Journal of Gastrointestinal Surgery

, Volume 16, Issue 6, pp 1116–1122

Effect of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Glucose and Gut Hormones: a Prospective Randomised Trial


    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
  • Silvia Salvans
    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
  • Xenia Crous
    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
  • Sonia Puig
    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
  • Albert Goday
    • Endocrinology and Nutrition UnitHospital Universitari del Mar
    • Department of MedicineUniversitat Autònoma de Barcelona
  • David Benaiges
    • Endocrinology and Nutrition UnitHospital Universitari del Mar
    • Department of MedicineUniversitat Autònoma de Barcelona
  • Lourdes Trillo
    • Service of AnaesthesiologyHospital Universitari del Mar
  • Manuel Pera
    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
  • Luis Grande
    • Section of Gastrointestinal Surgery, Institut de Recerca Hospital del Mar (IMIM-Hospital del Mar)Hospital Universitari del Mar
Original Article

DOI: 10.1007/s11605-012-1855-0

Cite this article as:
Ramón, J.M., Salvans, S., Crous, X. et al. J Gastrointest Surg (2012) 16: 1116. doi:10.1007/s11605-012-1855-0



Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common bariatric technique. Laparoscopic sleeve gastrectomy (LSG) is a restrictive procedure; the metabolic and endocrine effects of which remain unknown. We compared the effects of both procedures on glucose metabolism and fasting and meal-stimulated gut hormone levels.


Seven patients were randomised to LRYGB and eight to LSG. All patients were evaluated before and at 3 and 12 months postoperatively. Plasma levels of glucose, insulin, ghrelin, leptin, peptide YY (PYY), GLP-1 and pancreatic polypeptide were measured before and after 10 and 60 min of a standard test meal ingestion.


Age, body mass index and preoperative hormone levels were similar in both groups. A significant reduction of plasma glucose and insulin levels was observed after surgery. Moreover, a normalisation of homeostatic model assessment for insulin resistance value was also seen after both procedures. The fasting and postprandial leptin levels were significantly lower in the LRYGB group. LSG was followed by a significant reduction in fasting ghrelin levels. In the LRYGB group, GLP-1 levels increased significantly after the test meal.


LRYGB and LSG markedly improved glucose homeostasis. Only LSG decreased fasting and postprandial ghrelin levels, whereas GLP-1 and PYY levels increased similarly after both procedures.


Roux-en-Y gastric bypassSleeve gastrectomyGlucose metabolismGut hormones


Obesity is a first magnitude health problem because of the increased prevalence of this disease in Western countries and the difficulties involved in both prevention and treatment. Moreover, obesity is related to the development of chronic diseases increasing overall morbidity and mortality.1 Insulin resistance and the onset of type 2 diabetes mellitus (T2DM) represent one of these potential complications.2 In obese patients, the relative risk of developing T2DM is 5% in men and 8–20% in women.3 Weight loss in overweight or obese patients may delay or prevent the onset of T2DM in individuals with pre-diabetes or glucose intolerance4 and may improve glycaemic control in diabetic patients.

The effectiveness of behavioural, dietary and drug therapy in morbid obesity is limited (5-6). Bariatric surgery is the treatment of choice in selected morbid obese patients.57 Bariatric surgery is associated with long-term weight loss, improvement of cardiovascular profile, reversal of T2DM and amelioration of quality of life.6

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most widely used bariatric procedure.7 This procedure achieves a greater weight loss than restrictive techniques with no relevant malabsorptive symptoms,5 although the mechanism of action is not fully understood. Laparoscopic sleeve gastrectomy (LSG) is a purely restrictive technique with no malabsorptive effects and was originally developed as the first step of a biliopancreatic diversion with duodenal switch.8 However, this technique has recently been proposed as a single procedure9 because of its promising results in weight loss.10 Nonetheless, data on the effect of LSG on glucose metabolism and gastrointestinal hormone levels are limited. The purpose of this prospective, randomised study was to compare the effects of LRYGB and LSG on glucose metabolism and levels of gastrointestinal hormones such as ghrelin, leptin, GLP-1, peptide YY (PYY) and pancreatic polypeptide (PP) in morbid obese patients.

