Morbidity and mortality of diabetes with surgery

The prevalence of Type 2 diabetes mellitus (T2DM) has increased; as a result the number of patients with T2DM undergoing surgical procedures has also increased. This population is at high risk of macrovascular (cardiovascular disease, peripheral vascular disease) or microvascular (retinopathy, nephropathy or neuropathy) complications, both increasing their perioperative morbidity and mortality. Diabetes patients are more at risk of poor wound healing, respiratory infection, myocardial infarction, admission to intensive care, and increased hospital length of stay. This leads to increased inpatient costs. The outcome of perioperative glycaemia management remains a significant clinical problem without a universally accepted solution. The majority of evidence on morbidity and mortality of T2DM patients undergoing surgery comes from the setting of cardiac surgery; there was less evidence on non-cardiac surgery and bariatric surgery. Bariatric surgery is increasingly performed in patients with severe obesity complicated by T2DM, but is distinguished from general surgery as it immediately improves the glucose homeostasis postoperatively. The improvements in glycaemia are thought to be independent of weight loss and this requires different postoperative management. Patients usually have to follow specific preoperative diets which lead to improvement in glycaemia immediately before surgery. Here we review the available data on the mortality and morbidity of patients with T2DM who underwent elective surgery (cardiac, non-cardiac and bariatric surgery) and the current knowledge of the impact that preoperative, intraoperative and postoperative glycaemic management has on operative outcomes

Esophageal motility after laparoscopic sleeve gastrectomy

Background: Laparoscopic sleeve gastrectomy (LSG) modifies the upper gastrointestinal tract motility. Controversial data currently exist. The aim of the study was to evaluate esophageal motility before and after LSG. Patients and methods: Morbid obese patients scheduled for LSG underwent reflux symptoms evaluation and manometry preoperatively and postoperatively. The preoperative and postoperative results were compared and analyzed. Results: Eighteen patients were enrolled. Heartburn and regurgitation improved in 38.9% and 11.1% of the patients, but deteriorated in 11.1% and 27.8% of the patients, respectively. Lower esophageal sphincter (LES) total length decreased postoperatively (p=0.002). Resting and residual pressures tended to decrease postoperatively (mean difference [95% confidence interval]: −4 [−8.3/0.2] mmHg, p=0.060; −1.4 [−3/0.1] mmHg, p=0.071, respectively). Amplitude pressure decreased from 95.7±37.3 to 69.8±26.3 mmHg at the upper border of LES (p=0.014), and tended to decrease at the distal esophagus from 128.5±30.1 to 112.1±35.4 mmHg (p=0.06) and mid-esophagus from 72.7±34.5 to 49.4±16.7 mmHg (p=0.006). Peristaltic normal swallow percentage increased from 47.2±36.8 to 82.8±28% (p=0.003). Postoperative regurgitation was strongly negatively correlated with LES total length (Spearman’s r=−0.670). When groups were compared according to heartburn status, statistical significance was observed between the groups of improvement and deterioration regarding postoperative residual pressure and postoperative relaxation (p<0.002, p<0.002, respectively). With regard to regurgitation status, there was statistically significant difference between groups regarding preoperative amplitude pressure at the upper border of LES (p<0.056). Conclusion: Patients developed decreased LES length and weakened LES pressure after LSG. Esophageal body peristalsis was also affected in terms of decreased amplitude pressure, especially at the upper border of LES. Nevertheless, body peristalsis was normalized postoperatively. LSG might not deteriorate heartburn. Regurgitation might increase following LSG due to shortening of LES length, particularly in patients with range of preoperative amplitude pressure at the upper border of LES of 38.9–92.6 mmHg. © 2017 Sioka et al

Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis

AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. MATERIALS AND METHODS: We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. RESULTS: A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73 mmol/L, respectively, for lixisenatide to -1.21% and -1.97 mmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once-weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. CONCLUSIONS: The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA.National Institute for Health Research, Lifestyle & Physical ActivityPeer-reviewedPost-prin

Hepcidin levels in diabetes mellitus and polycystic ovary syndrome

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI,n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI,n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI,n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = –0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states

Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis

AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. MATERIALS AND METHODS: We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. RESULTS: A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73 mmol/L, respectively, for lixisenatide to -1.21% and -1.97 mmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once-weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. CONCLUSIONS: The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA

