Abstract
BackgroundFunctional properties of high density lipoproteins (HDL) are increasingly recognized to play a physiological role in atheroprotection. Type 2 diabetes mellitus (T2DM) is characterized by low HDL cholesterol, but the effect of chronic hyperglycemia on the anti-inflammatory capacity of HDL, a metric of HDL function, is unclear. Therefore, the aim of the present study was to establish the impact of T2DM on the HDL anti-inflammatory capacity, taking paraoxonase-1 (PON-1) activity and low grade inflammation into account.MethodsThe HDL anti-inflammatory capacity, determined as the ability to suppress tumor necrosis factor-α (TNF-α) induced vascular cell adhesion molecule-1 (VCAM-1) mRNA expression in endothelial cells in vitro (higher values indicate lower anti-inflammatory capacity), PON-1 (arylesterase) activity, hs-C-reactive protein (hs-CRP), serum amyloid A (SAA) and TNF-α were compared in 40 subjects with T2DM (no insulin or statin treatment) and 36 non-diabetic subjects.ResultsT2DM was associated with impaired HDL anti-inflammatory capacity (3.18 vs 1.05 fold increase in VCAM-1 mRNA expression; P < 0.001), coinciding with decreased HDL cholesterol (P = 0.001), apolipoprotein A-I (P = 0.038) and PON-1 activity (P = 0.023), as well as increased hs-CRP (P = 0.043) and TNF-α (P = 0.005). In all subjects combined, age- and sex-adjusted multivariable linear regression analysis demonstrated that impaired HDL anti-inflammatory capacity was associated with hyperglycemia (β = 0.499, P < 0.001), lower PON-1 activity (β = − 0.192, P = 0.030) and higher hs-CRP (β = 0.220, P = 0.016).ConclusionsThe HDL anti-inflammatory capacity is substantially impaired in T2DM, at least partly attributable to the degree of hyperglycemia, decreased PON-1 activity and enhanced low grade chronic inflammation. Decreased anti-inflammatory protection capacity of HDL conceivably contributes to the increased atherosclerosis risk associated with T2DM.
Highlights
Patients with type 2 diabetes mellitus (T2DM) have a substantially increased risk of atherosclerotic cardiovascularEbtehaj et al Cardiovasc Diabetol (2017) 16:132 the functionality of high density lipoproteins (HDL) particles could have a more pathophysiologically important impact [8, 9], together with determinations of HDL subpopulations and HDL particle numbers [10,11,12,13,14]
HDL from Type 2 diabetes mellitus (T2DM) patients exhibited a reduced capacity to protect low density lipoproteins (LDL) from oxidation [19,20,21], whereas we found previously that the anti-oxidative capacity of HDL is impaired in T2DM but only taking account of the diabetes-associated decrease in HDL cholesterol [22]
A positive association indicates a relationship with lower HDL anti-inflammatory capacity glucose, the HDL anti-inflammatory capacity was positively associated with glycated haemoglobin (HbA1c) and inversely with PON-1 activity (Table 2B, Model 1), positively with HbA1c and hs-C-reactive protein (hs-CRP) (Table 2B, Model 2), positively with HbA1c and hs-CRP, and inversely with PON-1 activity (Table 2B, Model 3). These results indicate that the HDL anti-inflammatory capacity is impaired in the context of chronic hyperglycemia, even independent of HDL cholesterol, diabetes-associated impaired PON-1 activity and enhanced low grade chronic inflammation
Summary
Patients with type 2 diabetes mellitus (T2DM) have a substantially increased risk of atherosclerotic cardiovascularEbtehaj et al Cardiovasc Diabetol (2017) 16:132 the functionality of HDL particles could have a more pathophysiologically important impact [8, 9], together with determinations of HDL subpopulations and HDL particle numbers [10,11,12,13,14]. HDL from T2DM patients exhibited a reduced capacity to protect low density lipoproteins (LDL) from oxidation [19,20,21], whereas we found previously that the anti-oxidative capacity of HDL is impaired in T2DM but only taking account of the diabetes-associated decrease in HDL cholesterol [22]. These differences might be related to the degree of metabolic control in the T2DM patients studied. The aim of the present study was to establish the impact of T2DM on the HDL anti-inflammatory capacity, taking paraoxonase-1 (PON-1) activity and low grade inflammation into account
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