Materials and Methods

Between April 2007 and March 2008, female patients (aged 18–60 years) with a body mass index (BMI) >40 kg/m2 or a BMI >35 kg/m2 with at least one severe comorbidity were eligible for a randomised clinical study. Exclusion criteria included superobese patients (BMI >50 kg/m2) and patients not suitable for bariatric laparoscopic surgery or undergoing revisional surgery. All the studies were performed according to the principles of the Declaration of Helsinki and the Local Research and Ethics Committee at the Hospital del Mar approved the study. All patients provided written informed consent before enrolment.

Preoperatively, the patients were allocated to LRYGB or LSG by computer-generated randomization. Operations were performed by the same surgical team with experience in laparoscopic bariatric surgery. LRYGB technique included a subcardial gastric pouch of 15–30 cc and a 150-cm antecolic Roux-limb with 25 mm circular pouch-jejunostomy and an exclusion of 50 cm of proximal jejunum. In LSG, a longitudinal resection of the stomach from 5 cm proximal to the pylorus to the angle of His was performed using a 36-French orogastric tube inserted along the lesser curvature.

For the meal studies, subjects were admitted to our Clinical Trial Unit, IMIM-Hospital del Mar, before the operation, and at 3 and 12 months after surgery. On each occasion, an overnight fast of at least 12 h preceded insertion of an antecubital vein catheter for blood collection. After taking the fasting samples, a liquid test meal (Ensure® containing 54% calories as carbohydrates, 16% as protein, and 30% as fat) was served to stimulate hormone release. Blood was drawn at 10 and 60 min after food intake. Blood samples were collected on ice into EDTA tubes. After centrifugation at 4°C, plasma samples were frozen at −20°C until analysis.

While the patients were fasted for undergoing hormone assessment, all medications were kept off for a period of 12 h. Drugs that could interfere with hormone assays, such as sitagliptine, vildagliptine, saxagliptine. exenatide, liraglutide, insulin, sulfonylurea, repaglinide and nateglinide were not allowed either during the preoperative or the postoperative period.

Glucose and Hormone Assays

Plasma glucose concentration was determined using Cobas Integra® 400 plus chemistry analyzer (Roche Diagnostics, Spain). Plasma insulin concentrations were measured by radioimmunoassay (Linco Research Inc, St Charles, MO, USA). Insulin resistance was estimated by the homeostatic model assessment for insulin resistance (HOMA-IR) index11 and defined as HOMA-IR index ≥3.29 according to the reference values of our population.12

Total ghrelin was measured with a commercially available kit (Linco Research Inc, St Charles, MO, USA). The lower level of ghrelin that can be detected by this assay is 100 pg/mL. The intra-assay and inter-assay coefficient of variation were <10 and 15%, respectively.

Total PYY was measured with a commercially available kit (Linco Research Inc, St Charles, MO, USA). The antibody used recognises both the 1-36 and 3-36 forms of human PYY. The lowest level of PYY that could be detected by this assay was 10 pg/mL. The intra-assay and inter-assay coefficients of variation were both less than 10%.

GLP-1 was measured after extraction of plasma with ethanol using a commercially available kit (Linco Research, Inc, St Charles, MO, USA). The antibody recognises shapes GLP7-36, GLP7-37, GLP9-36 amide, GLP9-37, GLP1 amide and GLP-1-36-37 amide, and binds specifically to the C-terminal portion of GLP-1 in both amidated and non-amidated forms. The sensitivity was 3 pM and the intra-assay and inter-assay coefficients of variation were 25 and 30%, respectively. Leptin and PP concentrations were determined by using a commercially available assay kit (Lincoplex Human Gut Hormone Multiplex Assay; Linco Research Inc, St Charles, MO, USA) with sensitivities of 137 and 13.7 pg/mL, respectively. The intra-assay and inter-assay coefficients of variation were <19% for leptin and <11% for PP.

