GASTRIC BYPASS SURGERY HAS GREATER EFFECT THAN CALORIE RESTRICTION ON INCRETIN RELEASE AND INSULIN SECRETION ALREADY ON POSTOP. DAY 1

Background: Gastric bypass surgery (GBP) provokes rapid improvement of type 2 diabetes (T2D) prior to significant weight loss. Thishas been attributed to altered secretion of the two incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependentinsulinotropic polypeptide (GIP). Here we studied the effects of very low calorie diet (VLCD) vs. the immediate effects of GBP onglycaemia and incretin release.Methods: Eight T2D obese women and 8 obese controls (C) underwent mixed meal tests (MMT) 4 w before (MMT-4w), 1 day before(MMT-1d), 1 day after (MMT+1d) and six weeks after (MMT+6w) gastric bypass. MMT-4w was performed before VLCD and MMT+1dconstituted the first postoperative meal. Glucose, insulin and incretins were analyzed. Gastric bypass surgery was standardized to a 50cm biliary limb and 150 cm alimentary limb and a 5 cm gastric pouch.OBES SURG (2015) 25 (Suppl 1):S1–S364 S85Results: Despite similar glucose levels, the insulin response was markedly increased at MMT+1d, compared to MMT-4w and MMT-1d(2.4- and 2.8-fold). At MMT+6w a more rapid rise was evident. GLP-1 levels were similar in all MMTs except MMT+6w where anincreased response was seen; this was stronger in T2D vs. C. The GIP-response was higher at MMT+1d, compared to MMT-4w andMMT-1d (1.6- and 1.4-fold). The increased GIP-response was attenuated in C at MMT+6w, but still evident in T2D.Conclusions: VLCD has minor impact on the parameters analyzed; rather GBP per se elicits an immediate stimulatory effect on insulinand GIP levels in response to an MMT as first meal on day 1 after surgery

Roux-en-Y gastric bypass versus calorie restriction: support for surgery as the direct contributor to aloncltered responses of insulin and incretins to a mixed meal

AbstractObjectiveTo study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR).SettingUniversity-affiliated bariatric surgery clinic.BackgroundRYGB induces remission of type 2 diabetes (T2 D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2 D is unknown.MethodsNine normoglycemic patients and 10 T2 D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on a very low calorie diet regimen (MMT-1 d), on the morning of the first day after surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured.ResultsCR lowered insulin in T2 D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2 D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2 D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB.ConclusionRYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR

Metabolic Effects of Gastric Bypass Surgery : Is It All About Calories?

Bariatric surgery is an efficient method to induce weight loss and also, frequently, remission of type 2 diabetes (T2D). Unpaired studies have shown bariatric surgery and dietary interventions to differentially affect multiple hormonal and metabolic parameters, suggesting that bariatric surgery causes T2D remission at least partially via unique mechanisms. In the current study, plasma metabolite profiling was conducted in patients with (n = 10) and without T2D (n = 9) subjected to Roux-en-Y gastric bypass surgery (RYGB). Mixed-meal tests were conducted at baseline, after the presurgical very-low-calorie diet (VLCD) intervention, immediately after RYGB, and after a 6-week recovery period. Thereby, we could compare fasted and postprandial metabolic consequences of RYGB and VLCD in the same patients. VLCD yielded a pronounced increase in fasting acylcarnitine levels, whereas RYGB, both immediately and after a recovery period, resulted in a smaller but opposite effect. Furthermore, we observed profound changes in lipid metabolism following VLCD but not in response to RYGB. Most changes previously associated with RYGB were found to be consequences of the presurgical dietary intervention. Overall, our results question previous findings of unique metabolic effects of RYGB and suggest that the effect of RYGB on the metabolite profile is mainly attributed to caloric restriction

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice : Results from the ARTIS programme

Objective Longitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). Methods Nationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. Results There were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. Conclusion Data from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks

Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis

Objectives Whether the increased risk of comorbidities, such as cardiovascular disease, in rheumatoid arthritis (RA) can be reverted by particular antirheumatic therapies, or response to these, is unclear but of critical clinical importance. We wanted to investigate whether response to tumour necrosis factor inhibitors (TNFi) translates into a reduced risk for acute coronary syndrome (ACS). Methods A cohort of patients with RA initiating a first TNFi 2001-2012 was identified in the Swedish Biologics Register. The association between European League Against Rheumatism (EULAR) response after 3-8 months of treatment (assessed using the first, the best and the measurement closest to 5 months, respectively), and the risk of incident ACS during the subsequent year was analysed in Cox regression models. Adjustments included cardiovascular risk factors, joint surgery, RA duration, education and work disability. Results During 6592 person-years among TNFi initiators (n=6864, mean age 55 years, 77% women), 47 ACS occurred. The adjusted HRs (95% CI), which were similar to the crude HRs, of the 1-year risk of ACS among EULAR good responders compared with nonresponders were 0.5 (0.2 to 1.4), 0.4 (0.2 to 0.9) and 0.5 (0.2 to 1.2), for the first, the best and the evaluation closest to 5 months, respectively. EULAR moderate responders had equal risk to that of EULAR non-responders, who, compared with the general population referents (n=34 229), had a more than twice the risk of ACS. For good responders, there was no statistically significant difference in risk versus the general population. Conclusions Optimised RA disease control has the potential to revert otherwise increased risks for ACS in RA

Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden : from infection severity to impact on care provision

Objectives To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision. Methods Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015–2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities. Results Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (−7%), visits to rheumatology units (−16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and −8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends. Conclusions Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed

Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population : a nationwide Swedish cohort study

Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies. Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression. Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited. Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks