The therapeutic efficacy of intensive medical therapy in ameliorating high-density lipoprotein dysfunction in subjects with type two diabetes

Abstract

Background: To determine whether 12 months of intensive medical therapy (IMT) improves HDL functionality parameters in subjects with type II diabetes (T2D).

Methods: Retrospective, randomized, and controlled 12-month IMT intervention trial that enrolled 13-subjects with T2D (age 51- years, fasting glucose 147 mg/dL, body mass index [BMI] 36.5 kg/m(2)) and nine healthy control (46-years, fasting glucose 90 mg/dL, BMI 26.5 kg/m2). Subjects with T2D underwent IMT and HDL functionality measures (pro-inflammatory index of high-density lipoprotein (pHDL)), paraoxonase one (PON1), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity were performed on samples at baseline and at 12-months following IMT.

Results: At baseline, pHDL index was significantly higher in subjects with T2D (p < 0.001) and apolipoprotein A-1 levels were significantly lower (p = 0.013) vs.

Controls: After 12-months, there was a trend for improved pHDL activity (p = 0.083), as indicated by intent-to-treat analysis, but when the non-adherent subject was omitted (per-protocol), significant attenuations in pHDL activity (p = 0.040) were noted; Δ pHDL activity at 12-months was associated with Δ weight (r = 0.62, p = 0.032) and Δ fasting glucose (r = 0.65, p = 0.022). Moreover, PON1 activity significantly improved (p < 0.001). The aforementioned occurred in association with improvements in inflammatory markers (i.e., C-reactive protein & tumor necrosis factor), hemoglobin A1C, fasting glucose, triglycerides, high-density lipoprotein levels and adipokines.

Conclusion: IMT ameliorates pHDL index and significantly improves anti-oxidative function, as measured by PON1. Improvements in weight and fasting glucose mediated the decrease in pHDL index. Pharmacological aids and lifestyle modification are required to improve cardiovascular risk factors, subsequent mortality risk, and promote T2D remission. Application of either form of therapy alone may only have relatively miniscule effects on the aforementioned factors, in relation to the aggregate.

Keywords: Intensive medical therapy; Myeloperoxidase; Paraoxonase one; Pro-inflammatory high-density lipoproteins.

Fig. 1

Box plot depicting differences in pHDL activity at baseline and after 12 months of IMT. As illustrated, there were significant differences at baseline between subjects with T2D and controls. After 12 months of IMT, a per-protocol analysis, which omitted the non-adherent subject, indicated that pHDL activity significantly decreased. p-values: Wilcoxon rank sum test for intergroup differences, whereas within-group differences were analyzed via the Wilcoxon signed rank test. DM, type II diabetics; pHDL, pro-inflammatory high-density lipoprotein activity

Fig. 2

a Positive correlation between Δ pHDL activity and Δ weight in subjects with T2D, after 12 months of IMT. b Positive association between Δ pHDL activity Δ fasting glucose in subjects with T2D, after 12 months of IMT. The figure highlights that large decreases in weight or glucose were related with heightened decrements in pHDL activity. Intent-to-treat analysis; r-value: Spearman correlation. pHDL, pro-inflammatory high-density lipoproteins