Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes
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- Jensen et al (2020)_European Journal of Endocrinology_Vol 182(2)_233-242
Final published version, 633 KB, PDF document
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 language | English |
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Journal | European Journal of Endocrinology |
Volume | 182 |
Issue number | 2 |
Pages (from-to) | 233-242 |
Number of pages | 10 |
ISSN | 0804-4643 |
DOIs | |
Publication status | Published - 2020 |
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