Legacy effect in diabetes mellitus: fact or fiction?

Abstract

The “legacy effect or metabolic memory” describes the long-term health benefits of intensive glycemic control early in the course of the disorder in reducing long-term diabetic complications compared to standard glucose control. The association between poor glycemic control and high rates of chronic diabetic complications in patients with type 1 and type 2 diabetes mellitus is well established. Several randomized control trials of intensive diabetes therapy have reported a substantial reduction in both micro- and macro-vascular complications compared to conventional therapy. Several landmark diabetes studies such as the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) have reported long-term reduction in the prevalence of micro- and macro-vascular complications that persist for decades after completion of these studies with intensive intervention compared to conventional diabetes therapy. Recent long-term follow-up of several multicenter studies has confirmed the beneficial effect on microvascular complications; however, has raised doubts regarding the benefits of the legacy effect in improving cardiovascular outcome and mortality in patients with type 2 diabetes. In this review, we discuss the epidemiologic evidence in favor and against the metabolic memory hypothesis in patients with type 1 and type 2 diabetes. In addition, we discuss potential underlying mechanisms that could play a role on the effects of glycemic exposure on vascular complications in patients with diabetes.

Keywords

• Legacy effect. Diabetes mellitus. Glycemic control. Vascular complication.