IN-VIVO GLUCOSE-METABOLISM, INSULIN-SECRETION AND, INSULIN ACTION IN EUROPIDS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM) AND THEIR FIRST-DEGREE RELATIVES

In this review we will mainly concentrate on the most common form of N IDDM in Europe, namely the form linked to overweight, arterial hyperte nsion, dyslipoproteinaemia and coronary heart disease (CHD)-the Insuli n Resistance Syndrome (IRS).(1,2) This form of NIDDM seems to be growi ng epidemically world wide following the industrial growth or the 'coc acolanization', as it has been mentioned.(3) Around 2-3 % of the popul ation in Europe suffers from this disease, but for subjects beyond 60 years of age the prevalence is 5-20 %.(3) Thus, we face an enormous ec onomical, social, and humanitarian challenge. Therefore it is importan t to continue the research on aetiology and pathophysiology of this sy ndrome. The results of treatment of NIDDM patients (often started at 6 0 years of age) have been rather disappointing; even properly treated NIDDM patients develop substantial complications, especially macroangi opathy.(2,3) Coronary heart disease is the main cause of death in thes e patients and the overall mortality rate in NIDDM patients is 3-4 tim es higher than in comparable non diabetic-subjects.(6) Furthermore, se veral complications may already be present at the diagnosis of the dis ease, which indicate that macroangiopathy may not be secondary to the diabetic state itself, but rather a part of the NIDDM phenotype(1). Ba sed on these findings it seems obvious that the IRS must be diagnosed in the prediabetic states before macroangiopathy has started or reache d a clinically manifest level. In this review, therefore, we will disc uss the metabolic background of NIDDM and especially focus on the path ophysiological mechanisms leading to hyperglycaemia, i.e. alterations in glucose effectivenesss, insulin action and insulin secretion in pre diabetic states.