The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk

Lipids Health Dis. 2017 Oct 30;16(1):207. doi: 10.1186/s12944-017-0594-3.

Abstract

Background: Diabetes mellitus (DM) is a major public health problem which prevalence is constantly raising, particularly in low- and middle-income countries. Both diabetes mellitus types (DMT1 and DMT2) are associated with high risk of developing chronic complications, such as retinopathy, nephropathy, neuropathy, endothelial dysfunction, and atherosclerosis.

Methods: This is a review of available articles concerning HDL subfractions profile in diabetes mellitus and the related cardiovascular risk. In this review, HDL dysfunction in diabetes, the impact of HDL alterations on the risk diabetes development as well as the association between disturbed HDL particle in DM and cardiovascular risk is discussed.

Results: Changes in the amount of circulation lipids, including triglycerides and LDL cholesterol as well as the HDL are frequent also in the course of DMT1 and DMT2. In normal state HDL exerts various antiatherogenic properties, including reverse cholesterol transport, antioxidative and anti-inflammatory capacities. However, it has been suggested that in pathological state HDL becomes "dysfunctional" which means that relative composition of lipids and proteins in HDL, as well as enzymatic activities associated to HDL, such as paraoxonase 1 (PON1) and lipoprotein-associated phospholipase 11 (Lp-PLA2) are altered. HDL properties are compromised in patients with diabetes mellitus (DM), due to oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein. Numerous studies confirm that the ability of HDL to suppress inflammatory signals is significantly reduced in this group of patients. However, the exact underlying mechanisms remains to be unravelled in vivo.

Conclusions: The understanding of pathological mechanisms underlying HDL dysfunction may enable the development of therapies targeted at specific subpopulations and focusing at the diminishing of cardiovascular risk.

Keywords: Cardiovascular risk; Diabetes mellitus; HDL cholesterol; Subfractions.

Publication types

  • Review

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / metabolism
  • Aryldialkylphosphatase / genetics
  • Aryldialkylphosphatase / metabolism
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Cholesterol, HDL / metabolism*
  • Cholesterol, LDL / metabolism
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Gene Expression Regulation
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Lipid Metabolism / genetics*
  • Risk Factors
  • Triglycerides / metabolism

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycation End Products, Advanced
  • Triglycerides
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Aryldialkylphosphatase
  • PON1 protein, human