β-Cell Dysfunction and Chronic Hyperglycaemia

Abstract

Type 2 diabetes mellitus is a complex illness with both genetic and environmental pathogenic elements. Disturbed insulin secretion(ß-cell dysfunction)and tissue insulin insensitivity(insulin resistance)are jointly found, and there is controversy as to which comes first, and how they interact to lead to diabetes mellitus. Studies in high risk populations for type 2 diabetes have delineated the natural history of type 2 diabetes mellitus (Figure 1): yet undefined genetic mutation(s) combine with metabolic and lifestyle factors to cause the diabetes phenotype. Insulin resistance and 0-cell dysfunction are shown at the bottom of Figure 1: they are present to some degree before glucose intolerance is detectable. The environmental factors aggravate insulin resistance (obesity, inactivity, aging, and pregnancy) or the 13-cell dysfunction (electrolyte abnormalities, several drugs, and malnutrition). However, the insulin resistance typically worsens little during the early stages of the disease, when glucose intolerance progresses to overt fasting hyperglycaemia. Instead, the factor determining whether diabetes occurs is 0-cell function. As long as 0-cells compensate for the insulin resistance through increased insulin secretion, glycaemia can be controlled. Frank diabetes is seen when the 0-cell compensation is lost — i.e.ß-cell failure(1-3).