Citation: Lui DTW, Tan KCB. High-density lipoprotein in diabetes: Structural and functional relevance. J Diabetes Investig. 2024;15(7):805-816. doi:10.1111/jdi.14172
URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC11215696/
What This Source Covers
Comprehensive narrative review covering HDL epidemiology, structure, subfractions, subspecies, functionality (CEC, anti-inflammatory, anti-oxidative, vasoactive), changes in both type 1 and type 2 diabetes (HDL-C levels, composition, proteome, lipidome), mechanisms of HDL dysfunction (glycation, carbamylation, oxidation, inflammation), anti-diabetic effects of HDL, and HDL-based therapeutics.
Key Claims
- HDL-C shows a U-shaped association with CVD (cardiovascular disease) risk, amplified in T2D — very high HDL-C is not protective (provenance: extracted).
- CEC is reduced in T2D, with selective attenuation of ABCA1-mediated efflux to small HDL due to reduced SERPINA1 content (provenance: extracted).
- HDL anti-inflammatory activity is impaired in T2D, partly from SAA enrichment that converts HDL to pro-inflammatory (provenance: extracted).
- PON1 activity is reduced in T2D, impairing HDL anti-oxidative capacity (provenance: extracted).
- Cardner et al. showed CEC does not predict other HDL functions — each function has distinct structural determinants (provenance: extracted).
- HDL proteome in T2D: increased SAA, fibrinogen, apoC-II/III; reduced apoA-I, apoA-II, apoE, apoM, PON1, PON3 (provenance: extracted).
- HDL lipidome in T2D: increased phosphatidylethanolamine; reduced ether-phosphatidylcholine, lysophosphatidylcholines, sphingomyelins, S1P (provenance: extracted).
- HDL and apoA-I increase insulin secretion and protect beta-cells via G-protein–cAMP–PKA–FoxO1 pathway and PDX1 upregulation (provenance: extracted).
- rHDL infusion in T2D patients acutely reduces plasma glucose by increasing insulin secretion and skeletal muscle glucose uptake (provenance: extracted).
- CETP inhibitors improve glycemic control despite mixed CV outcomes; new-onset diabetes reduced ~16% (provenance: extracted).
Limitations
- Review format — compiles existing evidence but does not present new primary data.
- T1D coverage is less comprehensive than T2D.
- Limited discussion of ancestry/ethnicity effects on HDL.
Connections
- This review provides the structural and mechanistic framework for understanding HDL dysfunction relevant to the PBMC ancestry paper’s interest in lipid metabolism and inflammation.
- The anti-diabetic properties of HDL (beta-cell function, insulin sensitivity) are directly relevant to HDL and Beta-Cell Function.
- HDL immunomodulation (SAA-driven pro-inflammatory conversion, monocyte adhesion) links to T2D PBMC Cholesterol Efflux and Scavenger Receptors.