An inadequate insulin response to orally administered glucose was demonstrated by prediabetic and diabetic subjects. The insulin deficiency was even more pronounced when oral and intravenous glucose loads were combined. The dose-response curves relating plasma-insulin to the blood-glucose level showed that the secretory capacity of the β-cells is progressively impaired during the development of diabetes from prediabetes. Comparison of the results with previous studies on the glucose/insulin dose-response relation after intravenously administered glucose suggested that intestinal factors enhance the insulinogenic effect of glucose by a factor of 3-4, and that the mechanisms which mediate the potentiating effect of intestinal factors on glucose-induced insulin release are not deranged in prediabetes and diabetes.