“A persistent deficit in HDL function is likely a significant contributor to the enhanced CVD risk in these patients.”
Diabetes is a lack of the hormone insulin or a resistance of cells to insulin that renders the body unable to control blood sugar levels. The World Health Organization estimates that diabetes affects 422 million adults worldwide and is responsible for 1.5 million deaths each year1. It is predicted that by 2040 there will be 642 million people with diabetes.
Patients who have type 1 diabetes are not able to produce any insulin. They therefore need regular insulin injections to keep blood glucose at a healthy level. Type 1 diabetes is a high-risk factor for developing cardiovascular disease2. However, the exact nature of this association is not clear.
Research has shown that high density lipoprotein (HDL) can afford protection against stroke and heart disease. Consequently, there has been much research into the link between lipid levels and cardiovascular risk in patients with diabetes. Indeed, it was recently shown lipid-lowering therapy can reduce the risk of cardiovascular disease in patients with type 1 diabetes by more than a fifth3.
The cardioprotective action of HDL stems from its role in removing cholesterol from the blood and transporting it to the liver to be metabolized. This function is determined that the protein on the surface of HDL, apolipoprotein A1. This protein allows HDL to bind to transporter proteins on liver cells so they can to be taken into the cell and broken down.
However, many cases of cardiovascular disease occur despite good levels of HDL. Recent research suggests that this may be because not all HDL is associated with active apolipoprotein A1. In order for the HDL to be internalized by liver cells, the apolipoprotein A1 must undergo a significant conformational change so that it can bind with the transporter protein.
It is therefore the function of HDL rather than absolute levels of HDL that is predictive of cardiovascular risk. In order to determine the level of atheroprotection provided by HDL, it is necessary to establish the proportion of HDL that is acting to sequester triglycerides and cholesterol.
Electron paramagnetic resonance (EPR) or fluorescent spectroscopy make it possible to measure the proportions of active HDL-apolipoprotein A1. Studies using these technologies have demonstrated that a high ratio of active HDL-apolipoprotein A1 correlates with a lower risk of cardiovascular disease4.
EPR using a Bruker BioSpin eScan EPR spectrometer has now been used to determine levels of active HDL-apolipoprotein A1 in 293 children and young adults with type 1 diabetes and 111 healthy controls5.
Patients with type 1 diabetes were found to have significantly lower proportions of active HDL-apolipoprotein A1 than the healthy controls, and this difference was still evident to a similar extent 5 years later.
Researchers also showed that the lower proportions of active HDL-apolipoprotein A1 in the diabetes group correlated significantly and inversely with HbA1c. The lowered levels of active HDL-apolipoprotein A1, and consequently reduced removal of lipids from the blood, occurred soon after the onset of type 1 diabetes and persisted over time.
This is likely to be a key contributing factor in the increased cardiovascular risk associated with type 1 diabetes.
References
World Health Organisation Diabetes Fact Sheet 2017. Available at http://www.who.int/diabetes/en/
Soedamah-Muthu SS, et al. High risk of cardiovascular disease in patients with type 1 diabetes in the UK: a cohort study using the general practice research database. Diabetes Care 2006;29:798–804.
Hero C, et al. Association Between Use of Lipid-Lowering Therapy and Cardiovascular Diseases and Death in Individuals With Type 1 Diabetes. Diabetes Care. 2016;39(6):996‑1003.
Borja MS, et al. HDLapoA-I exchange: rapid detection and association with atherosclerosis. PLoS ONE. 2013;8:e71541.
Heier M, et al. Reduced HDL function in children and young adults with type 1 diabetes. Cardiovasc Diabetol 2017;16:85