The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People With Type 1 and Type 2 Diabetes
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Liraglutide Pen Injector, Saline Injections.
- Who it may be relevant to
- Registry conditions: Type 1 Diabetes, Type 2 Diabetes. Basic parameters: 25 years — 70 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People
Overview
The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. There is evidence that α-cell proglucagon processing is subject to paracrine regulation by the β-cell3. It is unclear if the effects of GLP1R agonism on islet GLP-1 differ in Type 1 diabetes (T1DM) compared to T2DM. This experiment will examine the effect of glycemic control ± a GLP1R agonist on islet GLP-1 in people with (T2DM) and without (T1DM) β-cells.
Detailed description
The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-15,6. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin (basal and 1st phase) and glucagon secretion. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets.
There is evidence that α-cell proglucagon processing is subject to paracrine regulation by the β-cell. β-cell secretion of the signaling peptide 14-3-3-Zeta is decreased by GLP1R agonism (Fig.1), stimulating α-cell production of GLP-1. This is a testable hypothesis in humans; people with type 1 diabetes (T1DM) have dysregulated glucagon secretion and evidence of islet GLP-1. It is unclear if the effects of GLP1R agonism on islet GLP-1 differ compared to T2DM. This experiment will examine the effect of glycemic control ± a GLP1R agonist on islet GLP-1 in people with (T2DM) and without (T1DM) β-cells.
Interventions
- Drug Liraglutide Pen Injector
Liraglutide 0.6mg - Other Saline Injections
Saline in syringes to serve as placebo for single blind study
Primary outcome measures
- Effect of exendin 9-39 on fasting glucagon secretion rate before and after liraglutide treatment [Time frame: The change in fasting glucagon secretion rate (saline vs. exendin 9-39) in the baseline study will be compared with the change in fasting glucagon secretion rate (saline vs. exendin 9-39) after 30 days of treatment with liraglutide (post-liraglutide)]
- Effect of exendin 9-39 on glucagon secretion rate during hyperglycemia before and after liraglutide [Time frame: The change in glucagon secretion rate during hyperglycemia (saline vs. exendin 9-39) in the baseline study will be compared with the change (saline vs. exendin 9-39) after 30 days of treatment with liraglutide (post-liraglutide)]
Secondary outcome measures (2)
- Effect of exendin 9-39 on fasting glucagon secretion rate in people with type 1 diabetes vs type 2 diabetes [Time frame: The change in fasting glucagon secretion (saline vs. exendin 9-39) in the baseline studies will be compared in people with type 1 diabetes vs type 2 diabetes]
- Effect of exendin 9-39 on glucagon secretion rate during hyperglycemia in people with type 1 diabetes vs type 2 diabetes [Time frame: The change in glucagon secretion during hyperglycemia (saline vs. exendin 9-39) in the baseline studies will be compared in people with type 1 diabetes vs type 2 diabetes]
Eligibility criteria
Inclusion criteria
- Type 1 or type 2 diabetes treated with insulin
Exclusion criteria
- Age < 25 or > 70 years.
- HbA1c > 10.0%
- For female subjects: positive pregnancy test at the time of enrollment or study
- History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
- Prior use of GLP-1 receptor agonists in the previous year.
- Active systemic illness or malignancy.
- Symptomatic macrovascular or microvascular disease.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Single blind
- Primary purpose
- Basic science
Study locations
United States · 1 center
- Mayo Clinic in Rochester — Rochester
Identifiers
NCT: NCT06976619 · 24-007682