C-peptide Secretion In Patients Research Articles

Preserved C-peptide secretion in patients with type 1 diabetes and incipient chronic complications is associated with lower serum resistin and higher uric acid levels.

Previous studies suggested that long-term perseverance of beta-cell function in patients with type 1 diabetes (T1DM) is associated with lower incidence of microvascular complications. The objective of this study was to evaluate preserved C-peptide secretion in patients with T1DM without overt chronic complications and to explore associations with resistin and uric acid as biomarkers of microvascular complication pathogenesis. We assessed residual beta-cell function in 164 T1DM patients (male/female = 91/73; age/diabetes duration range = 18-70/1-30years) using an ultrasensitive C-peptide ELISA assay with detection limit of 2.5pmol/L and total coefficient of variation (CV) 5,8% (Mercodia, Sweden). Serum level of uric acid was measured by enzymatic method (AU680, Beckman Coulter, USA) while resistin concentration was determined by the ELISA assay (Biovendor, Czech Republic). C-peptide secretors had shorter diabetes duration (5.1 vs. 16years; p< 0,001), lower resistin (4.53 vs. 4.93mg/mL p= 0.045), and higher uric acid (259 vs 238μmol/L, p= 0.048) level than T1DM patients with no detectable C-peptide levels, while no differences in routine anthropometric and laboratory variables, including HbA1c, were observed. Although the proportion of C-peptide secretors significantly decreased across categories of diabetes duration (70%, 38%, 17% and 15% for <5, 5-10, 10-20 and 20-30years of duration, respectively; p< 0,001), detectable C-peptide was found in 5/23 T1DM patients who were diagnosed with T1DM more than 20years ago. The results of our study revealed that patients with detectable C-peptide had lower resistin and higher uric acid level compared to patients with undetectable C-peptide.

Efficacy and safety of low‐dose otelixizumab anti‐CD3 monoclonal antibody in preserving C‐peptide secretion in adolescent type 1 diabetes: DEFEND‐2, a randomized, placebo‐controlled, double‐blind, multi‐centre study

PhaseIII DEFEND-2 investigated whether otelixizumab (3.1mg over 8days) preserved C-peptide secretion in patients with new-onset Type1 diabetes, focusing on adolescents (12-17years). One hundred and seventy-nine patients (54 adolescents) were randomized to otelixizumab or placebo. The primary endpoint was change in 2-h mixed-meal-stimulated C-peptide area under the curve at month12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1. DEFEND-2 terminated early after 12months' efficacy and safety follow-up. Change from baseline C-peptide was not significantly different [∆=-0.09nmol/l (95%CI -0.17 to 0; P=0.051)]. No differential C-peptide effect was seen for otelixizumab in adolescents and more adverse events were reported. Efficacy and tolerability of otelixizumab was similar to DEFEND-1. The 3.1-mg dose was non-efficacious in adults and adolescents. Further investigation of the mechanism of action seen at higher doses and therapeutic window is required. Clinical Trials Registry No: NCT00763451.

Metabolic Factors Affecting Residual Beta Cell Function Assessed by C-Peptide Secretion in Patients with Newly Diagnosed Type 1 Diabetes

In recent onset of type 1 diabetes, the residual beta cell function, assessed by baseline and/or stimulated C-peptide secretion, can be a useful parameter to establish the extension of beta cell destruction. How metabolic parameters at diagnosis influence residual C-peptide secretion is not well established. We analyzed 553 consecutive patients with recent onset (<4 weeks) of type 1 diabetes (250 females and 303 males, mean age 15+/-8 years). Baseline and stimulated C-peptide by i.v. glucagon were evaluated using a highly sensitive radio-immunoassay. Metabolic parameters including blood glucose, HbA1c, insulin dose, and BMI were also evaluated. Baseline and stimulated C-peptide were 0.26+/-0.22 and 0.47+/-0.38 nmol/l and correlated positively with age (p<0.001). There was no significant correlation between C-peptide and blood glucose at diagnosis. BMI was positively correlated with both baseline and stimulated C-peptide secretion (p<0.001). By contrast, HbA1c levels inversely correlated with both baseline and stimulated C-peptide secretion (p<0.001). In type 1 diabetes at diagnosis, baseline and stimulated C-peptide are higher in pubertal and young adult patients compared with pre-pubertal patients suggesting that such parameter can be used as an end point marker for studies aimed at protecting and/or restoring beta cells in patients with substantial beta cell function. High levels of HbA1c and lower BMI are dependent variables of C-peptide values.

Lack of effect of improved glycemic control on C-peptide secretion in patients without residual B-cell function.

Ten patients with insulin-dependent diabetes mellitus underwent a program of intensification of therapy that resulted in marked improvement in glycemic control. C-peptide secretion in response to a test meal and to an intravenous glucagon challenge was used to assess pancreatic B-cell function in terms of residual endogenous insulin secretion. Patients, who had diabetes for a mean (+/- SEM) of 8.4 +/- 1.9 yr, had minimal or no C-peptide response at baseline evaluation. C-peptide responses remained unchanged when reassessed after 2, 4, and 6 mo of improved glycemic control.