Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms.
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.
Tonna
Stephen
S
Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3181, Australia.
El-Osta
Assam
A
Cooper
Mark E
ME
Tikellis
Chris
C
D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D044127:Epigenesis, Genetic; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents