Francois M. H. van Dielen

Neutrophil Activation in Morbid Obesity, Chronic Activation of Acute Inflammation

Recent studies show that morbid obesity is associated with activation of the innate immune response. Neutrophil activation is a fundamental process in the innate immune response. Therefore, the activation state of neutrophils in severely obese subjects and the effect of bariatric surgery on neutrophil activation was evaluated. Neutrophil activation was assessed by measuring circulating concentrations of myeloperoxidase (MPO) and calprotectin in 37 severely obese and 9 control subjects (enzyme‐linked immunosorbent assay). Moreover, membrane expression of CD66b on circulating neutrophils was measured using flow cytometry in a group of seven severely obese and six control subjects. Immunohistochemical detection of MPO was performed in adipose and muscle tissue. Plasma MPO and calprotectin levels were significantly increased in severely obese subjects as compared to healthy controls, 27.1 ± 10.8 vs. 17.3 ± 5.5 ng/ml (P < 0.001) and 115.5 ± 43.5 vs. 65.1 ± 23.1 ng/ml (P < 0.001) for MPO and calprotectin, respectively. In line, CD66b expression was significantly increased in severely obese individuals, 177.3 ± 43.7 vs. 129.7 ± 9.2 (mean fluorescence intensity) (P < 0.01). Bariatric surgery resulted in decreased calprotectin, but MPO plasma levels remained elevated. Adipose and muscle tissue did not contain increased numbers of MPO expressing cells in severely obese individuals. These results point out that circulating neutrophils are activated to a greater extent in severely obese subjects. Our data support the finding that the innate immune system is activated in severely obese individuals. Moreover, because neutrophils have a short life span, this indicates that the chronic inflammatory condition associated with morbid obesity is characterized by a continuous activation of the innate immune system.

Ghrelin, Leptin and Insulin Levels after Restrictive Surgery: a 2-Year Follow-up Study

Background: Ghrelin is a recently discovered orexigenic gastric hormone, whose production is induced by lack of food in the stomach. In morbidly obese individuals, ghrelin levels are low compared to lean persons. During dieting, plasma ghrelin levels increase, leading to an orexigenic signal, which could explain the lack of success of dieting in morbidly obese individuals. Morbid obesity is best treated with bariatric surgery, in which gastric bypass is reported to be more effective than restrictive surgery. A possible explanation could be the difference in plasma ghrelin levels after both operations for bariatric surgery. In this study, plasma ghrelin levels were investigated during a 2-year follow-up. Methods: 17 morbidly obese patients received gastric restrictive surgery. Plasma ghrelin, leptin and insulin levels were evaluated preoperatively and 1 year and 2 years postoperatively. Results: BMI decreased from 47.5 ± 6.2 kg/m2 to 33.2 ± 5.8 kg/m2 (P <0.001). Plasma ghrelin levels were significantly increased 1 year (P <0.05) and 2 years (P <0.02) postoperatively. Fasting plasma leptin and insulin levels were significantly lower at 2 years after surgery (P <0.001). Conclusion: After gastric restrictive surgery, ghrelin levels increased, in contrast to the reported fall in ghrelin levels after gastric bypass. This difference in ghrelin levels between these operations may be the k ey to understanding the superiority of gastric bypass in sustaining weight loss compared with restrictive surgery.

Endothelial activation markers and their key regulators after restrictive bariatric surgery.

Objective: Increased plasma levels of endothelial activation markers in obese subjects reflect the positive association between cardiovascular diseases and obesity. The pro‐inflammatory state associated with obesity is thought to play a major role in endothelial cell activation in severely obese individuals. Previous studies demonstrated that long‐term weight loss after bariatric surgery is accompanied by a decreased proinflammatory state. However, little is known about the long‐term effects of bariatric surgery on endothelial cell activation.

One-Year Cost-Effectiveness of Surgical Treatment of Morbid Obesity: Vertical Banded Gastroplasty versus Lap-Band®

Background: This study was designed as an economic evaluation alongside a randomized clinical trial. The object of this study was to evaluate the 1-year cost-effectiveness of surgical treatment of morbid obesity comparing two operations. Methods: 100 patients were assigned randomly to vertical banded gastroplasty (VBG) or Lap-Band® surgery. Both medical and non-medical costs were identified and measured. Costs data were combined with percentage Excess Weight Loss (%EWL) and with Quality Adjusted Life Years (QALYs) to obtain cost per %EWL and cost per QALY ratios. Results: At 1 year, the total costs were not significantly different between both groups (95% confidence interval E5,999 - E1,765). Also, the QALY gain after surgery was not significantly different between the two groups. However, %EWL was significantly higher in the VBG group compared to the Lap-Band® group, P-value .0001. The estimated incremental cost per %EWL was E105.83 (E1,885.91/-17.82). For the costs per QALY, the estimated ratio was dominant. The overall mortality in this study was 2%. 2 patients in the VBG group died within 30 days after surgery; 1 of these deaths was possibly related to the VBG procedure. Conclusion: At 1 year after surgery, the costs and QoL of the two treatment modalities were found to be equal. Therefore, the selection of the procedure can be based on the clinical aspects, effectivity and safety at 1 year. In addition, the results of a long-term cost-effectiveness analysis (e.g. with a follow-up of 36 months) planned in the future can also be helpful in the selection of the preferred treatment.

