Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes
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Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes. / Jensen, Nicole Jacqueline; Nilsson, Malin; Ingerslev, Jonas Schultz; Olsen, Dorte Aalund; Fenger, Mogens; Svart, Mads; Møller, Niels; Zander, Mette; Miskowiak, Kamilla Woznica; Rungby, Jørgen.
I: European Journal of Endocrinology, Bind 182, Nr. 2, 2020, s. 233-242.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 235774564