Impact of routine clinic measurement of serum C‐peptide in people with a clinician‐diagnosis of type 1 diabetes

Abstract

The aim of this study was to determine the impact of the routine use of serum C-peptide in an out-patient clinic setting on individuals with a cliniciandiagnosis of type 1 diabetes. Methods: In this single-centre study, individuals with type 1 diabetes of at least 3 years duration were offered random serum C-peptide testing at routine clinic review. A C-peptide ≥200 pmol/L prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet cell antibodies and genetic testing. Where appropriate, a trial of anti-diabetic co-therapies was considered. Results: Serum C-peptide testing was performed in 859 individuals (90% of the eligible cohort), of whom 114 (13.2%) had C-peptide ≥200 pmol/L. The cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). The majority of reclassifications were to type 2 diabetes (44 individuals; 5.1%), with a smaller proportion of monogenic diabetes (14 individuals; 1.6%). Overall, 13 individuals (1.5%) successfully discontinued insulin, while a further 16 individuals (1.9%) had improved glycaemic control following the addition of co-therapies.The estimated total cost of the testing programme was £23,262 (~€26,053), that is, £27 (~€30) per individual tested. In current terms, the cost of prior insulin therapy in the individuals with monogenic diabetes who successfully stopped insulin was approximately £57,000 (~€64,000). Conclusions/interpretation: Serum C-peptide testing can easily be incorporated into an out-patient clinic setting and could be a cost-effective intervention. C-peptide testing should be strongly considered in individuals with a clinician-diagnosis of type 1 diabetes of at least 3 years duration. K E Y W O R D SC-peptide, misclassification, monogenic diabetes, reclassification, type 1 diabetes, type 2 diabetes, type 1 diabetes genetic risk score Click here to access the podcast for this paper. of 1|FOTEINOPOULOU ET aL. F I G U R E 2 Distribution of C-peptide levels by final diagnosis. Data are from the 114 individuals with C-peptide ≥200 pmol/L. Median C-peptide was highest in those reclassified to type 2 diabetes, but there was substantial overlap between the three groups.

The absence of islet autoantibodies in clinically diagnosed older-adult onset type 1 diabetes suggests an alternative pathology, advocating for routine testing in this age group

“…As expected, this was lower in young-adults but still 45% of those negative for all islet autoantibodies and 6% of the entire age group. Our results are supported by another recent study which used C-peptide at over 3 years duration to define type 1 diabetes and found a similar rate of misclassification (20). Foteinopoulou et.…”

“…Foteinopoulou et. al showed the presence of non-type 1 diabetes in 14% and 7% of all individuals who were clinically thought to have type 1 diabetes aged ≥30 years and 18-30 years respectively at diagnosis (20). All the misclassifications in their study were seen in antibody negative participants.…”

“…Or could suggest the inclusion of people with non-type 1 diabetes, misclassified as type 1 diabetes thereby increasing the proportion of observed negative islet autoantibody cases. We and others have shown that misdiagnosis of older-adult onset type 1 diabetes is common (12, 19, 20). A high frequency of non-type 1 diabetes contributing to islet antibody negative clinically diagnosed adult onset type 1 diabetes would support routine testing of islet autoantibodies in this age group.…”

Type 1 or type 2 diabetes: has the ship already sailed?

“…This study enabled reclassification of diabetes type in 6.8% of patients; however, insulin treatment was only stopped in 1.5% of the patients studied. 10 The American Diabetes Association (ADA) standards of medical care for diagnosis and classification of diabetes type acknowledge that some individuals cannot be diagnosed with diabetes type at the time of diagnosis and that time may be required to appreciate beta cell deficiency. These standards suggest measuring islet autoantibodies in adults presenting with diabetes who do not have any traditional risk factors for type 2 diabetes such as obesity, hypertension, dyslipidaemia or a family history of type 2 diabetes, as would have been applicable for the case reported here at the time of diagnosis.…”

Outside in

“…However, diabetes subtype identification can be challenging for clinicians, so the publication of a stratified diagnostic pathway for diabetes subtype assignment is especially welcome. 10 The pathway, which includes the assessment of c-peptide, auto-antibodies and genetics where appropriate, can be implemented in any clinic and is effective in reassigning diagnoses, changing treatment and identifying families where genetic counselling may be helpful. For more discussion of this, head to the Diabetic Medicine podcast homepage where I interview the lead investigator (www.…”