The effect of long-term diphenylhydantoin therapy on glucose tolerance and insulin secretion: a controlled trial.

The influence of long-term administration of diphenylhydantoin (DPH) on glucose tolerance and insulin secretion was studied in a random controlled trial in non-epileptic patients receiving the drug for 2 years following recovery from myocardial infarction. While receiving DPH, insulin response to glucose was less than that in the control group, both in absolute terms and when related to the blood glucose level. Despite this, glucose tolerance did not differ from the control group. One month after cessation of DPH, the plasma insulin response had returned to the levels found in the control group, and glucose tolerance had improved to be significantly better than that found in the control group. Thus, the tendency of DPH to impair the insulin response to glucose has been confirmed in this controlled study. However, this does not result in significantly impaired glucose tolerance; it is suggested that the decreased insulin secretion is accompanied by improved insulin sensitivity.