Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes

Nicole Jacqueline Jensen, Malin Nilsson, Jonas Schultz Ingerslev, Dorte Aalund Olsen, Mogens Fenger, Mads Svart, Niels Møller, Mette Zander, Kamilla Woznica Miskowiak, Jørgen Rungby


Objective: Cognitive impairment in type 2 diabetes is associated with cerebral glucose hypometabolism. Providing a glucose substitute such as ketone bodies might restore metabolic balance in glucose-compromised neurones and improve cognitive performance. We aimed to investigate if β-hydroxybutyrate (ketone body) infusion acutely affects cognitive performance, measured by a neuropsychological test battery, in patients with type 2 diabetes.

Design: Randomised, placebo-controlled, double-blind cross-over trial.

Methods: Eighteen patients with type 2 diabetes received i.v. ketone body (β-hydroxybutyrate) and placebo (saline) infusion in a randomised order on two separate occasions. On both days of examination, blood glucose was clamped at 7.5 mmol/L and a neuropsychological test battery was used to assess global cognitive performance (primary outcome) and specialized cognitive measures of verbal memory, working memory, executive function, psychomotor speed, and sustained attention.

Results: During neurocognitive testing, β-hydroxybutyrate concentrations were 2.4 vs 0.1 mmol/L. Working memory assessed by Wechsler Adult Intelligence Scale letter-number-sequencing significantly improved by 1.6 points (95% CI: 0.7, 2.4; non-adjusted P < 0.001) corresponding to a 17% increase in performance during ketone infusion compared to placebo. There was no change for global cognitive performance or any other cognitive measure after adjusting for multiple comparisons. Blood concentrations of β-hydroxybutyrate and glycaemic status did not associate with test performance; however, insulin resistance measured by HOMA was related to improved working memory performance during ketone infusion (β = 4%; 95% CI: 1.1, 7.7; P = 0.012).

Conclusions: Ketone infusion specifically improved working memory performance in patients with type 2 diabetes in the absence of changes in global cognition.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Issue number2
Pages (from-to)233-242
Number of pages10
Publication statusPublished - Feb 2020


  • 3-Hydroxybutyric Acid/blood
  • Aged
  • Blood Glucose/metabolism
  • Cognition/physiology
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2/blood
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Memory, Short-Term/physiology
  • Memory/physiology
  • Mental Status and Dementia Tests
  • Middle Aged


Dive into the research topics of 'Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes'. Together they form a unique fingerprint.

Cite this