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Background: Obesity and physical inactivity are major global public health concerns, both of which increase the risk of insulin resistance and type 2 diabetes. Regulation of glucose homeostasis involves cross-talk between the central nervous system, peripheral tissues, and gut microbiota, and is affected by genetics. Systemic cross-talk between brain, gut, and peripheral tissues in glucose homeostasis: effects of exercise training (CROSSYS) aims to gain new systems-level understanding of the central metabolism in human body, and how exercise training affects this cross-talk. Methods: CROSSYS is an exercise training intervention, in which participants are monozygotic twins from pairs discordant for body mass index (BMI) and within a pair at least the other is overweight. Twins are recruited from three population-based longitudinal Finnish twin studies, including twins born in 1983–1987, 1975–1979, and 1945–1958. The participants undergo 6-month-long exercise intervention period, exercising four times a week (including endurance, strength, and high-intensity training). Before and after the exercise intervention, comprehensive measurements are performed in Turku PET Centre, Turku, Finland. The measurements include: two positron emission tomography studies (insulin-stimulated whole-body and tissue-specific glucose uptake and neuroinflammation), magnetic resonance imaging (brain morphology and function, quantification of body fat masses and organ volumes), magnetic resonance spectroscopy (quantification of fat within heart, pancreas, liver and tibialis anterior muscle), echocardiography, skeletal muscle and adipose tissue biopsies, a neuropsychological test battery as well as biosamples from blood, urine and stool. The participants also perform a maximal exercise capacity test and tests of muscular strength. Discussion:This study addresses the major public health problems related to modern lifestyle, obesity, and physical inactivity. An eminent strength of this project is the possibility to study monozygotic twin pairs that share the genome at the sequence level but are discordant for BMI that is a risk factor for metabolic impairments such as insulin resistance. Thus, this exercise training intervention elucidates the effects of obesity on metabolism and whether regular exercise training is able to reverse obesity-related impairments in metabolism in the absence of the confounding effects of genetic factors. Trial registration: ClinicalTrials.gov, NCT03730610. Prospectively registered 5 November 2018., The study is financially supported by the Academy of Finland (JCH decision 317332, KHP decisions 272376, 314383, 266286, and LL decision 295741), the Finnish Cultural Foundation (JCH, MAH, KHP), the Diabetes Research Foundation of Finland (JCH, MAH), the Juho Vainio Foundation (MAH), Novo Nordisk Foundation (KHP, NNF17OC0027232, NNF10OC1013354), Helsinki University Hospital (KHP), Government Research Funds (KHP), Finnish Medical Foundation (KHP), Gyllenberg Foundation (KHP), Sigrid Juselius Foundation (KHP), and University of Helsinki (KHP).

Publisher Copyright: © 2021 Background: The prognostic value of preoperative hemoglobin in patients undergoing esophagectomy is unknown. The aim of this study was to examine whether preoperative hemoglobin is associated with prognosis in patients undergoing esophagectomy for cancer. Materials and methods: This was a population-based nationwide retrospective cohort study in Finland, using Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with available preoperative hemoglobin measurement were included. Multivariable cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period of surgery, age at surgery, sex, comorbidity (Charlson Comorbidity Index), tumor histology, tumor stage, neoadjuvant therapy, type of surgery (minimally invasive or open) and annual hospital volume. Results: Of the 1313 patients, 932 (71.0%) were men and 799 (60.9%) had esophageal adenocarcinoma. Overall all-cause mortality was significantly higher in the lowest hemoglobin count tertile (HR 1.26 (1.07–1.47)) compared to the highest tertile, but this association was attenuated after adjustment for confounding. No differences were found between the preoperative hemoglobin groups in the adjusted analyses of 90-day all-cause, 5-year all-cause, and 5-year cancer-specific mortality. Conclusion: In this population-based nationwide study, preoperative hemoglobin count had no independent prognostic significance in esophageal cancer.

Bariatric surgery results in rapid weight loss and beneficial metabolic effects, but may have negative effects on the skeleton. The objective of this prospective study was to evaluate changes in bone metabolism in response to bariatric surgery with two surgical techniques. 46 morbidly obese subjects (mean 44.9years, BMI 42.1) with (n=19) or without (n=27) type 2 diabetes (T2DM) at baseline underwent either Roux-en-Y gastric bypass (RYGB, n=21) or sleeve gastrectomy (SG, n=25). Bone turnover markers (CTX, PINP, TRAcP5b, TotalOC and ucOC) were measured before and six months after surgery. Volumetric bone mineral density (vBMD) at lumbar spine and vertebral bone marrow (VBM) fat were measured in 21 subjects (7 RYGB and 14 SG) with three-dimensional quantitative computer tomography and 1H MR spectroscopy, respectively. 25 non-obese subjects were recruited as controls (mean 45.8years, BMI 23.0) and assessed at a single cross-sectional visit. Obese subjects had significantly lower bone turnover at baseline when compared to non-obese controls. Bone metabolic markers markedly increased post-operatively (p

