title: Plasma C-peptide and cognitive performance in older men without diabetes.
abstract: BACKGROUND
  Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels.
  
  
  OBJECTIVE
  The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes.
  
  
  METHODS
  The study setting was the Physicians' Health Study-U.S. male physicians.
  
  
  METHODS
  Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years).
  
  
  METHODS
  The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors.
  
  
  RESULTS
  On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant.
  
  
  CONCLUSIONS
  Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes.
authors.affiliation: Division of Aging, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA. ookereke@partners.org
authors.forename: Olivia
authors.initials: O
authors.lastname: Okereke
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Francine
authors.initials: F
authors.lastname: Grodstein
mesh_terms: D002096:C-Peptide / Q000097:blood*; D003071:Cognition / Q000502:physiology*; D003920:Diabetes Mellitus / Q000097:blood; D006304:Health Status; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D013689:Telephone
chemical_list: D002096:C-Peptide