The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People With Type 1 and Type 2 Diabetes

Summary

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.

Eligibility

Inclusion Criteria:

* Type 1 or type 2 diabetes treated with insulin

Exclusion Criteria:

1. Age \< 25 or \> 70 years.
2. HbA1c \> 10.0%
3. For female subjects: positive pregnancy test at the time of enrollment or study
4. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
5. Prior use of GLP-1 receptor agonists in the previous year.
6. Active systemic illness or malignancy.
7. Symptomatic macrovascular or microvascular disease.

Conditions3

Locations1 site

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