The Pattern of Response of Plasma Insulin and Glucose to Meals and Fasting During Chlorpropamide Therapy

SUMMARY

Frequent determinations of insulin and glucose were done in a group of obese diabetics during a 48-hr test period consisting of 24 hr in which normal dietary intake was permitted followed by a 24-hr period of fasting. The subjects were then treated with 500 mg of chlorpropamide per day for 5 days, and the study was repeated. Four patients were also restudied after 5 weeks of drug treatment. Before treatment, both insulin and glucose rose after standard meals from a stable fasting level in a manner similar to that expected in normals and then fell back toward base-line values in the interval between meals. During the fasting study day both glucose and insulin tended to fall slightly. After treatment with chlorpropamide for 5 days the basic pattern of glucose and insulin levels was unchanged, although the plasma glucose was significantly lower at all time points, and insulin levels were higher than control values, both after meals and during fasting. The reduction of plasma glucose present after 5 days of treatment was maintained after 5 weeks of treatment, but insulin levels returned to control levels after the more prolonged treatment period. There was no evidence to suggest that chlorpropamide had increased insulin secretion independently of usual physiologic stimuli. Analysis of the relationships between insulin and glucose suggests that the drug may act in part by increasing the sensitivity of the beta cell to a glucose stimulus.