Glucagon Response to Prandial Insulin Administration in Persons With Type 1 Diabetes

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Treatments: Glucagon; Glucagon-Like Peptide 1; Insulin; Insulin, Globin Zinc

Criteria

Inclusion Criteria:

• 10 persons with T1D for >5 years age >18.

• HbA1c <9.5%

• Patients using either MDI or insulin pumps will be included.

• Patients using CGM will continue the use during the study, however glucoses will be measured by laboratory methods.

• Persons of all races, ethnicity and genders will be included

• Participants should have normal hemoglobin, hematocrit and eGFR >60 ml/min/1.73m2.

Exclusion Criteria:

• Persons with type 2 diabetes, monogenic diabetes, pancreatic diseases.

• Pregnancy, prisoners, other vulnerable populations or persons unable to understand the protocol and provide written informed consent.

• Persons who take daily steroids, any route, for any purpose