Glucagon Response to Prandial Insulin Administration in Persons With Type 1 Diabetes
Status:
Active, not recruiting
Trial end date:
2021-12-31
Target enrollment:
Participant gender:
Summary
Glucagon regulation and response in persons with T1D at the basal state and in response to
various stimuli remains unclear. Dr. Philip Cryer has previously reported that, in T1D young
adults with a course of the disease of 16+9 years, the absence of endogenous insulin
secretion results in increased glucagon secretion after a mixed meal, concluding that
endogenous insulin reciprocally regulates the alpha-cell glucagon secretion and also
suggesting that glucagon dysregulation may play an important role in post-prandial
hyperglycemia in T1D. Interestingly, recent research on human islets have shown that insulin
inhibits counter-regulatory glucagon secretion by a paracrine effect mediated by
SGLT2-dependent stimulation of somatostatin release. An important gap in our knowledge is
whether the timing of prandial insulin doses affects the glucagon response to a hyperglycemic
stimulus in patients with T1D who have undetectable C-peptide.
Whether appropriately timed exogenous insulin can modify the glucagon response to glucose
fluctuations has not been studied. As such, this pilot study aims to characterize the
glucagon response to meal-time hyperglycemia and to compare the difference in glucagon
secretion when mealtime bolus insulin is given before the meal versus after the meal with the
objective of understanding factors that contribute to the peak post-prandial blood glucose
and AUC of blood glucose after a mixed meal in this target population.