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C-Peptide May Improve Sub-clinical Neuropathy in Type I Diabetics: Presented at EASD

By Emma Hitt
Special to DG News

BUDAPEST, HUNGARY -- September 4, 2002 -- C-peptide may ameliorate early signs of sensory nerve dysfunction in type 1 diabetics with sub-clinical neuropathy, according to new research.

Until recently, C-peptide was thought to be biologically inactive, but recent studies suggest that C-peptide may, in fact, bind to a G-protein coupled cell membrane receptor and activate Ca²⁺-dependent intracellular signaling pathways.

"C-peptide has been shown in vivo to stimulate Na⁺,K⁺ATPase activity and blood flow in several tissues, including peripheral nerves," Dr. Karin Ekberg, with the Department of Surgical Sciences at the Karolinska Institutet, Stockholm, Sweden, said in an interview.

"Since diabetic neuropathy is accompanied by reductions in both nerve blood flow and nerve Na⁺,K⁺ATPase activity, we hypothesized that C-peptide may have a beneficial effect on nerve function," she said.

Dr. Ekberg and colleagues presented their findings Tuesday, September 3^rd during the European Association for the Study of Diabetes (EASD) meeting in Budapest, Hungary.

The researchers randomised 49 patients without symptoms of neuropathy to receive placebo or three months of subcutaneous C-peptide treatment, 600 nmol administered in four doses, every 24 hours, together with their regular insulin therapy.

Forty-six patients completed the study. Their average age was 29 years, average diabetes duration was 10 years, average body mass index (BMI) was less than 30, and average HbA_1c was 7 percent.

Before and during the treatment period, the researchers bilaterally assessed nerve conduction velocity and quantitative sensory ability in the lower extremities.

At baseline, the study participants showed reduced nerve conduction velocities in both the sural and peroneal nerves, compared to a matched control group, suggesting that the participants began the study with sub-clinical neuropathy.

After six weeks of treatment, the C-peptide-treated group experienced an increase in sensory conduction velocity (SCV), and after 12 weeks, the increase was significantly improved (p<0.05 as compared to placebo).

Furthermore, the change in SCV was accompanied by an improvement in vibration perception in the patients receiving C-peptide (p<0.05 as compared to placebo).

In contrast, no significant differences could be detected in motor conduction velocity (MCV) or in cold or heat perception between the C-peptide and placebo groups.

"This is the first study in patients to document these positive effects of C-peptide in humans," Dr. Ekberg pointed out.

According to Dr. Ekberg, efficacy in patients with symptomatic rather than sub-clinical diabetic neuropathy will be required for C-peptide to be recommended as a treatment.

"However, if proven efficacious, all patients with type 1 diabetes might benefit from C-peptide as preventive medication for neuropathy, and possibly other diabetic complications," she said.

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