Impact case study database

4.1. A new diagnostic technology has been adopted in the UK to measure how much insulin patients are making themselves

Prior to the research outlined above, C-peptide was rarely measured as part of the clinical care of patients with diabetes, with use confined to investigation of unexplained hypoglycaemia (low blood glucose) in patients without diabetes. The Exeter team’s research has changed this completely. Most diabetes teams in the UK now use this test to help classification and treatment of patients, and many perform the test in all patients with insulin-treated diabetes.

The novel urine c-peptide creatinine ratio (UCPCR) test is now widely available and testing services are offered by seven NHS specialist clinical laboratories across the UK [5.1]. The Blood Sciences laboratory at the Royal Devon and Exeter NHS Foundation Trust alone received over 8,000 NHS referrals for this test in 2019 and has received samples from over 120 hospitals and laboratories in the UK and Ireland. Many other hospital laboratories also use the UCPCR test, including the University of Rochester Medical Centre in New York [5.2]. The test is also now used as a practical measure of insulin secretion in research outside Exeter, with at least 18 papers reporting its use in the past 6 years [5.3].

4.2. Changed national and international diabetes policy and guidelines

National and international guidelines now advocate C-peptide testing as a result of the research from the Exeter group; including from the UK National Institute for Health and Care Excellence (NICE) [5.4]; the Association of British Clinical Diabetologists [5.5]; and the International Society of Pediatric and Adolescent Diabetes [5.6]. NHS National Services Scotland has recently commissioned routine C-peptide testing of everyone diagnosed with type 1 diabetes in Scotland, representing more than 30,000 patients, commencing in February 2021 [5.7].

Professor Strachan, who led the application for national commissioning of C-peptide testing in Scotland, said [5.7]: “ It is in no way an exaggeration to say that the Exeter research completely informed the design of our C-peptide testing program in Edinburgh and that it would have been impossible for us to introduce such a program and the forthcoming national program in Scotland without the Exeter data.”

4.3. Quality of life for people with diabetes has been enhanced through improved diabetes classification and treatment

Between 6-12% of people with insulin-treated diabetes are reclassified following a C-peptide test, and most of them subsequently receive a different treatment. In those previously thought to have type 1 diabetes, a high C-peptide after 3 years duration will confirm either type 2 diabetes (if over 35 years old) or, in younger patients, mean a high likelihood of monogenic diabetes.

In type 2 diabetes adding oral agents to insulin greatly improves glucose control in comparison to insulin alone (reducing risk of diabetes complications), and many patients can stop insulin which has substantial quality of life and cost benefits. Most patients with adolescent or adult onset monogenic diabetes (called MODY) can replace insulin with specific inexpensive tablet therapy and substantially improve glucose levels with large cost savings to the NHS: universal C-peptide testing as part of a strategy to identify MODY has been shown to be cost effective [5.8].

The experience of Edinburgh Royal Infirmary demonstrates the impact of C-peptide testing on patients, as described in the statement from a Consultant Diabetologist [5.7]. By offering testing to all those diagnosed with type 1 diabetes in a single clinic, 58 people previously diagnosed and treated as having type 1 diabetes were reclassified: 14 of these patients actually had monogenic diabetes, and 44 had type 2 diabetes. Thirteen of these patients, who were previously thought to have a lifelong requirement for insulin injections, were able to discontinue insulin and the associated glucose monitoring, and instead use inexpensive tablet therapies. This included young patients who were receiving pump therapy, at a cost of over £3000 per year; and a patient receiving continuous glucose monitoring, which cost about £2000 per year. The money saved by switching the treatment of just one of these patients has covered the entire cost of the C-peptide screening program at the infirmary.

Other patients who added tablets to their insulin therapy as a result of reclassification markedly improved their glucose control, measured by HbA1c, which reduced by 15mmol/mol. Improved glucose control is associated with substantial reductions in diabetes related complications, for example in the UKPDS study (Stratton et.al. BMJ 2000) an 11mmol/mol lower HbA1c was associated with reductions of 37%, 14% and 21% in microvascular complications, myocardial infarction and diabetes related death respectively. Other hospitals have reported similar outcomes, for example selective UCPCR testing in 80 patients at the Surrey and Sussex Healthcare Trust led to 42 patients being reclassified, with 31 changing treatment [5.9].