HUMAN PROINSULIN IN INSULIN-TREATED JUVENILE DIABETICS

Abstract. Human proinsulin was determined in a group of 73 diabetics, aged 5–20 years, with onset of diabetes at the age of 1–16 years and a duration of diabetes of 2–17 years. At the time of the investigation, the patients were receiving conventional 5 times crystallized insulin and all had detectable insulin binding IgC. Because of the binding of human proinsulin to insulin antibodies the serum was extracted with acid ethanol. Proinsulin was then determined in fasting serum after removal of human C-peptide which would have interfered with the proinsulin radioimmunoassay. The detection limit in normal serum not containing antibodies was 0.01 pmol/ml. The detection limit in sera that had to be extracted was approximately 0.05 pmol/ml. 31 of the patients (42 %) had detectable serum proinsulin, ranging from 0.055 to 2.00 pmol/ml. In the same group of patients, 19 (26%) had detectable C-peptide. There was a strong correlation between the concentration of human proinsulin and C-peptide ( P < 0.001). 38 normal fasting sera contained from 0 to 0.033 pmol/ml, mean ±S.D.: 0.009 ± 0.008 pmol/ml. The human proinsulin constituted from 0.1 to 92% of the total immunoreactive insulin (IRI) in the 31 patients with detectable proinsulin (mean: 8.5%). Thus it appears that proinsulin was secreted in 42% of 73 insulin treated juvenile diabetics who had had diabetes for 3–14 years, whereas C-peptide was found in 26% of the patients. The insulin antibodies bind a portion of the secreted proinsulin, prolonging its half-life and increasing its serum concentration. Hence, the levels of proinsulin in patients having insulin antibodies are not comparable to those in persons without antibodies.