Ghrelin: a Gut-Brain Hormone: Effect of Gastric Bypass Surgery

Background: Ghrelin is a newly recognized gastric hormone with orexigenic and adipogenic properties, produced primarily by the stomach. Ghrelin is reduced in obesity.Weight loss is associated with an increase in fasting plasma ghrelin. We assessed the effect of massive weight loss on plasma ghrelin concentrations and its correlation with serum leptin levels and the presence of type 2 diabetes mellitus (DM) in severely obese patients. Methods: A prospective study was conducted on 28 morbidly obese women (BMI 56.3±10.2 kg/m²) who underwent gastric bypass, divided into 2 groups: 14 non-diabetics (NGT) and 14 type 2 diabetics (DM2). Ghrelin and leptin were evaluated before silastic ring transected vertical gastric bypass, and again 12 months postoperatively. Results: Fasting plasma ghrelin concentrations were 56% lower in NGT and 59% lower in DM2 compared with a lean control group (P<0.001). There was no difference in ghrelin levels between NGT and DM2 groups before and after surgery (P>0.05). Ghrelin was negatively correlated with leptin before gastric bypass surgery (r=0.51, P<0.01). The mean plasma ghrelin concentration decreased significantly after surgery in both groups (P<0.001). Conclusion: Ghrelin was inversely related to leptin concentrations. Presence of diabetes did not affect the ghrelin pattern. Reduced production of ghrelin after gastric bypass could be partly responsible for the lack of hyperphagia and thus for the weight loss.     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Ghrelin and Apolipoprotein AIV Levels Show Opposite Trends to Leptin Levels During Weight Loss in Morbidly Obese Patients

Background

Although bariatric surgery is the most common procedure used to induce weight loss in morbidly obese patients, its effect on plasma satiety factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim of this work was to analyze these parameters before and at different times after surgery.

Methods

Plasma was obtained from 34 patients before undergoing Roux-en-Y gastric bypass and during weight loss in the 12 months following surgery.

Results

Morbidly obese patients had significantly higher values (147%) of leptin than normal-weight (NW) persons, while their ghrelin levels were 46% less than NW. Apo-AIV levels had approximately the same value in both groups (obese and NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%. Both parameters reached values less than or near NW, respectively, at 1 year after surgery. During the first month after surgery, apo-AIV plasma levels decreased (47%) but later increased and finally returned to preoperative values. Apo-AIV levels were correlated negatively with leptin and positively with ghrelin. High-density lipoprotein (HDL) levels were positively correlated with those of ghrelin and apo-AIV.

Conclusions

During weight loss, plasma leptin and ghrelin could be good markers of total fat decrease. Ghrelin could also indicate gastric mucous improvement, whereas apo-AIV could indicate the recovery of intestinal function. Changes produced in the HDL levels of morbidly obese patients during weight loss suggest a decreased risk of coronary disease.     

Long-term Changes in Leptin, Chemerin and Ghrelin Levels Following Different Bariatric Surgery Procedures: Roux-en-Y Gastric Bypass and Sleeve Gastrectomy

Background

Different studies have evaluated changes in adipo/cytokine levels after bariatric surgery and have given conflicting results. The adipo/cytokines, leptin and chemerin, and the orexigenic hormone, ghrelin, have been shown to play a role in the regulation of metabolism and appetite. The aims of our study were to test the levels of these molecules after bariatric surgery and to compare the results between Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy.

Methods

We analysed circulating levels of chemerin, ghrelin and leptin in 30 morbidly obese women (body mass index of >40 kg/m²). Subjects were studied at three time points: baseline (before the surgery started), and after 6 and 12 months.

