Study Examines Impact of Higher C-Peptide Levels on T1D

The new findings come from a 15-year study examining the natural course of C-peptide in children and adolescents with type 1 diabetes (T1D).

A marker of pancreatic function in patients with diabetes may have implications for insulin requirements and diabetes complications over time, suggest new findings.

The new findings come from a 15-year study examining the natural course of C-peptide in children and adolescents with type 1 diabetes (T1D). C-peptide, which connects insulin’s A-chain to B-chain, is more stable and has a longer half-life than insulin and as a result has been used to examine insulin secretion capacity in patient with T1D.

“Previously, C-peptide was considered as a byproduct generated during insulin synthesis and only used in estimating the pancreatic function of diabetes mellitus (DM) patients,” described the researchers. “However, many recent studies have re-evaluated the clinical importance of C-peptide as a representative marker of insulin secretary function. Some studies have reported that residual beta cell function displays a protective effect against the development of diabetes complications and hypoglycemia.”

The researchers noted that longitudinal data on patterns of C-peptide levels, and its impact, over time is scarce. Adding to the limited data, they found that patients who had higher levels of serum C-peptide at diagnosis and after 15 years were treated with lower doses of insulin.

These patients also had a reduced risk of diabetic ketoacidosis (6.8% vs 23.7%).

According to the group, these findings signal that monitoring of serum C-peptide could be leveraged for longitudinal management of the condition. There were no significant associations between serum C-peptide levels and HbA1c levels or microvascular complications.

In total, data from 234 patients were collected; the median age of diagnosis was 8.3 years. Following diagnosis, serum C-peptide levels dropped throughout the study period, with a significant dip in levels at 3 years postdiagnosis. By year 15, just over one-fourth (26.2%) of patients had detectable serum C-peptide.

“Several hypotheses are presented to explain the clinical implications of residual C-peptide secretion in T1DM. Some previous studies suggested that C-peptide acts as an endogenous antioxidant, which protects pancreatic beta cells by increasing catalase expression and reducing peroxisomal oxidative stress,” wrote the researchers. “Additionally, Thivolet et al. reported an association between residual C-peptide levels and reduction in response to glucagon-like peptide-1 (GLP-1). Although the mechanism is not clearly elucidated yet, the clinical benefit from preserved C- peptide secretion in DM patients is widely known.”

In a stratified analysis, the researchers found that patients who were older at diagnosis have higher mean serum C-peptide levels, although the group-by-time results were not statistically significant. Similar findings were seen with body mass index (BMI). While patients with higher BMI at baseline had higher levels of serum C-peptide, the group-by-time results were not significant. The researchers noted no significant differences between sex, family history of diabetes, or history of diabetes complications.


Suh J, Lee H, Lee M, et al. Insulin requirement and complications associated with serum C-peptide decline in patients with type 1 diabetes mellitus during 15 years after diagnosis. Front Endocrinol. Published online April 19, 2022. doi:10.3389/fendo.2022.869204

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