The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10-12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGs), was much reduced in the evening (AM 2.98 +/- 0.45, PM 1.86 +/- 0.33 min-1, P less than 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 +/- 0.31 min-1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 +/- 0.18 min-1, P greater than 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 +/- 2.9, PM 10.2 +/- 1.9 x 10(-5) min-1/pM, P less than 0.01) and reduced beta-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 +/- 441, PM 1825 +/- 381 pM/10 min, P less than 0.05) and the potentiation slope (AM 462 +/- 68, PM 267 +/- 35 pM/mM, P less than 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 +/- 0.7, PM 4.9 +/- 1.0 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 250 WORDS)