| 1. |
- Cohen, R. V., et al.
(författare)
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Effect of Gastric Bypass vs Best Medical Treatment on Early-Stage Chronic Kidney Disease in Patients With Type 2 Diabetes and Obesity A Randomized Clinical Trial
- 2020
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Ingår i: Jama Surgery. - : American Medical Association (AMA). - 2168-6254. ; 155:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Early-stage chronic kidney disease (CKD) characterized by microalbuminuria is associated with future cardiovascular events, progression toward end-stage renal disease, and early mortality in patients with type 2 diabetes. OBJECTIVE To compare the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) surgery vs best medical treatment in patients with early-stage CKD, type 2 diabetes, and obesity. DESIGN, SETTING, AND PARTICIPANTS For this randomized clinical trial, patients with established type 2 diabetes and microalbuminuria were recruited from a single center from April 1, 2013, through March 31, 2016, with a 5-year follow-up, including prespecified intermediate analysis at 24-month follow-up. INTERVENTION A total of 100 patients with type 2 diabetes, obesity (body mass indexes of 30 to 35 [calculated as weight in kilograms divided by height in meters squared]), and stage G1 to G3 and A2 to A3 CKD (urinary albumin-creatinine ratio [uACR] >30 mg/g and estimated glomerular filtration rate >30 mL/min) were randomized 1:1 to receive best medical treatment (n = 49) or RYGB (n = 51). MAIN OUTCOMES AND MEASURES The primary outcome was remission of albuminuria (uACR <30 mg/g). Secondary outcomes were CKD remission rate, absolute change in uACR, metabolic control, other microvascular complications, quality of life, and safety. RESULTS A total of 100 patients (mean [SD] age, 51.4 [7.6] years; 55 [55%] male) were randomized: 51 to RYGB and 49 to best medical care. Remission of albuminuria occurred in 55% of patients (95% CI, 39%-70%) after best medical treatment and 82% of patients (95% CI, 72%-93%) after RYGB (P = .006), resulting in CKD remission rates of 48% (95% CI, 32%-64%) after best medical treatment and 82% (95% CI, 72%-92%) after RYGB (P = .002). The geometric mean uACRs were 55% lower after RYGB (10.7 mg/g of creatinine) than after best medical treatment (23.6 mg/g of creatinine) (P < .001). No difference in the rate of serious adverse events was observed. CONCLUSIONS AND RELEVANCE After 24 months, RYGB was more effective than best medical treatment for achieving remission of albuminuria and stage G1 to G3 and A2 to A3 CKD in patients with type 2 diabetes and obesity.
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| 2. |
- Elliott, J. A., et al.
(författare)
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Changes in gut hormones, glycaemic response and symptoms after oesophagectomy
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:6, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oesophagectomy is associated with reduced appetite, weight loss and postprandial hypoglycaemia, the pathophysiological basis of which remains largely unexplored. This study aimed to investigate changes in enteroendocrine function after oesophagectomy. Methods: In this prospective study, 12 consecutive patients undergoing oesophagectomy were studied before and 10 days, 6, 12 and 52weeks after surgery. Serial plasma total fasting ghrelin, and glucagon-like peptide 1 (GLP-1), insulin and glucose release following a standard 400-kcal mixed-meal stimulus were determined. CT body composition and anthropometry were assessed, and symptom scores calculated using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires. Results: At 1 year, two of the 12 patients exhibited postprandial hypoglycaemia, with reductions in bodyweight (mean(s. e. m.) 17.1(3.2) per cent, P < 0.001), fat mass (21.5(2.5) kg versus 25.5(2.4) kg before surgery; P = 0.014), lean body mass (51.5(2.2) versus 54.0(1.8) kg respectively; P = 0.003) and insulin resistance (HOMA-IR: 0.84(0.17) versus 1.16(0.20); P = 0.022). Mean(s. e. m.) fasting ghrelin levels decreased from postoperative day 10, but had recovered by 1 year (preoperative: 621.5(71.7) pg/ml; 10 days: 415.1(59.80) pg/ml; 6weeks: 309.0(42.0) pg/ml; 12weeks: 415.8(52.1) pg/ml; 52weeks: 547.4(83.2) pg/ml; P< 0.001) and did not predict weight loss (P = 0.198). Postprandial insulin increased progressively at 10 days, 6, 12 and 52weeks (mean(s. e. m.) insulin AUC0-30 min: fold change 1.7(0.4), 2.0(0.4), 3.5(0.7) and 4.0(0.8) respectively; P = 0.001). Postprandial GLP-1 concentration increased from day 10 after surgery (P < 0.001), with a 3.3(1.8)-fold increase at 1 year (P < 0.001). Peak GLP-1 level was inversely associated with the postprandial glucose nadir (P = 0.041) and symptomatic neuroglycopenia (Sigstad score, P = 0.017, R2 = 0.45). GLP-1 AUC predicted loss of weight (P = 0.008, R2 = 0.52) and fat mass (P = 0.010, R2 = 0.64) at 1 year. Conclusion: Altered enteroendocrine physiology is associated with early satiety, weight loss and postprandial hypoglycaemia after oesophagectomy.
