Dapagliflozin in Physical Exercise in Type 1 Diabetes
Status:
Recruiting
Trial end date:
2022-11-30
Target enrollment:
Participant gender:
Summary
Inhibitors of sodium-dependent glucose-transporter 2 (SGLT-2 inhibitors, including
dapagliflozin) inhibit glucose reabsorption in renal tubular cells, hereby increasing
glycosuria in the hyperglycemic state. Its mechanisms of action are independent of insulin,
which makes SGLT-2 inhibitors a potential adjunct to insulin in type 1 diabetes mellitus
(T1DM).
However, a higher risk for diabetic ketoacidosis (DKA) was reported in patients with T1DM
taking SGLT-2 inhibitors. DKA depends on an accumulation of ketone bodies in the blood
stream, which equals an accumulation of acids that lead to acidosis. The underlying
mechanisms of this observation are unknown. Ketone body production depends on the molar ratio
of glucagon to insulin, with insulin suppressing but glucagon stimulating ketone body
production. This translates into higher production during relative insulin deficiency,
carbohydrate deficiency, and prolonged fasting, which occurs during sickness but also
physical exercise. Physical exercise is a recommended cornerstone in the treatment of T1DM
and current treatment guidelines recommend both, reductions of insulin doses and ingestion of
additional carbohydrates to avoid hypoglycemic events. These adaptions might increase
relative insulin deficiency, hyperglycemia and glycaemic variability, which might in turn
promote ketone body production. The addition of SGLT-2 inhibitors further may promote
ketogenesis even though there are reports of SGLT-2 inhibitors increase
Glucagon-like-peptide-1 (GLP-1) in patients with T1DM. GLP-1 is a suppressor of glucagon
secretion. In summary, knowledge about the effects of SGLT-2 inhibition on ketone body
production is scarce, especially during exercise in patients with T1DM.
The study seeks to illustrate the effect of SGLT-2 inhibition on glycemic variability and
ketone body production during and after recreational exercise in patients with T1DM. The
results of study 2 will provide the basis for future studies investigating the underlying
mechanisms of potentially modified ketone body production during and after exercise under
SGLT-2 inhibition.