INSULIN DEFICIENCY AND INCREASED PLASMA-CONCENTRATION OF INTACT AND 32/33 SPLIT PROINSULIN IN SUBJECTS WITH IMPAIRED GLUCOSE-TOLERANCE

In order to determine insulin status and beta cell function during the oral glucose tolerance test (OGTT), in impaired glucose tolerance (IGT), 51 such subjects and matched controls, identified during a population survey for diabetes, underwent a 75 g OGTT. Fasting, 30 min and 2 h insulin and intact proinsulin, and fasting and 2 h 32/33 split proinsulin, were measured by specific two-site immunoradiometric assays. The subjects with IGT had higher fasting (geometric mean +/- SD, 5.0 +/- 4.0 pmol-1 vs 2.9 +/- 1.7, p < 0.02) and 2 h intact proinsulin (23 +/- 14 vs 14 +/- 12, p < 0.0001), and fasting (3.2 +/- 3 pmol-1 vs 1.8 +/- 1.8, p < 0.0007) and 2 h 32/33 split proinsulin (18.3 +/- 19 pmol-1 vs 6.6 +/- 15, p < 0.0001). Despite higher plasma glucose concentrations, the IGT group had similar fasting insulin, lower 30 min insulin (216 +/- 124 pmol-1 vs 278 +/- 130, p < 0.02), and a lower 30 min insulin/glucose ratio (23.7 +/- 2.1 vs 34.8 +/- 2.3, p < 0.002). The percentage of fasting proinsulin-like to total insulin-like molecules was higher in those with IGT (15.3 +/- 8 % vs 11.6 +/- 8, p < 0.04). After 6 months, at repeat OGTT, the same subjects with IGT were classified as 'persisters' or 'reverters'. The persister (24/51 47.1 %), at initial OGTT, had a higher 2 h glucose level, a greater BMI and higher systolic blood pressure, but other parameters were similar to the reverters. In the reverters, when baseline variables were compared to those recorded at six month follow-up, there was a reduction in 2 h intact (23.8 +/- 13 pmol-1 vs 19.4 +/- 10, p < 0.02) and 32/33 split proinsulin (20.4 +/- 18 pmol-1 vs 13.8 +/- 13, p < 0.006), and an increase in fasting insulin (41 +/- 30 pmol-1 vs 54 +/- 35, p < 0.02), respectively, despite no change in fasting glucose. These findings show that IGT is associated with beta cell dysfunction and reduced early insulin secretion during the OGTT. In some subjects with IGT these abnormalities show improvement in the short term.