Glycemic Variability: Clinical and Prognostic Significance

Abstract

Minimizing development or progression of chronic diabetic micro and macro-vascular
complications has been always the goal of glycemic control. In recent years, much attention
has been focused on the possibility that glycemic variability confers an additional risk factor
for diabetic complications independent of glycated hemoglobin (HbA1c). Evidence suggests
that fluctuating glucose levels produce endothelial dysfunction as well as an increase in free
radicals, the key link between hyperglycemia and diabetic complications and that these changes
are greater than those produced by sustained hyperglycemia in in vitro and in animal studies.
In humans studies, experimental setting also support the hypothesis that plasma glucose fluctuations
produce a higher increase in oxidative stress as well as endothelial dysfunction than
those produced by sustained hyperglycemia in type 2 diabetes. Moreover, glycemic variability
may have a role in the prediction of severe hypoglycemia, which may act as a precipitating
factor of diabetic complications. Based on review of available evidence, we advocate decreasing
hyperglycemia and diminishing glycemic variability as well as avoiding hypoglycemia in
diabetic patients as targets of diabetic therapy. Future trials targeting the influence of the control
of plasma glucose fluctuations on the development of diabetic micro-and macro-vascular complications
are needed to further strengthen the evidence base.