One-time serum C-peptide testing detected patients misclassified as having type 1 diabetes

In a recent study, a serum C-peptide testing program resulted in reclassification of the cause of diabetes in about 7% of the cohort tested at one diabetes center in Scotland. Reclassification was most likely in those diagnosed at age 30 years or older.

Serum C-peptide testing may be a cost-effective strategy to identify outpatients with a clinician diagnosis of type 1 diabetes who have been misclassified, a study found.

Researchers at one outpatient diabetes clinic in Edinburgh, Scotland, offered serum C-peptide testing to individuals with type 1 diabetes of at least three years' duration. Testing was done on a nonfasting sample at routine clinic review. The test is most discriminatory when used in patients who have had diabetes for at least three years. All patients had started insulin therapy within three years of diagnosis. A C-peptide level of 200 pmol/L or greater prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet-cell antibodies and genetic testing. Insulin cessation was considered a potential option for individuals with C-peptide levels of 600 pmol/L or greater or with a sulfonylurea-sensitive form of monogenic diabetes (diabetes caused by a single gene mutation). Clinicians also considered a trial of antidiabetic co-therapies when appropriate. Results were published online on Nov. 1 by Diabetic Medicine.

A total of 859 participants had serum C-peptide testing, and 114 (13.3%) had a C-peptide level of 200 pmol/L or more and entered the investigation pathway. They were older at diagnosis than those with a C-peptide level less than 200 pmol/L (median [range] age, 36 [10 to 76] years vs. 19 [1 to 73] years; P<0.01). Only nine of 364 (2.5%) participants who were younger than age 18 years at diagnosis had a C-peptide level of 200 pmol/L or greater, compared with 34 of 221 (15.4%) of those diagnosed at ages 18 to 30 years and 71 of 274 (25.9%) of those diagnosed at ages 30 years and older (P<0.01). Fifty-four of the 114 individuals met the diagnostic criteria for type 1 diabetes, and the cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). Two individuals did not complete the investigation pathway. The majority of reclassifications were to type 2 diabetes (n=44; 5.1%), and the remainder were to monogenic diabetes (n=14; 1.6%). Overall, 13 participants (1.5%) discontinued and remained off insulin, and an additional 16 individuals (1.9%) had improved glycemic control following the addition of antidiabetic co-therapies to insulin. The estimated total one-time costs of the testing program were £23,262 (an average of £27 per individual tested). Cessation of insulin in participants reclassified to type 2 diabetes was broadly cost neutral, as savings were offset by the cost of alternative antidiabetic medication. The net savings for the two individuals with monogenic diabetics who were able to discontinue insulin were about £1,780 per year. Their total duration of insulin therapy, prior to reclassification, was 64 years at a cost of about £57,000.

Among other limitations, the study was performed in one center in a predominantly White population, the authors noted. Since a higher proportion of reclassification to type 2 diabetes may occur in populations with greater ethnic diversity, the study should be replicated in multiple centers with greater ethnic heterogeneity, they said.

“Overall, C-peptide testing was a very cost effective intervention and should be strongly considered in individuals with type 1 diabetes of ≥3 years duration,” the authors concluded.