Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms

Nat Rev Nephrol. 2010 Jun;6(6):332-41. doi: 10.1038/nrneph.2010.55. Epub 2010 Apr 27.


Many clinical studies have shown that intensive glycemic control in patients with diabetes can reduce the incidence and progression of diabetic nephropathy and can also reduce the incidence of other complications. These beneficial effects persist after patients return to usual (often worse) glycemic control. The Diabetes Control and Complications Trial was the first to refer to this phenomenon as 'metabolic memory'. Many patients with diabetes, however, still develop diabetic nephropathy despite receiving intensified glycemic control. Preliminary work in endothelial cells has shown that transient episodes of hyperglycemia can induce changes in gene expression that are dependent on modifications to histone tails (for example, methylation), and that these changes persist after return to normoglycemia. The persistence of such modifications cannot yet be fully explained, but certain epigenetic changes, as well as biochemical mechanisms such as advanced glycation, may provide new and interesting clues towards explaining the pathogenesis of this phenomenon. Further elucidation of the molecular events that enable prior glycemic control to result in end-organ protection in diabetes may lead to the development of new approaches for reducing the burden of diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Glucose / metabolism*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / metabolism*
  • Disease Progression
  • Endothelium, Vascular / metabolism
  • Epigenesis, Genetic*
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hypoglycemic Agents / therapeutic use


  • Blood Glucose
  • Glycation End Products, Advanced
  • Hypoglycemic Agents