Secondary drug failure in non insulin dependent diabetes

Abstract: SECONDARY DRUG FAILURE IN NON INSULIN DEPENDENT DIABETESON CAUSES AND ASPECTS OF TREATMENTPer Clauson, MD, Department of Endocrinology and Diabetology, KarolinskaInstitute, Stockholm, Sweden Non Insulin Dependent Diabetes (NIDDM) represents a major healthproblem with increased risk of atherosclerotic disease and early death. Thegrave consequences of NIDDM are partly due to inadequate and insufficienttreatment. The purpose of the present study was to study the causes oftreatment failure and evaluate new strategies of treatment.The main aims were1) to study the prevalence of secondary failure (to sulphonylurea drugs) in an area-based NIDDM population (where diabetes of autoimmune origin had been excluded) and the relationship of secondary failure to pancreatic beta-cell function,2) to study reversibility of decreased beta-cell function by short term correction of hyperglycemia,3) to evaluate a combination treatment with sulphonylurea and insulin versus insulin alone,4) to study insulin absorption kinetics in NIDDM patients.The results of this thesis indicate1) that diabetes duration associates with deterioration of metabolic control and a decrease in endogenous insulin secretion,2) that short term correction of hyperglycemia improves insulin secretion to a variable extent,3) that a combination of daytime sulphonylurea and bedtime insulin in secondary failure in NIDDM is as efficient as intensive insulin treatment in improving metabolic control. One advantage of the combination treatment is that it leads to a lesser degree of weight gain after one year compared to intensive insulin treatment,4) that the absorption rate of rapid acting insulin in NIDDM subjects is decreased between 15 and 45% compared to insulin dependent diabetes mellitus (IDDM) patients.Altogether, the study shows that NIDDM is a progressive disease using thepresent therapeutic strategy. New treatment alternatives are needed as wellas better use of existing alternatives.Key words: Non insulin dependent diabetes, treatment failure, insulin,sulphonylurea, insulin-like growth factor-I, insulin-like growth factor bindingprotein-1, insulin secretion, insulin sensitivity, insulin absorption.ISBN 91-628-1949-6