Abstract
BackgroundInterventions that acutely increase blood ketone concentrations simultaneously lower blood glucose levels, although the explanation for this phenomenon is unknown. The hypoglycaemic effect of acute ketosis is greater in people with type 2 diabetes (T2D) in whom gluconeogenesis contributes significantly to their hyperglycaemia. One gluconeogenic substrate secreted by skeletal muscle at higher levels in people with T2D is L-alanine. Infusion of ketones lowers circulating L-alanine blood levels, so here we sought to determine whether supplementation with L-alanine would attenuate the hypoglycaemic effect of a ketone ester (KE) drink. MethodsThis crossover study involved two separate visits for 10 healthy human volunteers who fasted for 24 hours prior to the ingestion of 25 g of d-β-hydroxybutyrate (βHB) monoester (ΔG®). During one of the visits participants ingested 2 g of L-alanine. Blood L-alanine, L-glutamine, glucose, βHB, free fatty acids (FFA), lactate, and C-peptide were measured. FindingsThe KE drinks elevated blood βHB concentrations from negligible to 4.5 ± 1.24 mM/l, and lowered both glucose, from 4.97 to 3.77 ± 0.4 mM/l, and L-alanine from 0.56 to 0.41 ± 0.9 mM/l. L-alanine in the KE drink elevated blood L-Alanine to 0.56 ± mM/l, but had no significant effect on blood βHB, L-glutamine, FFA, lactate, or C-peptide concentrations. Preventing the KE-induced decrease in L-alanine by supplementing it significantly attenuated the glucose drop from mean 28% to 16% (p<0.001). (Illustrated in Figure 1).ConclusionsThe hypoglycaemic effect of acutely elevated βHB is, at least partially, due to βHB decreasing L-alanine availability as a substrate for gluconeogenesis.
Swallowing food without chewing; a simple way to reduce postprandial glycaemia