Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Metabolic Effects of Roux-en-Y Gastric Bypass in Obese Adolescents and Young Adults
Sinha, Manasi*; Stanley, Takara L.*; Webb, Jessica*; Scirica, Christina†; Corey, Kathleen†; Pratt, Janey†; Boepple, Paul A.*; Hoppin, Alison†; Misra, Madhusmita*
*Pediatric Endocrine Unit
†Weight Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Takara Stanley, MD, LON5-207, Massachusetts General Hospital, Boston, MA 02114 (e-mail: email@example.com).
Received 18 September, 2012
Accepted 17 December, 2012
Drs Sinha and Stanley were the co-first authors in this study.
Funding provided in part by National Institutes of Health T32HD052961 to M.S. and K23DK089910 to T.L.S., by the MGH Multicultural Affairs Office Summer Research Trainee Program to J.W., and by the American Association for the Study of Liver Disease Clinical and Translational Research Award to K.C.
The authors report no conflicts of interest.
ABSTRACT: Weight loss surgery is an increasingly common treatment option for obese adolescents, but data are limited regarding the metabolic effects of surgical weight loss procedures. We performed a retrospective review of the electronic medical record to determine metabolic outcomes for 24 adolescents and young adults ages 15 to 22 years undergoing Roux-en-Y gastric bypass from 2009 to 2011 as well as 24 age-, sex-, and BMI-matched controls. During a median follow-up of 6 months after Roux-en-Y gastric bypass, fasting glucose, hemoglobin A1c, low-density lipoprotein, triglyceride, and high-sensitivity C-reactive protein decreased significantly. Changes in these measures were not significantly associated with age or extent of weight loss.
Weight loss surgery (WLS) is increasingly used in severely obese adolescents who have failed attempts at lifestyle modification or pharmacologic therapy. In adults, WLS is a highly effective treatment for comorbidities of obesity (1–3). In contrast, less is known about outcomes of WLS in adolescents and young adults, and few studies compare postsurgical metabolic changes with metabolic changes in nonsurgical controls. The objectives of the present study were to evaluate metabolic changes in mature adolescents and young adults ages 15 to 22 years undergoing Roux-en-Y gastric bypass (RYGB) and to compare results to a nonsurgical cohort. Our hypothesis was that RYGB would lead to improvement in body mass index (BMI), glucose homeostasis, lipids, and pro-inflammatory markers as compared to matched nonsurgical controls.
This retrospective electronic medical record review was approved by the Partners Health Care institutional review board. Requirement for informed consent was waived by the institutional review board based on the minimal risk to subjects and impracticability of obtaining consent for this retrospective review. We reviewed data on all patients 22 years or younger who were referred to the Weight Center at Massachusetts General Hospital (MGH) and underwent an RYGB procedure from 2009 to 2011. Adolescent eligibility criteria for WLS at the MGH Weight Center include BMI ≥35 kg/m2 with severe comorbidities or BMI ≥40 kg/m2 with minor comorbidities, completion of statural growth, demonstration of previous sustained efforts at nonsurgical weight loss (ie, lifestyle changes including nutritional changes and physical activity), and determination by a physician, psychologist, and nutritionist that sufficient maturity exists to recognize the risks and benefits of the procedure and to implement required postoperative behavioral changes. A control subject between the ages of 15 and 23 years was selected to match each RYGB subject using a patient database that included only sex, age, and BMI information. These control subjects were also evaluated at the MGH Weight Center for obesity, but were managed with lifestyle intervention. Median (interquartile range [IQR]) of BMI difference between patients undergoing RYGB and controls was 0.9 kg/m2 (−0.1 to 3.1). Information collected included height and weight measured at clinical visits by clinical staff as well as laboratory values obtained at MGH and its affiliates. Excess BMI was determined as the difference between a subject's BMI and a BMI of 25 kg/m2, and percent excess BMI loss (% EBMIL [excess body mass index loss]) was calculated as (BMI loss/[preoperative BMI − 25]) × 100 (4,5). Preoperative data were collected within 1 year of surgery. When possible, follow-up data were collected between 6 and 12 months postoperatively. To maximize available data, some laboratory values outside this time frame were included. Not all data were available for all patients during the follow-up period. Statistical analysis was performed using the statistical software package JMP 9.0 (SAS Institute Inc, Cary, NC). The majority of data were not normally distributed, and results are presented as median (IQR) unless otherwise indicated. Wilcoxon rank sum test was used to assess differences between groups. To assess differences within groups between baseline and follow-up, the paired t test was used when differences were normally distributed, and the paired Wilcoxon signed rank test was used when differences were not normally distributed.
