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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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- Holmer, Helene, et al.
(författare)
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Fracture incidence in GH-deficient patients on complete hormone replacement including GH
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:12, s. 1842-1850
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Tidskriftsartikel (refereegranskat)abstract
- Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients wilh confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR. 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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| 8. |
- Johansson, H.-E., et al.
(författare)
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Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
- 2007
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 24:11, s. 1213-1220
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Tidskriftsartikel (refereegranskat)abstract
- Aims Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). Methods Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) ± SD, 34.8 ± 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 ± 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 ± 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. Results Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). Conclusions MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.
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| 9. |
- Johansson, Lars, et al.
(författare)
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Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy
- 2008
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 18:10, s. 1297-1304
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.
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| 10. |
- Lind, Lars, et al.
(författare)
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Vasoreactivity is rapidly improved in obese subjects after gastric bypass surgery
- 2009
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 33:12, s. 1390-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. We investigated vasoreactivity in conduit and resistance arteries in morbidly obese subjects, and the effect of weight loss after gastric bypass surgery. METHODS: A total of 19 obese subjects (body mass index (BMI): 43.8+/-3.1 kg m(-2), 75% female, mean age 41 years) were investigated before surgery and after 1 and 12 months of surgery. Nineteen non-obese controls matched for age and gender were examined. Vasoreactivity was evaluated by ultrasound to measure flow-mediated dilation (FMD, evaluating a conduit vessel) and pulse-wave analysis with terbutaline provocation (change in reflectance index (RI), evaluating resistance vessels). RESULTS: Before surgery, the obese showed a low change in RI (18+/-12 vs 37+/-15% in controls, P=0.0001), but not significantly regarding FMD (7.9+/-6.4 vs 8.9+/-5.4% in controls). Surgery resulted in a weight loss of 9% at 1 month and 30% at 1 year. Change in RI markedly improved to 36+/-12% at 1 month (P=0.0001 vs baseline) and further to 44+/-11% at 1 year (P=0.014 vs 1 month). FMD did not change significantly. Heart rate and brachial artery diameter were reduced, with no significant change in blood pressure. The improvement in resistance vessel vasodilation, estimated as change in RI, was not correlated to changes in weight or measures of glucose and lipid metabolism. CONCLUSIONS: Obese patients showed impaired vasoreactivity in resistance arteries that was normalized already 1 month after gastric bypass surgery. The basis for this remarkable outcome, not significantly related to changes in body weight and metabolic variables, remains to be clarified.
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