Long-Acting C-Peptide Improved Vibration Perception Threshold in Diabetic Neuropathy

While there was no overall improvement, treatment with long-acting C-peptide improved vibration perception threshold.

Subcutaneous administration of long-acting C-peptide once a week for 52 weeks did not improve sural nerve conduction velocity or peripheral neuropathy, but it significantly improved vibration perception threshold in type 1 diabetes patients with peripheral neuropathy, when compared with placebo, according to data recently published in Diabetes Care.

Patients with type 1 diabetes who have a lack of C-peptide can develop additional microvascular complications. However, previous studies have shown that replacing C-peptide has improved peripheral nerve function in type 1 diabetes, prompting researchers to evaluate the safety and efficacy of a long-acting C-peptide in patients with type 1 diabetes with mild or moderate peripheral neuropathy.

Researchers enrolled 250 patients with type 1 diabetes and peripheral neuropathy in the study. The participants received pegylated C-peptide in weekly doses of 0.8 mg (n=71) or 2.4 mg (n=73) or placebo (n=106) for 52 weeks. They measured sural nerve conduction velocity and vibration perception threshold on the big toe at start of the study and at26 and 52 weeks, and used modified Toronto Neuropathy Score (mTCNS) to grade the peripheral neuropathy.

Plasma concentrations of C-peptide rose to 1.8 nmol/L to 2.2 nmol/L for the low-dose group and 5.6 nmol/L to 6.8 nmol/L for the high-dose group. After 52 weeks of treatment, sural nerve conduction velocity increased by 1.30 meters per second (P<.005) among the patients receiving C-peptide in the low-dose group, and by 0.64 meters per second (P<.025) in the high-dose group. However, a similar increase was also observed in the placebo group (1.19 meters per second).

The authors note that the improvement in the placebo group could be due to extra care and attention given to the participants during the clinical trial, or due to changes in lifestyle inspired by the study.

“Irrespective of the mechanism involved, the present and previous findings of a marked placebo response for [sural nerve conduction velocity] in clinical trials of diabetic neuropathy raises the question whether [nerve conduction velocity] is an optimal and biologically meaningful outcome variable in studies of this type,” they stated.

The mTCNS remained unchanged throughout the study. Levels of vibration perception threshold, however, lowered gradually for both the low-dose group (P<.003) and the high-dose group (P<.02) over the course of the study. The low-dose group had lowered their vibration perception threshold by an average of 31% and the high-dose group by 19%. Researchers observed very little change in vibration perception threshold in the placebo group.

“The marked [vibration perception threshold] improvement observed in the current study, although associated with nonsignificant changes in [sural nerve conduction velocity], other electrophysiological variables, or mTCNS, can be interpreted as targeted improvement in a key aspect of sensory function,” the authors noted.

“The longer duration of the current study and an improved technique of recording [vibration perception threshold] possibly contributed to the present distinctive improvement.”


  1. Wahren J, Foyt H, Daniels M, Arezzo JC. Long-Acting C-peptide and Neuropathy in Type 1 Diabetes—A 12-Month Clinical Trial. Diabetes Care. 2016;39. doi: 10.2337/dc15-2068.