Stimulated Glucagon as a Biomarker of Hypoglycemic Risk in Type 1 Diabetes

Summary

Type 1 diabetes (T1D) results from destruction of insulin producing beta cells by the body's own immune system (autoimmunity) causing an individual to lose the ability to make enough insulin to control their blood sugar levels and need to have insulin injections to lower blood glucose levels. Whilst high blood sugar level is a problem for people with Type 1 diabetes, taking insulin medication to lower sugar levels, delayed meals and exercise can all result in dangerously low blood sugar levels (hypoglycaemia). The biological causes of hypoglycaemia, and ways to prevent it are poorly understood. In non-diabetic individuals, a hormone called glucagon is secreted naturally to raise blood glucose levels but it is unclear why glucagon secretion is impaired during hypoglycaemia in individuals with T1D.

The aim of this prospective observational study is to test the relationship between a glucagon stimulation test and risk of hypoglycaemia in T1D. It is hoped this research will establish whether this relationship could be used as a blood test and be a clinically useful biomarker of hypoglycaemia risk and, therefore, directly inform clinical care of people with T1D, particularly those with highest risk of hypoglycaemia.

Assessment of beta cell decline has traditionally relied on timed C-peptide measures following a standardised liquid meal known as the mixed meal tolerance test (MMTT). Home finger prick blood spot C-peptide measurement might be a practical, cheap, and non-invasive alternative to a MMTT and would allow regular assessment of beta cell function over time. If proven that this sample type is a robust alternative to the gold standard MMTT venous C-peptide, it would dramatically decrease the cost and participant burden of T1D research into beta cell function.

Conditions

• Type 1 Diabetes
• Hypoglycemia

Interventions

OTHER

Mixed Meal Tolerance Test (MMTT)

At either Visit 1 or Visit 2, participants will be given Ensure HP or Fortisip (a drink containing the same amounts of carbohydrates, protein and fats as there would be in a meal; 6ml/kg to a max of 360mls), and have blood samples collected, to measure insulin (C-peptide), glucose, and glucagon, at specific intervals: -10, 0, 30, 60, 90, 120 minutes post meal. This test is used to measure how a participant's beta cells are working to produce insulin after a meal and to check for reactive hypoglycaemia.

OTHER

Arginine Stimulation Test (AST)

At either Visit 1 or Visit 2, and Visit 3, participants will be given a dose of Arginine Hydrochloride (5 g Arginine during 1 min) by intravenous injection, and have blood samples collected to measure insulin (C-peptide), glucose, and glucagon, at specific intervals: -10, 0, 2, 5, 10, 15 and 30 minutes following the Arginine bolus injection. This test is designed primarily to test the maximum insulin secretion capacity of a participant's beta cells.

OTHER

Home Finger Prick Sample

Participants will be provided with a kit to collect an optional home finger prick sample the day after each visit, and return the sample using the prepaid addressed padded envelope provided.

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust

  collaborator OTHER

• University of Exeter

  lead OTHER

Principal Investigators

• Richard A Oram, MRCP (neph) · University of Exeter

Eligibility

Min Age

16 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-05-03

Primary Completion

2025-01-28

Completion

2025-09-30

Countries

• United Kingdom

Study Locations