Statistical Analysis

The sample size was calculated according to data reported in the study of Le Roux et al.13 in which, after a test meal, there was an increase in PYY levels from 16.0 pg/mL (8.1) at baseline to 40.4 pg/mL (7.8) after the LRYGB in obese subjects. The alpha risk was established at 0.05 and the beta risk at 0.20 in a bilateral design. Six patients were allocated to each arm, in order to detect a difference equal to or greater than 15 pg/mL of variation. It assumed a common standard deviation of 8.35.

Statistical analysis for categorical data was performed using chi-squared test or Fisher’s exact test and t test for parametric quantitative data. Mann–Whitney test was used for analysing nonparametric continuous data. Statistical significance was set at a p value < 0.05. Results were analysed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA).


Thirty patients were assessed for surgery during the study period. Fifteen patients were not eligible for the study (five patients were males, four patients had BMI >50 kg/m2 and six patients refused entering into the study). A total of 15 patients were randomised, seven patients underwent LRYGB and eight LSG. The mean age for the whole group was 48.1 ± 8.8 years old (46.1 ± 18 and 49.8 ± 9 in the LRYGB and LSG, respectively). The two groups of patients had similar preoperative BMI (44.2 ± 2 for LRYGB vs 43.5 ± 3 for LSG). The comorbidities of the two groups are shown in Table 1. All four patients with T2DM were on oral antidiabetics drugs. All patients had a complete clinical evaluation at all time periods of the follow-up. A significant reduction in BMI was observed in both groups after surgery (Fig. 1). Moreover, mean BMI at 12 months after surgery was significantly lower in the LRYGB as compared to LSG (p = 0.016).
Table 1

Comorbidities in both surgical groups



LSG N = 8

p valuea


5 (71.4)

7 (87.5)


Diabetes mellitusb

2 (28.6)

2 (25.0)



5 (71.4)

5 (62.5)



4 (57.1)

6 (75.0)


Gastroesophageal reflux disease

0 (0)

1 (12.5)


Urinary incontinence

3 (42.9)

6 (75)



4 (57.1)

7 (87.5)


Obstructive sleep apnoea syndrome

2 (28.6)

2 (25.0)


Results are expressed as N (in percent)

LRYGB laparoscopic Roux-en-Y gastric bypass, LSG laparoscopic sleeve gastrectomy

aChi-squared test or Fisher’s exact test

bAll were treated with metformin
Fig. 1

Body mass index (BMI, in kilograms per square metre) in the two study groups [laparoscopic Roux-Y gastric bypass (LRYGB)—black and laparoscopic sleeve gastrectomy (LSG)—grey] before and 3 and 12 months after surgery

Glucose Metabolism

Fasting plasma glucose levels decreased and even normalised in both groups at 3 months after surgery (Fig. 2a). This reduction was observed when patients were still obese (BMI > 30 kg/m2) (Fig. 1). There were no statistically significant differences in serum glucose levels between the two techniques at any study period. All four diabetic patients were able to withdraw antidiabetic drugs within the first 3 months postoperatively.
Fig. 2

Fasting plasma glucose (in milligrams per decilitre) a, insulin (microunits per millilitre) b and HOMA-IR index c in the two study groups [laparoscopic Roux-Y gastric bypass (LRYGB)—black and laparoscopic sleeve gastrectomy (LSG)—grey] before and 3 and 12 months after surgery. Dashed lines in a and b represent upper and lower normal limits in our laboratory. Dashed line in c represents upper limit of normality in our population [12]

No significant differences in preoperative fasting insulin levels and HOMA-IR index between the two groups were observed (Fig. 2b, c). Postoperatively, fasting insulin levels were reduced significantly in both groups at 3 months after surgery. These levels remained stable at 12 months. Preoperatively, ten patients fulfilled the criteria for insulin resistance (six patients in the LRYBP group and four patients in the LSG), and postoperatively all patients normalised their HOMA-IR values except one patient in the LSG group (Fig. 2c). Although insulin plasma levels and HOMA-IR index were lower in the LRYGB, no significant differences between groups were detected.

