Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis : A Randomized Controlled Trial.

BACKGROUND: Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. OBJECTIVE: To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. DESIGN: Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tønsberg]). (ClinicalTrials.gov: NCT01778738). SETTING: Tertiary care obesity center in Norway. PARTICIPANTS: 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). INTERVENTION: From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. MEASUREMENTS: The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. RESULTS: Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. LIMITATIONS: Single-center study, short follow-up time, and lack of power for secondary outcomes. CONCLUSION: With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. PRIMARY FUNDING SOURCE: Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

BACKGROUND AND AIMS: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. PATIENTS AND METHODS: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. RESULTS: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. CONCLUSIONS: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study.

BACKGROUND: Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI). RESULTS: A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen's d = 0.75), and (0.7 [0.3-1.1], Cohen's d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. CONCLUSIONS: Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778738.

Association of Bariatric Surgery vs Medical Obesity Treatment With Long-term Medical Complications and Obesity-Related Comorbidities.

Importance: The association of bariatric surgery and specialized medical obesity treatment with beneficial and detrimental outcomes remains uncertain. Objective: To compare changes in obesity-related comorbidities in patients with severe obesity (body mass index ≥40 or ≥35 and at least 1 comorbidity) undergoing bariatric surgery or specialized medical treatment. Design, Setting, and Participants: Cohort study with baseline data of exposures from November 2005 through July 2010 and follow-up data from 2006 until death or through December 2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway. Consecutive treatment-seeking adult patients (n = 2109) with severe obesity assessed (221 patients excluded and 1888 patients included). Exposures: Bariatric surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956) including individual or group-based lifestyle intervention programs. Main Outcomes and Measures: Primary outcomes included remission and new onset of hypertension based on drugs dispensed according to the Norwegian Prescription Database. Prespecified secondary outcomes included changes in comorbidities. Adverse events included complications retrieved from the Norwegian Patient Registry and a local laboratory database. Results: Among 1888 patients included in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean [SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years [range, 0.2-10.1]). Surgically treated patients had a greater likelihood of remission and lesser likelihood for new onset of hypertension (remission: absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%-23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%, RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9 [95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD, 2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids: AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]). Surgical patients had a greater risk for undergoing at least 1 additional gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%-18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin levels was significantly greater in the surgical group (26% vs 12%, P < .001). Conclusions and Relevance: Among patients with severe obesity followed up for a median of 6.5 years, bariatric surgery compared with medical treatment was associated with a clinically important increased risk for complications, as well as lower risks of obesity-related comorbidities. The risk for complications should be considered in the decision-making process.

Dietary changes in obese patients undergoing gastric bypass or lifestyle intervention: a clinical trial.

We compared changes in the dietary patterns of morbidly obese patients undergoing either laparoscopic gastric bypass surgery or a comprehensive lifestyle intervention programme. The present 1-year non-randomised controlled trial included fifty-four patients in the lifestyle group and seventy-two in the surgery group. Dietary intake was assessed by a validated FFQ. ANCOVA was used to adjust for between-group differences in sex, age, baseline BMI and baseline values of the dependent variables. Intakes of food groups and nutrients did not differ significantly between the intervention groups at baseline. At 1-year follow-up, the lifestyle group had a significantly higher daily intake of fruits and vegetables (561 (sd 198) v. 441 (sd 213) g, P= 0·002), whole grains (63 (sd 24) v. 49 (sd 16) g, P< 0·001) and fibre (28 (sd 6) v. 22 (sd 6) g, P< 0·001) than the surgery group and a lower percentage of total energy intake of saturated fat (12 (sd 3) v. 14 (sd 3) %, P< 0·001). The intake of red meat declined significantly within both groups, vegetables and fish intake were reduced significantly in the surgery group and added sugar was reduced significantly in the lifestyle group. The lifestyle patients improved their dietary patterns significantly (compared with the surgery group), increasing their intake of vegetables, whole grains and fibre and reducing their percentage intake of saturated fat (ANCOVA, all P< 0·001). In conclusion, lifestyle intervention was associated with more favourable dietary 1-year changes than gastric bypass surgery in morbidly obese patients, as measured by intake of vegetables, whole grains, fibre and saturated fat.

