GLUCOSE-METABOLISM IN OBESE SUBJECTS - LESSONS FROM OGTT, IVGTT AND CLAMP STUDIES

Impaired glucose tolerance and overt diabetes are more frequent in pre sence than in absence of obesity, In obese subjects. glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism. the latter resulting from b oth increased insulin secretion and reduced insulin clearance. Impaire d glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significa nt increase in plasma glucose levels and a late insulin hyperresponsiv eness. Both hyperinsulinaemia and hyperglycaemia are then able to over come peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired su ppression of hepatic glucose output, Overt diabetes then occurs with p ersistent post-absorptive hyperglycaemia, All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weig ht, arguing for acquired rather than inherited metabolic defects in pr esence of morbid obesity. If a sufficient weight reduction can not be obtained. pharmacological approaches may be considered to improve insu lin resistance of obese subjects, especially those with impaired gluco se tolerance or overt diabetes.