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| 3. |
- Maghsoodi, N., et al.
(författare)
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Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass
- 2017
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Ingår i: Annals of Clinical Biochemistry. - : SAGE Publications. - 0004-5632. ; 54:4, s. 495-500
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Tidskriftsartikel (refereegranskat)abstract
- Background Roux-en-Y gastric bypass increases circulating bile acid concentrations, known mediators of postprandial suppression of markers of bone resorption. Long-term data, however, indicate that Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. Methods Thirty-six obese individuals, median age 44 (26-64) with median body mass index at baseline of 42.5 (40.4-46) were studied before and 15 months after Roux-en-Y gastric bypass. After an overnight fast, patients received a 400kcal mixed meal. Blood samples were collected premeal then at 30-min periods for 120min. Pre and postmeal samples were analysed for total bile acids, parathyroid hormone and C-terminal telopeptide. Results Body weight loss post Roux-en-Y gastric bypass was associated with a median 4.9-fold increase in peak postprandial total bile acid concentration, and a median 2.4-fold increase in cumulative food evoked bile acid response. Median fasting parathyroid hormone, postprandial reduction in parathyroid hormone and total parathyroid hormone release over 120min remained unchanged after surgery. After surgery, median fasting C-terminal telopeptide increased 2.3-fold, peak postprandial concentrations increased 3.8-fold and total release was increased 1.9-fold. Conclusions Fasting and postprandial total bile acids and C-terminal telopeptide are increased above reference range after Roux-en-Y gastric bypass. These changes occur in spite of improved vitamin D status with supplementation. These results suggest that post-Roux-en-Y gastric bypass increases in total bile acids do not effectively oppose an ongoing resorptive signal operative along the gut-bone axis. Serial measurement of C-terminal telopeptide may be of value as a risk marker for long-term skeletal pathology in patients post Roux-en-Y gastric bypass.
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| 4. |
- Abdelaal, M., et al.
(författare)
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Morbidity and mortality associated with obesity
- 2017
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and its repercussions constitute an important source of morbidity, impaired quality of life and its complications can have a major bearing on life expectancy. The present article summarizes the most important co-morbidities of obesity and their prevalence. Furthermore, it describes classification and grading systems that can be used to assess the individual and combined impact of co-morbid conditions on mortality risk. The literature was screened for assessment tools that can be deployed in the quantification of morbidity and mortality risk in individual patients. Thirteen specific domains have been identified that account for morbidity and mortality in obesity. Cardiovascular disease (CVD) and cancer account for the greatest mortality risk associated with obesity. The King's Criteria and Edmonton Obesity Staging System (EOSS) were identified as useful tools for the detection and monitoring of individual patient mortality risk in obesity care. The stark facts on the complications of obesity should be capitalized on to improve patient management and knowledge and referred to in the wider dissemination of public health messages aimed at improving primary prevention.
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| 5. |
- Abdelaal, M., et al.
(författare)
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Validated Scoring Systems for Predicting Diabetes Remission After Bariatric Surgery
- 2017
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Ingår i: Bariatric Surgical Practice and Patient Care. - : Mary Ann Liebert Inc. - 2168-023X .- 2168-0248. ; 12:4, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolic surgery is a new term used to emphasize the metabolic benefits of a variety of bariatric surgery procedures, particularly with relationship to the treatment of type 2 diabetes and its complications. Means by which the likely impact of metabolic surgery on diabetes could be assessed in individual patients would be of clinical value. Methods: Two main scoring systems (ABCD and DiaRem) have been proposed to predict remission of diabetes after metabolic surgery. We present a description of these systems, discuss the sources of differences in their predictive power, and suggest means by which to improve predictive power. Results: ABCD is more predictive in patients with intermediate and poorer scores. Neither score is validated as a means of predicting, which patients will benefit most from the repercussions of improved glycemic control in terms of complications. Conclusion: A composite scoring system derived from ABCD and DiaRem may improve prediction of postoperative remission rates. Such a system should be considered principally as an aid to decision-making. Excessive focus on prediction of long-term remission of type 2 diabetes mellitus should be avoided in favor of identifying which patients may stand to benefit most, even if full clinical remission is not achieved.