Changes in dietary intake, food tolerance, hedonic hunger, binge eating problems, and gastrointestinal symptoms after sleeve gastrectomy compared with after gastric bypass; 1-year results from the Oseberg study-a randomized controlled trial.

BACKGROUND: The randomized Oseberg study compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the 1-y remission of type 2 diabetes and ß-cell function (primary outcomes). However, little is known about the comparable effects of SG and RYGB on the changes in dietary intakes, eating behavior, and gastrointestinal discomfort. OBJECTIVES: To compare 1-y changes in intakes of macro- and micronutrients, food groups, food tolerance, hedonic hunger, binge eating, and gastrointestinal symptoms after SG and RYGB. METHODS: Among others, prespecified secondary outcomes were dietary intake, food tolerance, hedonic hunger, binge eating, and gastrointestinal symptoms assessed with a food frequency questionnaire, food tolerance questionnaire, Power of food scale, Binge eating scale, and Gastrointestinal symptom rating scale, respectively. RESULTS: A total of 109 patients (66% females), with mean (SD) age 47.7 (9.6) y and body mass index of 42.3 (5.3) kg/m2, were allocated to SG (n = 55) or RYGB (n = 54). The SG group had, compared with the RYGB group, greater 1-y reductions in the intakes of: protein, mean (95% CI) between-group difference, -13 (-24.9, -1.2) g; fiber, -4.9 (-8.2, -1.6) g; magnesium, -77 (-147, -6) mg; potassium, -640 (-1237, -44) mg; and fruits and berries, -65 (-109, -20) g. Further, the intake of yogurt and fermented milk products increased by >2-folds after RYGB but remained unchanged after SG. In addition, hedonic hunger and binge eating problems declined similarly after both surgeries, whereas most gastrointestinal symptoms and food tolerance remained stable at 1 y. CONCLUSIONS: The 1-y changes in dietary intakes of fiber and protein after both surgical procedures, but particularly after SG, were unfavorable with regard to current dietary guidelines. For clinical practice, our findings suggest that health care providers and patients should focus on sufficient intakes of protein, fiber, and vitamin and mineral supplementation after both SG and RYGB. This trial was registered at [clinicaltrials.gov] as [NCT01778738].

Patient-reported outcomes, weight loss, and remission of type 2 diabetes 3 years after gastric bypass and sleeve gastrectomy (Oseberg); a single-centre, randomised controlled trial.