Results

After surgery, chemerin (baseline, 95.03?±?23.79; after 12 months, 76.80?±?21.51; p?=?0.034) and leptin levels (baseline, 248.17?±?89.16; after 12 months, 63.85?±?33.48; p?<?0.001) were significantly lower than their baseline levels, whereas ghrelin was higher (baseline, 0.87?±?0.38; after 12 months, 1.08?±?0.31; p?=?0.010). Fasting glucose, insulin and homeostasis model assessment of insulin resistance levels were markedly lower postoperatively. High-density lipoprotein levels moderately increased and triglyceride levels sharply decreased. There were no differences between the types of bariatric surgery in terms of weight reduction, general metabolic state or adipo/cytokine levels after surgery.

Conclusions

Our study demonstrates a marked decrease in fasting leptin and chemerin levels, and an increase in ghrelin levels, after bariatric surgery-induced weight loss, independently of the type of surgery performed. Further studies are needed on the interrelation between the changes in the circulating levels of these molecules and the efficacy of the bariatric surgery procedures to induce the beneficial metabolic changes and to sustain body weight loss.     

Serum Ghrelin, Leptin and Adiponectin Levels before and after Weight Loss: Comparison of Three Methods of Treatment – A Prospective Study

Background: Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Leptin and adiponectin are the two adiposity products that participate in body weight control. Leptin always decreases and adiponectin increases after weight loss. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we compare the changes in fasting ghrelin, leptin and adiponectin levels in 3 groups of patients who achieved weight loss by either diet, MacLean vertical banded gastroplasty (VBG) or biliopancreatic diversion with duodenal switch (BPD-DS). Methods: Serum fasting ghrelin, leptin and adiponectin concentration was measured in 40 obese patients who achieved weight loss by either diet (n=14), VBG (n=13) or BPD-DS (n=13), before and after weight loss. The follow-up period was 18 months for BPD-DS and VBG and 6 months for diet. Serum ghrelin level was measured by ELISA. Results: BMI was significantly decreased in all 3 groups: 9.2±2.4% (P<0.01) following diet, 38.47±7.26% (P<0.01) after VBG, and 42.88±9.09% after BPD-DS (P<0.01). Serum fasting ghrelin level increased after diet (110.45±117.84%, P=0.002) and VBG (65.48±92.93%, P=0.001),but decreased after BPD-DS (−21.63±28.63%, P=0.019). Leptin concentration decreased and adiponectin increased in all groups. Conclusions: Unlike after diet or gastric restrictive surgery, BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of this operation. Sleeve gastrectomy seems to be the main cause of this reduction.     

The Serial Changes of Ghrelin and Leptin Levels and Their Relations to Weight Loss After Laparoscopic Minigastric Bypass Surgery

Background The ghrelin and leptin levels have been reported to be correlated with weight loss after bariatric surgery. However, the serial changes of ghrelin and leptin levels after laparoscopic minigastric bypass surgery (LMGBP) have not been reported yet. Therefore, we aimed to evaluate their serial changes and to analyze their relations to weight reduction after LMGBP. Methods Serial fasting serum leptin and ghrelin concentrations were measured in 68 morbidly obese patients before (M0) and 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months after LMGBP surgery. The correlations between ghrelin, insulin, and leptin concentrations and weight reduction were analyzed. Results Leptin levels were significantly reduced at 1, 3, 6, and 12 months after surgery, respectively (vs M0, p < 0.001), whereas the ghrelin concentrations were not significantly changed after surgery. The percent of excess BMI lost (%EBL) 12 months after surgery was negatively correlated with higher preoperative ghrelin concentrations (p = 0.004) and larger preoperative BMI (p = 0.002) in the multivariate analysis. Conclusion Higher preoperative ghrelin concentrations and larger BMI are predictive of less %EBL at 12 months after LMGBP surgery.     