Esophageal motility after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) modifies the upper gastrointestinal tract motility. Controversial data currently exist. The aim of the study was to evaluate esophageal motility before and after LSG. PATIENTS AND METHODS: Morbid obese patients scheduled for LSG underwent reflux symptoms evaluation and manometry preoperatively and postoperatively. The preoperative and postoperative results were compared and analyzed. RESULTS: Eighteen patients were enrolled. Heartburn and regurgitation improved in 38.9% and 11.1% of the patients, but deteriorated in 11.1% and 27.8% of the patients, respectively. Lower esophageal sphincter (LES) total length decreased postoperatively (p=0.002). Resting and residual pressures tended to decrease postoperatively (mean difference [95% confidence interval]: -4 [-8.3/0.2] mmHg, p=0.060; -1.4 [-3/0.1] mmHg, p=0.071, respectively). Amplitude pressure decreased from 95.7±37.3 to 69.8±26.3 mmHg at the upper border of LES (p=0.014), and tended to decrease at the distal esophagus from 128.5±30.1 to 112.1±35.4 mmHg (p=0.06) and mid-esophagus from 72.7±34.5 to 49.4±16.7 mmHg (p=0.006). Peristaltic normal swallow percentage increased from 47.2±36.8 to 82.8±28% (p=0.003). Postoperative regurgitation was strongly negatively correlated with LES total length (Spearman's r=-0.670). When groups were compared according to heartburn status, statistical significance was observed between the groups of improvement and deterioration regarding postoperative residual pressure and postoperative relaxation (p<0.002, p<0.002, respectively). With regard to regurgitation status, there was statistically significant difference between groups regarding preoperative amplitude pressure at the upper border of LES (p<0.056). CONCLUSION: Patients developed decreased LES length and weakened LES pressure after LSG. Esophageal body peristalsis was also affected in terms of decreased amplitude pressure, especially at the upper border of LES. Nevertheless, body peristalsis was normalized postoperatively. LSG might not deteriorate heartburn. Regurgitation might increase following LSG due to shortening of LES length, particularly in patients with range of preoperative amplitude pressure at the upper border of LES of 38.9-92.6 mmHg

Effectiveness and cost of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in obesity services (STRIVE study): Study protocol of an open-label, real-world, randomised, controlled trial

Introduction In the UK and Ireland, severe and complex obesity is managed in specialist weight management services (SWMS), which provide multicomponent lifestyle interventions to support weight loss, and use of medication if available. Liraglutide 3 mg (LIRA 3 mg) is an effective weight-loss medication, but weight loss in individual patients is variable, and its efficacy has not been assessed in SWMS. This study aims to investigate whether a targeted prescribing pathway for LIRA 3 mg with multiple prespecified stopping rules could help people with severe obesity and established complications achieve ≥15% weight loss in order to determine whether this could be considered a clinically effective and cost-effective strategy for managing severe and complex obesity in SWMS.Methods and analysis In this 2-year, multicentre, open-label, real-world randomised controlled trial, 384 adults with severe and complex obesity (defined as body mass index ≥35 kg/m2 plus either prediabetes, type 2 diabetes, hypertension or sleep apnoea) will be randomised via a 2:1 ratio to receive either standard SWMS care (n=128) or standard SWMS care plus a targeted prescribing pathway for LIRA 3 mg with prespecified stopping rules at 16, 32 and 52 weeks (n=256).The primary outcome is to compare the proportion of participants achieving a weight loss of ≥15% at 52 weeks with a targeted prescribing pathway versus standard care. Secondary outcomes include a comparison of (1) the weight loss maintenance at 104 weeks and (2) the budget impact and cost effectiveness between the two groups in a real-world setting.Ethics and dissemination The Health Research Authority and the Medicines and Healthcare products Regulatory Authority in UK, the Health Products Regulatory Authority in Ireland, the North West Deanery Research Ethics Committee (UK) and the St Vincent’s University Hospital European Research Ethics Committee (Ireland) have approved the study. The findings of the study will be published in peer-reviewed journals.Trial registration number ClinicalTrials.gov—Identifier: NCT03036800.European Clinical Trials Database—Identifier: EudraCT Number 2017-002998-20.</div