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


CONCLUSIONS
Newly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.
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.
Chin-Chou
CC
Huang
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.
Chia-Min
CM
Chung
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.
Hsin-Bang
HB
Leu
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.
Liang-Yu
LY
Lin
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.
Chun-Chih
CC
Chiu
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.
Chien-Yi
CY
Hsu
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.
Chia-Hung
CH
Chiang
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.
Po-Hsun
PH
Huang
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.
Tzeng-Ji
TJ
Chen
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.
Shing-Jong
SJ
Lin
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.
Jaw-Wen
JW
Chen
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.
Wan-Leong
WL
Chan
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models