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| 6. |
- Abdelhafez, A. H. K., et al.
(författare)
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Impact of Abdominal Subcutaneous Fat Reduction on Glycemic Control in Obese Patients with Type 2 Diabetes Mellitus
- 2018
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Ingår i: Bariatric Surgical Practice and Patient Care. - : Mary Ann Liebert Inc. - 2168-023X .- 2168-0248. ; 13:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effect on type 2 diabetes mellitus (T2DM) when adipose tissue is removed is controversial. This study aimed to evaluate and compare the effect of the abdominoplasty and bariatric surgery on glycemic control in patients with T2DM. Methods: Patients with T2DM undergoing abdominoplasty for cosmesis were studied (n=25). Subjects were 36.91.3 years with a preoperative body mass index (BMI) of 40.60.5kg/m(2) and mean glycated hemoglobin (HbA1c) of 7.4%+/- 0.2%. Fifteen matched patients undergoing bariatric surgery were selected as a comparator group. Weight, BMI, waist circumference (WC), random blood glucose (RBG), and HbA1c were evaluated at baseline and 3, 6, and 12 months postsurgery. Results: By 12 months, abdominoplasty reduced weight by 5.6 +/- 0.3kg p<0.01), and HbA1c was reduced to 6.8%+/- 0.3% (p<0.01). After 12 months, bariatric surgery reduced BMI from 42.2 +/- 1kg/m(2) to 26.6 +/- 0.4kg/m(2) (p<0.01). HbA1c reduced from 7.9%+/- 0.4% to 5.5%+/- 0.2% (p<0.01). WC was similar between both groups at 3 months, although HbA1c reductions were superior after bariatric surgery. Conclusions: Reducing subcutaneous adipose tissue with abdominoplasty results in a small improvement in glycemic control in patients with T2DM. Despite equivalent WC at 3 months, bariatric surgery outperformed abdominoplasty on all metabolic parameters then and thereafter.
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| 7. |
- Al-Najim, Werd, et al.
(författare)
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Food intake and eating behavior after bariatric surgery
- 2018
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Ingår i: Physiological Reviews. - : American Physiological Society. - 0031-9333 .- 1522-1210. ; 98:3, s. 1113-1141
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in the last decade. Herein we review the proposed mechanisms governing changes in eating behavior, food intake, and body weight after bariatric surgery. Additive or synergistic effects of both conditioned and unconditioned factors likely account for the complete picture of changes in eating behavior. Considered application of strategies designed to support the underlying principles governing changes in eating behavior holds promise as a means of optimizing responses to surgery and long-term outcomes. © 2018 American Physiological Society. All rights reserved.
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| 8. |
- Al-Najim, W., et al.
(författare)
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Integrated insights into the role of alpha-melanocyte stimulatory hormone in the control of food intake and glycaemia
- 2018
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 100, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Identifying peptide hormones with multipotent actions on both weight and glycaemia can have a significant impact on therapeutic options in the treatment of obesity and diabetes. This has been exemplified by recent advances involving pharmacological exploitation of glucagon-like peptide 1 biology. Herein, we summarise evidence supporting the potential candidacy in this light of alpha-melanocyte stimulatory hormone, an endogenous peptide hormone and a breakdown product of the neuropeptide pro-opiomelanocortin. We reference its well described central actions in the control of food intake and moreover highlight new data pointing to an important role for this peptide hormone in the periphery, in relation to glycaemic control.
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| 9. |
- Arora, Tulika, et al.
(författare)
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Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass
- 2017
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Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 11:9, s. 2035-2046
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Tidskriftsartikel (refereegranskat)abstract
- Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with shamoperated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham-and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGBversus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.
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| 10. |
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| 11. |
- Docherty, Neil G., et al.
