The role of “metabolic memory” in the natural history of diabetes mellitus

Abstract

role of "meta bolic memory" in the natural history of diabetes mellitus 493 Preclinical evidence One of the first trials which suggested a prolonged negative effect of hyperglycemia on blood vessels despite achieving tight glycemia control was conducted by Engerman and Kern. 6 The aim of this study was to evaluate whether improved meta bolic control could inhibit the progression of retinopathy in dogs with alloxan-induced diabetes mellitus. Diabetic dogs were categorized into three groups according to glycemic control: the first with poor control for 5 years, the second with hyperglycemia for 2.5 years and with good control for the next 2.5 years, and the third with good control achieved by insulin administration and maintained during 5 years of observation. The reference group comprised nondiabetic dogs. It was observed that the introduction of intensive glucose level lowering treatment during 2 months since diabetes induction inhibited the development of microaneurysms and other histopatho logical lesions in the retinal vessels. However, such response was not observed when

Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review

“…It is a term used to describe the beneficial effects of immediate intensive treatment of hyperglycaemia with a sustained benefit with respect to the outcomes for many years, regardless of glycaemia in the later course of diabetes . It is suggested that early glycaemia normalization can halt hyperglycaemia‐induced pathological processes associated with enhanced oxidative stress and glycation of cellular proteins and lipids . In the Action to Control Cardiovascular Risk in Diabetes Eye study, intensive control of HbA1c (median of 6.4%) decreased the progression of DR from 10.4% to 7.3% over 4 years.…”

“…56 It is suggested that early glycaemia normalization can halt hyperglycaemia-induced pathological processes associated with enhanced oxidative stress and glycation of cellular proteins and lipids. 57 In the Action to Control Cardiovascular Risk in Diabetes Eye study, intensive control of HbA1c (median of 6.4%) decreased the progression of DR from 10.4% to 7.3% over 4 years. However, the results may carry limited clinical relevance as the author defined progression of DR as 3+ ETDRS steps on a 17-point scale, and this finding was only applicable to those with mild retinopathy.…”

Diabetic retinopathy: Breaking the barrier

“…However, these drugs do not, for the most part, treat the underlying microvascular mechanisms contributing to DR. Studies have indicated that despite tight glycemic control, retinal microvascular complications will continue to develop and the factors leading to these complications will persist in DR [10–12]. This phenomenon has been termed ‘metabolic memory’ [13–15], where hyperglycemic vascular stresses continue even after the normalization of blood glucose levels. Many factors have been attributed to this phenomenon, such as advanced glycation end products [16], mitochondrial damage and oxidative stress [17], and epigenetic changes [7, 18, 19], all of which will be discussed in detail later in the review.…”

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

“…Short-term hyperglycemia induces long-term changes in chromatin modifications (3). Poor glycemic control is associated with elevated oxidative stress and advanced glycation end products, which damage mitochondrial DNA in kidney, which in turn accentuates the risk of cardiovascular diseases (4). Dysregulated polyols, hexosamine fluxes, and activation of PKC isoforms induced by hyperglycemia also mediate renal damage (2).…”