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• W2748086556 abstract "Type 2 diabetes is suggested to increase the risk of Alzheimer's disease (AD) and vascular dementia. However, the mechanisms are still unclear. Diabetes might affect the brain through glucose toxicity, changes in insulin and amyloid metabolism, microvascular disease or through insulin resistance leading to atherosclerosis. We investigated the longitudinal association between diabetes, insulin sensitivity, early insulin response (EIR) and AD. There are no previous studies on insulin sensitivity measured by the euglycaemic insulin clamp for prediction of dementia. The subjects were participants of the Uppsala Longitudinal Study of Adult Men (ULSAM), which started when they were 50 years old. In the present study, baseline data were collected from a follow–up at age 70 (n=888). Measurements included fasting plasma glucose, insulin, oral glucose tolerance test (OGTT) and peripheral insulin sensitivity estimated by the euglycemic clamp technique. EIR was based on 30 minutes data from the OGTT. Cognitive function was assessed three times during the follow–up and participants with signs of impairment underwent a detailed diagnostic work–up. Additional cases of dementia were identified through medical records. By the end of 2005, median 11.6 years after baseline, 61 men had developed AD according to the NINCDS–ADRDA and DSM IV criteria. CT scans were consistent with the diagnosis. Associations were analyzed using Cox proportional hazard analyses. We did not find any association between diabetes, insulin sensitivity and AD. In the non–diabetic subjects (n=798), however, a decreased early insulin response was associated with higher risk of AD (HR/1SD 1.30, CI 1.06–1.48, p=0.019). The same odds ratio was obtained after adjustment for the insulin sensitivity index (M/I ratio), APOE genotype, BMI, hypertension, total cholesterol and education level (HR/1SD 1.27, CI 0.99–1.47 p=0.054). Studies on the association between glucose metabolism and vascular dementia and MCI (mild cognitive impairment) are in progress. In this longitudinal study, insulin sensitivity measured by the euglycemic clamp technique was not associated with AD. An impaired early insulin response, a marker of β–cell dysfunction, was associated with higher risk of AD even after adjustment for other risk factors." @default.
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• W2748086556 date "2006-07-01" @default.
• W2748086556 modified "2023-09-27" @default.
• W2748086556 title "P1-234: Diabetes, insulin resistance and risk of Alzheimer's disease" @default.
• W2748086556 doi "https://doi.org/10.1016/j.jalz.2006.05.611" @default.
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