Magnus Sundbom | Uppsala University (original) (raw)

Papers by Magnus Sundbom

JAMA network open, Jun 3, 2024

The Western sedentary lifestyle and calorie excess is causing an increased incidence of obesity a... more The Western sedentary lifestyle and calorie excess is causing an increased incidence of obesity and type 2 diabetes. When untreated, these diseases are associated with heartand vascular disease, stroke, cancer, neuropathic pain, renal failure and infertility. The expected lifespan of type 2 diabetic patents is reduced by ~5-10 years compared to the healthy population. Presently there are several available therapies to treat type 2 diabetic patients, but no drug can normalise the high blood glucose level characteristic of the disease. There is a need to further understand the underlying mechanisms of the type 2 diabetes and to bring more efficient drugs to the patients. Decreasing calorie intake and increasing physical exercise are valuable tools for the treatment of type 2 diabetes. Unfortunately, lifestyle is a challenge to change and many patients are not able to perform physical activity. The enzyme AMP-activated protein kinase (AMPK) is activated by both fasting and muscle contraction. We have sought to illuminate the impact of chronic activation with a chemically synthesised AMPK-activator, 5-aminoimidazole-4-carboxy-amide-1-Dribofuranoside (AICAR), in rodent models of type 2 diabetes (study I and II). Type 2 diabetes is associated with increased glucocorticoid levels, which concomitantly lead to a decrease in adiponectin levels. Cortisone is transformed to its active form cortisol, via 11 hydroxysteroid dehydrogenase (HSD) type 1. In study III, we sought to ascertain if inhibition of 11 HSD1, with a new adipose-tissue-specific inhibitor, BVT116429, affects the concentration of circulating adiponectin with accompanying amelioration of glucose homeostasis in diabetic mice. The ob/ob, KKA y and KKA y-CETP mice, were used to study the pharmacodynamic parameters and biomarkers of AMPK activation and 11 HSD1 inhibition. The three animal models feature severe obesity, hyperinsulinaemia and hyperglycaemia. Activation of AMPK via AICAR-treatment and inhibition of 11 HSD1 with BVT116429 resulted in improved glucose homeostasis. Clinical chemistry parameters were improved, including decreased plasma glucose. The underlying mechanisms for the improvements in glucose homeostasis were studied. Acute AMPK activation normalised insulin-stimulated glucose uptake, which is in accordance with an observed twofold increase in protein expression of GLUT-4, hexokinase II, and myocyte enhancer factor 2. Inhibition of 11 HSD1 with BVT116429 increased the concentration of adiponectin both in vivo and in vitro. Pharmacodynamic studies were performed in well-validated models of type 2 diabetes, which increases the chance of succeeding in future clinical trails. This may increase the opportunity to help people with type 2 diabetes to live a longer and healthier life. Drug discovery involves a complex series of steps, where the potential drug must pass several phases to reach the market and the patient. The chemical substances used in these studies were subjected to early drug discovery and analysis. The observed effects of these chemicals provide evidence for the usefulness of targeting AMPK and 11 HSD1 in vivo for the treatment of metabolic disturbances in type 2 diabetes and obesity.

Diabetes, Mar 4, 2021

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic co... more While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre-and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18 F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post-versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post-and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post-versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Clinical obesity, Jul 10, 2023

SummaryBariatric surgery is the most medically and cost‐effective treatment for adults with obesi... more SummaryBariatric surgery is the most medically and cost‐effective treatment for adults with obesity and type 2 diabetes mellitus (T2DM). Our findings suggest initial improvements in health‐related quality of life that may decline as support from follow‐up care ends. How patients experience long‐term support is not well described. This study therefore aimed to investigate how adults with previous T2DM perceived different sources of support 2 years after bariatric surgery. In this qualitative study, individual interviews were conducted with 13 adults (10 women) 2 years after surgery. Using thematic analysis, one overarching theme (compiling complementary elements of support after gastric‐bypass surgery), four themes and nine subthemes emerged. The results show that support was given and received from various sources, support needs varied over time depending on where the patient was in the process and that the sources of support were complementary. To conclude, our results show that support needs change in adults who have undergone bariatric surgery. Long‐term professional and day‐to‐day support from family and other networks are essential and complementary elements of support. Healthcare staff should consider these findings, especially during the early follow‐up period.