Different Effects of Vertical Banded Gastroplasty and Roux-en-Y Gastric Bypass on Meal Inhibition of Ghrelin Secretion in Morbidly Obese Patients

A decrease in ghrelin plasma levels in morbidly obese patients subjected to bariatric surgery has been considered to help increase body weight loss. Contradictory results have been described after Roux-en-Y gastric bypass (RYGBP), and no study to date has compared RYGBP and vertical banded gastroplasty (VBG), the two main operations performed in the United States. We investigated the effects of RYGBP (10 patients) and VBG (12 patients) on basal and postmeal ghrelin plasma levels in 22 morbidly obese patients (20 F and 2 M), mean age 42.1 ± 3.7 years, mean weight 115 ± 3.9 kg, mean body mass index (BMI) 43.5 ± 1.7. Before surgery and after a 20% reduction in BMI, ghrelin concentrations (pg/mL; radioimmunoassay [RIA], DRG Diagnostics, Germany) were measured in all patients 45 min before and for 3 h after a standard liquid meal (Osmolite RTH solution, 500 mL, 504 kcal). The results were expressed as mean ± SD. Differences between times and groups were evaluated by Student's t-test and one-way analysis of variance (ANOVA). We found that basal ghrelin plasma levels were reduced after RYGBP (to 73.1 ± 6 pg/mL, p <. 05) but increased after VBG (to 172 ± 26 pg/mL, p <. 0009). After a standard liquid meal, ghrelin plasma levels decreased significantly over 1 h in VBG patients, whereas they remained unchanged in RYGBP patients. Since these results were obtained under the same metabolic and anthropometric conditions, we conclude that RYGBP acts through permanent inhibition of ghrelin secretion, whereas VBG merely restores the mechanisms of ghrelin regulation by nutrients.     

Fasting Plasma Ghrelin Concentrations 6 Months after Gastric Bypass are not Determined by Weight Loss or Changes in Insulinemia

Background: Ghrelin is a gastric peptide with potent orexigenic effects. Circulating ghrelin concentrations are increased in obese subjects, but increase after weight loss. However, in patients undergoing Roux-en-Y gastric bypass (RYGBP), a decrease in ghrelin levels has been reported. The effect of comparable weight loss induced by either adjustable gastric banding (AGB), RYGBP or conventional dietary treatment (Conv) on ghrelinemia was studied. Methods: 24 matched obese male patients in whom similar weight loss had been achieved by either AGB (n=8), RYGBP (n=8) or Conv (n=8) were studied before and 6 months after treatment start. The independence of ghrelin concentrations from body mass index (BMI) and weight loss was further analyzed in a group of patients with total gastrectomy (TtGx, n=6). Results: Comparable weight loss after 6 months exerted significantly different effects on plasma ghrelin concentrations, depending on the procedure applied (AGB: 424.6 ± 32.8 pg/ml; RYGBP: 131.4 ± 13.5; Conv: 457.3 ± 18.7; P<0.001). Without significant differences in body weight and BMI, patients who had undergone the RYGBP exhibited a statistically significant decrease in fasting ghrelin concentrations, while the other two procedures (AGB and Conv) showed a weight loss-induced increase in ghrelin levels. Despite significant differences in BMI between RYGBP and TtGx patients after 6 months (31.9 ± 2.2 vs 22.0 ± 0.7 kg/m², respectively; P<0.05), both groups showed similar ghrelin concentrations. Conclusion: The reduction in circulating ghrelin concentrations in RYGBP patients after 6 months of surgery are not determined by an active weight loss or an improved insulin-sensitivity but rather depend on the surgically-induced bypass of the ghrelin-producing cell population of the fundus.     

The Effect of Biliopancreatic Diversion with Pylorus-Preserving Sleeve Gastrectomy and Duodenal Switch on Fasting Serum Ghrelin, Leptin and Adiponectin Levels: Is there a Hormonal Contribution to the Weight-Reducing Effect of this Procedure?

