TY - JOUR

T1 - Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes

AU - Jensen, Nicole Jacqueline

AU - Nilsson, Malin

AU - Ingerslev, Jonas Schultz

AU - Olsen, Dorte Aalund

AU - Fenger, Mogens

AU - Svart, Mads

AU - Møller, Niels

AU - Zander, Mette

AU - Miskowiak, Kamilla Woznica

AU - Rungby, Jørgen

N1 - CURIS 2020 NEXS 098

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1530/EJE-19-0710

DO - 10.1530/EJE-19-0710

M3 - Journal article

C2 - 31821157

AN - SCOPUS:85078564028

VL - 182

SP - 233

EP - 242

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 2

ER -