Endothelial Dysfunction in Young People With Diabetes Mellitus in the Absence of Clinical Vascular Disease: A Review

Introduction

Diabetes mellitus has become a leading public health problem in the second half of the last century and it will continue to be so well into the second millennium 1. This diabetes epidemic is mainly attributable to type-2 diabetes that has accompanied the upsurge of obesity, sedentary life style, and global changes in dietary habits 2. A totally new phenomenon is that a significant element of the diabetes syndrome has started to appear among children and teenage populations 3, 4. This, in its own right, will represent a significant future public health problem 5 as diabetes is a chronic disease with significant chronic complications known to be related to diabetes duration 6 plus other factors including glycemic control 7, 8. Vascular disease, as a consequence, will be a major problem to tackle in people with diabetes in years to come, an area which has not been a priority for health management in pediatric populations 5. The enigma of the plausible rise of vascular disease stemming from such a rise in the rate of type-2 diabetes in young people will be further compounded by a lack of insight into the interaction of various risk factors of vascular disease in this new population with metabolic disease coming to the forefront.

Abstract

Endothelial dysfunction is an early surrogate of future vasculopathy. Children and adolescents with diabetes have a high future risk of clinical vascular disease and we and others have demonstrated that biophysical abnormalities of endothelial dysfunction and the markers of endothelial cell activation tend to be perturbed early in this group of patients. The endothelial dysfunction is manifest well in advance of clinical vascular disease. The mechanisms of early endothelial dysfunction are complex and many underlying factors act in concert to initiate such dysfunction: with the sustained hyperglycemia acting as a prime mover; the subsequent metabolic derangements as perpetuators; and along with obesity, smoking, and lack of physical exercise, all contribute to a progression of this dysfunction into full angiopathy. Strategies to ameliorate such dysfunction have been explored. This review aims at shedding light on this area that has received much attention in the last two decades.

Keywords

endothelial dysfunction, diabetes mellitus, adolescent diabetes, atherosclerosis, oxidative stress, nitric oxide, free radical markers, intima media thickness