HDL and type 2 diabetes: the chicken or the egg?

Abstract

HDL is a complex macromolecular cluster of various components, such as apolipoproteins, enzymes and lipids. Quality evidence from clinical and epidemiological studies led to the principle that HDL-cholesterol (HDL-C) levels are inversely correlated with the risk of CHD. Nevertheless, the failure of many cholesteryl ester transfer protein inhibitors to protect against CVD casts doubts on this principle and highlights the fact that HDL functionality, as dictated by its proteome and lipidome, also plays an important role in protecting against metabolic disorders. Recent data indicate that HDL-C levels and HDL particle functionality are correlated with the pathogenesis and prognosis of type 2 diabetes mellitus, a major risk factor for CVD. Hyperglycaemia leads to reduced HDL-C levels and deteriorated HDL functionality, via various alterations in HDL particles' proteome and lipidome. In turn, reduced HDL-C levels and impaired HDL functionality impact the performance of key organs related to glucose homeostasis, such as pancreas and skeletal muscles. Interestingly, different structural alterations in HDL correlate with distinct metabolic abnormalities, as indicated by recent data evaluating the role of apolipoprotein A1 and lecithin-cholesterol acyltransferase deficiency in glucose homeostasis. While it is becoming evident that not all HDL disturbances are causatively associated with the development and progression of type 2 diabetes, a bidirectional correlation between these two conditions exists, leading to a perpetual self-feeding cycle.

Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

“…Nevertheless, contrasting findings have also been reported [ 155 , 156 ]. There seems to be a bidirectional relationship between T2D and HDL whereby diabetes could also modulate the composition and function of HDL [ 157 ]. Concentration of large HDL particle and HDL particle size have been found to be increased in patients with T1D compared with participants without diabetes, while small HDL and total HDL particle concentration were reduced [ 158 ].…”

Relationship of Para and Perirenal Fat and High-Density Lipoprotein and Its Function in Patients with Type 2 Diabetes Mellitus

“…Our previous work has suggested that HDL dysfunction including cholesterol efflux capacity and inhibitory on endothelial lipase existed in patients with T2DM [ 14 ]. Some investigators have explored the possible mechanism of the reduction of HDL level and its function in T2DM [ 15 , 16 ]. Our further research has showed that patients with T2DM have a lower serum HDL level and different components compared with non-T2DM patients [ 17 ].…”

Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio: A valuable predictor of type 2 diabetes mellitus incidence

“…Besides this, HDL-C can reflect genomic changes, for example, changes in HMGCR polymorphisms can lead to a reduction in HDL-C, which is thought to be associated with the risk of T2DM ( 36 ). ABCA1 gene variants are capable of contributing to T2MD development by reducing HDL-C levels leading to β-cell lipotoxicity ( 37 ). In addition to concentration, the particle size of HDL has been proved to be associated with the maintenance of glucose homeostasis.…”