BACKGROUND: Little is known about the comparative effects of various bariatric procedures on patient-reported outcomes. We aimed to compare 3-year effects of gastric bypass and sleeve gastrectomy on patient-reported outcome measures in patients with obesity and type 2 diabetes. METHODS: The Oseberg trial was a single-centre, parallel-group, randomised trial at Vestfold Hospital Trust, a public tertiary obesity centre in Tønsberg, Norway. Eligible patients were aged 18 years or older with previously verified BMI 35·0 kg/m2 or greater. Diabetes was diagnosed if glycated haemoglobin was at least 6·5% (48 mmol/mol) or by their use of anti-diabetic medications with glycated haemoglobin at least 6·1% (43 mmol/mol). Eligible patients were randomly assigned (1:1) to gastric bypass or sleeve gastrectomy. All patients received identical preoperative and postoperative treatment. Randomisation was done with a computerised random number generator and a block size of ten. Study personnel, patients, and the primary outcome assessor were blinded to allocations for 1 year. The prespecified secondary outcomes reported here were 3-year changes in several clinically important patient-reported outcomes, weight loss, and diabetes remission. Analyses were done in the intention to treat population. This trial is ongoing, closed to recruitment and is registered with ClinicalTrials.gov, NCT01778738. FINDINGS: Between Oct 15, 2012 and Sept 1, 2017, 319 consecutive patients with type 2 diabetes scheduled for bariatric surgery were assessed for eligibility. 101 patients were not eligible (29 did not have type 2 diabetes according to inclusion criteria and 72 other exclusion criteria) and 93 declined to participate. 109 patients were enrolled and randomly assigned to sleeve gastrectomy (n=55) or gastric bypass (n=54). 72 (66%) of 109 patients were female and 37 (34%) were male. 104 (95%) of patients were White. 16 patients were lost to follow up and 93 (85%) patients completed the 3-year follow-up. Three additional patients were contacted by phone for registration of comorbidities Compared with sleeve gastrectomy, gastric bypass was associated with a greater improvement in weight-related quality of life (between group difference 9·4, 95% CI 3·3 to 15·5), less reflux symptoms (0·54, 0·17 to -0·90), greater total bodyweight loss (8% difference, 25% vs 17%), and a higher probability of diabetes remission (67% vs 33%, risk ratio 2·00; 95% CI 1·27 to 3·14). Five patients reported postprandial hypoglycaemia in the third year after gastric bypass versus none after sleeve-gastrectomy (p=0·059). Symptoms of abdominal pain, indigestion, diarrhoea, dumping syndrome, depression, binge eating, and appetitive drive did not differ between groups. INTERPRETATION: At 3 years, gastric bypass was superior to sleeve gastrectomy in patients with type 2 diabetes and obesity regarding weight related quality of life, reflux symptoms, weight loss, and remission of diabetes, while symptoms of abdominal pain, indigestion, diarrhoea, dumping, depression and binge eating did not differ between groups. This new patient-reported knowledge can be used in the shared decision-making process to inform patients about similarities and differences between expected outcomes after the two surgical procedures. FUNDING: Morbid Obesity Centre, Vestfold Hospital Trust. TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.

Validation of Ad-DiaRem and ABCD Diabetes Remission Prediction Scores at 1-Year After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in the Randomized Controlled Oseberg Trial.

BACKGROUND: Prediction of type 2 diabetes (T2DM) remission is an important part of risk-benefit assessment before bariatric surgery. STUDY DESIGN: Advanced-DiaRem (Ad-DiaRem) and ABCD diabetes remission scores for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were calculated using baseline data. Differences in model discrimination using area under the curve of receiver operating curve (AUC-ROC) and model calibration were tested for complete remission (HbA1c ≤ 6.0% without antidiabetic medications) in the two groups. Optimal cutoff scores were calculated using the Youden index. RESULTS: We randomized 109 patients to either SG or RYGB. With one patient lost to follow-up in each group, the scores were calculated for 54 patients in the SG group and 53 patients in the RYGB group. Both models showed moderate predictive power without any significant difference between the groups: AUC-ROCs (95% CI) for the Ad-DiaRem score (SG versus RYGB) were 0.872 (0.780-0.964) versus 0.843 (0.733-0.954), p = 0.69, and for the ABCD score 0.849 (0.752-0.946) versus 0.750 (0.580-0.920), p = 0.32, respectively. Using optimal cutoff points derived from the whole study population, the actual proportion of diabetes remission was significantly higher than predicted for both the Ad-DiaRem and ABCD scores in the RYGB group. Diabetes duration and glycated haemoglobin predicted diabetes remission in the entire Oseberg population. CONCLUSION: Both the Ad-DiaRem and ABCD scores showed moderate ability to discriminate between those who achieved remission of T2DM and those who did not after SG and RYGB. Larger studies are needed for the identification of procedure-specific optimal cutoffs. Trial Registration ClinicalTrials.gov Identifier: NCT01778738.

Gastrointestinal Hormones and ß-Cell Function After Gastric Bypass and Sleeve Gastrectomy: A Randomized Controlled Trial (Oseberg).