Peripheral blood flow and noradrenaline responsiveness: the effect of physiological hyperinsulinemia

OBJECTIVE Insulin seems to have vasodilator properties, but it is unclear if insulin in postprandial concentrations is a specific vasodilator of skeletal muscle resistance arterioles only or that various types of vessels are affected. The aim of the present study was to determine the direct effects and the time course of regional/local physiological hyperinsulinemia on skeletal muscle arterioles, skin blood flow and peripheral venous tone and the responsiveness of these different vascular beds to noradrenaline. METHODS In protocol I (n = 12) we infused insulin into the brachial artery for 180 min (3.5 mU/min) and evaluated the effects on forearm (muscle) blood flow (FBF) and skin blood flow (SBF). Furthermore, noradrenaline (0.025, 0.01 and 0.4 microgram/min) was infused (i.a.) at baseline, at 90 and 180 min after the start of insulin. In protocol 2 (n = 10) the same regional forearm hyperinsulinemia was achieved, but now the local venous responsiveness to noradrenaline (1.7-55 ng/min, at baseline and at 90 and 180 min) was measured in a dorsal hand vein. In protocol 3 we evaluated the local effects of different doses of insulin (1-100 mU/min) infused directly into hand veins preconstricted with phenylephrine. RESULTS Forearm hyperinsulinemia (approximately 50 mU/l) led to a significant increase in FBF after 180 min (median 26%, interq ranges 5-50, P < 0.05), while SBF was not altered. Forearm hyperinsulinemia did not affect the noradrenergic responsiveness in skeletal muscle or skin. Infused locally into hand veins only the highest dose of insulin (100 mU/min) caused a minor venodilation (7% [2.4-12.5], P < 0.05). CONCLUSION Regional forearm physiological hyperinsulinemia has a vasodilator effect on resistance vessels in skeletal muscle, but is slow in onset (180 min). However, skin vasculature and peripheral veins are not affected by this hyperinsulinemia.

Leptin in Morbidly Obese Patients: No Role for Treatment of Morbid Obesity but Important in the Postoperative Immune Response

Despite the current opinion that leptin can no longer be seen as a hormone which could be used therapeutically to prevent an energy surplus (it rather protects the organism for an energy deficit), leptin may still have an impact in clinical medicine. Leptin was shown to have several important functions. The pleiotropic properties of leptin include a regulatory function in the immune system. Reviewing the effects of leptin on different parts of the immune system reveals that the immune system is deregulated in an environment low in leptin. A strong reduction in leptin levels occurs in situations of starvation as seen after bariatric surgery. We postulate the hypothesis that the starvation-induced postoperative decrease of leptin is causative of the more serious course of complications observed after bariatric surgery.

Early insulin sensitivity after restrictive bariatric surgery, inconsistency between HOMA-IR and steady-state plasma glucose levels

BACKGROUND The low-grade inflammatory condition present in morbid obesity is thought to play a causative role in the pathophysiology of insulin resistance (IR). Bariatric surgery fails to improve this inflammatory condition during the first months after surgery. Considering the close relation between inflammation and IR, we conducted a study in which insulin sensitivity was measured during the first months after bariatric surgery. Different methods to measure IR shortly after bariatric surgery have given inconsistent data. For example, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels have been reported to decrease rapidly after bariatric surgery, although clamp techniques have shown sustained insulin resistance. In the present study, we evaluated the use of steady-state plasma glucose (SSPG) levels to assess insulin sensitivity 2 months after bariatric surgery. METHODS Insulin sensitivity was measured using HOMA-IR and SSPG levels in 11 subjects before surgery and at 26% excess weight loss (approximately 2 months after restrictive bariatric surgery). RESULTS The SSPG levels after 26% excess weight loss did not differ from the SSPG levels before surgery (14.3 +/- 5.4 versus 14.4 +/- 2.7 mmol/L). In contrast, the HOMA-IR values had decreased significantly (3.59 +/- 1.99 versus 2.09 +/- 1.02). CONCLUSION During the first months after restrictive bariatric surgery, we observed a discrepancy between the HOMA-IR and SSPG levels. In contrast to the HOMA-IR values, the SSPG levels had not improved, which could be explained by the ongoing inflammatory state after bariatric surgery. These results suggest that during the first months after restrictive bariatric surgery, HOMA-IR might not be an adequate marker of insulin sensitivity.

Increased adipocyte size, macrophage infiltration, and adverse local adipokine profile in perirenal fat in cushing's syndrome

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushings syndrome.

Long-Term Results of Laparoscopic Sleeve Gastrectomy for Morbid Obesity: 5 to 8-Year Results

With great interest we read the study of Gadiot and colleagues regarding the long-term results of laparoscopic sleeve gastrectomy (LSG) in the January 2017 edition of Obesity Surgery [1]. First, we would like to express our appreciation of this very nice report portraying long-term data on a sizeable cohort of patients with LSG. Second, we would like to ask a few questions concerning the study. In Table 3, the authors report on the failure rates at respectively 5 to 8 years postoperatively. Regarding inadequate weight loss following bariatric surgery, it is favourable to divide between weight loss failure (WLF)—inability to achieve 50% excessweight loss—andweight regain (WR)—significant weight gain after initial weight loss success. Is it possible to provide us with the WLF and WR percentages? Furthermore, could the authors elaborate on the mentioned percentage of subsequent revision to laparoscopic Roux-en-Y gastric bypass (LRYGB), specifically whether these patients managed to return to adequate weight loss after revision? Last, did the results in this study have specific implications on your patient selection nowadays, with regard to eligibility for either LSG or LRYGB?