Type 3 diabetes is sporadic Alzheimer׳s disease: mini-review

Eur Neuropsychopharmacol. 2014 Dec;24(12):1954-60. doi: 10.1016/j.euroneuro.2014.06.008. Epub 2014 Jun 28.


Alzheimer׳s disease (AD) is the most common cause of dementia in North America. Growing evidence supports the concept that AD is a metabolic disease mediated by impairments in brain insulin responsiveness, glucose utilization, and energy metabolism, which lead to increased oxidative stress, inflammation, and worsening of insulin resistance. In addition, metabolic derangements directly contribute to the structural, functional, molecular, and biochemical abnormalities that characterize AD, including neuronal loss, synaptic disconnection, tau hyperphosphorylation, and amyloid-beta accumulation. Because the fundamental abnormalities in AD represent effects of brain insulin resistance and deficiency, and the molecular and biochemical consequences overlap with Type 1 and Type 2 diabetes, we suggest the term "Type 3 diabetes" to account for the underlying abnormalities associated with AD-type neurodegeneration. In light of the rapid increases in sporadic AD prevalence rates and vastly expanded use of nitrites and nitrates in foods and agricultural products over the past 30-40 years, the potential role of nitrosamine exposures as mediators of Type 3 diabetes is discussed.

Keywords: Alzheimer׳s; Diabetes; Glucose Metabolism; Insulin resistance; Nitrosamines.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Nerve Degeneration / metabolism
  • Nitrosamines / adverse effects
  • Oxidative Stress
  • Somatomedins / metabolism
  • Tauopathies / complications
  • Tauopathies / metabolism


  • Amyloid beta-Peptides
  • Insulin
  • Nitrosamines
  • Somatomedins
  • Glucose

Supplementary concepts

  • Diabetes Mellitus, Noninsulin-Dependent, 3