Background: Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we investigate the hypothesis that because ghrelin is mainly produced by the fundus of the stomach, biliopancreatic diversion with sleeve gastrectomy with total resection of the gastric fundus and duodenal switch (BPD-DS) will cause substantial decrease in circulating ghrelin levels. Methods: Serum fasting ghrelin, leptin and adiponectin concentrations were measured by ELISA in 13 patients with morbid obesity who achieved weight loss by BPD-DS, before the operation and 18 months after. Results: After BPD-DS, BMI decreased significantly, from 59.15±15.82 kg/m² to 32.91±6.46 kg/m² (P=0.001). Serum fasting ghrelin level decreased from 1.44±0.77 ng/ml to 0.99±0.35 ng/ml (P=0.019). Serum leptin level decreased from 1.81±0.38 ng/ml to 1.65±0.32 ng/ml, (P=0.196), and adiponectin level increased from 37.85±11.24 μg/ml to 39.84±16.27 μg/ml (P=0.422). Conclusions: BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the longlasting weight-reducing effect of the procedure. Leptin levels decreased and adiponectin increased, as expected, after weight loss. Sleeve gastrectomy with resection of the gastric fundus seems to be the main cause of the postoperative reduction in ghrelin levels.     

Vertical Banded Gastroplasty Modifies Plasma Ghrelin Secretion In Obese Patients

Background: Restrictive bariatric surgery causes weight loss through substantial decline of appetite with satiety after meals. Reduction of plasma ghrelin levels after Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding could contribute to these effects, although contradictory results have been reported. The only restrictive operation still not yet investigated is vertical banded gastroplasty (VBG). We studied the effects of VBG on basal plasma ghrelin levels and meal-mediated inhibition. Methods: 12 morbidly obese patients, 11 female and 1 male, were studied before and after VBG, when the BMI fell by 20%. The control group consisted of 6 lean volunteers. Active ghrelin was determined by RIA after overnight fasting and after the administration of a liquid meal. Results: Obese patients preoperatively had significantly lower basal plasma ghrelin levels than lean volunteers, and the meal did not inhibit ghrelin secretion. After VBG and 20% BMI loss, basal plasma ghrelin levels increased and the reduction caused by a meal recovered. Conclusions: Weight loss caused by VBG is associated with higher plasma ghrelin levels in obese patients. The operation restores the normal adaptation of the A- cells of the stomach to a meal.     

The Decrease in Plasma Ghrelin Concentrations following Bariatric Surgery Depends on the Functional Integrity of the Fundus

Background: Gastric bypass surgery, which involves the production of a reduced stomach pouch,has been shown to markedly suppress circulating ghrelin concentrations. Since bypassing the ghrelin-producing cell population may be relevant to the disruption of fundic-derived factors participating in food intake signaling, the effect of weight loss induced by either adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD) was studied. Methods: 16 matched obese patients [35.0 + 2.4 years; initial body weight 124.8 ± 5.7 kg; body mass index (BMI) 47.1 ± 2.2 kg/m²] in whom similar weight loss had been achieved by either AGB (n=7), RYGBP (n=6) or BPD (n=3) were studied. Blood was obtained for biochemical and hormonal analyses. Body composition was assessed by air-displacement-plethysmography. Results: Comparable weight loss (AGB: 26.1 ± 5.1 kg; RYGBP: 32.1 ± 5.0; BPD: 31.7 ± 6.1; P=NS) and decrease in percentage body fat (AGB: 10.0 ± 1.5%; RYGBP: 14.2 ± 2.8; BPD: 10.3 ± 1.0; P=NS) induced by bariatric surgery exerted significantly different (P=0.004) effects on plasma ghrelin concentrations, depending on the surgical procedure applied (AGB: 480 ± 78 pg/ml; RYGBP: 117 ± 34; BPD: 406 ± 86). Without significant differences in BMI, body fat, glucose, triglycerides, cholesterol, insulin and leptin levels, patients who had undergone the RYGBP exhibited statistically significant diminished circulating fasting plasma ghrelin concentrations compared with the other two bariatric techniques which conserve direct contact of the fundus with ingested food (P=0.003 vs AGB and P=0.020 vs BPD). Conclusion: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.     

