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.

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].

Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity.

AIM: Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. METHODS: This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. RESULTS: Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB -30 ± 6.9%, diet -3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. CONCLUSION: Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.

The association between severity of King's Obesity Staging Criteria scores and treatment choice in patients with morbid obesity: a retrospective cohort study.

BACKGROUND: The King's Obesity Staging Criteria (KOSC) comprises of a four-graded set of health related domains. We aimed to examine whether, according to KOSC, patients undergoing bariatric surgery differed from those opting for conservative treatment. METHODS: We graded 2142 consecutive patients with morbid obesity attending our centre from 2005-10 into the following KOSC domains: airway/apnoea, body mass index (BMI), cardiovascular risk (CV-risk), diabetes mellitus, economic complications, functional limitations, gonadal dysfunction, and perceived health status/body image. Both patients and physicians agreed upon treatment choice through a shared decision making process. RESULTS: A total of 1329 (62%) patients opted for lifestyle intervention and 813 (37%) for bariatric surgery as their first treatment choice. The patients treated with bariatric surgery were younger (42 vs. 44 years, p < 0.001), had a higher BMI (45.4 vs. 43.8 kg/m2, p < 0.001) and had a lower ten year estimated CV-risk (9.4 vs. 10.7%, p = 0.004) than the lifestyle intervention group. Compared with having BMI < 40 kg/m2, BMI ≥ 40 kg/m2 was associated with 85% increased odds of bariatric surgery (OR 1.85 [95% CI 1.48, 2.30]). Conversely, patients with ≥20% ten year CV-risk, had lower odds of bariatric surgery than patients with <20% CV-risk (0.68 [0.53, 0.87]). CONCLUSION: BMI was the strongest KOSC-domain associated with subsequent bariatric surgery after a shared decision making process. Prospective studies are required to assess whether the use of KOSC can help guide patients and clinicians to identify the most appropriate choice of treatment for morbid obesity.

A controlled clinical trial of the effect of gastric bypass surgery and intensive lifestyle intervention on nocturnal hypertension and the circadian blood pressure rhythm in patients with morbid obesity.

BACKGROUND: Nocturnal hypertension, increased night-to-day systolic blood pressure (BP) ratio and nondipper status (night-to-day systolic BP ratio > 0.9) are associated with an increased risk of cardiovascular disease. Our aim was to compare the 1-year effect of Roux-en-Y gastric bypass (RYGB) versus a program of intensive lifestyle intervention (ILI) only on nocturnal hypertension and circadian BP rhythm. METHODS: The study participants were part of a 1-year, controlled clinical trial comparing the effect of RYGB or ILI on obesity-related comorbidities. Ninety participants (49 in the RYGB group) successfully completed 24-hour ambulatory BP monitoring at baseline and follow-up and were eligible subsequently for analysis. RESULTS: A total of 71 subjects (79%) had nocturnal hypertension at baseline. The number of subjects with nocturnal hypertension decreased from 42 to 14 in the RYGB group (P ≤ .001) and from 29 to 27 (P = .791) in the ILI group. Subjects in the RYGB group had a lesser adjusted odds ratio (OR) of nocturnal hypertension at follow-up (OR 0.15; 95% confidence interval, 0.05-0.42; P ≤ .001); however, after further adjustment for weight loss, there was no additional beneficial effect of RYGB (P = .674). No differences between groups regarding improvement in the night-to-day systolic BP ratio were found after adjustment for 24-hour systolic pressure (P = .107). Both interventions showed a decrease in the proportion of subjects classified as nondippers, namely, 44% (P ≤ .001) and 28% (P = .002) in the RYGB and ILI groups, respectively. CONCLUSION: Only RYGB was associated with a decrease in the prevalence of nocturnal hypertension. Both interventions showed an improvement in dipper status, although RYGB was more effective.

FTO, type 2 diabetes, and weight gain throughout adult life: a meta-analysis of 41,504 subjects from the Scandinavian HUNT, MDC, and MPP studies.

OBJECTIVE: FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span. RESEARCH DESIGN AND METHODS: Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS: The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 × 10(-8)) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 × 10(-8)). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m(2) per risk allele; P = 2.0 × 10(-26)), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (ΔBMI = 0.0 [-0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS: We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter.