Globally, mean body mass index (BMI) has increased progressively since 1980 (1). Moreover, a 33% increase in obesity prevalence and a 130% increase in severe obesity prevalence have been projected over the next 2 decades (2). Excess mortality above the BMI range of 22.5–25 kg/m² is mainly attributed to vascular disease (3). The outcome of the Swedish obese subjects (SOS) trial indicated that bariatric surgery, when compared with usual care, was associated with a long-term reduction in overall mortality and reduced incidence of type 2 diabetes (T2DM), myocardial infarction, stroke, and cancer (4). Indeed 72% of patients with T2DM at baseline were in remission 2 years after surgery and high baseline insulin and/or high glucose predicted favorable treatment effects, whereas high BMI did not (4).

There is evidence that high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNFα), monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, P-selectin, resistin, and leptin may be mediators of insulin resistance, vascular inflammation, and endothelial dysfunction in those with obesity (5–9). It has been suggested that adiponectin increases insulin sensitivity and reduces the risk of atherosclerosis (10). Leptin and adiponectin are primarily released from the adipocytes whereas hsCRP, TNFα, MCP-1, and ICAM-1 are chiefly released from non-fat cells in adipose tissue (11).

While some studies have shown a significant reduction in mediators of vascular inflammation after bariatric surgery at 6 months (12) and 12 months (13–16), but not at 1 month (17). Other studies have reported no significant change in mediators of vascular inflammation 6 months after bariatric surgery (18).

In this study, we hypothesized a significant improvement in lipids, lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction at 6 and 12 months after Roux-en-Y bariatric surgery in obese patients with and without diabetes. Outcomes:

Effect size of time since surgery on dependent variables associated with lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction at 6 and 12 months after Roux-en-Y bariatric surgery (as small, medium, and large).

Of the 37 obese patients in the study, the mean age was 49 (range, 26–63) years, mean BMI 52 (9), 17 (45%) had T2DM, 23 (60%) had hypertension, 8 (20%) were smokers, 5 (15%) were known to have ischemic heart disease, and 22 (60%) patients took a statin. In the non-diabetes patients (n = 20), eight (40%) were on statins (Atorvastatin equivalent dose 10–40 mg/day), whereas in the diabetes patients (n = 17), 15 (90%) patients were on a statin (Atorvastatin equivalent dose 10–40 mg/day). Characteristics of all patients, non-diabetes patients and diabetes patients at baseline, 6, and 12 months have been presented in Table 1 and Figure 1.

In this study of morbidly obese patients with or without diabetes followed over 6 and 12 months after Roux-en-Y gastric bypass surgery, we found a significant reduction in pro-atherosclerotic lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction.

Bariatric surgery has been shown to consistently achieve significant and sustained weight loss; however, the effect on various markers of inflammation is quite variable. A recent meta-analysis evaluated the changes in blood levels of CRP and TNFα after bariatric surgery (21). There was a 54 and 81% reduction in CRP at 6 and 12 months, respectively, which is comparable to our study where we show a 47 and 78% reduction in CRP. While TNFα was only reduced by 1.3 and 1.2% at 6 and 12 months, respectively, in our study we report a 9 and 66% reduction. The much greater reduction in TNFα in our study compared with the meta-analysis could be due to a higher baseline BMI which was 52 kg/m² compared to other studies included in the meta-analysis where the average BMI was <50 kg/m². It could also reflect the use of Roux-en-Y surgery in our study compared to a variety of procedures, such as laparoscopic-adjustable gastric banding (LAGB), biliopancreatic diversion (BPD), or sleeve gastrectomy (SG) in the meta-analysis. There could also be significant differences in the number of patients with non-alcoholic steatohepatitis or ectopic adipose tissue, where the effect of weight loss may differ. Indeed Bachmayer et al. have reported no significant change in TNFα, MCP-1, or adiponectin, 12 months after Roux-en-Y, SG, and BPD (22). Auguet et al. have demonstrated a significant reduction in weight, insulin resistance, and CRP and circulating TNF receptors at both 6 and 12 months, with an increase in adiponectin at 6 but not 12 months after bariatric surgery (23). Sdralis et al. have demonstrated a significant fall in insulin with an increase in adiponectin with no change in TNFα even at 12 months (24). Thus, this area of research needs larger trials with a more uniform baseline weight and postoperative weight loss as well as surgical intervention such as Roux-en-Y surgery as it may lead to an exaggerated glucagon-like peptide-1 response, which may not be seen with LAGB, SG, and BPD (25).

In human studies, the role of resistin in insulin resistance and glucose metabolism is inconclusive (26, 27). Bariatric surgery results in a significant reduction in resistin levels at 12 months which correlates with insulin resistance (28). Our study confirms the significant reduction in resistin levels 12 months after bariatric surgery.

Tumor necrosis factor-alpha may play a direct role in the development of atherosclerosis through induction of ICAM-1, MCP-1, P-selectin, and E-selectin in endothelial and vascular smooth muscle cells resulting in endothelial cell apoptosis (29). Moreover, resistin augments the expression of endothelin-1, MCP-1, and ICAM-1 in endothelial cells (30, 31). The continued reduction in resistin and TNFα in the obese diabetic group up to 12 months after surgery may explain the reduction in HOMA-IR, MCP-1, and ICAM-1 in this group over the same period.

SdLDL apoB is a LDL subtype closely associated with diabetes and atherosclerosis (32), because of its greater susceptibility to undergo oxidative modification and glycation compared with more buoyant LDL (33, 34). While LAGB has been shown to modestly reduce sdLDL apoB at 12 months (35), our study shows a much more robust reduction in sdLDL apoB at 6 months with Roux-en-Y bariatric surgery.

We also demonstrate no change in apo-A1 but a significant increase in HDL-C after surgery which may indicate increased cholesterol cargo of HDL lipoproteins returning from the peripheral vasculature back to the liver, i.e., reverse cholesterol transport.

In the DM group, TC and LDL-C did not change significantly probably reflecting the fact that 90% of the DM group were already on long-term statins.

Lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction improve most 6 months after bariatric surgery in obese patients with and without diabetes. The greater reduction in inflammatory markers in our study compared to published meta-analyses may reflect a greater impact of Roux-en-Y surgery on weight loss achieved and may in the long-term translate to more pronounced cardiovascular benefit.

This study was carried out in accordance with the recommendations of NRES Committee North West—Greater Manchester Central with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the NRES Committee North West—Greater Manchester Central.

HS, PD, and BA designed the study. RY, AS, SH, RA, JN, SA, and JH recruited patients and organized follow-ups. HS, RY, SH, YL, JS, MF, SA, TS, JH, PP, MJ, and RD did laboratory work and data analysis. RY, SH, RM, RD, PD, BA, JS, TS, RA, SD, and HS prepared the first draft. All authors contributed in revising the manuscript for important intellectual content. All authors approved of the version to be published. All authors agreed to be accountable for all aspects of the work.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.