Surgery for Obesity and Related Diseases, May 1, 2020

Background: Laparoscopic Roux-en-Y (LRYGB) gastric bypass is an effective treatment for morbid ob... more Background: Laparoscopic Roux-en-Y (LRYGB) gastric bypass is an effective treatment for morbid obesity. Acid-related complications after LRYGB could be prevented by prophylactic proton pump inhibition (PPI). Objective: To identify the effect of PPI prophylaxis on short-term, acid-related complications in a large cohort. Setting: National Registry, Sweden. Methods: A total of 37,301 patients who underwent LRYGB in Sweden from 2009 to 2014 were identified in the Scandinavian Obesity Surgery Registry. Patient-specific factors were cross matched with socioeconomic variables and information on PPI dispensation. A logistic regression model was used to analyze acid-related complications (e.g., marginal ulcer, stricture, and perforation) within 30 days and at 1 year postoperatively. Results: PPI prophylaxis did not reduce the rate of acid-related complications. Instead, prolonged operation time (odds ratio [OR] 2.19 [1.53-3.13]) and immigrant background (OR 1.72 [1.17-2.53]) increased the risk of marginal ulcer within 30 days. At 1 year, medical treatment for diabetes (OR 1.75 [1.14-2.67]) and dyspepsia (OR 1.71 [1.06-2.75]), larger gastric pouch (OR 2.19 [1.528-3.248]), longer operation time (OR 1.67 [1.11-2.51]), smoking (OR 2.59 [1.77-3.78]), and immigrant background (OR 1.60 [1.08-2.36]) increased the risk for marginal ulcer, while older age (OR 2.20 [1.05-4.63]) predisposed for stricture. Inferior weight loss was associated with marginal ulcer at 1 year (OR 1.50 [1.04-2.15]). Conclusion: PPI prophylaxis did not reduce the risk for marginal ulcer and stricture. The risk for these complications was increased by several co-morbidities, smoking, immigrant background, and surgical factors. Routine use of PPI prophylaxis cannot be recommended, but smoking cessation and optimal surgery could be important.

Obesity Surgery, Jul 19, 2018

Introduction The global prevalence of obesity has increased in recent decades, and bariatric surg... more Introduction The global prevalence of obesity has increased in recent decades, and bariatric surgery has become a part of the treatment algorithm of obesity. National high-quality registries enable large-scale evaluations of the use and outcome of bariatric surgery and may allow for improved knowledge. The main objective was to evaluate the rate and type of complications after primary bariatric surgery in three NorthWestern European countries using nationwide registries. Materials and Methods Data from three registries for bariatric surgery were used (January 2015-December 2016). All registries have nationwide coverage with data on patient characteristics, obesity-related diseases, surgical technique, complications, grading of complications, reinterventions, readmissions, and mortality. Eligibility criteria for bariatric surgery were similar and included body mass index of ≥ 40.0 or ≥ 35.0 kg/m 2 , with one or more obesity-associated diseases. Results A total of 35,858 procedures (32,177 primary) were registered. The most common procedure was gastric bypass in the Netherlands (78.9%) and Sweden (67.0%), and sleeve gastrectomy in Norway (58.2%). A total of 904 (2.8%) patients developed major complications after primary surgery and 12 patients (0.04%) died within 30 days. Total number of complications between the registries were comparable (p = 0.939). However, significant differences were seen for Clavien-Dindo Classification grades IIIb and IV (p < 0.001). Pooled readmission rates were 4.3% (n = 1386). Discussion Bariatric surgery is safely performed in the three evaluated countries. Standardization of registries and consensus of variables are essential for international comparison and may contribute to improved quality of treatment across nations.

Annals of Surgery, Mar 25, 2019

Journal of Hepatology, Jun 1, 2023

MedEdPublish, May 12, 2023

Grant information: The author(s) declared that no grants were involved in supporting this work.

