Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Polymorphisme -493G/T de la Microsomal Triglyceride Transfer Protein et stéatose hépatique lors de l'obésité morbide

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Aspirin in people with diabetes: Time to clean up the prescription list?

International audienceThe effect of aspirin in primary cardiovascular (CV) prevention in people with diabetes is still a matter of debate. Recent results of ASCEND trial suggest that the absolute benefit on CV events is largely counter-balanced by the bleeding risk. However, one crucial question is whether aspirin should be maintained or withdrawn from the prescription list of those who are already under this therapy since a while ago. Indeed, large epidemiological data reported that the aspirin discontinuation was associated to an increased risk of CV events. Moreover, besides the CV outcome, potential positive impact of aspirin on cancer is still under investigation. To conclude, there is no more systematic indication for aspirin in people with diabetes free of CV disease, especially when diabetes and all other CV risk factors are optimally controlled. For those already on aspirin, data are not conclusive enough for a systematic approach and benefit/risk balance must be discussed with patients to take a shared decision

Anti-Programmed Death 1 (PD-1) Antibodies and the Pancreas: A Diabetic Storm Ahead?

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Vascular Events and Carotid Atherosclerosis: A 5-Year Prospective Cohort Study in Patients with Type 2 Diabetes and a Contemporary Cardiovascular Prevention Treatment

Background and Aims . European recommendations on cardiovascular prevention suggest that carotid atherosclerosis assessment by duplex ultrasonography could help in some cases to better assess CV risk. We investigated whether the presence of carotid atherosclerosis determined by duplex ultrasonography is associated with cardiovascular events in patients with type 2 diabetes and could therefore help to reclassify cardiovascular risk. Methods . Among 624 consecutive patients with type 2 diabetes and carotid atherosclerosis assessment by duplex ultrasonography between January and December 2012, 583 (93%) were included and followed up prospectively. The primary endpoint was the occurrence of cardiovascular events. The rate of new cardiovascular events was compared between patients with ( n = 104 ) and those without ( n = 479 ) prior cardiovascular events. Results . A total of new 104 cardiovascular events occurred in 72 patients (12.5%) during a mean ± SD follow-up period of 5.1 ± 1.6 years. At baseline, for 202 patients (34.6%), carotid evaluation was normal; 381 (65.4%) had a carotid atherosclerosis lesion. The presence of carotid atherosclerosis at baseline was not significantly associated with an increased risk of new cardiovascular events in both groups. The rate of new cardiovascular events was more than twice as high in patients with prior cardiovascular event than those without. Conclusion. Systematic carotid atherosclerosis assessment by duplex ultrasonography in patients with type 2 diabetes and a contemporary cardiovascular prevention treatment does not offer additional information as to the risk of cardiovascular events. This trial is registered with ClinicalTrials.gov (ID: NCT02929355 )

Evaluation of the Use of Antibiofilmogram Technology in the Clinical Evolution of Foot Ulcers Infected by Staphylococcus aureus in Persons Living with Diabetes: A Pilot Study.

International audienceInfected diabetic foot ulcers (DFUs) represent a serious threat to public health because of their frequency and the severity of their consequences. DFUs are frequently infected by bacteria in biofilms, obstructing antibiotic action. Antibiofilmogram was developed to assess the impact of antibiotics to inhibit biofilm formation. This pilot study aimed to determine the benefits of this technology in predicting antibiotic activity on the outcome of 28 patients with Grade 2 DFUs that were infected by a monomicrobial Staphylococcus aureus. Patients with diabetes were followed during the antibiotic treatment (day 14) and the follow-up period of the study (day 45). The contribution of Antibiofilmogram was compared between patients with non-concordant results (n = 13) between antibiogram and Antibiofilmogram versus concordant results (n = 15). The clinical improvement of wounds (80.0% vs. 38.5%, p = 0.0245) and the absence of exudates (0% vs. 33.3%, p = 0.0282) were observed in concordant vs. discordant groups. This pilot study provides promising results for the interest of Antibiofilmogram in the prescription of antibiotics to prevent biofilm formation in infected DFUs

Neurovascular Response to Pressure in Patients with Diabetic Foot Ulcer

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Use of the SINBAD score as a predicting tool for major adverse foot events in patients with diabetic foot ulcer: A French multicentre study

Abstract Objective To assess the relationship between the site, ischaemia, neuropathy, bacterial infection, area, depth (SINBAD) score and major adverse foot events in patients with diabetes and foot ulcers. Methods For this retrospective ancillary study, patients ( n = 537) followed for a diabetic foot ulcer (DFU) in six French hospitals were included between 1 February 2019 and 17 March 2019, and between 1 February 2020 and 17 March 2020. The SINBAD score was assessed at inclusion. The frequency of a composite outcome consisting of eight major adverse foot events (MAFE) was assessed after 5–6 months of follow‐up: hospitalisation for DFU, septic surgery, revascularisation, minor amputation, major amputation, death, secondary infection and ulcer recurrence. A logistical regression explored the link between the SINBAD score and MAFE and each of its component. Results A low SINBAD score (from 0 to 3) was observed in 61% of patients and a high (from 4 to 6) in 39%. MAFE occurred in, respectively, 24% and 28% of these patients. Multivariate analyses showed a significant relationship between the SINBAD score and MAFE, with the continuous SINBAD score: odds ratio (OR) 1.72 [95% CI (1.51–1.97)] or dichotomic SINBAD score (values: 0–3 and 4–6): OR 3.71 [95% CI (2.54–5.42)]. The SINBAD score (continuous or dichotomic) at inclusion was also significantly associated with six out of the eight components of the MAFE. Conclusions The SINBAD score is a useful tool for predicting major adverse foot events

FTO is increased in muscle during type 2 diabetes, and its overexpression in myotubes alters insulin signaling, enhances lipogenesis and ROS production, and induces mitochondrial dysfunction.

International audienceOBJECTIVE: A strong association between genetic variants and obesity was found for the fat mass and obesity-associated gene (FTO). However, few details are known concerning the expression and function of FTO in skeletal muscle of patients with metabolic diseases. RESEARCH DESIGN AND METHODS: We investigated basal FTO expression in skeletal muscle from obese nondiabetic subjects and type 1 and type 2 diabetic patients, compared with age-matched control subjects, and its regulation in vivo by insulin, glucose, or rosiglitazone. The function of FTO was further studied in myotubes by overexpression experiments. RESULTS: We found a significant increase of FTO mRNA and protein levels in muscle from type 2 diabetic patients, whereas its expression was unchanged in obese or type 1 diabetic patients. Moreover, insulin or glucose infusion during specific clamps did not regulate FTO expression in skeletal muscle from control or type 2 diabetic patients. Interestingly, rosiglitazone treatment improved insulin sensitivity and reduced FTO expression in muscle from type 2 diabetic patients. In myotubes, adenoviral FTO overexpression increased basal protein kinase B phosphorylation, enhanced lipogenesis and oxidative stress, and reduced mitochondrial oxidative function, a cluster of metabolic defects associated with type 2 diabetes. CONCLUSIONS: This study demonstrates increased FTO expression in skeletal muscle from type 2 diabetic patients, which can be normalized by thiazolidinedione treatment. Furthermore, in vitro data support a potential implication of FTO in oxidative metabolism, lipogenesis and oxidative stress in muscle, suggesting that it could be involved in the muscle defects that characterize type 2 diabetes