(författare)
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Urinary sodium excretion after gastric bypass surgery
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 13:9, s. 1506-1514
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut-kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. Objectives: We set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. Methods: Five female patients (age range: 28-50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). Results: Increases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. Conclusions: Renal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure. (C) 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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| 12. |
- Doody, A., et al.
(författare)
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Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with Type 2 diabetes
- 2018
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Ingår i: Journal of Diabetes and Its Complications. - : Elsevier BV. - 1056-8727. ; 32:1, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Elevated plasma soluble tumour necrosis factor receptor 1 (TNFR1) predicts long-term progression of chronic kidney disease. We investigated the association between elevated TNFR1 and the presence of renal disease in patients with Type 2 diabetes mellitus registering a haemoglobin Mc (HbA1c) >48 mmol/mol despite medical therapy. Methods: Using sensitivity, specificity and regression analyses we interrogated the association between plasma TNFR1 and presence of chronic kidney disease as assessed by the presence of microalbuminuria and/or an estimated glomerular filtration rate of less than 60 ml/min/1.73 m(2) (stages 3-5 chronic kidney disease). The association of TNFR1 with C-reactive protein and leptin-adiponectin ratio as plasma markers of systemic inflammation and adipose stress respectively was also investigated. Results: Upper quartile TNFR1 is independently associated with elevated urinary albumin-creatinine ratios, reductions in eGFR and strongly predicts the presence of stages 3-5 chronic kidney disease in regression modelling. Elevated TNFR1 levels are associated with increased plasma C-reactive protein and augmented leptin-adiponectin ratio. Conclusions: Our study confirms plasma TNFR1 as a surrogate of renal structural and functional impairment in patients with type 2 diabetes mellitus. Association of TNFR1 with markers of systemic inflammation and adipose stress indicates that TNFR1 may be a biomarker of these processes as components of the pathogenesis of diabetic kidney disease. (C) 2017 Elsevier Inc. All rights reserved.
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| 13. |
- Elliott, J. A., et al.
(författare)
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Physiology, pathophysiology and therapeutic implications of enteroendocrine control of food intake
- 2016
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Ingår i: Expert Review of Endocrinology & Metabolism. - : Informa UK Limited. - 1744-6651 .- 1744-8417. ; 11:6, s. 475-499
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: With the increasing prevalence of obesity and its associated comorbidities, strides to improve treatment strategies have enhanced our understanding of the function of the gut in the regulation of food intake. The most successful intervention for obesity to date, bariatric surgery effectively manipulates enteroendocrine physiology to enhance satiety and reduce hunger. Areas covered: In the present article, we provide a detailed overview of the physiology of enteroendocrine control of food intake, and discuss its pathophysiologic correlates and therapeutic implications in both obesity and gastrointestinal disease. Expert commentary: Ongoing research in the field of nutrient sensing by L-cells, as well as understanding the role of the microbiome and bile acid signaling may facilitate the development of novel strategies to combat the rising population health threat associated with obesity. Further refinement of post-prandial satiety gut hormone based therapies, including the development of chimeric peptides exploiting the pleiotropic nature of the gut hormone response, and identification of novel methods of delivery may hold the key to optimization of therapeutic modulation of gut hormone physiology in obesity.
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| 14. |
- Elliott, J. A., et al.
(författare)
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Risk factors for loss of bone mineral density after curative esophagectomy
- 2019
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- .Summary Micronutrient and fat malabsorption and altered enteroendocrine signaling occur after esophagectomy for cancer; however, the impact of malnutrition on bone health in this cohort has not been previously investigated. In this study, the prevalence of osteoporosis increased after curative surgery, associated with disease-specific, treatment-related, and population risk factors.PurposeImproved oncologic outcomes in esophageal cancer (EC) have resulted in increased survivorship and a focus on long-term quality of life. Malnutrition and micronutrient malabsorption are common among patients with EC, but the effect on bone metabolism is not known. The aim of this study was to characterize changes in bone mineral density (BMD) following curative esophagectomy.MethodsConsecutive disease-free patients who underwent esophagectomy with gastric conduit for pathologically node-negative disease from 2000 to 2014 were included. BMD was assessed at vertebral levels T12-L5 by computed tomography using a simple trabecular region-of-interest attenuation technique, and serum markers of nutritional status and bone metabolism were examined. Independent risk factors for osteoporosis were identified by multivariable logistic regression.ResultsSeventy-five consecutive patients were studied. Osteoporosis was present in 25% at diagnosis. BMD declined at 1 and 2years postoperatively (144.345.8 versus 128.6 +/- 46.2 and 122.7 +/- 43.5 Hounsfield Units (HU), P<0.0001), with increased osteoporosis prevalence to 38% and 44% (P=0.049), respectively. No significant postoperative change in vitamin D, calcium, or phosphate was observed, but alkaline phosphatase increased significantly (P<0.001). While female sex (P=0.004) and ASA grade (P=0.043) were independently associated with osteoporosis at diagnosis, age (P=0.050), female sex (P=0.023), smoking (P=0.024), and pathologic T stage (P=0.023) were independently predictive of osteoporosis at 1year postoperatively.Conclusions p id=Par5 Osteoporosis is prevalent among disease-free patients post-esophagectomy for EC, associated with disease-specific, treatment-related, and population risk factors. Strategies which minimize BMD decline should be considered to avoid fragility fractures in this cohort.
