Abstract
The accumulated wisdom of the last decade has fuelled a view of diabetes as an unusually severe form of cardiovascular disease (CVD) with a poor prognosis. Diabetic patients expect an up to 3-fold increase in coronary heart disease (CHD) events, independent of other traditional CVD risk factors, but those with CVD fair worse than their nondiabetic counterparts. The available therapeutic agents with the strongest current evidential support in prevention of CVD in diabetes are not those which primarily reduce blood glucose levels but rather those which reduce low density lipoprotein cholesterol or blood pressure. Current results from clinical trials are rather disappointing in reducing CVD events. Despite important reductions in relative risk in trials of statins, antihypertensive agents and those targeting the renin-angiotensin system there is a desperate need for new effective agents that can combat atherogenic factors including low high density lipoprotein cholesterol and raised triglyceride-rich particles, hyperinsulinaemia and notably the effects of high glucose on the arterial wall; not only to prevent CVD (macrovascular) but also the microvascular complications that are the cause of so much morbidity. To achieve this goal we must elucidate the pathophysiological role of glucose in endothelial dysfunction and atherogenesis, and begin to explain how elevated blood glucose itself (independent of other atherogenic features of the metabolic syndrome) might damage the arterial wall. Finally, we need to know to what extent any adverse effects of elevated glucose may be reversed if blood glucose levels are normalised. Unique model systems will contribute to understanding the direct and isolated effect of hyperglycaemia on the atherogenic process. We hope that this knowledge will help correct the anomalous situation whereby glucose-lowering drugs fail to demonstrate significant benefits in prevention of CVD.
Keywords: Cardiovascular disease, hyperglycaemia, dyslipidaemia, hypertension, diabetes mellitus, atherosclerosis, arterial wall, glucose, cardiovascular risk