Dyslipidaemia in Type 1 Diabetes: Molecular Mechanisms and Therapeutic Opportunities

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.

Association of glycemic variability and time in range with lipid profile in type 1 diabetes

“…Contrastingly, in well-controlled patients, triglyceride levels are usually normal or even lower than the general population due to peripheral hyperinsulinemia [ 17 ]. The administration of subcutaneous insulin increases LPL activity and subsequently very low density lipoproteins (VLDL) turnover, resulting in the so called “supernormal” lipid profile seen in T1D patients [ 18 ].…”

“…In former studies, T1D patients with poor glycemic control frequently have higher LDL cholesterol levels, whereas those with optimal glycemic control have LDL cholesterol levels that are normal or even slightly decreased [ 3 ]. This is also part of the abovementioned “supernormal” lipid profile [ 18 ]. The increased LDL levels in T1D patients with poor glycemic control may be related not only to high plasma glucose levels but also to other factors (e.g., diet and physical activity).…”

Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis

“…Thus, extra-glycaemic parameters are probably involved in this accelerated atherosclerosis. In addition to several conventional [4] and non-conventional [5] cardiovascular risk factors, circulating lipids are thought to play an important role in CVD pathogenesis [6,7]. In fact, in a large cohort study, an increase of 1 mmol/L of low density lipoprotein-cholesterol (LDL-cholesterol) was associated with a 35-50% greater risk of overall CVD [8].…”

Mediterranean Diet and Its Association with Cardiovascular Disease Risk Factors: A Scoping Review

“…Although the relationship between the MedDiet and CVD has been studied in various populations across the world, individuals with T1D are not fully represented in this research and are largely left out of clinical trials that investigate the relationship between a MedDiet and atherosclerosis [4,33,37]. However, individuals with T2D have been included in recent studies, but much of the research focuses on dietary patterns and glycemic control rather than atherosclerosis [30,36].…”