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| 15. |
- Gorman, D. M., et al.
(författare)
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The effect of bariatric surgery on diabetic retinopathy: Good, bad, or both?
- 2016
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Ingår i: Diabetes and Metabolism Journal. - : Korean Diabetes Association. - 2233-6079 .- 2233-6087. ; 40:5, s. 354-364
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery, initially intended as a weight-loss procedure, is superior to standard lifestyle intervention and pharmacological therapy for type 2 diabetes in obese individuals. Intensive medical management of hyperglycemia is associated with improved microvascular outcomes. Whether or not the reduction in hyperglycemia observed after bariatric surgery translates to improved microvascular outcomes is yet to be determined. There is substantial heterogeneity in the data relating to the impact of bariatric surgery on diabetic retinopathy (DR), the most common microvascular complication of diabetes. This review aims to collate the recent data on retinal outcomes after bariatric surgery. This comprehensive evaluation revealed that the majority of DR cases remain stable after surgery. However, risk of progression of pre-existing DR and the development of new DR is not eliminated by surgery. Instances of regression of DR are also noted. Potential risk factors for deterioration include severity of DR at the time of surgery and the magnitude of glycated hemoglobin reduction. Concerns also exist over the detrimental effects of postprandial hypoglycemia after surgery. In vivo studies evaluating the chronology of DR development and the impact of bariatric surgery could provide clarity on the situation. For now, however, the effect of bariatric surgery on DR remains inconclusive. © 2016 Korean Diabetes Association.
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| 16. |
- Holland, J. A., et al.
(författare)
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Impact of intentional weight loss on diabetic kidney disease
- 2019
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:10, s. 2338-2341
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) and obesity constitute interwoven pandemics challenging healthcare systems in developed countries, where diabetic kidney disease (DKD) is the most common cause of end-stage renal disease. Obesity accelerates renal functional decline in people with T2DM. Intentional weight loss (IWL) strategies in this population hold promise as a means of arresting DKD progression. In the present paper, we summarize the impact of IWL strategies (stratified by lifestyle intervention, medications, and metabolic surgery) on renal outcomes in obese people with DKD. We reviewed the Medline, EMBASE and Cochrane databases for relevant randomized control trials and observational studies published between August 1, 2018 and April 15, 2019. We found that IWL improves renal outcomes in the setting of DKD and obesity. Rate of progression of DKD slows with IWL, but varying outcome measures among studies makes direct comparison difficult. Furthermore, established means of estimating renal function are imperfect owing to loss of lean muscle mass with IWL strategies. The choice of optimal IWL strategy needs to be individualized; future work should establish the comparative efficacy of IWL strategies in obese people with DKD to better inform such decisions.
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| 17. |
- Kapoor, N., et al.
(författare)
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Shifts in Food Preferences After Bariatric Surgery: Observational Reports and Proposed Mechanisms
- 2017
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Ingår i: Current Obesity Reports. - : Springer Science and Business Media LLC. - 2162-4968. ; 6:3, s. 246-252
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is currently the most effective treatment for obesity. Roux-en-Y gastric bypass (RYGB) is the most commonly performed bariatric procedure and results in long-term weight loss. Alterations in food preference and choices may contribute to the long-term benefits of RYGB. This manuscript reviews the available literature documenting changes in food preference in both humans and experimental animals after RYGB and discusses the current theory on the underlying mechanisms involved. Obesity is associated with an increased preference for sweet and high-fat foods, and the most consistent evidence has been the shift away from these calorie-dense foods in both animal and human studies after RYGB. Self-reporting is the most common method used to record food preferences in humans, while more direct approaches have been used in animal work. This methodological heterogeneity may give rise to inconsistent findings. Future studies in humans should focus on direct measures to permit corroboration of mechanistic insights gained from animal studies.