CONTEXT: Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and ß-cell function in type 2 diabetes remains unclear. OBJECTIVE: We aimed to compare gastrointestinal hormones and ß-cell function, assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery, hypothesizing higher glucagon-like peptide-1 (GLP-1) levels and greater ß-cell response to glucose after RYGB than after SG. METHODS: This study was a randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcomes were diabetes remission and IVGTT-derived ß-cell function. Participants with obesity and type 2 diabetes were allocated (1:1) to RYGB or SG. We measured gastrointestinal hormone profiles and insulin secretion as ß-cell glucose sensitivity (ß-GS) derived from 180-minute OGTTs. RESULTS: Participants were 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1 year were higher after RYGB than after SG (77% vs 48%; P = 0.002). Incremental area under the curve (iAUC0-180) GLP-1 and ß-GS increased more after RYGB than after SG, with 1-year between-group difference 1173 pmol/L*min (95% CI, 569-1776; P = 0.0010) and 0.45 pmol/kg/min/mmol (95% CI, 0.15-0.75; P = 0.0032), respectively. After surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher ß-GS and higher GLP-1 secretion. CONCLUSION: RYGB was associated with greater improvement in ß-cell function and higher postprandial GLP-1 levels than SG.

Type 2 diabetes and pre-diabetes are associated with obstructive sleep apnea in extremely obese subjects: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) is a common yet underdiagnosed condition. The aim of our study is to test whether prediabetes and type 2 diabetes are associated with obstructive sleep apnea (OSA) in extremely obese (BMI ≥ 40 kg/m²) subjects. METHODS: One hundred and thirty seven consecutive extremely obese patients (99 females) from a controlled clinical trial [MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent somnography with Embletta® and a 2-hour oral glucose tolerance test (OGTT). OSA was defined by an apnea-hypopnea index (AHI) ≥ 5 events/hour. Patients were categorized into three groups according to criteria from the American Diabetes Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple logistic regression analysis was used to identify possible determinants of OSA. RESULTS: The patients had a mean (SD) age of 43 (11) years and a body mass index (BMI) of 46.9 (5.7) kg/m². Males had significantly higher AHI than females, 29 (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55% of women, p = 0.008. Twenty-nine percent of subjects had normal glucose tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2 diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was significantly lower in the OSA than in the non-OSA group, while other measures of inflammation did not differ significantly between groups. CONCLUSIONS: Type 2 diabetes and pre-diabetes are associated with OSA in extremely obese subjects. TRIAL REGISTRATION: MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104).

[Follow-up after bariatric surgery]. / Oppfølging etter fedmekirurgi.

BACKGROUND: The number of bariatric surgical procedures in Norway is increasing. Patients who undergo bariatric surgery may experience surgical, medical and nutritional complications. Follow-up of these patients is therefore important. METHODS: The article is based on non-systematic literature searches in PubMed and on the clinical experience of the authors. RESULTS: Bariatric surgery induces significant and sustained weight loss and improves obesity-related disorders. Gastric bypass is the most commonly performed bariatric procedure in Norway. This procedure is associated with a 30-day mortality of below 0.5 %, while severe complications occur in approximately 5 % of patients. Late complications include internal herniation, intestinal ulcers and gallbladder disease. After surgery all patients are given iron, vitamin D/calcium and vitamin B12 supplements to prevent vitamin and mineral deficiencies. Gastrointestinal symptoms and postprandial hypoglycaemia after surgery can be improved by dietary modifications, and the need for anti-diabetic and blood pressure lowering medications is reduced. Dose adjustment of other medications may also be necessary. Pregnancy is not recommended during the first year after bariatric surgery. Many patients need plastic surgery after the operation. INTERPRETATION: Complications after bariatric surgery may manifest in the long term. Regular follow-up is required. General practitioners should be responsible for follow-up in the long term, and should be familiar with common and serious complications as well as normal symptomatology after bariatric surgery.

Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg).

CONTEXT: Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health. OBJECTIVE: To compare changes in bone mineral density and markers of bone turnover 1 year after SG and RYGB. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (1:1) to SG or RYGB. MAIN OUTCOME MEASURES: Changes in areal bone mineral density (aBMD) and bone turnover markers. RESULTS: Femoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n = 44) than after SG (n = 48) (mean [95% confidence interval] between group differences -2.8% [-4.7 to -0.8], -3.0% [-5.0 to -0.9], -4.2% [-6.4 to -2.1], and -0.5% [-1.6 to 0.6], respectively). The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG (between group difference at 1 year, both P < 0.001). The changes in femoral neck, total hip, and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P < 0.05) and not weight change. CONCLUSIONS: Roux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.