Laparoscopic fundoplication compared with laparoscopic gastric bypass in morbidly obese patients with gastroesophageal reflux disease

BackgroundGastroesophageal reflux disease (GERD) is commonly associated with morbid obesity. Laparoscopic fundoplication is a standard surgical treatment for GERD, and laparoscopic gastric bypass has been shown to effectively resolve GERD symptoms in the morbidly obese. We sought to compare the in-hospital outcomes of morbidly obese patients who underwent laparoscopic fundoplication for the treatment of GERD versus laparoscopic gastric bypass for the treatment of morbid obesity and related conditions, including GERD, at U.S. academic medical centers.MethodsUsing the “International Classification of Diseases, 9th Revision” procedural and diagnoses codes for morbidly obese patients with GERD, we obtained data from the University HealthSystem Consortium database for all patients who underwent laparoscopic fundoplication or laparoscopic gastric bypass from October 2004 to December 2007 (n = 27,264). The outcome measures included the patient demographics, length of stay, in-hospital overall complications, mortality, risk-adjusted mortality ratio (observed to expected mortality), and hospital costs.ResultsCompared with the patients who underwent laparoscopic gastric bypass, those who underwent laparoscopic fundoplication had a lower severity of illness score (P <.05). The overall in-hospital complications were significantly lower in the laparoscopic gastric bypass group (P <.05). The mean length of stay, observed mortality, risk-adjusted mortality, and hospital costs were comparable between the 2 treatment groups.ConclusionLaparoscopic gastric bypass is as safe as laparoscopic fundoplication for the treatment of GERD in the morbidly obese. Hence, morbidly obese patients with GERD should be referred for bariatric surgery evaluation and offered laparoscopic gastric bypass as a surgical option.     

Impact of accreditation in bariatric surgery

BackgroundSeveral studies have shown improved outcomes associated with accredited bariatric centers. The aim of our study was to examine the outcomes of bariatric surgery performed at accredited versus nonaccredited centers using a nationally representative database. Additionally, we aimed to determine if the presence of bariatric surgery accreditation could lead to improved outcomes for morbidly obese patients undergoing other general laparoscopic operations.MethodsUsing the Nationwide Inpatient Sample database, for data between 2008 and 2010, clinical data of morbidly obese patients who underwent bariatric surgery, laparoscopic antireflux surgery, cholecystectomy, and colectomy were analyzed according to the hospital’s bariatric accreditation status.ResultsA total of 277,068 bariatric operations were performed during the 3-year period, with 88.4% of cases performed at accredited centers. In-hospital mortality was significantly lower at accredited compared to nonaccredited centers (.08% versus .19%, respectively). Multivariate analysis showed that nonaccredited centers had higher risk-adjusted mortality for bariatric procedures compared to accredited centers (odds ratio [OR] 3.1, P<.01). Post hoc analysis showed improved mortality for patients who underwent gastric bypass and sleeve gastrectomy at accredited centers compared to nonaccredited centers (.09% versus .27%, respectively, P<.01). Patients with a high severity of illness who underwent bariatric surgery also had lower mortality rates when the surgery was performed at accredited versus nonaccredited centers (.17% versus .45%, respectively, P<.01). Multivariate analysis showed that morbidly obese patients who underwent laparoscopic cholecystectomy (OR 2.4, P<.05) and antireflux surgery (OR 2.03, P<.01) at nonaccredited centers had higher rates of serious complications.ConclusionAccreditation in bariatric surgery was associated with more than a 3-fold reduction in risk-adjusted in-hospital mortality. Resources established for bariatric surgery accreditation may have the secondary benefit of improving outcomes for morbidly obese patients undergoing general laparoscopic operations.     

