Response to lowering plasma glucose is characterised by decreased oxyntomodulin: Results from a randomised controlled trial

Background

With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood.

Aim

To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders.

Methods

The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www.ClinicalTrials.gov as NCT03889210). Following an overnight fast, participants consumed ketone β-hydroxybutyrate (KEβHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and ‘non-responders' subgroups based on their glycaemic changes following the ingestion of KEβHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEβHB and placebo beverages.

Results

Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC_0-150 for oxyntomodulin was significantly lower following the KEβHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs_0-150 were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders.

Conclusion

Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.