In vivo glucose metabolism, insulin secretion and, insulin action in Europids with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives

Abstract

In this review we will mainly concentrate on the most common form of NIDDM in Europe, namely the form linked to overweight, arterial hypertension, dyslipoproteinaemia and coronary heart disease (CHD)-the Insulin Resistance Syndrome (IRS). This form of NIDDM seems to be growing epidemically world wide following the industrial growth or the 'cocacolanization', as it has been mentioned. Around 2-3% of the population in Europe suffers from this disease, but for subjects beyond 60 years of age the prevalence is 5-20%. Thus, we face an enormous economical, social, and humanitarian challenge. Therefore it is important to continue the research on aetiology and pathophysiology of this syndrome. The results of treatment of NIDDM patients (often started at 60 years of age) have been rather disappointing; even properly treated NIDDM patients develop substantial complications, especially macroangiopathy. Coronary heart disease is the main cause of death in these patients and the overall mortality rate in NIDDM patients is 3-4 times higher than in comparable non diabetic-subjects. Furthermore, several complications may already be present at the diagnosis of the disease, which indicate that macroangiopathy may not be secondary to the diabetic state itself, but rather a part of the NIDDM phenotype. Based on these findings it seems obvious that the IRS must be diagnosed in the prediabetic states before macroangiopathy has started or reached a clinically manifest level. In this review, therefore, we will discuss the metabolic background of NIDDM and especially focus on the pathophysiological mechanisms leading to hyperglycaemia, i.e. alterations in glucose effectiveness, insulin action and insulin secretion in prediabetic states.