Secondary drug failure in non insulin dependent diabetes : on causes and aspects of treatment

Abstract: Non Insulin Dependent Diabetes (NIDDM) represents a major health problem with increased risk of atherosclerotic disease and early death. The grave consequences of NIDDM are partly due to inadequate and insufficient treatment. The purpose of the present study was to study the causes of treatment failure and evaluate new strategies of treatment. The main aims were 1) 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 indicate 1) 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 the present therapeutic strategy. New treatment alternatives are needed as well as better use of existing alternatives.