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

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.Participants will be asked to complete:a Mixed Meal Tolerance Test (MMTT) at Visit 1 or 2an Arginine Stimulation Test (AST) at Visit 1 or 2a Light MMTT or repeat AST at Visit 3 (approx 6-7 months of Visit 1)continuous glucose monitoring (CGM) and self-reported time spent in hypoglycaemia will be undertaken for 2 weeks following Visits 1 and 3.

Inclusion Criteria:Clinical diagnosis of Type 1 diabetesInsulin treatedKnown urine C-peptide status (using Urinary C-Peptide Creatinine Ratio [UCPCR], positive/negative defined by UCPCR 0.2nmol/mmol cut-off)Age 16-65 years inclusiveAble and willing to provide informed consent/assent.Exclusion Criteria:Age less than 16 year or over 65 yearsPregnant or lactating (as this may limit blood sampling and affect T cell function)Any medical condition that, in the opinion of the investigator, would affect the safety of the subject's participation, or validity of results.