ABSTRACT
Cardiovascular complications remain the major cause of morbidity and mortality in the diabetic population (Cooper and Johnston 2000). Patients with type 1 or type 2 diabetes have a two-to fourfold higher risk of cardiovascular disease compared to healthy individuals (Hu et al. 2001; Fox et al. 2004), and those with impaired glucose tolerance alone have a cardiovascular disease risk comparable to type 2 diabetics (Qiao et al. 2002). It is increasingly appreciated that exposure to high glucose is the major factor leading to these complications. Furthermore, there appears to be a “metabolic memory” (Nathan et al. 2005) or “legacy effect” (Chalmers and Cooper 2008) whereby diabetic complications, particularly vascular events, continue to develop and progress even in individuals who have returned to normal glycemic control after a period of transient hyperglycemia. In the latest follow-up from the Diabetes Control Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, it is evident that the deleterious effects in the vasculature of both conventional and intensiˆed glycemic control continue to operate more than 5 years after the patients have returned to normoglycemia (Nathan et al. 2005). Further to this, the results of the action in diabetes and vascular disease-preterax and diamicron MR controlled evaluation (ADVANCE) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials-raise the debate about whether tight glucose control is beneˆcial at all in diabetes (Patel et al. 2008; Gerstein et al. 2008). Whereas the initial interpretation of the results from the UK Prospective Diabetes Study (UKPDS) showed no signiˆcant effect of strict glycemic
9.1 Glycemic Variability and Diabetic Complications ....................................... 215 9.2 Epigenetic Mechanisms-Back to Basics .................................................... 216 9.3 Nutritional Intervention and Epigenetic Mechanisms ..................................220 9.4 Epigenetic Regulation of Diabetic Complications ........................................ 221 9.5 The Role of Histone-Modifying Enzymes in Glycemic Memory ................ 221 9.6 The Current Landscape and Perspectives-Where to Next? ....................... 223 References ..............................................................................................................224