IMPORTANCE: Laparoscopic sleeve gastrectomy (LSG) is currently the predominant bariatric procedure, although long-term weight loss and quality-of-life (QoL) outcomes compared with laparoscopic Roux-en-Y gastric bypass (LRYGB) are lacking. OBJECTIVE: To determine weight loss equivalence of LSG and LRYGB at 7 years in patients with morbid obesity, with special reference to long-term QoL. DESIGN, SETTING, AND PARTICIPANTS: The SLEEVE vs byPASS (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted between March 10, 2008, and June 2, 2010, in Finland. The trial enrolled 240 patients with morbid obesity aged 18 to 60 years who were randomized to undergo either LSG or LRYGB with a 7-year follow-up (last follow-up, September 26, 2017). Analysis was conducted on an intention-to-treat basis. Statistical analysis was performed from June 4, 2018, to November 8, 2019. INTERVENTIONS: Laparoscopic sleeve gastrectomy (n = 121) or LRYGB (n = 119). MAIN OUTCOMES AND MEASURES: The primary end point was percentage excess weight loss (%EWL) at 5 years. Secondary predefined follow-up time points were 7, 10, 15, and 20 years, with included 7-year secondary end points of QoL and morbidity. Disease-specific QoL (DSQoL; Moorehead-Ardelt Quality of Life questionnaire [range of scores, –3 to 3 points, where a higher score indicates better QoL]) and general health-related QoL (HRQoL; 15D questionnaire [0-1 scale for all 15 dimensions, with 1 indicating full health and 0 indicating death]) were measured preoperatively and at 1, 3, 5, and 7 years postoperatively concurrently with weight loss. RESULTS: Of 240 patients (167 women [69.6%]; mean [SD] age, 48.4 [9.4] years; mean [SD] baseline body mass index, 45.9 [6.0]), 182 (75.8%) completed the 7-year follow-up. The mean %EWL was 47% (95% CI, 43%-50%) after LSG and 55% (95% CI, 52%-59%) after LRYGB (difference, 8.7 percentage units [95% CI, 3.5-13.9 percentage units]). The mean (SD) DSQoL total score at 7 years was 0.50 (1.14) after LSG and 0.49 (1.06) after LRYGB (P = .63), and the median HRQoL total score was 0.88 (interquartile range [IQR], 0.78-0.95) after LSG and 0.87 (IQR, 0.78-0.95) after LRYGB (P = .37). Greater weight loss was associated with better DSQoL (r = 0.26; P

Obesity is associated with lowered brain's grey (GM) and white matter (WM) density as measured by voxel-based morphometry (VBM). Nevertheless, it remains unknown whether obesity has a causal influence on cerebral atrophy. We recruited 47 morbidly obese subjects (mean BMI = 42.2, SD = 4.0, 42 females and five males) eligible for bariatric surgery and 29 non-obese subjects (mean BMI = 23.2, SD = 2.8, 23 females and six males) served as controls. Baseline scans were acquired with T1-weighted magnetic resonance imaging (MRI) at 1.5 Tesla; obese participants were scanned again six months after the surgery. Local GM and WM densities were quantified using VBM. Full-volume analyses were used for comparing baseline between-group differences as well as the effects of surgery-induced weight loss in the morbidly obese. Metabolic variables were used in linear models to predict WM and GM densities. Obese subjects had initially lower GM densities in widespread cortical areas including frontal, parietal, and temporal regions as well as insulae. Lower WM densities were observed throughout the WM. Bariatric surgery and concomitant weight loss resulted in global increase in WM density. Grey matter increase was limited to occipital and inferior temporal regions. Metabolic variables were associated with brain densities. We conclude that weight loss results in global recovery of WM as well as local recovery of grey matter densities. These changes likely reflect improved brain tissue integrity. Hum Brain Mapp 37:3745-3756, 2016. © 2016 Wiley Periodicals, Inc.

OBJECTIVE We investigated fat distribution and tissue-specific insulin-stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. RESEARCH DESIGN AND METHODS A total of 23 obese patients (BMI 43.0 ± 3.6 kg/m2; 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [18F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. RESULTS At baseline, visceral fat GU was 30 ± 7% of muscle GU in control subjects and 57 ± 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (∼40%) more than subcutaneous fat (7%). Tissue-specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. CONCLUSIONS Bariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose.