Gut Hormone Levels

Preoperative fasting ghrelin levels were similar in both groups (Table 2). Postoperatively, fasting ghrelin levels decreased significantly at 3 and 12 months (p = 0.002 and p = 0.001, respectively) in the LSG group. After the test meal, although there was no statistically significance between groups, the pattern of ghrelin secretion was different. While the values in the LSG group remained low and unchanged, in the LRYGB group, a reduction of ghrelin levels at 10 and 60 min was observed at 3 and 12 postoperative months, respectively.
Table 2

Meal-induced changes in serum levels of gastrointestinal hormones in the two study groups


Ghrelin (pg/mL)

Leptin (pg/mL)


PYY (pg/mL)

PP (pg/mL)











Fasting condition


584 (493–645.4)

610.15 (449.8–775)

18,287 (13,728–31,883)

34,940.5 (26,843–59,169.5)

7.3 (4.7–9.1)

7.4 (3.3–11.7)

73.1 (68.7–99.5)

61.25 (47.1–74.9)

32.8 (14.9–108)

46 (31.9–74)

 3 months

682.6 (551697.9)

354.5* (281.8–403)

4,948 (3,410–8,562)

20,863* (16,296.8–22,833)

6.4 (3.6–15.1)

3.75 (2.7–5.)

76.4 (58.2–88.6)

47.4 (38.1–65.1)

44.3 (13.7–85.1)

50.05 (24.1–75.3)

 12 months

730 (611–866.7)

342* (316.1–445.6)

3,454 (2,375–7,263)

11.814* (10,059–23,450)

5.5 (5.3–7.1)

3.6* (2.9–4.7)

75.7 (66.9–81.1)

64.2 (41.1–76.8)

32.4 (20–84.4)

37.6 (23.7–52.5)

Postprandial 10 min


544.9 (475–600.6)

591.85 (463.3–875.5)

16,907 (13,474–36,109)

33,220.5 (30,529.5–48,046.3)

14.9 (12.7–19.1)

18.5 (12.4–25.6)

87.2 (70.1–118.2)

68.5 (59.1-102.8)

175.1 (65.6–297.8)

153.65 (117.5–292.6)

 3 months

599.4 (496–656.6)

358.2 (315.3–521.3)

4,735 (3,357–7,498)

19,811.5* (16,666.8–23,932.5)

71.6 (28.9–91.3)

43.4 (25.6–91.5)

126.2 (103.5–180.3)

93.75 (68.8–285.95)

128.8 (55.6–191.3)

192.7 (133.3–248.1)

 12 months

694 (516–772.2)

332 (315–396.6)

2,876 (2,318–6,232)

10,631* (8,687–23,614)

51.8 (36.3–58.1)

27.7* (18.1–33.2)

121.7 (109.1–163.7)

87.1 (57.7–133.6)

115.9 (66.9–188)

186.9 (150–271.5)

Postprandial 60 min


465.9 (402–577)

492.85 (465.6–754.75)

19,515 (15,444–33,282)

37,915 (28,587.5–50,700)

5.8 (3.9–12.7)

13.95 (12.1–23.3)

84.3 (71.1–92.5)

86.25 (69.1–94.9)

145.3 (67.7–185.8)

118 (73.1–187.8)

 3 months

405.6 (404–591)

339.35 (270.8–487)

4,795 (3,562–7,012)

20,919.5* (17,310.8–23,175.3)

17.4 (7.9–71.7)

24.5 (7.7–56.7)

153.8 (79.1–210.5)

118.3 (60.6–277.8)

94.6 (50.4–142.7)

78.95 (41.5–190.1)

 12 months

623 (485–680.1)

340.7 (243–361.6)

3,212 (2,534–6,788)

11,241* (9,537–22,286)

7.9 (4.8–13.9)

4.6 (3.4–7.8)

107.9 (74.4–141.5)

84.4 (61.1–116.1)

114.2 (36.4–145.9)

125.8 (42.9–167.2)

Data shown as median and interquartile range (25th–75th percentile)

LRYGB laparoscopic Roux-en-Y gastric bypass, LSG laparoscopic sleeve gastrectomy

*p > 0.05 vs LRYGB group

Postoperatively, fasting and meal-induced leptin levels were significantly reduced in both groups when compared with preoperative concentrations (Table 2). In addition, there was a significant change in leptin levels in the LRYGB group compared to the LSG group, both fasting (p = 0.001 at 3 months postoperative, p = 0.001 at 12 months) and after meal intake at 10 min (p = 0.005 at 3 months postoperative, p = 0.018 at 12 months) and 60 min (p = 0.005 at 3 months and p = 0.009 at 12 months).