Bariatric Surgery Cannot Prevent Tryptophan Depletion Due to Chronic Immune Activation in Morbidly Obese Patients

Background: Increased activity of the immuno-modulatory enzyme indoleamine-2,3-dioxygenase (IDO) during immune activation, results in tryptophan depletion. Tryptophan metabolic changes reduce serotonin production and cause mood disturbances, depression, and impaired satiety, ultimately leading to increased food intake and obesity. Bariatric surgery significantly diminishes immune mediators by substantial weight reduction. We examined IDO-mediated tryptophan-catabolism in morbidly obese patients compared to lean individuals. Methods: Serum concentrations of kynurenine and tryptophan, calculated kynurenine to tryptophan ratios (kyn trp-1) as an indirect estimate of IDO activity, and neopterin levels reflecting IFN-γ mediated immune activation, were assessed before and after bariatric surgery. The study population included 22 morbidly obese individuals and 20 normal-weight volunteers. Results: Median weight loss after 24.4±5.1 months was 40.6 kg resulting in a reduction of BMI from 44.1 kg/m² to 29.9 kg/m² (P<0.001). Preoperative kyn trp-1 in morbidly obese patients was significantly increased compared to the control group (41.6±20.1 mmol/mol vs 26.5±5.1 mmol/mol; P<0.001). Postoperative weight reduction did not lead to normalization of kyn trp-1 (37.9±14.0 mmol/mol). As a consequence, tryptophan levels were significantly lower in morbidly obese patients (pre-: 51.5±9.2 μmol L⁻¹ and postoperatively: 46.9±7.6 μmol L⁻¹) when compared with those of normal-weight controls (64.8±9.5 μmol L⁻¹; P<0.001). In addition, neopterin levels were elevated in the study population pre- and postoperatively compared to normal-weight volunteers (both P<0.001). Conclusions: Tryptophan depletion in morbidly obese patients is due to chronic immune activation and persists in spite of significant weight reduction following bariatric surgery. This might thereby be responsible for diminished serotonin functions, leading to unchanged satiety dysregulation and a reward-deficiency-syndrome.     

Pre- and Post-prandial Plasma Ghrelin Levels Do Not Correlate with Satiety or Failure to Achieve a Successful Outcome after Roux-en-Y Gastric Bypass

Background: We tested the hypothesis that the amount of weight lost after Roux-en-Y gastric bypass (RYGBP) correlates with plasma ghrelin levels. Methods: 36 morbidly obese patients were studied 3 years after RYGBP (6 men, 30 women) with mean initial BMI 51 kg/m² and 8 healthy controls (2 men, 6 women) with mean BMI 25 kg/m². Subjects consumed a light breakfast, and the first blood sample was drawn at 1200 hrs immediately before lunch and the second sample at 1400 hrs. Satiety was assessed using a Visual Analog Scale (VAS). Patients were stratified as success (current BMI <35) or failures (current BMI ≥35). Results: Plasma ghrelin levels were significantly lower in patients after RYGBP (269 ± 66 pcg/ml) compared with lean controls (616 ± 112 pcg/ml, P<0.001). Ghrelin levels pre or post meals were not different between patients who had a successful weight loss (preoperative BMI 47, current BMI 29, 72% EWL) or those who achieved a less then ideal weight loss (preoperative BMI 48, current BMI 41, 29% EWL). There was no correlation between any of the VAS scores and plasma ghrelin. There was a strong inverse correlation between pre-prandial ghrelin levels and the preoperative or current BMI. Conclusion: Failure to lose weight after RYGBP does not correlate with pre- or post-prandial ghrelin plasma levels. Ghrelin levels were inversely proportional to BMI and did not correlate with satiety. These data do not support a role for higher plasma ghrelin levels for inadequate weight loss after RYGBP.     

Effects of Bariatric Surgery on Vitamin D Status and Secondary Hyperparathyroidism: A Prospective Study

