Clinical trial NCT04098549: The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes
Official title: The Effect of Rapid and Slow Glucose Fall on the Subsequent Glucose Production in People With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Blood Glucose, Low
Glucose Metabolism Disorders
Keywords: Type 1 Diabetes
Glucose Metabolism
Hypoglycemia
Glucagon
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2019-09-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Positive incremental area under the glucose curve (PI-AUC) (using the plasma glucose concentration before glucagon administration as basal level)
timeFrame: from 0-120 minutes after glucagon administration
Secondary outcomes:
measure: Total area under the glucose curve (AUC)
timeFrame: from 0-120 minutes after glucagon administration
measure: Peak plasma glucose
timeFrame: from 0-120 minutes after glucagon administration
measure: Incremental plasma glucose peak
timeFrame: from 0-120 minutes after glucagon administration
measure: Time-to-peak plasma glucose
timeFrame: from 0-120 minutes after glucagon administration
measure: Plasma glucose level
timeFrame: 120 minutes after glucagon administration
measure: Duration of plasma glucose above 4.0 mmol/l
timeFrame: from 0-120 minutes after glucagon administration
measure: Duration of plasma glucose above baseline
timeFrame: from 0-120 minutes after glucagon administration
measure: Number of subjects who, after reaching a plasma glucose value > 3.9 mmol/l following glucagon administration, maintain a plasma glucose level in the range of 3.9-10 mmol/l
timeFrame: throughout phase 4 (until 120 minutes after glucagon administration)
measure: Number of subjects who, after reaching a PG > 3.9 mmol/l following glucagon administration, maintain a plasma glucose level in the range of 3.9-7.8 mmol/l
timeFrame: throughout phase 4 (until 120 minutes after glucagon administration)
measure: Time from glucagon administration to reaching a plasma glucose level > 3,9 mmol/l
timeFrame: from 0-120 minutes after glucagon administration
measure: Duration of a plasma glucose level in the range of 3.9-10 mmol/l
timeFrame: from 0-120 minutes after glucagon administration
measure: Duration of a plasma glucose level in the range of 3.9-7.8 mmol/l
timeFrame: from 0-120 minutes after glucagon administration
measure: Change in insulin levels (measured as area under the curve)
timeFrame: 0-120 minutes after glucagon administration
measure: Change in insulin levels (measured as peak change)
timeFrame: from baseline to 120 minutes after glucagon administration
measure: Change in glucagon levels (measured as area under the curve)
timeFrame: 0-120 minutes after glucagon administration
measure: Change in glucagon levels (measured as peak change)
timeFrame: 0-120 minutes after glucagon administration
measure: Average changes in Edinburgh Hypoglycemia Scale
timeFrame: measured at baseline, 5 minutes prior to the end of phase 2, 5 minutes prior to the end of phase 3 and 30 and 115 minutes after glucagon administration
measure: Average change in visual analogue scale score for nausea, headache, stomach ache and palpitations
timeFrame: measured at baseline, 5 minutes prior to the end of phase 2, 5 minutes prior to the end of phase 3 and 30 and 115 minutes after glucagon administration
measure: Number of subjects experiencing vomiting
timeFrame: from 0-120 minutes after glucagon administration
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
References: