The Effect of Glucose-dependent Insulinotropic Polypeptide on the Alpha Cell Response to Hypoglycaemia in Patients with Type 1 Diabetes
- Conditions
- Type1diabetesHypoglycemiaType 1 Diabetes
- Interventions
- Other: Infusion of GIP[1-42], GIP[1-30] or placebo
- Registration Number
- NCT06137586
- Lead Sponsor
- University Hospital, Gentofte, Copenhagen
- Brief Summary
The goal of this clinical trial is to evaluate the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP) and its two isoforms, GIP\[1-30\] and GIP\[1-42\], in patients with type 1 diabetes. The main question it aims to answer is:
• What dose and isoform of GIP can most potently stimulate glucagon secretion during low blood sugar in patients with type 1 diabetes?
Participants will go through 5 experimental days that are identical except for an intravenous infusion of either placebo (saline), high or low dose GIP\[1-42\] or high or low dose GIP\[1-30\]. On all days, blood sugar will be lowered to around 2.5mmol/l for around 20-30min.
- Detailed Description
After being informed about the study and the potential risks, each participant giving written informed consent will participate in five double-blinded experimental days (Day A-E) in a randomized order. Each experimental day is identical except for an intravenous infusion of either placebo (saline), high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP\[1-42\] or high (8pmol/kg/min) or low (4pmol/kg/min) dose GIP\[1-30\].
Each experimental day will consist of an induction period where the participant's blood sugar is adjusted to around 5-6mmol/l with either insulin or glucose. Then the infusion of either placebo or hormone will be initiated and continued for 135 minutes.
After 30 minutes of hormone infusion, a separate infusion of insulin (1.5mU/kg/min) will be initiated and continued for 60 minutes. Based on frequent bed-side plasma glucose measurements and an adjustable 20% glucose infusion, plasma glucose will be clamped at 2.5 mmol/l until the insulin infusion is terminated. Following this is a 45 minute recovery period, during which a minimum of glucose is infused, to ensure a steady rise from 2.5mmol/l to 3.5mmol/l.
After the study day, patients will receive a meal to prevent subsequent hypoglycemia.
The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
- Caucasian men
- Body mass index between 18-27kg/m2
- Type 1 diabetes (T1D) (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/mol (<8.5%)
- T1D duration of 2-30 years
- C-peptide negative (stimulated C-peptide ≤ 100 pmol/l)
- Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months
- Informed consent
- Anaemia (haemoglobin below normal range)
- Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
- Late microvascular complications except mild nonproliferative retinopathy
- Allergy or intolerance to ingredients included in the standardized meals
- Prior myocardial infarction or other cardiac events
- Any physical or psychological condition that the investigator feels would interfere with trial participation
- Treatment with any glucose-lowering drugs beside insulin
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Infusion of GIP[1-42], GIP[1-30] or placebo Infusion of GIP[1-42], GIP[1-30] or placebo This is a single arm study. All participants will go through all five experimental days in a randomized order. The interventions are A) 4pmol/kg/min GIP\[1-42\] B) 8pmol/kg/min GIP\[1-42\] C) 4pmol/kg/min GIP\[1-30\] D) 8pmol/kg/min GIP\[1-30\] E) Saline (placebo)
- Primary Outcome Measures
Name Time Method Total glucagon response 0-135minutes Difference in baseline subtracted area under the curve (bsAUC) for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
- Secondary Outcome Measures
Name Time Method Total insulin response 0-135minutes Difference in plasma levels of insulin between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in carboxy-terminal collagen crosslinks (CTX) 0-135minutes Difference in plasma levels of CTX between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Glucagon response during insulin infusion 30-90minutes Difference in bsAUC for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively during the insulin infusion
Difference in epinephrine 0-135minutes Difference in plasma levels of epinephrine between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP) 0-135minutes Difference in plasma levels of P1NP between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Total c-peptide response 0-135minutes Difference in plasma levels of c-peptide between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in blood pressure 0-135minutes Difference in blood pressure between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Glucagon response after blood glucose (BG) falls below 3.0 mmol/L t[BG<3.0] and the following 30 minutes Difference in bsAUC for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively in the 30 minutes following a blood glucose of below 3.0 mmol/L
Glucagon response during recovery 90-135minutes Difference in bsAUC for glucagon between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively during the recovery period
Difference in cortisol 0-135minutes Difference in plasma levels of cortisol between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in growth hormone hormones 0-135minutes Difference in plasma levels of growth hormone between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Amount of glucose infused 0-135minutes Difference in infusion rates for glucose between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in norepinephrine 0-135minutes Difference in plasma levels of norepinephrine between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Difference in heart rate 0-135minutes Difference in heart rate between study days with GIP\[1-42\], GIP\[1-30\] and placebo, respectively
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research, Gentofte Hospital
🇩🇰Hellerup, Copenhagen, Denmark