Abnormal proinsulin/C-peptide ratio in juvenile diabetes

B-cell function was studied in 20 diabetic children, with an age at onset of diabetes between 1.16 years (8.8 +/- 4.0). Serum samples were taken before the first insulin injection and after 1, 3, 6, 9 and in a few patients after 18 months. At 3, 9, and 18 months the patients were also given a standardized breakfast load. Serum proinsulin, C-peptide, IRI and insulin antibodies (IgG) were determined. At onset 19 patients had measurable C-peptide (0.22 +/- 0.17 pmol/ml; range 0.05-0.58). Proinsulin varied between 0.000-0.25 pmol/ml (0.069 +/- 0.071) and at onset amounted to 31.3 +/- 29.4 (0.100)% of C-peptide as compared to 3.3 +/- 1.1 (1.7-6.6) in non-diabetics. A long partial remission was significantly correlated to a low proinsulin/C-peptide ratio at onset. In patients with low fasting proinsulin and no insulin antibodies, breakfast stimulation was accompanied by an increased proinsulin release at 3 and 9 months. The results suggest that abnormal proinsulin secretion is a feature of the 'B-cell exhaustion' complex in juvenile-onset diabetes.