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- Holdstock, Camilla, et al.
(författare)
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CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects
- 2005
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 29:10, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk ofcardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent theinsulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypasssurgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies onthe regulation of inflammatory markers.DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well asmarkers of glucose and lipid metabolism.RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRPcorrelated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, whencorrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the changein body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4(insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended toparallel the changes in CRP, but were less informative.CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers andimproves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistantpatients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather thanenergy supply.
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- Holdstock, Camilla, 1975-
(författare)
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Gastric Bypass in Morbid Obesity : Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.
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- Holdstock, Camilla, et al.
(författare)
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Postprandial changes in gut regulatory peptides in gastric bypass patients
- 2008
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32, s. 1640-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding. DESIGN: The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal. SUBJECTS: Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41+/-7 years; mean BMI 44+/-3 kg/m(2)), 10 operated with RYGBP (age 45+/-5 years; BMI 35+/-6 kg/m(2)), 10 aged-matched lean (age 44+/-5 years; BMI 24+/-3 kg/m(2)) and 10 young lean subjects (age 26+/-2 years; BMI 23+/-2 kg/m(2)). MEASUREMENTS: Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained. RESULTS: PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect. CONCLUSION: RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre- and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.
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- Sundbom, Magnus, et al.
(författare)
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Early Changes in Ghrelin following Roux-en-Y Gastric Bypass : Influence of Vagal Nerve Functionality?
- 2007
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 17:3, s. 304-310
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Tidskriftsartikel (refereegranskat)abstract
- Background Roux-en-Y gastric bypass (RYGBP) effectively produces massive weight reduction, improving health in morbidly obese patients. The mechanisms for the weight loss, and the fate of the excluded gastric mucosa, are not fully clarified. To what extent the appetite-stimulating gastric peptide ghrelin is affected remains controversial. Methods Circulating concentrations of ghrelin, pancreatic polypeptide (PP), pepsinogen I (PGI) and gastrin were examined in 15 morbidly obese patients (median BMI 45 kg/m2) preoperatively, and on days 1, 2, 4, 6 and at months 1, 6 and 12 after RYGBP. Results Ghrelin levels fell on postoperative day 1 and increased after 1 month to preoperative levels, and rose further at 6 and 12 months. PP concentrations decreased on day 1 and subsequently returned to preoperative levels. PGI levels peaked transiently the first days after surgery and subsequently declined to lower than preoperative levels. Gastrin levels were gradually reduced postoperatively. Conclusion Ghrelin and PP fall transiently after surgery, possibly due to vagal dysfunction, and ultimately, as weight loss ensues, ghrelin secretion increases to higher than preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected by a transient increase in circulating PGI, and subsequently, the mucosa in the excluded stomach is at rest, as shown by low levels of PGI and gastrin.
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