Importance of Treatment Status in Links Between Type 2 Diabetes and Alzheimer's Disease

Diabetes Care. 2019 May;42(5):972-979. doi: 10.2337/dc18-1399. Epub 2019 Mar 4.


Objective: To investigate relationships among type 2 diabetes treatment, Alzheimer's disease(AD) biomarkers, and risk for dementia.

Research design and methods: Participants were from the Alzheimer's Disease Neuroimaging Initiative (N = 1,289) and were dementia-free at baseline and underwent health assessment, cognitive testing, and MRI. A subset (n = 900) obtained a lumbar puncture to determine cerebrospinal fluid (CSF) phosphorylated tau (p-tau), total tau (t-tau), and β-amyloid 1-42 (Aβ1-42). Participants were grouped by fasting blood glucose and medication history: euglycemia (EU), prediabetes (PD), untreated diabetes (UD), and treated diabetes (TD). Relationships were investigated between treatment status and CSF biomarkers and risk for dementia.

Results: The UD group displayed greater p-tau, t-tau, and p-tau/Aβ1-42 levels than the EU, PD, and TD groups (P values <0.05) and higher t-tau/Aβ1-42 than the EU and PD groups (P values <0.05). The UD group progressed to dementia at higher rates than the EU group (hazard ratio 1.602 [95% CI 1.057-2.429]; P = 0.026).

Conclusions: Treatment status may alter the relationship between type 2 diabetes and both AD biomarker profile and risk for dementia. UD is associated with elevated tau pathology and risk for dementia, whereas TD is not. Although this study is observational and therefore causality cannot be inferred, findings support the potential importance of treatment status in AD risk associated with type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / blood
  • Biomarkers / analysis
  • Biomarkers / blood
  • Cognition / physiology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / psychology*
  • Diabetes Mellitus, Type 2 / therapy*
  • Disease Progression
  • Female
  • Health Status
  • Humans
  • Male
  • Middle Aged
  • Survival Analysis
  • tau Proteins / analysis
  • tau Proteins / blood


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins