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 (IG T), 51 such subjects and matched controls, identified during a populat ion 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 proin sulin, were measured by specific two-site immunoradiometric assays. Th e 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 concentrati ons, 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 insul in/glucose ratio (23.7 +/- 2.1 vs 34.8 +/- 2.3, p < 0.002). The percen tage of fasting proinsulin-like to total insulin-like molecules was hi gher 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 systol ic blood pressure, but other parameters were similar to the reverters. In the reverters, when baseline variables were compared to those reco rded 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 (2 0.4 +/- 18 pmol-1 vs 13.8 +/- 13, p < 0.006), and an increase in fasti ng insulin (41 +/- 30 pmol-1 vs 54 +/- 35, p < 0.02), respectively, de spite no change in fasting glucose. These findings show that IGT is as sociated with beta cell dysfunction and reduced early insulin secretio n during the OGTT. In some subjects with IGT these abnormalities show improvement in the short term.