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

NCT04098549 | Completed

• 1 other identifier: H-19034585
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Keywords

Type 1 Diabetes; Glucose Metabolism; Hypoglycemia; Glucagon

Outcome Measures

Primary Outcomes (1)

• Positive incremental area under the glucose curve (PI-AUC) (using the plasma glucose concentration before glucagon administration as basal level)

  from 0-120 minutes after glucagon administration

Secondary Outcomes (19)

• Total area under the glucose curve (AUC)

  from 0-120 minutes after glucagon administration

• Peak plasma glucose

  from 0-120 minutes after glucagon administration

• Incremental plasma glucose peak

  from 0-120 minutes after glucagon administration

• Time-to-peak plasma glucose

  from 0-120 minutes after glucagon administration

• Plasma glucose level

  120 minutes after glucagon administration

Study Arms (2)

Rapid-Slow

EXPERIMENTAL

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.

Other: Rapid lowering of plasma glucose; Other: Slow lowering of plasma glucose

Slow-Rapid

EXPERIMENTAL

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.

Other: Rapid lowering of plasma glucose; Other: Slow lowering of plasma glucose

Interventions

Rapid lowering of plasma glucose OTHER

Rapid lowering of plasma glucose using hypoglycemic clamp technique

Rapid-Slow; Slow-Rapid

Slow lowering of plasma glucose OTHER

Slow lowering of plasma glucose using hypoglycemic clamp technique

Rapid-Slow; Slow-Rapid

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• University of Copenhagen: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 23, 2019
• Study Start: September 12, 2019
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: June 25, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

DK (1)