Insulin resistance is associated with poorer verbal fluency performance in women

Diabetologia. 2015 Nov;58(11):2545-53. doi: 10.1007/s00125-015-3715-4. Epub 2015 Aug 15.


Aims/hypothesis: Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association.

Methods: The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests.

Results: Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02).

Conclusions/interpretation: To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.

Keywords: APOE*E4 genotype; Alzheimer’s disease; Categorical verbal fluency; Cognition; HOMA-IR; Insulin resistance; Sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics
  • Blood Glucose
  • Cognition / physiology*
  • Female
  • Genotype
  • Humans
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Risk Factors
  • Sex Factors
  • Verbal Behavior / physiology*


  • Apolipoproteins E
  • Blood Glucose