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| 18. |
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| 19. |
- Mangan, A. M., et al.
(författare)
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Effect of Macronutrient Type and Gastrointestinal Release Site on PYY Response in Normal Healthy Subjects
- 2019
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:9, s. 3661-3669
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Enteroendocrine L cells release satiety inducing hormones in response to stimulation by luminal macronutrients. We sought to profile the differential effect of macronutrient type and site of release on circulating concentrations of the L cell-derived enteroendocrine hormone peptide tyrosine tyrosine (amino acids 1 to 36) (PYY). Materials and Methods: Eight healthy volunteers were recruited to a randomized, double-blinded, six-way crossover study. At each visit, the participants consumed a 500-kcal drink containing carbohydrate, protein, or fat in either gastric or small intestinal release formulations. Plasma PYY concentrations and hunger ratings were assessed for 3 hours after consumption of the test drink. The food intake was recorded thereafter at an ad libitum lunch. Results: Microcapsular formulations targeting the distal small intestinal delivery of fat, but not carbohydrate or protein, markedly enhance PYY release relative to macronutrient delivery in gastric release formulations. Food intake at an ad libitum meal was lowest after consumption of the formulation releasing fat at the distal small intestine. Conclusion: Targeting of fat to the distal small intestine in delayed release microcapsules enhanced PYY release and was associated with reductions in food intake.
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| 20. |
- Martin, William P., et al.
(författare)
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Dietary restriction and medical therapy drive PPARα-regulated improvements in early diabetic kidney disease in male rats
- 2022
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Ingår i: Clinical science (London, England : 1979). - 1470-8736. ; 136:21, s. 1485-1511
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Tidskriftsartikel (refereegranskat)abstract
- The attenuation of diabetic kidney disease (DKD) by metabolic surgery is enhanced by pharmacotherapy promoting renal fatty acid oxidation (FAO). Using the Zucker Diabetic Fatty and Zucker Diabetic Sprague Dawley rat models of DKD, we conducted studies to determine if these effects could be replicated with a non-invasive bariatric mimetic intervention. Metabolic control and renal injury were compared in rats undergoing a dietary restriction plus medical therapy protocol (DMT; fenofibrate, liraglutide, metformin, ramipril, and rosuvastatin) and ad libitum-fed controls. The global renal cortical transcriptome and urinary 1H-NMR metabolomic profiles were also compared. Kidney cell type-specific and medication-specific transcriptomic responses were explored through in silico deconvolution. Transcriptomic and metabolomic correlates of improvements in kidney structure were defined using a molecular morphometric approach. The DMT protocol led to ∼20% weight loss, normalized metabolic parameters and was associated with reductions in indices of glomerular and proximal tubular injury. The transcriptomic response to DMT was dominated by changes in fenofibrate- and peroxisome proliferator-activated receptor-α (PPARα)-governed peroxisomal and mitochondrial FAO transcripts localizing to the proximal tubule. DMT induced urinary excretion of PPARα-regulated metabolites involved in nicotinamide metabolism and reversed DKD-associated changes in the urinary excretion of tricarboxylic acid (TCA) cycle intermediates. FAO transcripts and urinary nicotinamide and TCA cycle metabolites were moderately to strongly correlated with improvements in glomerular and proximal tubular injury. Weight loss plus pharmacological PPARα agonism is a promising means of attenuating DKD.
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| 21. |
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| 22. |
- Martin, W. P., et al.
(författare)
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Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in atertiary nephrology centre
- 2020
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Ingår i: Clinical Obesity. - : Wiley. - 1758-8103 .- 1758-8111. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3(rd)August, 2018 and 18(th)January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean +/- SD BMI was 28.6 +/- 5.8 kg/m(2)(n = 374). Overweight and obesity class 1 were more common in males (P= .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean +/- SD age, n (%) female and median[IQR] eGFR were 64.1 +/- 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r= 0.21,P= .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m(2)higher in those treated with 4-5 versus 0-1 antihypertensives (P= .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.
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| 23. |
- Martin, W. P., et al.
(författare)
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Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA(1c)>= 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR)<= 60 mL/min/BSA) (n=118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by -0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of >= 40% decline in CKD-EPI eGFR (HR 1.5, p=0.001) and doubling of serum creatinine (HR 2.0, p<0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p=0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.
