Fifty-two normal non-obese males and 77 male offspring of two diabetic parents, aged 15-72 years, were studied to identify possible reasons for discordance between the oral glucose tolerance test (OGTT) and hemoglobin A1c (Hb A1c). Subjects were classified into four study groups: group 1 (n = 83), normal OGTT and normal Hb A1c; group 2 (n = 19), normal OGTT and abnormal Hb A1c; group 3 (n = 9), abnormal OGTT and normal Hb A1c; and group 4 (n = 18), abnormal OGTT and abnormal Hb A1c. Glucose and insulin response were analyzed in each study group. Group 2 showed slightly higher mean glucose areas during the first 60 min of OGTT testing when compared with group 1 (P less than 0.01). Insulin levels, insulin areas and insulin/glucose regression coefficients on group 2 did not differ significantly from group 1 during OGTT. Group 3 showed significantly higher mean blood glucose levels than subjects in group 1 (P less than 0.0001) or group 2 (P less than 0.001), but significantly lower mean blood glucose levels than subjects in group 4 (P less than 0.04) throughout the OGTT. During the OGTT, group 3 showed marked absolute hyperinsulinism when compared with all other groups (P less than or equal to 0.002). Also, relative hyperinsulinism in group 3 was suggested by the elevated insulin/glucose regression coefficient (1.86 +/- 0.50) when compared with group 1 (1.17 +/- 0.09), group 2 (0.92 +/- 0.011) or group 4 (0.55 +/- 0.17) (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)