The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes

NCT ID: NCT04098549

Last Updated: 2020-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-12
• Study Completion Date: 2020-01-15

Brief Summary

In the effort of better understanding the glucose control in people with type 1 diabetes, in-depth insight into the physiology of hepatic glucose production and its influencing factors is essential. Previously, a number of potential influencing factors of hepatic glucose production have been investigated, including insulin-on-board, low carbohydrate diet, preceding ethanol intake, exercise and multiple stimulations of hepatic glucose production. Previous post-hoc analysis of dual-hormone closed-loop systems has indicated that the rate of fall in blood glucose influences the following stimulation of hepatic glucose response. However, the rate of fall in blood glucose is highly related to insulin levels, which may explain those findings. Thus, in this study the investigators want to examine whether the different rates of fall in blood glucose with similar insulin levels on board affect the hepatic glucose response in individuals with type 1 diabetes. In the study, which will be conducted at Steno Diabetes Center Copenhagen, participants will complete two study visits. On each visit, a hypoglycemic clamp technique will be used to lower the blood glucose levels of the participants (using either a rapid or slow decline rate), whereupon hepatic glucose production will be stimulated using low-dose glucagon. The study days are divided into four phases: 1) preparation phase, 2) hyperinsulinemic euglycemic phase (stabilization of blood glucose), 3) hyperinsulinemic hypoglycemic phase (rapid or slow decline in blood glucose) and 4) post-glucagon administration phase. This design will allow the investigators to examine whether differences in hepatic glucose response exist depending on preceding rate of fall in blood glucose. We hypothesize that the rate of fall in blood glucose does not affect the hepatic glucose production.

Conditions

Type 1 Diabetes; Blood Glucose, Low; Glucose Metabolism Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Rapid-Slow

This arm will begin with intervention "rapid" (rapid rate of fall in plasma glucose) for the first study visit and proceed to intervention "slow" (slow rate of fall in plasma glucose) for the second study visit.

Group Type: EXPERIMENTAL

Rapid lowering of plasma glucose

Intervention Type: OTHER

Rapid lowering of plasma glucose using hypoglycemic clamp technique

Slow lowering of plasma glucose

Intervention Type: OTHER

Slow lowering of plasma glucose using hypoglycemic clamp technique

Slow-Rapid

This arm will begin with intervention "slow" (slow rate of fall in plasma glucose) for the first study visit and proceed to intervention "rapid" (rapid rate of fall in plasma glucose) for the second study visit.

Group Type: EXPERIMENTAL

Rapid lowering of plasma glucose

Intervention Type: OTHER

Rapid lowering of plasma glucose using hypoglycemic clamp technique

Slow lowering of plasma glucose

Intervention Type: OTHER

Slow lowering of plasma glucose using hypoglycemic clamp technique

Interventions

Rapid lowering of plasma glucose

Rapid lowering of plasma glucose using hypoglycemic clamp technique

Intervention Type: OTHER

Slow lowering of plasma glucose

Slow lowering of plasma glucose using hypoglycemic clamp technique

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 18-70 years
• Duration of Type 1 Diabetes ≥ 3 years
• Insulin pump use > 6 months

Exclusion Criteria

• Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
• Allergy or intolerance to lactose or GlucaGen (Novo Nordisk, Bagsværd, DK)
• Use of medications that are known to cause QT interval prolongation
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
• Females who have different basal insulin pattern depending on their menstrual cycle
• Inability to understand the individual information and to give informed consent
• Current participation in another clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject
• Other concomitant medical or psychological condition that according to the investigator's assessment makes the individual unsuitable for study participation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Steno Diabetes Center Copenhagen

Gentofte Municipality, , Denmark

Countries

Denmark

Other Identifiers

H-19034585

Identifier Type: -

Identifier Source: org_study_id