Background: Morbidly obese patients have been reported to present with vitamin D insufficiency and secondary hyperparathyroidism. Scattered data are available regarding the effects of bariatric surgery on vitamin D status. We studied calcium metabolism and vitamin D status before and after bariatric surgery. Methods: In this prospective study, 64 patients (M5/F59) fulfilled the inclusion criteria (i.e. 2 calcidiol serum determinations in the winter season) among 457 morbidly obese individuals who underwent Roux-en-Y gastric bypass (RYGBP) a mean of 36 months previously. Laboratory data (serum calcium, phosphorus, creatinine, alkaline phosphatase, albumin, calcidiol, albumin and iPTH) were determined before and after RYGBP. Pre- and postoperative calcidiol levels were categorized as being normal (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L). Pre- and postoperative mild secondary hyperparathyroidism was defined as iPTH >7.3 pmol/L with simultaneous normal values for creatinine, calcium and phosphorus. Results: RYGBP produced a significant weight loss coupled with a simultaneous increase in calcidiol (+28%, P<0.0005) and decrements in total alkaline phosphatase (-53%, P<0.0005) and iPTH (-74%, P=0.001). Corrected serum calcium, phosphorus, and creatinine levels were indistinguishable before and after RYGBP. Additionally, 37.5% of the patients maintained their calcidiol category, while 42.2 % improved it and 20.3% lost one category. Conclusions: RYGBP does not completely correct pre-existing vitamin D deficient states with secondary hyperparathyroidism. Low calcidiol bioavailability and or insufficient sunlight exposure do probably persist after bariatric surgery. While randomized controlled studies are warranted, it seems advisable to support vitamin D supplementation as well as increasing sunlight exposure in the morbidly obese population.     

The effects of gastric surgery on systemic ghrelin levels in the morbidly obese

HYPOTHESIS: Circulating ghrelin, produced primarily in the stomach, is a powerful orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline postprandially. Early alterations in ghrelin levels in morbidly obese patients undergoing weight reduction surgery may be attributed to gastric partitioning. DESIGN AND PATIENTS: Thirty-four patients underwent Roux-en-Y gastric bypass with a completely divided gastroplasty to create a 15-mL vertically oriented gastric pouch. Eight other patients underwent other gastric procedures that did not involve complete division of the stomach, including 4 vertical banded gastroplasties and 4 antireflux surgical procedures. Six additional patients undergoing antireflux surgery served as lean control subjects. Plasma samples were obtained before surgery and immediately after surgery. In a substudy, plasma was collected after Roux-en-Y limb formation and after dividing the stomach to identify any changes in plasma ghrelin levels. SETTING: Tertiary university medical center. MAIN OUTCOME MEASURES: Ghrelin levels at different stages of surgical intervention. RESULTS: Mean +/- SEM preoperative and postoperative ghrelin levels in the gastric bypass group were 355 +/- 20 and 246 +/- 13 pg/mL, respectively (P<.001). In the vertical banded gastroplasty group and in all patients undergoing antireflux surgery, ghrelin levels were not significantly changed. CONCLUSIONS: Compared with morbidly obese humans, lean controls had significantly higher plasma ghrelin levels at baseline. A divided gastroplasty creating a small proximal gastric pouch results in significant early declines in circulating ghrelin levels that are not observed with other gastric procedures. This may explain, in part, the loss of hunger sensation and rapid weight loss observed following gastric bypass surgery.     

Expression of ghrelin in fundus is increased after gastric banding in morbidly obese patients

Background Ghrelin, a 28 amino-acid acylated orexigenic peptide secreted by the stomach, acts on the hypothalamic arcuate nucleus which stimulates feeding behavior. Serum ghrelin level increases during fasting and decreases after a meal. Serum ghrelin is low in obese patients. Whether ghrelin is implicated in weight loss in obese patients after laparoscopic adjustable gastric banding (LAGB) is still debated. In this study, we assessed serum ghrelin level and gastric fundus expression before and 1 year after LAGB. Methods Gastric fundus expression of ghrelin was assessed by immunohistochemistry using a rabbit anti-human ghrelin antibody simultaneously with serum total ghrelin levels (RIA) in 13 obese patients (2 men and 11 women) after an overnight fast, before LAGB and 1 year after. Immunostaining was “blindly” analyzed by a single pathologist, measuring the density of stained fundic cells near muscularis mucosa. Results Mean age of the 13 patients was 41 years, and mean baseline BMI was 46 kg/m². Pre- and post- LAGB gastric expression of ghrelin was analyzable in 11 patients. It was always identified, mostly with moderate or intense staining. Mean density of stained cells significantly increased 1 year after LAGB: 31/mm² (21–38) before vs 38/mm² (27–57) after surgery (P < 0.01). This increase did not correlate with changes in BMI, nor did pre- or postoperative gastric expression of ghrelin correlate with the corresponding serum values. Conclusion We showed for the first time that ghrelin expression assessed by immunohistochemistry was present in the fundus of all 11 obese patients and that it was significantly increased 1 year after LAGB, which would exclude a pathogenetic role of ghrelin in weight loss after LAGB.     

