ; Hsu, Chien Yi ; Chiang, Chia Hung ; Huang, Po Hsun ; Chen, Tzeng Ji ; Lin, Shing Jong ; Chen, Jaw Wen ; Chan, Wan Leong. / Diabetes mellitus and the risk of Alzheimer's disease : A nationwide population-based study. In: PLoS One. 2014 ; Vol. 9, No. 1.
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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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AU - Chiu, Chun Chih

AU - Hsu, Chien Yi

AU - Chiang, Chia Hung

AU - Huang, Po Hsun

AU - Chen, Tzeng Ji

AU - Lin, Shing Jong

AU - Chen, Jaw Wen

AU - Chan, Wan Leong

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N2 - 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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