Bariatric Surgery Improves HDL Function Examined by ApoA1 Exchange Rate and Cholesterol Efflux Capacity in Patients with Obesity and Type 2 Diabetes.

Shuhui Wang Lorkowski,Daniel M Rotroff,Ali Aminian,Deepak L Bhatt,Sangeeta R Kashyap,Jonathan D Smith,Gregory Brubaker,Philip R Schauer,Steven E Nissen

doi:10.3390/biom10040551

Shuhui Wang Lorkowski, Daniel M Rotroff + Show 7 more

Open Access

https://doi.org/10.3390/biom10040551

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Abstract

Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who were randomized to intensive medical therapy (n = 20), Roux-en-Y gastric bypass (RYGB, n = 37), or sleeve gastrectomy (SG, n = 33) as part of the STAMPEDE clinical trial. We examined serum HDL function by two independent assays, apolipoprotein A-1 exchange rate (AER) and cholesterol efflux capacity (CEC). Compared with baseline, AER was significantly higher at 5 years for participants in all treatment groups, but only increased significantly at 1 year in the RYGB and SG groups. CEC was divided into ABCA1-dependent and independent fractions, and the later was correlated with AER. ABCA1-independent CEC increased significantly only at 5 years in both surgical groups, but did not significantly change in the medical therapy group. There was no significant change in ABCA1-dependent CEC in any group. The increase in AER, but not ABCA1-independent CEC, was correlated with the reduction in body mass index and glycated hemoglobin levels among all subjects at 5 years, indicating that AER as a measure of HDL function would be a better reflection of therapy versus CEC.

Highlights

Bariatric surgery has been demonstrated as an efficient treatment for patients with obesity and type 2 diabetes mellitus by successfully achieving glycemic control in several small randomized clinical trials [1,2,3,4,5]
We examined two assays of HDL function, cholesterol efflux capacity (CEC) and A-1 exchange rate (AER), in patients with obesity and type 2 diabetes who were enrolled in the STAMPEDE clinical trial, which is a randomized, nonblinded, single-center trial to evaluate the efficacy of intensive medical therapy alone versus intensive medical therapy plus Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in 150 patients with obesity and type 2 diabetes
The concept is building that low HDL function, rather than low HDL-C, is mechanistically linked with cardiovascular disease (CVD); HDL function may be a better target for therapeutic intervention than HDL-C levels [30]

Summary

Introduction

Bariatric surgery has been demonstrated as an efficient treatment for patients with obesity and type 2 diabetes mellitus by successfully achieving glycemic control in several small randomized clinical trials [1,2,3,4,5]. A recent large matched cohort study further supports the superiority of this treatment showing that metabolic surgery, compared with nonsurgical management, decreases major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity [6]. The current gold standard HDL function assay, the cholesterol efflux capacity (CEC), is a cell-based assay to examine the cholesterol efflux capacity of exogenous acceptors (apoA1 or apoB-depleted serum) from radiolabeled-macrophages (usually RAW264.7 or J774) in which ABCA1 expression can be regulated, allowing the determination of total, ABCA1-dependent, and ABCA1-independent CEC [18]. The CEC of apoB-depleted serum has been used in many studies to investigate the association between CEC and CVD [19,20,21]

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