Fasting and meal-stimulated preoperative concentrations of GLP-1 (Table 2) were similar in both groups. Postoperatively, we observed an increment in GLP-1 levels in fasting and at 10 min after meal stimulation in both groups but significantly higher in the LRYGB group (p = 0.017 in fasting, p = 0.002 at 10 min).

Preoperative fasting PYY levels were similar in both groups. At 3 months, meal-stimulated levels were higher in the LRYGB without reaching statistical significance (Table 2). PP levels had a similar meal response pattern in both groups at any study period without observing any significant difference (Table 2).


The LRYGB is an effective procedure to control T2DM in obese patients.14 This benefit on glucose metabolism appears in the early postoperative period before any significant loss of weight.7, 14, 15 This observation has not been described after performing a restrictive technique such as gastric banding.1618 One of the mechanisms proposed to explain the glycaemic control after LRYGB is the changes in gastrointestinal hormone levels.19, 20 Therefore, the aim of this study was to detect if this beneficial effect appears also after LSG and its relation to gastrointestinal hormone secretion. Some studies suggest that glycaemic control after LSG is achieved through a caloric restriction mechanism since the passage of nutrients through the proximal intestine is unchanged compared to LRYGB.

This prospective randomised study provides preliminary evidence of the effects of laparoscopic RYGB and SG on glucose metabolism and gastrointestinal hormones comparing the response to a test meal before operation and 3 and 12 months postoperatively. Both surgical techniques were associated with early improvement in glucose metabolism, already seen at 3 months after surgery when patients are still obese (BMI greater than 30 kg/m2) and maintain normal glucose levels at least 1 year after surgery. In addition, HOMA-IR normalised in 14 of 15 patients at 3 months postoperatively with no differences between surgical procedures. Indeed, the two diabetic patients in the LSG group normalised blood glucose and insulin levels and being able to withdraw hypoglycaemic medication at 3 months, as happened with the two diabetic patients in the LRYGB group. Other studies have demonstrated that LSG resulted in an early and dramatic improvement of glucose metabolism with superior glycaemic control than other restrictive techniques as adjustable gastric banding.2123

One possible explanation for these results could be as a consequence of limited caloric intake by small amounts of food eaten in the immediate postoperative period. This would lead to a negative energetic balance conditioning, an improvement of glucose tolerance. This mechanism can be applied to both procedures, since the improvement of insulin sensitivity associated with weight loss is well known.24 Another reason for the improved glycaemic control in both procedures could be related to changes in the secretion of gastrointestinal hormones involved in insulin secretion and/or action.13

Changes in the GLP-1 appear to be critical for improving the response to insulin. The GLP-1 is an anorexigenic neuropeptide synthesised primarily in the L cells of small intestine and colon.25 Its release is triggered by the arrival of food into the distal intestine and acts on pancreatic beta cells stimulating the release of insulin.26 Preoperatively, GLP-1 levels are low in obese patients. However, after surgery there is an increase in postprandial GLP-1 which cannot only be justified by caloric restriction since its secretion depends on the arrival of food into the distal small bowel. Low levels of GLP-1 detected in obese patients may reflect the state of functional deficiency that contributes to poor glycaemic control in these patients. An increase in postprandial GLP-1 level, in addition to its incretin effect, acts as a signal of satiety promoting weight loss. The higher postprandial secretion of GLP-1 in LRYGB patients compared to the levels found after LSG could be explained by the earlier arrival of nutrients to the ileum in the first group. Nonetheless, Braghetto et al.27 demonstrated a rapid gastric emptying for liquids as well as for solids and an acceleration of intestinal transit in patients with LSG, which might explain the small differences of GLP-1 levels observed between the two techniques.

