In order to investigate pancreatic islet cell function under long-term treatment with oral hypoglycemic drugs used for maturity-onset diabetics glucose tolerance and immunoreactive insulin (IRI) after a restricted diet were traced in 28 maturity-onset diabetics before and during the 3rd to 42nd months of therapy. In 31 patients with maturity-onset diabetics under long-term treatment hypoglycemic drugs, the functional reverse of insulin secretion was evaluated by the glucose-glucagon-tolbutamide stimulation test proposed by Ryan. The secretory response of insulin to the initial load of 100 g of glucose (reaction A) as a physiological stimulus was compared with that to the successive stimulus by the intravenous administration of glucagon and tolbutamide (reaction B). The concomitant changes in the levels of free fatty acid (NEFA) and human growth hormone (HGH) following the test were also evaluated. The results were as follows.
1) In the groups treated with tolbutamide and acetohexamide plus dietary measures, the insulin glucose index (I/G) at the peak levels slightly increased by the month and thereafter decreased to approach pretreatment levels in the 3rd or 4th year.
2) In the groups receiving N (p-chlorobenzensulfonyl)-N'-pyrrolidinourea (CBPU) and chlorpropamide (p 607) no significant changes in I/G were observed during therapy.
3) A gradual increase in JIG was observed in the group treated with sulfonylurea plus biguanide, though the ratio was less than that of any of the other groups.
4) In 3 patients treated with biguanide plus dietary measures the levels of IRI decreased after therapy, despite the improvement of glucose tolerance.
5) The diabetics who had an improvement or no change in GTT after long-term treatment with hypoglycemic drugs, showed a normal functional reserve of insulin secretion.
6) The insulin levels in reaction B had no correlation with those in reaction A. Good responses of IRI to the intravenous administration of glucagon and tolbutamide were observed in one out of 3 patients who showed lowered IRI responses to the glucose load during long-term therapy with p607.
7) The diabetics with angiopathy, especially retinopathy, showed lowered response of IRI and HGH to the glucose-glucagon-tolbutamide stimulation test.
8) In the obese diabetics the responses of IRI to the test increased, while the responses of HGH decreased.
From these results it was suggested that sulfonylurea therapy for periods up to at least 3 years does not appear to induce an exhaustion of insulin secretory activity.
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