Baseline characteristics are shown in Tables 1 and 2. Hemoglobin A1c (HbA1c) was higher in the RYGB group compared with controls (P = 0.01), but there were no other differences between the groups at baseline. The median (IQR) for BMI follow-up was 191 days (141–294), and for postoperative laboratories 198 days (155–312) (P = 0.62 for difference). Follow-up intervals for both laboratories and BMI tended to be 1 to 2 months longer in controls compared with RYGB, but this was not statistically significant (P = 0.09 for laboratories, P = 0.11 for BMI). As expected, RYGB led to significant weight loss. Subjects undergoing RYGB lost 44% (33 to 55) excess BMI, with a range of 20% to 90% EBMIL. Of note, there was no difference in EBMIL between those RYGB subjects who had follow-up laboratories available and those who did not (P = 0.79).
As shown in Table 2, fasting glucose and HbA1c decreased significantly in the RYGB group. In the limited subset of subjects (N = 9) who had fasting insulin available, fasting insulin changed by −22 μU/mL (−31 to −11, P = 0.003), and homeostatic model assessment-insulin resistance (HOMA-IR) changed by −4.7 (−7.0 to −2.3, P = 0.004). In the 2 patients who had type 2 diabetes mellitus (T2DM) before surgery, diabetes was noted to be resolved at follow-up. Total cholesterol, low-density lipoprotein, and triglycerides also significantly decreased (Table 2).
In the RYGB group as a whole, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) did not significantly change following surgery (Table 2). Among the subgroup (N = 6) of patients who had elevated ALT or AST at baseline, however, RYGB resulted in a significant decline in AST (−12 U/L [−23 to −3], P = 0.03) and ALT (−27 U/L [−46 to −11], P = 0.03). Serum creatinine showed a small but significant decrease following RYGB (Table 2, P = 0.03).
High-sensitivity C-reactive protein (hsCRP) changed by −6 mg/L (−13 to −2) following RYGB (P = 0.0007). Although sample size was limited, the decrease in CRP in girls was greater than in boys (P = 0.03). Sedimentation rate changed by −9 mm/h (−18 to −6) in the RYGB group during follow-up (P = 0.0001). White blood cell count (−2.2 cells/mm3 [−4.0 to −0.8], P = 0.001) and platelet count (−41 cells/mm3 [−81 to −2], P = 0.004) also decreased. In univariate analysis within the RYGB group, age at surgery was not associated with changes in weight or changes in metabolic variables. Of note, postsurgical changes in body weight were not significantly associated with changes in fasting glucose, HbA1c, lipid, or systemic inflammatory markers (hsCRP, erythrocyte sedimentation rate [ESR]); P > 0.2 for all.
Changes in controls during the follow-up period are shown in Table 2. The control group did not experience significant weight loss during the follow-up period, and, compared with controls, the %EBMIL in the RYGB group was highly significant (P < 0.0001). Changes in fasting glucose (P = 0.02) and HbA1c (P = 0.02) were also significant in RYGB versus controls. There were not sufficient data in controls to compare changes in fasting insulin or HOMA-IR. The decrease in low-density lipoprotein after RYGB was significant (P = 0.03) compared with controls, whereas the change in triglycerides was not significant (P = 0.4). Declines in white blood cell count (P = 0.002) and platelets (P = 0.003) were significant in RYGB versus controls, whereas there were not sufficient control data to compare changes in hsCRP or ESR. There was a small decrease in creatinine in the RYGB group that just reached statistical significance as compared with controls (P = 0.05).
Our data demonstrate improvements in multiple metabolic parameters following RYGB in adolescents and young adults, many of which were highly significant compared with controls. Age was not significantly associated with outcomes. Moreover, the magnitude of metabolic improvement was not significantly associated with the degree of weight loss, supporting recent research that RYGB alters critical endocrine and metabolic pathways independent of caloric restriction and weight loss (6–8); however, our small sample size may have limited our ability to detect associations between magnitude of weight loss and improvement in metabolic variables.
As shown in previous studies in adolescents, glucose homeostasis improved in our cohort following RYGB (9,10). In the 2 of 24 RYGB subjects who had T2DM at baseline, T2DM resolved postsurgically, consistent with previous reports in adolescents and adults (10). Although the majority of our cohort was nondiabetic, significant improvements were seen in HbA1c (−0.4%), fasting glucose (−9 mg/dL), insulin (−22 μU/mL), and HOMA-IR (−4.7). The magnitude of these changes is similar to changes reported in other RYGB cohorts (9,11).