Aims/hypothesis The intestine is the main site for glucose absorption and it has been suggested that it exhibits insulin resistance. Bariatric surgery has been shown to reverse insulin resistance and type 2 diabetes, but its effects on human intestinal metabolism are unknown. Our aim was to evaluate the effects of insulin on intestinal glucose metabolism before and after bariatric surgery. Methods Twenty-one morbidly obese individuals undergoing bariatric surgery and ten age-matched healthy individuals were recruited and intestinal and skeletal muscle glucose uptake (GU) was measured using [18F]fluoro-2-deoxyglucose and positron emission tomography at fast and during hyperinsulinaemia. MRI was used as anatomical reference. Obese participants were studied again 6 months postoperatively. Results In contrast to healthy individuals, insulin had no effect on intestinal GU in obese participants with or without diabetes, suggesting that intestinal insulin resistance is present early in morbid obesity. Postoperatively, jejunal GU increased in line with whole-body and muscle GU. Postoperative GU values in the intestine correlated with whole-body insulin sensitivity, indicating that the intestinal mucosa may reflect the overall glycaemic state and potentially mediate obesity-associated insulin resistance. Conclusions/interpretation This study shows that insulin is a potent stimulator of GU in the healthy intestine and that intestinal insulin resistance is ameliorated after bariatric surgery. In our study, obese individuals had intestinal insulin resistance regardless of their glycaemic status. Persistent changes in intestinal glucose metabolism are likely to influence both local processes in the gut and systemic glucose homeostasis.

Background and Aims: The long-term efficacy of laparoscopic Roux-en-Y gastric bypass in the treatment of morbid obesity has already been demonstrated. Laparoscopic sleeve gastrectomy has shown promising short-term results, but the long-term efficacy is still unclear. The aim of this prospective randomized multicenter study is to compare the results of Roux-en-Y gastric bypass and sleeve gastrectomy. Material and Methods: A total of 240 morbidly obese patients were randomized to undergo either Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point of study was weight loss, and the secondary end points were resolution of comorbidities and morbidity. The short-term results at 6 months were analyzed. Results: The mean excess weight loss at 6 months was 49.2% in the sleeve gastrectomy group and 52.9% in the Roux-en-Y gastric bypass group (p = 0.086). Type 2 diabetes was resolved or improved in 84.3% of patients in the sleeve gastrectomy group and 93.3% in the Roux-en-Y gastric bypass group (p = 0.585). The corresponding results for arterial hypertension were 76.8% and 81.9% (p = 0.707) and for hypercholesterolemia 64.1% and 69.0% (p = 0.485). There was no mortality at 6 months. There was one major complication following sleeve gastrectomy and two after Roux-en-Y gastric bypass (p = 0.531). Eight sleeve gastrectomy patients and 11 Roux-en-Y gastric bypass patients had minor complications (p = 0.403). Conclusion: The short-term results of sleeve gastrectomy and Roux-en-Y gastric bypass regarding weight loss, resolution of obesity-related comorbidities and complications were not different at 6 months.

Obesity and insulin resistance are associated with altered brain glucose metabolism. Here, we studied brain glucose metabolism in 22 morbidly obese patients before and 6 months after bariatric surgery. Seven healthy subjects served as control subjects. Brain glucose metabolism was measured twice per imaging session: with and without insulin stimulation (hyperinsulinemic-euglycemic clamp) using [18F]fluorodeoxyglucose scanning. We found that during fasting, brain glucose metabolism was not different between groups. However, the hyperinsulinemic clamp increased brain glucose metabolism in a widespread manner in the obese but not control subjects, and brain glucose metabolism was significantly higher during clamp in obese than in control subjects. After follow-up, 6 months postoperatively, the increase in glucose metabolism was no longer observed, and this attenuation was coupled with improved peripheral insulin sensitivity after weight loss. We conclude that obesity is associated with increased insulin-stimulated glucose metabolism in the brain and that this abnormality can be reversed by bariatric surgery.

The long-term efficacy of laparoscopic Roux-en-Y gastric bypass (RYGB) in the treatment of morbid obesity has been demonstrated. Laparoscopic sleeve gastrectomy (SG) as a single procedure has shown promising short-term results, but the long-term efficacy of SG has not yet been demonstrated. The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospective multicenter randomized setting.A total of 240 morbidly obese (BMI = 35-66 kg/m²) patients evaluated by a multidisciplinary team were randomized to undergo either RYGB or SG. There were 117 patients in the RYGB group and 121 in the SG group; two patients had to be excluded after randomization. Both study groups were comparable regarding age, gender, BMI, and comorbidities.There was no 30-day mortality. The median operating time was significantly shorter in the SG group (66 min vs. 94 min, p0.001). All complications were recorded thoroughly. There were 7 (5.8 %) major complications following SG and 11 (9.4 %) after RYGB (p = 0.292). Nine (7.4 %) SG patients and 20 (17.1 %) RYGB patients had minor complications (p = 0.023). The overall morbidity was 13.2 % after SG and 26.5 % after RYGB (p = 0.010). There were three (2.5 %) early reoperations after SG and four (3.3 %) after RYGB (p = 0.719).At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB. There were no significant differences in major complications or early reoperations. Long-term follow-up is required to determine the effect on weight loss, resolution of obesity-related comorbidities, and improvement of quality of life.

Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. Design, Setting, and Participants The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Interventions Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Results Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9,[SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and Relevance Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins. Trial Registration clinicaltrials.gov Identifier:NCT00793143