DIAGNOSIS AND TREATMENT: SHOULD ORAL HYPOGLYCEMIC AGENTS BE USED IN PEDIATRIC AND PREGNANT PATIENTS?

Abstract

Two Groups of hypoglycemic agents– the sulfonylureas and biguanides* – have achieved widespread acceptance over the past 10 years as therapeutic tools in selected cases of ketosis-resistant diabetes beginning in maturity. From experimental evidence concerning their modes of action and their successful clinical maintenance of normoglycemia in these patients, some investigators have proposed using oral hypoglycemic agents either alone in prediabetes or to supplement insulin in labile diabetes with onset during growth. The use of sulfonylureas and biguanides in diabetes beginning in maturity was originally based on two principal actions of these drugs: 1. The sulfonylureas have a beta-cytotropic effect, which refers to their stimulation of insulin output from islet cells. 2. Both the sulfonylureas and the biguanides enhance insulin action, but by different mechanisms. The enhancement by tolbutamide is not completely understood, but in vivo depends upon the presence of either infused insulin or secreting pancreatic beta-cells.2 In contrast to the sulfonylureas, the biguanides have no effect upon insulin secretion2 but also enhance the hypoglycemic effect of insulin. This action of the biguanides, which manifests itself only in fasting or diabetic man, appears to be caused by both inhibition of hepatic gluconeogenesis and by enhanced glycolysis leading to increased systemic glucose uptake.3 If therapeutic success in diabetes is measured by the maintenance of normal blood sugar rather than by a favorable effect upon vascular disease, these drugs will maintain normoglycemia in appropriate adult patients provided the islet beta-cells are responsive to either pharmacological or physiological stimuli. Since the two classes of drugs have different modes of action, they also have been used to supplement each other in oral therapy.4