Markers of chronic inflammation, including CRP and ESR, decreased significantly in RYGB subjects. Reduction in CRP has been reported in adult WLS cohorts (12,13), but to our knowledge this is the first report of reductions in hsCRP and ESR in adolescents and young adults following RYGB. We also noted reductions in leukocyte and platelet counts after RYGB. Before the widespread use of hsCRP as a marker of inflammation, population studies showed strong positive associations between leukocyte count and future cardiovascular disease risk (14,15). Thrombocytosis is also associated with systemic inflammation (16) and obesity (17), and relatively higher platelet counts predict future cardiovascular disease (18). To our knowledge, the small but significant decrease in serum creatinine after RYGB has not yet been reported in adolescents and young adults but is consistent with data in adults showing a 0.1-mg/dL decrease in creatinine 6 months after RYGB (19).
There are important limitations to the present study. This was a retrospective study dependent on clinical data, which were not consistently collected in all patients. RYGB patients and controls were matched only on the basis of sex, age, and BMI, and we were not able to match on other potentially important factors such as earlier weight history and follow-up interval. Height and weight were collected by multiple clinical staff rather than a single evaluator. In addition, we have a relatively small sample size and limited time frame for evaluation of postoperative changes. More important, previous studies have shown a modest decline in success rates 2 to 3 years postoperatively in patients after gastric bypass, and it will be necessary to follow adolescents undergoing RYGB further to assess this issue; however, given the relatively limited data on outcomes of WLS in adolescents and young adults, we believe our data, in combination with reports from other relatively small cohorts, contribute to our knowledge of metabolic outcomes of RYGB in this age group. Consistent with other studies, we demonstrate significant improvements in glucose homeostasis and lipid measures, and, for the first time in this age group, we show significant changes in markers of inflammation, including CRP, as well as improvements in creatinine. Further studies are necessary to elucidate the mechanisms of these changes.
1. Sugerman HJ, Wolfe LG, Sica DA, et al. Diabetes and hypertension in severe obesity and effects of gastric bypass-induced weight loss. Ann Surg
2. Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med
3. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med
4. Deitel M, Greenstein RJ. Recommendations for reporting weight loss. Obes Surg
5. Dixon JB, McPhail T, O’Brien PE. Minimal reporting requirements for weight loss: current methods not ideal. Obes Surg
6. Korner J, Bessler M, Cirilo LJ, et al. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab
7. Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg
8. Bayham BE, Greenway FL, Bellanger DE, et al. Early resolution of type 2 diabetes seen after Roux-en-Y gastric bypass and vertical sleeve gastrectomy. Diabetes Technol Ther
9. Lawson ML, Kirk S, Mitchell T, et al. One-year outcomes of Roux-en-Y gastric bypass for morbidly obese adolescents: a multicenter study from the Pediatric Bariatric Study Group. J Pediatr Surg
10. Inge TH, Miyano G, Bean J, et al. Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk factors after surgical weight loss in adolescents. Pediatrics
11. Teeple EA, Teich S, Schuster DP, et al. Early metabolic improvement following bariatric surgery in morbidly obese adolescents. Pediatr Blood Cancer
12. Illan-Gomez F, Gonzalvez-Ortega M, Orea-Soler I, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg
13. Miller GD, Nicklas BJ, Fernandez A. Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery. Surg Obes Relat Dis
14. Kannel WB, Anderson K, Wilson PW. White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA
15. Margolis KL, Manson JE, Greenland P, et al. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study. Arch Intern Med
16. Santimone I, Di Castelnuovo A, De Curtis A, et al. White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population: results from the MOLI-SANI project. Haematologica
17. Samocha-Bonet D, Justo D, Rogowski O, et al. Platelet counts and platelet activation markers in obese subjects. Mediators Inflamm
18. Thaulow E, Erikssen J, Sandvik L, et al. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation
19. Getty JL, Hamdallah IN, Shamseddeen HN, et al. Changes in renal function following Roux-en-Y gastric bypass: a prospective study. Obes Surg
adolescence; glucose; high-sensitivity C-reactive protein; obesity; roux-en-Y gastric bypass
© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
Highlight selected keywords in the article text.
Connect With Us
Visit JPGN.org on your smartphone. Scan this code (QR reader app required) with your phone and be taken directly to the site.