The Effect of Endogenous GLP-1 on Glucagon Secretion in Type 1 Diabetes

Summary

Type 1 diabetes is a serious and burdensome disease that carries the risk of severe complications and premature death, partly due to low blood sugar, also called hypoglycaemia. This is a constant threat, as individuals with type 1 diabetes lack the body's natural safeguard against low blood sugar: the hormone glucagon, which is normally released from the pancreas. Recent research in mice suggests that this missing safeguard may be due to an imbalance in the hormones released from different cells in the pancreas. More specifically, glucagon-like peptide-1 (GLP-1) appears to play a role in the lack of glucagon secretion. By blocking this hormone using the substance exendin(9-39)NH₂, normalization of glucagon release during low blood sugar has been observed in mice with type 1 diabetes. The present study aims to investigate whether the same mechanism applies in humans with type 1 diabetes. If confirmed, this finding could form the basis for a novel adjunct treatment to insulin therapy and thereby potentially reduce the risk of hypoglycaemia in this patient group.

Eligibility

Inclusion Criteria:

* Caucasian ethnicity
* Age between 18 and 70 years
* T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c \<69 mmol/mol (\<8.5%)
* Body mass index between 19 and 30 kg/m2
* T1D duration of 2-30 years
* C-peptide negative (5 gram arginine-stimulated C-peptide ≤100 pmol/l)
* Treatment with a stable basal-bolus or insulin pump regimen for ≥3 months

Exclusion Criteria:

* Anaemia (haemoglobin below normal range)
* Late microvascular complications except mild non-proliferative retinopathy
* Liver disease (Evaluated by alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) \>2 times normal values) or a history of hepatobiliary disorder
* Kidney disease (serum creatinine above normal range)
* Treatment with any glucose-lowering drugs beside insulin
* Active or recent (within 5 years) malignant disease
* Regular tobacco smoking or use of other nicotine-containing products
* Any condition considered incompatible with participation by the investigators.

Conditions2

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