Can bariatric surgery improve cardiovascular risk factors in the metabolically healthy but morbidly obese patient?

BackgroundBariatric surgery has been shown to be effective in resolving co-morbid conditions even in patients with a body mass index (BMI)<35 kg/m². A question arises regarding the metabolic benefits of bariatric surgery in metabolically healthy but morbidly obese (MHMO) patients, characterized by a low cardiometabolic risk. The objective of this study was to assess the effects of bariatric surgery on cardiometabolic risk factors among MHMO and metabolically unhealthy morbidly obese (MUMO) adults.MethodsA nonrandomized, prospective cohort study was conducted on 222 severely obese patients (BMI>40 kg/m²) undergoing either laparoscopic roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy. Patients were classified as MHMO if only 1 or no cardiometabolic factors were present: high blood pressure, triglycerides, blood glucose (or use of medication for any of these conditions), decreased high-density lipoprotein-cholesterol (HDL-C) levels, and insulin resistance defined as homeostasis model assessment for insulin-resistance (HOMA-IR)> 3.29.ResultsForty-two (18.9%) patients fulfilled the criteria for MHMO. They were younger and more frequently female than MUMO patients. No differences between groups were observed for weight, BMI, waist and hip circumference, total and LDL-C. MHMO patients showed a significant decrease in blood pressure, plasma glucose, HOMA-IR, total cholesterol, LDL-C and triglycerides and an increase in HDL-C 1 year after bariatric surgery. Weight loss 1 year after bariatric surgery was similar in both groups.ConclusionEighteen percent of patients with morbid obesity fulfilled the criteria for MHMO. Although cardiovascular risk factors in these patients were within normal range, an improvement in all these factors was observed 1 year after bariatric surgery. Thus, from a metabolic point of view, MHMO patients benefited from bariatric surgery.     

High Ghrelin Concentration is Not a Predictor of Less Weight Loss in Morbidly Obese Women Treated with Laparoscopic Adjustable Gastric Banding

Background: We analyzed the role of high plasma ghrelin concentrations at surgery as a negative predictor of weight loss in morbidly obese patients treated with laparoscopic gastric banding (LAGB). Methods: Fasting plasma ghrelin concentrations were measured in 113 women before LAGB, and 16 of them were identified as having ghrelin concentrations clearly higher than expected according to the BMI levels. The 2-year postoperative outcome of these 16 patients was compared to the outcome of the remaining subjects. Results: Mean fasting plasma ghrelin concentration in the group with hyperghrelinemia was 82.3±23.1 pg/ml and in women with normal ghrelin was 27.1±11.3 pg/ml (P <0.001). No differences in age, age at onset of obesity or degree of obesity were observed between the two groups. Women with hyperghrelinemia had a weight gain during the waiting time similar to women with normal ghrelin. The prevalence of comorbities and eating behavior disturbances was similar in the two groups, but depression was 2.5 fold more prevalent in the hyperghrelinemic women than in the women with normal ghrelin. The %EWL after LAGB surgery was similar in women with high and normal ghrelin concentrations, with no differences in levels of postoperative band filling. No differences in band-related complications or revisional surgery rate were observed between the two groups. Conclusion: A high fasting ghrelin concentration at baseline did not significantly affect the outcome after LAGB in morbidly obese women, in terms of weight loss and complications rate.