Obesity Surgery, Feb 7, 2017

Introduction Bariatric procedures result in massive weight loss, however, not without side effect... more Introduction Bariatric procedures result in massive weight loss, however, not without side effects. Gastric acid is known to cause marginal ulcers, situated in the small bowel just distal to the upper anastomosis. We have used the wireless BRAVO™ system to study the buffering effect of the duodenal bulb in duodenal switch (DS), a procedure in which the gastric sleeve produces a substantial amount of acid. Methods We placed a pre-and a postpyloric pH capsule in 15 DS-patients (seven men, 44 years, BMI 33) under endoscopic guidance and verified the correct location by fluoroscopy. Patients were asked to eat and drink at their leisure, and to register their meals for the next 24 h. Results All capsules but one could be successfully placed, without complications. Total registration time was 17.2 (1.3-24) hours prepyloric and 23.1 (1.2-24) hours postpyloric, with a corresponding pH of 2.66 (1.74-5.81) and 5.79 (4.75-7.58), p < 0.01. The difference in pH between the two locations was reduced from 3.55 before meals to 1.82 during meals, p < 0.01. Percentage of time with pH < 4 was 70.0 (19.9-92.0) and 13.0 (0.0-34.6) pre and postpylorically, demonstrating a large buffering effect. Conclusion By this wireless pH-metric technique, we could demonstrate that the duodenal bulb had a large buffering effect, thus counteracting the large amount of gastric acid passing into the small bowel after duodenal switch. This physiologic effect could explain the low incidence of stomal ulcers.

BMJ open diabetes research & care, 2020

Superior socioeconomic status in patients with type 2 diabetes having gastric bypass surgery: a c... more Superior socioeconomic status in patients with type 2 diabetes having gastric bypass surgery: a case-control analysis of 10 642 individuals.

Surgery for Obesity and Related Diseases, Sep 1, 2017

Background: Closing the remaining opening in a linear stapled anastomosis, for example in laparos... more Background: Closing the remaining opening in a linear stapled anastomosis, for example in laparoscopic Roux-en-Y gastric bypass (LRYGB), can be challenging. Objectives: To evaluate if the novel unidirectional barbed suture (BS) is of value in LRYGB compared with polyfilament (PS) suture. We have compared operative time, early complications, and length of stay, as well as anastomotic strictures and small bowel obstruction during the first year. Setting: Retrospective study from the Scandinavian Obesity Surgery Registry (SOReg). Methods: A nationwide cohort of 25,006 primary LRYGB (2211 BS and 22,795 PS) from SOReg were studied. No preoperative differences in age or gender were noted; however, BS patients had lower Body Mass Index (BMI) (41.3 versus 42.3 kg/m 2 , P o .001) and less diabetes (13.7% versus 15.4%, P ¼ .03). Results: Total operative time was 11 minutes (16%) shorter using BS compared with PS (58 versus 69 minutes, P o .001), although the mesenteric openings were more frequently closed among BS patients (94% versus 71%, P o .001). No differences were seen in early complications; anastomotic leaks or intra-abdominal abscesses were noted in 1.8% and 1.4%, respectively, P ¼ .17. The incidence of anastomotic strictures was similar (.13% versus .17%, P ¼ .73) as was the incidence of surgery for small bowel obstruction (1.8% versus 1.6%, P ¼ .69). Conclusions: The use of barbed suture for closing the remaining opening in the gastrojejunostomy shortened the operative time without increasing the risk of complications. BS is still uncommon in LRYGB, but its implementation could have significant impact on operative time.

Journal of Internal Medicine, Mar 6, 2017

Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obes... more Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

Scandinavian Journal of Gastroenterology, 2011

Surgery for Obesity and Related Diseases, Aug 1, 2023

Roux-en-Y gastric bypass (RYGBP) sustains weight loss and ameliorates diseases common in the morb... more Roux-en-Y gastric bypass (RYGBP) sustains weight loss and ameliorates diseases common in the morbid obese (BMI>40 kg/m 2), but leaves the stomach and duodenum inaccessible. Morbidly obese patients have increased operative risks and in other fields minimal surgery is known to facilitate the postoperative course. The aim of this thesis was to evaluate hand-assisted laparoscopy in RYGBP and develop techniques to study the excluded stomach. The hand-assisted technique was developed in 13 patients and subsequently compared to open surgery in a blinded, prospective, randomised trial of 50 patients. Hand-assistance was feasible with a low need for conversions or re-operations. The duration of surgery was longer (150 versus 85 minutes) and postoperative results were similar to those in open surgery. Thus, the patients did not appear to derive benefits from hand-assisted laparoscopy. Interventional radiology accessed the excluded stomach and allowed endoscopy, barium studies and acid measurements. Chronic gastritis and low acid production were found. After RYGBP, 8 of 22 patients (36%) had duodenogastric bile reflux (DGBR), when studied by HIDA-scintigraphy. No DGBR was seen among controls. The gastric mucosa was evaluated by serology (pepsinogen I (PGI), H. pylori and H,K-ATPase) in 64 patients before and 1-4 years after operation. RYGBP, in contrast to gastric restriction, had reduced PGI levels postoperatively. According to serology, the mucosa is atrophic or in a resting state. This study focuses on safety in RYGBP. Hand-assisted laparoscopy was feasible, but not favourable compared to an optimised open procedure. The excluded stomach is no longer inaccessible and characterised by chronic gastritis, low acid production and frequent bile reflux.

