Increment of serum C-peptide measured by glucagon test closely correlates with human relative beta-cell area

Abstract

Pancreatic beta-cell mass contributes to glucose tolerance. The aim of this study was to evaluate the relationships between human beta-cell mass and various clinical parameters, including insulin secretory capacity. The study included 32 Japanese patients who underwent pancreatectomy and were naive to oral hypoglycemic agents and insulin. They were classified into those with normal glucose tolerance (n=13), impaired glucose tolerance (n=9) and diabetes (n=10), and their insulin secretory capacity and insulin resistance were evaluated. Immunohistochemistry was used to determine relative beta-cell area (%) which represented the proportion of insulin-positive cell area to whole pancreatic section. Increment of C-peptide immunoreactivity level by glucagon test (ΔC-peptide, increment of serum C-peptide [nmol/L] at 6 min after intravenous injection of 1-mg glucagon; r=0.64, p=0.002), homeostasis model assessment of beta-cell function (HOMA-beta, fasting immunoreactive insulin [μIU/mL] x 20 / (fasting plasma glucose [mmol/L] - 3.5); r=0.50, p=0.003), C-peptide index (CPI, fasting C-peptide [nmol/L] / fasting plasma glucose [mmol/L]; r=0.36, p=0.042), and fasting immunoreactive insulin (F-IRI [pmol/L]; r=0.36, p=0.044) correlated significantly and positively with the relative beta-cell area. The area under the curve of plasma glucose level from 0 to 120 min by 75 g-OGTT (AUC0-120) also correlated significantly and inversely with the relative beta-cell area (r=-0.36, p=0.045). Stepwise multiple regression analysis identified ΔC-peptide as the only independent and significant determinant of the relative beta-cell area. We conclude that ΔC-peptide, HOMA-beta, CPI, F-IRI and AUC0-120 correlated closely with the relative beta-cell area, and ΔC-peptide was the most valuable index for the prediction of the area.