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| 24. |
- Nair, M., et al.
(författare)
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Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease
- 2020
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Ingår i: Bmj Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Roux-en-Y gastric bypass surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modeling in experimental diabetic kidney disease demonstrates that improvements in glomerular structure likely underpin these findings. Research design and methods In adult male Zucker diabetic fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterize the transcriptional alterations governing the renal reparative response to RYGB. Results In parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of transforming growth factor (TGF)-beta superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy. Conclusions Improved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-beta-driven early profibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and type 2 diabetes.
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| 25. |
- Neff, Karl J., et al.
(författare)
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Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289 .- 1878-7533. ; 13, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 American Society for Bariatric Surgery Background Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. Objectives To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. Setting University laboratories. Methods Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. Results Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. Conclusion Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery.
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| 26. |
- Sinclair, P., et al.
(författare)
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Metabolic Effects of Bariatric Surgery
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity can be defined as a chronic subcortical brain disease, as there is an important neurophysiological component to its etiology based on changes in the functioning of those areas of the brain controlling food intake and reward. Extensive metabolic changes accompany bariatric surgery-based treatment of obesity. Consequently, the term "metabolic" surgery is being increasingly adopted in relation to the beneficial effects these procedures have on chronic diseases like type 2 diabetes. CONTENT: In the present review, we focus on the key biochemical and physiological changes induced by metabolic surgery and highlight the beneficial effects accrued systemically with the use of an organ-based approach. Understanding the impact on and interactions between the gut, brain, adipose tissue, liver, muscle, pancreas, and kidney is key to understanding the sum of the metabolic effects of these operations. SUMMARY: Further mechanistic studies are essential to assess the true potential of metabolic surgery to treat metabolic comorbidities of obesity beyond type 2 diabetes. Approaches that may mitigate the metabolic side effects of surgery also require attention. Understanding the positive impact of metabolic surgery on metabolic health may result in a wider acceptance of this intervention as treatment for metabolic, comorbid conditions.
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| 27. |
- Wallenius, Ville, 1970, et al.
(författare)
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Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets-Data from a Randomized Cross-Over Study in Healthy Subjects.
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.
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| 28. |
- Wallenius, Ville, 1970, et al.
(författare)
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Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet.
- 2020
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 69:8, s. 1423-1431
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Tidskriftsartikel (refereegranskat)abstract
- Food intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms.Jejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures.The most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline.Intestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.
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| 29. |
- Werling, Malin, 1967, et al.
(författare)
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Biliopancreatic Diversion is associated with greater increases in energy expenditure than Roux-en-Y Gastric Bypass
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective The greater weight loss achieved following Biliopancreatic Diversion with Duodenal Switch (BPDS) versus Roux-en-Y Gastric Bypass (RYGB) has been attributed to the malabsorptive effects of BPDS. Increased weight loss after BPDS could also be underpinned by larger increases in energy expenditure. Hypothetically, the more radical reconfiguration of the small intestine in BPDS could result in an accentuated increase in meal associated thermogenesis (MAT). Female subjects (baseline mean age 40 years, mean BMI-55kg/m(2)) were assessed four years after randomization to BPDS (n = 6) or RYGB (n = 6). Energy expenditure (EE) and respiratory quotient (RQ) were measured by indirect calorimetry over 24 hours. A detailed protocol allowed for discrimination of basal metabolic rate (BMR), fasting EE and MAT as components of total energy expenditure (TEE) normalised for total and lean tissue by dual energy x-ray absorptiometry. Median weight loss at follow-up was 1.5-fold higher following BPDS relative to RYGB, resulting in respective median BMIs of 29.5 kg/m 2 (21.7 to 36.7) after BPDS and 37.8 kg/m(2) (34.1 to 45.7) after RYGB (p = 0.015). The BPDS group had a lower fat:lean ratio compared to the RYGB group (p = 0.009). Overall 24-hour TEE adjusted for total tissue was higher in the BPDS group, as were BMR, fasting EE and MAT (all p<0.05). Differences between RYGB and BPDS in BMR and TEE were nullified when normalised for lean mass. Postprandial RQ increased significantly but to a similar extent in both groups. Enhanced and prolonged MAT and lower fat:lean mass ratios after BPDS may explain relative increases in total energy expenditure as compared to RYGB.
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