Standard versus distal Roux-en-Y gastric bypass in patients with BMI 50-60 kg/m2: 5-year outcomes of a double-blind, randomized clinical trial.

BACKGROUND: The optimal surgical weight loss procedure for patients with a BMI of 50 kg/m2 or more is uncertain. This study compared distal Roux-en-Y gastric bypass (RYGB) with standard RYGB. METHODS: In this double-blind RCT, patients aged 18-60 years with a BMI of 50-60 kg/m2 were allocated randomly to receive standard (150 cm alimentary, 50 cm biliopancreatic limb) or distal (150 cm common channel, 50 cm biliopancreatic limb) RYGB. The primary outcome (change in BMI at 2 years) has been reported previously. Secondary outcomes 5 years after surgery, such as weight loss, health-related quality of life, and nutritional outcomes are reported. RESULTS: Between May 2011 and April 2013, 123 patients were randomized, 113 received an intervention, and 92 attended 5-year follow-up. Mean age was 40 (95 per cent c.i. 38 to 41) years and 73 patients (65 per cent) were women; 57 underwent standard RYGB and 56 distal RYGB. BMI was reduced by 15.1 (95 per cent c.i. 13.9 to 16.2) kg/m2 after standard and 15.7 (14.5 to 16.9) kg/m2 after distal RYGB; the between-group difference was -0.64 (-2.3 to 1.0) kg/m2 (P = 0.447). Total cholesterol, low-density lipoprotein cholesterol, and haemoglobin A1c levels declined more after distal than after standard RYGB. High-density lipoprotein cholesterol levels increased more after standard RYGB. Vitamin A and vitamin D levels were lower after distal RYGB. Changes in bone mineral density, resting metabolic rate, and total energy intake were comparable. CONCLUSION: Distal RYGB did not enable greater weight loss than standard RYGB. Differences in other outcomes favouring distal RYGB may not justify routine use of this procedure in patients with a BMI of 50-60 kg/m2. Registration number: NCT00821197 (http://www.clinicaltrials.gov).Presented in part as abstract to the IFSO (International Federation for the Surgery of Obesity and Metabolic disorders) conference, Madrid, Spain, August 2019.

Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study.

BACKGROUND: Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome. Serum creatinine may serve as a surrogate marker of muscle mass, and a possible relationship between low serum creatinine and type 2 diabetes has recently been demonstrated. We aimed to validate this finding in a population of Caucasian morbidly obese subjects. METHODS: Cross-sectional study of 1,017 consecutive morbidly obese patients with an estimated glomerular filtration rate >60 ml/min/1.73 m2. Logistic regression (univariate and multiple) was used to assess the association between serum creatinine and prevalent type 2 diabetes, including statistically testing for the possibility of non-linearity in the relationship by implementation of Generalized Additive Models (GAM) and piecewise linear regression. Possible confounding variables such as age, family history of diabetes, waist-to-hip ratio, hypertension, current smoking, serum magnesium, albuminuria and insulin resistance (log HOMA-IR) were adjusted for in three separate multiple logistic regression models. RESULTS: The unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 mumol/l increase in serum creatinine was associated with 6% (95% CI; 3%-8%) and 7% (95% CI; 2%-13%) lower odds of diabetes below serum creatinine levels of 69 and 72 mumol/l in women and men, respectively. Above these breakpoints the serum creatinine concentrations did not reduce the odds further. Adjustments for non-modifiable and modifiable risk factors left the piecewise effect for both women and men largely unchanged. In the fully adjusted model, which includes serum magnesium, albuminuria and log HOMA-IR, the piecewise effect for men was statistically non-significant, but it remained present for women. Patients with creatinine levels below median had approximately 50% (women) and 75% (men) increased odds of diabetes. CONCLUSIONS: Low serum creatinine is a predictor of type 2 diabetes in Caucasian morbidly obese patients, independent of age, gender, family history of diabetes, anthropometric measures, hypertension, and current smoking. Longitudinal studies of both obese and non-obese populations are needed to investigate whether serum creatinine may be causally linked with type 2 diabetes, and if so, precisely how they are linked.