PYY is an anorexigenic neuropeptide with satiating action as GLP-1. This is mainly synthesised in the distal portion of the digestive tract. In obese patients, PYY levels are reduced and also have a lower response28 contributing to an increased appetite and impaired glucose tolerance. Postoperative increased plasma PYY concentrations were detected in this study and may explain the weight loss and improved glycaemic control observed in our patients. Different studies have shown increased postprandial PYY after LRYGB,29, 30 and recently in agreement with our study, an increased PYY after LSG at 3 and 12 months postoperatively have also been reported.31

Ghrelin is a peripheral orexigenic neuropeptide, synthesised primarily in the fundus oxyntic cells.32 Fasting increases ghrelin up to a peak before a meal and then decreases in the postprandial period. Ghrelin has several diabetogenic effects, among which the inhibition of insulin is the most relevant.33 Low levels of ghrelin, GLP-1 and PYY concentrations in obese patients may reflect a functional deficiency status that contributes to poor glycaemic control in these patients.34 The recovery of decreased ghrelin levels in the postprandial period after LRYGB produces a suppression of appetite unlike what happens after other forms of loss of weight.35 This decrease of ghrelin also promotes insulin secretion in pancreatic beta cells.36 However, in our work, we found that LSG does not alter the response of ghrelin after ingestion. The normoglycaemia in these patients could be explained by the suppression of ghrelin production secondary to resection of gastric fundus. As it has been described by other authors,29, 31 there were significant differences between both techniques in the values of fasting ghrelin, with these levels being significantly lower in the LSG group at 3 and 12 months postoperatively.

Leptin is an anorexigenic neuropeptide with considerable antagonistic satiating action of ghrelin and is mainly synthesised in adipose tissue. It is considered a marker of energetic reserves.37 Unlike ghrelin, leptin levels are higher in obese patients and also a resistance to its action has been reported.38 We detected a decrease in leptin levels after surgery, as has been described previously.39, 40 Some studies have suggested that a reduction in these values is secondary to weight loss.41 However, other studies show that this reduction in leptin is independent of fat mass loss;42 thus, this observation might indicate a role for leptin in improving glucose homeostasis.

The PP is a peripheral anorexigenic neuropeptide synthesised primarily in the pancreatic PP cells. This peptide increases after meals leading to gastric emptying, although it also inhibits the intestinal motility.43 In our study, the PP showed a similar pattern of secretion in both groups. Although the values of PP in patients undergoing LRYGB were higher than those of patients having LSG, the difference was not statistically significant.

It should be noted that the present results, however, should be interpreted taking into account the small number of patients included in the study. Further studies in a larger study population are needed to confirm these preliminary findings. On the other hand, more pure nutrient sources or different volumes as well as solid foods were not tested, so that hormones responses to these challenges may be assessed in future studies. Also, direction for further investigation would be to determine hormonal changes after longer postoperative periods.

In summary, the present preliminary data suggest that LSG is more than a purely restrictive technique. It has an antidiabetic effect in the early postoperative period as has been described by other authors.29, 31, 44 These results question the exclusion of the proximal intestine as an essential step to achieve improved glucose tolerance. Our study confirms that the postprandial response of ghrelin, GLP-1 and PYY is maintained in patients undergoing LSG, at least for 12 months after surgery similar to patients having LRYGB, and could explain the good results of surgery in relation to weight loss and glycaemic control. In conclusion, both LSG and LRYGB significantly improved glucose homeostasis, with similar changes in intestinal hormone levels.


This work was supported by a research grant from the Fondo de Investigación Sanitaria (nº PI 06/90639), Instituto de Salud Carlos III. Ministry of Health, Spain. The authors thank the team of the Pharmacology Unit (Professor Magi Farré and Ms. Esther Menoyo) for their expert technical help and Susana Gonzalez for patients follow-up. We also thank Marta Pulido for editorial assistance.

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© The Society for Surgery of the Alimentary Tract 2012