HDL and type 2 diabetes: the chicken or the egg? – published online 13/07/2021

Eva Xepapadaki, Ioanna Nikdima, Eleftheria C. Sagiadinou, Evangelia Zvintzou, Kyriakos E. Kypreos

Clinical and epidemiological evidence suggests an optimal range of plasma HDL-cholesterol concentrations, while very low and very high HDL-cholesterol levels are equally associated with high risk of mortality. In addition to plasma HDL-cholesterol levels, the recent observation that the HDL proteome dictates its lipidome, and subsequently HDL particle functionality, indicates that alterations in the HDL metabolic pathway may substantially influence its properties. In this issue, Xepapadaki et al (https://doi.org/10.1007/s00125-021-05509-0) review the accumulating evidence that suggests a bidirectional correlation between HDL dysfunction and type 2 diabetes, leading to a perpetual cycle. Although not all HDL disturbances are causatively associated with the development and progression of type 2 diabetes, many contribute to reduced secretory performance of beta cells in pancreatic islets and skeletal muscle insulin sensitivity. The interrelation between HDL lipidome, proteome and particle functionality remains a missing part of the puzzle that needs to be solved. The authors conclude that understanding HDL functionality and the factors affecting it in individuals with diabetes will be a crucial step towards better glucose homeostasis. The figure from this review is available as a downloadable slide.

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