Comparison of the effect of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Bariatric surgery is an effective treatment option for patients with type 2 diabetes mellitus (T2DM) and obesity. This study aims to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on remission of T2DM. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies published between database inception and 21 November 2019. A meta-analysis, using a random effects model, was performed to calculate relative risk (RR) of T2DM remission between the groups in randomized controlled trials (RCTs). Of 2650 records identified, 12 records from 10 different RCTs were finally included. The studies comprised 705 patients with follow-up from 1 to 5 years. The remission rate of T2DM at 1 year was higher among those undergoing RYGB (156/276, 57%) compared with those undergoing SG (128/275, 47%), RR (95% CI) 1.20 (1.00-1.45), P = .047, I2 = 24.9%, moderate-quality evidence. Among studies with 2- to 5-year follow-up, there was no difference in remission rates between the RYGB (132/263, 50%) and SG (121/266, 46%) groups, RR 1.06 (0.94-1.20), P = .34, I2 = 0.0%, low-quality evidence. RYGB resulted in a higher rate of T2DM remission compared with SG after 1 year. The T2DM remission rates did not differ in studies with 2- to 5-year follow-up.

Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study.

BACKGROUND: Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. METHODS: Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. RESULTS: A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (< 29%) and did not differ significantly between groups, while the proportions of patients with esophagitis were high both in the T2DM and non-T2DM group, 58% versus 47%, p = 0.16. The majority of patients with esophagitis did not have GERD-symptoms (68-80%). Further, 55% of the patients with T2DM had pathologic acid reflux. Among these, 71% also had erosive esophagitis, whereof 67% were asymptomatic. CONCLUSIONS: The prevalence of GERD was similar in bariatric patients with or without T2DM, and the proportion of patients with asymptomatic GERD was high independent of the presence or absence of T2DM. Accordingly, GERD may be underdiagnosed in patients not undergoing a preoperative endoscopy or acid reflux assessment. TRIAL REGISTRATION: Clinical Trials.gov number NCT01778738.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study.

BACKGROUND: The prevalence of vitamin D insufficiency and secondary hyperparathyroidism is high among morbidly obese subjects. Further, low serum levels of 25-hydroxyvitamin D (25 [OH]D) and magnesium have been associated with increased risk of the metabolic syndrome (MS), and recently, a possible link between PTH and MS has been reported. Although it is well known that the synthesis and secretion of PTH is regulated by serum levels of calcium, phosphate, magnesium and 25(OH)D, less is known about the possible clustered affiliation of these parameters with MS. We aimed to explore whether MS is associated with abnormal serum levels of PTH, 25(OH)D and magnesium in a population of morbidly obese patients. METHODS: Fasting serum levels of 25(OH)D, PTH and magnesium were assessed in a cross-sectional cohort study of 1,017 consecutive morbidly obese patients (68% women). Multiple logistic regression analyses were used to assess the independent effect of PTH, 25(OH)D and magnesium on the odds for MS (National Cholesterol Education Program [NCEP]) after adjustment for confounding factors. RESULTS: Sixty-eight percent of the patients had MS. Patients with MS had lower mean serum magnesium (P < 0.001) and higher mean PTH (P = 0.067) than patients without MS, whereas mean 25(OH)D did not differ significantly. Patients with PTH levels in the second to fourth quartiles had higher odds of prevalent MS (odds ratio 1.47 [95% CI 0.92-2.35], 2.33 [95% CI 1.40-3.87] and 2.09 [95% CI 1.23-3.56], respectively), after adjustment for 25(OH)D, magnesium, calcium, phosphate, creatinine, age, gender, season of serum sampling, BMI, current smoking, albuminuria, CRP, insulin resistance and type 2 diabetes. Further, PTH was significantly correlated with systolic and diastolic pressure (both P < 0.001), but not with the other components of MS. The levels of 25(OH)D and magnesium were not associated with MS in the multivariate model. CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.