Surgery for Obesity and Related Diseases, Nov 1, 2021

BACKGROUND Although severe complications (SCs) after laparoscopic Roux-en-Y gastric bypass (LRYGB... more BACKGROUND Although severe complications (SCs) after laparoscopic Roux-en-Y gastric bypass (LRYGB) are rare, they can be devastating for the affected patient. OBJECTIVE To access the impact of SCs (Clavien-Dindo ≥3b) 2 years after LRYGB by using a nationwide Swedish cohort of 48,201 primary cases between 2007 and June 2016. SETTING University hospital, Sweden. METHODS Patients with SC were matched 1:1 on age, sex, diabetic status, body mass index (BMI), and year of operation to patients without an SC. Weight loss, patient-scored quality of life (QoL), antidepressant use, proton pump inhibitors (PPI) and opioids, and in-hospital care were gathered from 3 national registers. RESULTS A total of 1411 (2.9%) patients suffered an SC and 16 (.03%) died. In total, 1403 patients with SC (mean age, 42 yr; female, 75%; with diabetes, 15.7%; mean BMI, 41.9 kg/m2) could be matched. Both groups had a total body weight loss of 32% at 2 years. A lower physical QoL was observed in SCs throughout the study period. Antidepressant, PPI and opioid use was higher among patients with SC, even 2 years after surgery. At this time point, a doubling of oral morphine equivalents (7.3 to 17.0 mg/d) was found in patients with SC compared with prior to surgery. The SC group required more in-hospital care after the initial 30 days (3.8 versus .9 d in the remaining part of the first year). CONCLUSION An SC resulted in higher antidepressant, PPI and opioid use as well as higher need for in-hospital care during the first 2 postoperative years. Affected patients should therefore receive special attention during follow up.

Surgery for Obesity and Related Diseases, Jul 1, 2021

Background: The association between severe obesity and chronic pain makes opioid use common among... more Background: The association between severe obesity and chronic pain makes opioid use common among bariatric patients. Preoperative opioid use has been identified as a risk factor in other surgical procedures. Objectives: To examine the impact of preoperative opioid use on complications after primary bariatric surgery. Setting: Sweden. Methods: All primary laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) patients from 2007-2017 were identified in the Scandinavian Obesity Surgery Register. Prescriptions for opioids within 90 days prior to surgery were retrieved from the Swedish Prescribed Drug Register and converted into oral morphine equivalents (OMEs). Patients with 2 prescription of opioids within 90 days prior to surgery were defined as chronic opioid users. Generalized linear regression was used to adjust for age, sex, body mass index, procedure type, year of operation, and co-morbidities. Results: Of the 56,183 patients who had undergone primary LRYGB (n 5 49,615) or LSG (n 5 6568), 17.5% (n 5 9825) had at least 1 prescription of opioids prior to surgery, of which 4.3% (n 5 2390) were defined as chronic opioid users. Chronic opioid use was associated with a higher risk of severe complications (Clavien Dindo grade 3b; odds ratio [OR], 1.67; 95% confidence interval [CI], 1.37-2.04), increased lengths of stay (relative risk, 1.11; 95% CI, 1.08-1.14), and higher rates of readmission (OR, 1.70; 95% CI, 1.49-1.94) and reoperation (OR, 1.87; 95% CI, 1.53-2.27; all P values , .001). Furthermore, higher OME exposure was associated with stepwise higher risks. Conclusion: Preoperative opioid use was an independent risk factor for severe complications, as well as prolonged lengths of stay, readmission, and reoperation after primary bariatric surgery.