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Aims/hypothesis <p>Postprandial hyperglycaemia and hyperlipidaemia are independent risk factors for CVD in individuals with type 2 diabetes. We aimed to test whether a ketone monoester (KE) and ketone salts (KS) reduce postprandial glucose and lipid excursions in individuals with type 2 diabetes.</p> Methods <p>In two randomised, participant-blind crossover studies we investigated individuals with type 2 diabetes treated with either metformin monotherapy or a lifestyle intervention alone. In study 1, 14 participants received 30 g of KE, KS or placebo 30 min before a mixed meal test on three separate occasions. The primary outcome was the incremental AUC (iAUC) for glucose. In study 2, ten participants were investigated on six separate occasions, consuming various doses (0 g, 10 g, 20 g and 40 g) of KE 30 min, 60 min or immediately before an OGTT. Both studies were conducted at Aarhus University Hospital, Denmark, with the primary investigator randomly assigning the intervention order.</p> Results <p>We found that the iAUC for glucose decreased by 36% (95% CI 14, 57) with KE and 22% (95% CI 1, 44) with KS compared with placebo. Both ketone supplements lowered postprandial NEFA and ghrelin concentrations, and KE reduced triglycerides (<i>n</i>=14). Furthermore, KE dose-dependently lowered the iAUC of glucose, with the strongest effect when ingested 30 min or 60 min before the OGTT (<i>n</i>=10). No serious adverse events occurred; however, transient mild gastrointestinal symptoms, including nausea and diarrhoea, were reported.</p> Conclusions/interpretation <p>Pre-meal ketone supplementation reduced postprandial glucose, lipid and ghrelin concentrations. These findings support the therapeutic potential of KE supplementation in the management of type 2 diabetes.</p> Trial registration <p>ClinicalTrials.gov NCT05263401 and NCT05581043</p> Funding <p>Novo Nordisk Foundation (NNF19OC0058872 and NNF22OC0081911), the Health Research Foundation of Central Denmark Region and the Aase Einar Danielsen Foundation (Jr. No. 23-10-0145)</p> Graphical Abstract <p></p>

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Ketone supplementation dose-dependently lowers postprandial blood glucose, lipid and ghrelin levels in individuals with type 2 diabetes: a randomised crossover study

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • Maj Bangshaab,
  • Mads B. Bengtsen,
  • Stine Smedegaard,
  • Esben Søndergaard,
  • Niels Møller,
  • Mads V. Svart,
  • Nikolaj Rittig

摘要

Aims/hypothesis

Postprandial hyperglycaemia and hyperlipidaemia are independent risk factors for CVD in individuals with type 2 diabetes. We aimed to test whether a ketone monoester (KE) and ketone salts (KS) reduce postprandial glucose and lipid excursions in individuals with type 2 diabetes.

Methods

In two randomised, participant-blind crossover studies we investigated individuals with type 2 diabetes treated with either metformin monotherapy or a lifestyle intervention alone. In study 1, 14 participants received 30 g of KE, KS or placebo 30 min before a mixed meal test on three separate occasions. The primary outcome was the incremental AUC (iAUC) for glucose. In study 2, ten participants were investigated on six separate occasions, consuming various doses (0 g, 10 g, 20 g and 40 g) of KE 30 min, 60 min or immediately before an OGTT. Both studies were conducted at Aarhus University Hospital, Denmark, with the primary investigator randomly assigning the intervention order.

Results

We found that the iAUC for glucose decreased by 36% (95% CI 14, 57) with KE and 22% (95% CI 1, 44) with KS compared with placebo. Both ketone supplements lowered postprandial NEFA and ghrelin concentrations, and KE reduced triglycerides (n=14). Furthermore, KE dose-dependently lowered the iAUC of glucose, with the strongest effect when ingested 30 min or 60 min before the OGTT (n=10). No serious adverse events occurred; however, transient mild gastrointestinal symptoms, including nausea and diarrhoea, were reported.

Conclusions/interpretation

Pre-meal ketone supplementation reduced postprandial glucose, lipid and ghrelin concentrations. These findings support the therapeutic potential of KE supplementation in the management of type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT05263401 and NCT05581043

Funding

Novo Nordisk Foundation (NNF19OC0058872 and NNF22OC0081911), the Health Research Foundation of Central Denmark Region and the Aase Einar Danielsen Foundation (Jr. No. 23-10-0145)

Graphical Abstract