Beta cell failure: causes and consequences

In recent years a great deal of discussion has focused on the relative role s of insulin resistance and beta -cell dysfunction in the pathogenesis of t ype 2 diabetes. When considering their relative importance it is critical t hat the two variables are considered in concert. Alterations in insulin sec retion are present in patients with type 2 diabetes and can be demonstrated in high risk individuals well before diagnosis. Loss of the early phase of insulin secretion can be demonstrated following oral or intravenous glucos e administration. The relationship of early insulin secretion to insulin se nsitivity in normal individuals is represented by a hyperbolic curve in kee ping with the existence of a feedback loop. Deviations from standardised cu rves demonstrate defects in both insulin secretion and sensitivity in indiv iduals who are at risk of developing diabetes. The reduction in the early p hase insulin response results in impaired suppression of hepatic glucose pr oduction. Glucose output by the liver is not inversely proportionate to glu cose influx, resulting in postprandial hyperglycaemia. Therapeutic approach es must address defects in both the early insulin response and insulin sens itivity. New oral agents that stimulate early insulin secretion and rapid-a cting insulin analogues are targeting this early insulin secretion defect.