The pathogenesis of type II diabetes mellitus. A brief survey

Type II, non-insulin-dependent, diabetes mellitus occurs worldwide, though with great variations in prevalence rates: the highest rates--about 30-35%--are reported for the Pima Indians and for the population of the island Nauru in the Pacific. The disease is to some extent inherited, but the mode of inheritance is unknown. Recent studies of the length polymorphism of the insulin gene, however, suggest that it may be possible to find a genetic marker for the disease. Obesity is common among type II diabetics, and the occurrence of the type II diabetes increases with age. One possible explanation is that both obesity and advanced age are associated with a decrease in insulin sensitivity. Insulin resistance is a common finding in type II diabetes; it has been demonstrated with several methods, including the euglycaemic insulin clamp technique. The role of insulin receptor and post-receptor defects in the pathogenesis of this insulin resistance is currently being studied with great interest. In addition to impairment of insulin sensitivity, there is a reduction in glucose-stimulated insulin secretion in individuals with type II diabetes. The primary defect of the disease, however, has yet to be established. Type II diabetes may well be a heterogeneous disorder with several different aetiologies; one argument for heterogeneity within the disease is the chlorpropamide alcohol flush reaction that can be demonstrated among about one third of type II diabetics. Further investigations of the pathogenesis of the disease are needed, and it is hoped that these will pave the way for the development of more specific therapy, and even prevention of the disease.