The British Journal of Diabetes & Vascular Disease

To review the management of blood glucose in acute coronary syndrome (ACS) a literature search was undertaken using Medline and Embase databases (January 1950—July 2008), bibliographies of retrieved articles, review articles and Department of Health reports. Trials were eligible for inclusion in the review if they (i) included patients with ACS and hyperglycaemia with or without diabetes or compared insulin infusion or glucose-potassium-insulin infusion with active controls, (ii) were randomised, and (iii) assessed mortality and morbidity. Eight trials met the above criteria (two of which have yet to report). Only two of the remaining six trials reported that insulin therapy significantly reduces mortality in ACS patients with hyperglycaemia. In conclusion ACS is of major public health importance in the UK and hyperglycaemia in the setting of ACS is associated with worse outcome. Current variability in management of blood glucose in ACS reflects a paucity of robust evidence to guide practice. Two ongoing trials may resolve the uncertainty about optimum blood glucose management in ACS.

The vascular glycocalyx is a gel layer between endothelium and the blood, 0.5 µm thick. Evidence is presented from published studies to indicate that hyperglycaemia causes damage to the vascular glycocalyx. This damage results in microalbuminuria, excess fluid transfer to the interstitium, reduction in nitric oxide (NO) production by arterial endothelium, and leukocyte and platelet adhesion to endothelium leading to atherothrombosis. The lack of NO production proceeds from the fact that glycocalyx is the mechanotransducer transmitting the signal for increased shear stress between blood and arterial wall, and this function is inhibited by hyperglycaemia. When hyperinsulinaemia is also present, the problem is compounded by general arterial dilatation leading to low shear rates throughout the arterial tree. These findings explain the predisposition to atherothrombosis in the pre-diabetic condition of insulin resistance/metabolic syndrome/obesity and diabetes mellitus. It is proposed that greater efforts than ever are required to detect occult insulin resistance, to treat such patients and diabetics with ever more strict blood glucose control while minimising insulin levels, and to carry out further research into how glycocalyx structure and function can be preserved.

Macrovascular complications such as cardiovascular disease and peripheral vascular disease are the leading cause of increased mortality and morbidity, respectively, in patients with diabetes mellitus. The aetiopathogenesis of macrovasculopathy in diabetes is multifactorial and differs in types 1 and 2 diabetes. Endothelial cell dysfunction is an early feature of diabetic vasculopathy and is associated with poor glycaemic control. Chronic hyperglycaemia may promote an adverse vascular milieu leading to early endothelial cell apoptosis, in the long run. The presence of apoptotic cells in the vascular lumen may trigger a cascade of reactions between the promoters and inhibitors of arterial calcification. Medial arterial calcification, a characteristic feature of diabetes, is an important predictor of cardiovascular disease and occurs independently of atherosclerosis. Medial arterial calcification may occur in the presence of normal serum calcium and phosphate levels. Osteoprotegerin is an important modulator of mineral metabolism and manifests its effects in the bone and arteries. It is hypothesised that osteoprotegerin is a key inhibitor of arterial calcification which is released by endothelial cells as a protective measure for survival in adverse conditions. It is a potential risk marker for early identification and monitoring of disturbed mineral metabolism and vasculopathy in diabetes.

B-type natriuretic peptide (BNP) is a natriuretic peptide released primarily by ventricular myocytes in response to various physiological and pathological stimuli. In addition to its established diagnostic role in patients with heart failure, a growing body of evidence suggests that raised levels of BNP in the absence of heart failure can indicate myocardial ischaemia. This appears to be the case in patients with symptomatic, and even asymptomatic coronary artery disease (CAD). In this review, we discuss the current evidence supporting the role of BNP as a simple marker of cardiac ischaemia and CAD. We also propose some therapeutic interventions that may be useful when BNP detects silent myocardial ischaemia.

International travel, including patients travelling with diabetes mellitus, is predicted to increase in the coming decades. These patients will require pre-travel education regarding adjusting insulin and oral antidiabetic agents during their journey especially if they fall ill. The spectrum of travel-related illnesses includes food and waterborne diseases, airborne and vector-borne diseases, zoonoses, sexually transmitted and blood-borne diseases, and diseases transmitted by soil. This article reviews the pre-travel vaccines and immunisations and infectious diseases of potential risk to diabetic travellers. Furthermore investigation of fever in returned diabetic travellers with particular reference to physical signs of common tropical illnesses is also discussed.

Patients with diabetes and renal failure may already be receiving biosimilar epoetin and may receive biosimilar insulin in the near future. Because these biosimilar pharmaceuticals (or follow-on biologics) are complex protein molecules manufactured in lengthy and inherently variable processes involving living organisms, they have the potential to induce an immunogenic, rather than a therapeutic, response. This response is dependent as much on the method of manufacture and formulation, as on the protein itself. Apparently small and innocuous differences in manufacture and formulation can lead to unforeseen clinical consequences. This article discusses two case studies illustrating this principle, that of three insulin formulations which were physicochemically similar to comparator insulins, but with pharmacokinetic and pharmacodynamic profiles sufficiently different to have potentially serious clinical consequences and that of Eprex, for which an apparently minor change in one formulation caused an upsurge of cases of pure red cell aplasia which resulted in fatalities or complete transfusion dependence. Comprehensive and rigorous testing and long-term pharmacovigilance programmes are essential to detect and forestall such consequences.

If the 1990s was the decade of evidence-based medicine the following decade has seen a gradual move towards evidence-based care delivery. The translation of discovery research into actual improvements in care is a challenging transition. Quality improvement techniques developed in industry are an attempt to bridge this gap. Unprecedented improvements in the safety of air travel, oil exploration and nuclear power have occurred because of cultural change after major disasters. In contrast healthcare deals with life and death every day. The quality improvement movement has now reached healthcare. NHS Scotland has a long history of innovation in quality and safety. The most recent is the Scottish Patient Safety Programme, an initiative designed to reduce acute hospital mortality by 15% and adverse events by 30%. NHS Scotland is launching a Quality Strategy to lay the foundations for further improvements in safety, clinical effectiveness and patient centredness.