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E-pub ahead of print

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

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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 intravenous 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. 0.1mmol/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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Endocrinology
ISSN0804-4643
DOI
StatusE-pub ahead of print - 1 dec. 2019

ID: 58597413