Acute and Chronic Effect of Chlorpropamide in M.O. Diabetes

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Abstract
The effect of orally administered chlorpropamide to diabetic patients receiving 4 isocaloric meals per day was studied, measuring the serial plasma glucose and insulin levels before and after the 1st dose of chlorpropamide and then after 2-4 wk of continuous treatment. Five diabetic subjects, aged 52-67 years, within .+-. 10% of their ideal body weight were selected. The patients received 4 identical isocaloric meals per day, i.e., breakfast 0900 h; lunch 1300 h; tea 1600 h and dinner 1900 h for each of the 6 days. The exercise per day was also standardized. On the 4th day at 0830 h an i.v. cannula was placed in a median cubital vein and blood samples were then obtained 1/2 hourly for 12 h. The same procedure was undertaken on the 5th day with in addition the oral administration of 250 mg of chlorpropamide (Diabinese) at 0830 h. The patients were discharged from hospital on the 6th day and advised to take chlorpropamide each morning. The patients were re-admitted 2-4 wk later for a further period of 6 days. On the 5th day of the 2nd admission 1/2 hourly samples were again obtained for glucose and insulin over a 12 h period. A lowering of plasma glucose levels of day 1 and a further very significant reduction by day 14-28 was evident in all patients although in 1 patient the 1st day of treatment did not show a clear cut lowering of the plasma glucose. There is a very predictable effect on plasma glucose but a variable and unpredictable effect on plasma insulin. While there was in terms of the glucose lowering response a similarity between the patients, this certainly was not the case for the plasma insulin response. In all patients except one (no. 5) there was an acute increase in plasma insulin levels although by day 14-28 values had returned to pre-treatment levels. The plasma insulin changes were not significant due to the wide individual variation. The correlation between glucose and insulin improved during the course of study, from a significantly negative correlation pre-treatment (r [correlation coefficient] = -0.863) a non-existent association (r = 0.009) after the 1st dose to a significant positive correlation by day 14-28 (r = 0.295). Chlorpropamide has a prolonged half life which may explain its delayed or cumulative glucose response. This aspect can so easily be forgotten in the management of diabetic patients with this compound. A further assessment of the patient newly treated with this agent needs to be made in 2-4 weeks after its commencement in order to avoid excessive hypoglycemia, particularly nocturnal hypoglycemia. The normalization of the glucose/insulin relationship observed may suggest an improvement in insulin sensitivity which may result in a reduced hepatic glucose output and or suppression of glucose production.

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