Abstract
Cardiovascular disease (CVD) is the leading cause of death in Type 1 Diabetes (T1D). The molecular basis for atherosclerosis in T1D is heavily influenced by hyperglycaemia and its atherogenic effects on LDL. Ongoing research into the distinct pathophysiology of atherosclerosis in T1D offers exciting opportunities for novel approaches to calculate CVD risk in patients with T1D and to manage this risk appropriately. Currently, despite the increased risk of CVD in the T1D population, there are few tools available for estimating the risk of CVD in younger patients. This poses significant challenges for clinicians in selecting which patients might benefit from lipid-lowering therapies over the long term. The current best practice guidance for the management of dyslipidaemia in T1D is generally based on evidence from patients with T2D and the opinion of experts in the field. In this review article, we explore the unique pathophysiology of atherosclerosis in T1D, with a specific focus on hyperglycaemia-induced damage and atherogenic LDL modifications. We also discuss the current clinical situation of managing these patients across paediatric and adult populations, focusing on the difficulties posed by a lack of strong evidence and various barriers to treatment.
Highlights
Cardiovascular disease (CVD) is the most common cause of death in Type 1 Diabetes (T1D) [1] and suboptimal glycaemic control is a significant risk factor for CVD [2]
This creates an environment that favours the adhesion of circulating macrophages and invasion into the arterial intima where they are activated and take up lipoproteins, leading to the formation of foam cells and the fatty streak, which are the hallmarks of early atherosclerosis [15,22]
Current recommendations on management of dyslipidaemia in paediatrics are based on adult studies or on evidence of preclinical atherosclerosis, as there are no trials in paediatrics showing a relationship between treatment cut-offs and a decrease in CVD
Summary
CVD is the most common cause of death in Type 1 Diabetes (T1D) [1] and suboptimal glycaemic control is a significant risk factor for CVD [2]. Factors other than hyperglycaemia must contribute to the accelerated atherosclerosis seen in T1D One of these other risk factors is dyslipidaemia, with a recent large-scale epidemiological study of patients with T1D showing a 35–50% increase in risk of CVD for every 1 mmol/L increase in LDL-C [3]. The majority of cases of T1D are diagnosed in the paediatric population and the incidence of the condition appears to be increasing [12] This is important as the morbidity related to atherosclerosis is observed in adult patients, but there is evidence that the onset of atherosclerosis begins in childhood. The Bogalusa heart study demonstrated the presence of fatty streaks and fibrous plaques in the aortas and coronary arteries of young people at post-mortem The extent of these findings was positively correlated with known CVD risk factors including dyslipidaemia, hypertension, and obesity [13]. The aim of this review article is to describe the pathophysiology of dyslipidaemia in T1D and to examine the current evidence for the screening and management of dyslipidaemia in patients with T1D across both paediatric and adult populations
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