Epigenetic phenomena linked to diabetic complications.
Diabetes mellitus (type 1 and type 2) and the complications associated with this condition are an urgent public health problem, as the incidence of diabetes mellitus is steadily increasing. Environmental factors, such as diet and exposure to hyperglycemia, contribute to the etiology of diabetes mellitus and its associated microvascular and macrovascular complications. These vascular complications are the main cause of the morbidity and mortality burden of diabetes mellitus. The DCCT-EDIC and UKPDS epidemiological studies correlated poor glycemic control with the development of vascular complications in patients with type 1 or type 2 diabetes mellitus. The findings of these studies suggest that early exposure to hyperglycemia predisposes individuals to the development of diabetic complications, a phenomenon referred to as metabolic memory or the legacy effect. The first experimental evidence for metabolic memory was reported >20 years ago and the underlying molecular mechanisms are currently being characterized. Interestingly, transient exposure to hyperglycemia results in long-lasting epigenetic modifications that lead to changes in chromatin structure and gene expression, which mediate these persistent metabolic characteristics.
Epigenetics in Human Health and Disease Laboratory, The Alfred Medical Research and Education Precinct, Baker IDI Heart and Diabetes Institute, 5th Floor, 75 Commercial Road, Melbourne, VIC 3004, Australia.
Luciano
L
Pirola
Aneta
A
Balcerczyk
Jun
J
Okabe
Assam
A
El-Osta
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology / Q000235:genetics; D008954:Models, Biological
D001786:Blood Glucose