title: Diabetes and Alzheimer's Disease: Can Elevated Free Copper Predict the Risk of the Disease?
abstract: Defective copper regulation, primarily referred to as chelatable redox active Cu(II), has been involved in the etiology of diabetes, and Alzheimer's disease (AD).
  
  
  
  However, no study has determined levels of labile copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in the blood of subjects with diabetes compared with that of AD patients.
  
  
  
  To this aim, values of non-Cp Cu were measured in 25 Type 1 (T1D) and 31 Type 2 (T2D) subjects and in28 healthy controls, along with measurements of C-reactive protein, glycated hemoglobin A1c, cholesterol, and triglycerides. Non-Cp Cu levels were compared with those of an AD group previously studied.
  
  
  
  T2D subjects had significantly higher non-Cp Cu levels than Controls and T1D subjects (both p < 0.001 after adjusting for age, sex, and body mass index). A multinomial logistic model revealed that a one unit standard deviation increase of non-Cp Cu increased the relative risk of having T2D by 9.64 with respect to Controls (95% CI: 2.86-32.47). The comparison of non-Cp Cu levels in T2D with those of an AD population previously studied shows rising blood non-Cp Cu copper levels from Controls to T2D and AD.
  
  
  
  These results suggest the involvement of catalytically-active Cu(II) and glucose dysregulation in oxidative stress reactions leading to tissue damage in both diseases.
authors.affiliation: Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Simonelli
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.|Department of Surgery, Cell Transplant Program, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000097:blood*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003300:Copper / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D015415:Biomarkers; D003300:Copper
keywords: Alzheimer’s disease; Type 1; Type 2; copper; diabetes; free copper