Evaluating differences in the clinical impact of a free online weight loss programme, a resource-intensive commercial weight loss programme and an active control condition: a parallel randomised controlled trial.

BACKGROUND: Finding effective intervention strategies to combat rising obesity levels could significantly reduce the burden that obesity and associated non-communicable diseases places on both individuals and the National Health Service. METHODS: In this parallel randomised-controlled trial, 76 participants who are overweight or obese (50 female) were given free access to a fitness centre for the duration of the 12-week intervention and randomised to one of three interventions. The commercial intervention, the Healthy Weight Programme, (HWP, n = 25, 10/15 men/women) consisted of twelve 1-h nutrition coaching sessions with a nutritionist delivered as a mixture of group and 1 to 1 sessions. In addition, twice-weekly exercise sessions (24 in total) were delivered by personal trainers for 12 weeks. The NHS intervention (n = 25, 8/17 men/women) consisted of following an entirely self-managed 12-week online NHS resource. The GYM intervention (n = 26, 8/18 men/women) received no guidance or formal intervention. All participants were provided with a gym induction for safety and both the NHS and GYM participants were familiarised with ACSM physical activity guidelines by way of a hand-out. RESULTS: The overall follow-up rate was 83%. Body mass was significantly reduced at post-intervention in all groups (HWP: N = 18, - 5.17 ± 4.22 kg, NHS: N = 21-4.19 ± 5.49 kg; GYM: N = 24-1.17 ± 3.00 kg; p < 0.001) with greater reductions observed in HWP and NHS groups compared to GYM (p < 0.05). Out with body mass and BMI, there were no additional statistically significant time x intervention interaction effects. CONCLUSIONS: This is the first study to evaluate the efficacy of both a free online NHS self-help weight-loss tool and a commercial weight loss programme that provides face-to-face nutritional support and supervised exercise. The findings suggest that both interventions are superior to an active control condition with regard to eliciting short-term weight-loss. TRIAL REGISTRATION: ISRCTN Registry - ISRCTN31489026. Prospectively registered: 27/07/16.

Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation.

BACKGROUND: The global burden of type 2 diabetes mellitus (T2DM), together with the presence of cardiovascular risk in this population, is reaching pandemic levels. A prominent feature of T2DM is chronic and systemic inflammation, with the accompanying presence of circulating and dysregulated inflammatory biomarkers; which in turn is associated with abnormal clot formation. METHODS: Here, we investigate the correlation between abnormal blood clotting, using thromboelastography (TEG), clot ultrastructure using scanning electron microscopy (SEM) and the presence of a dysregulated inflammatory cytokine profile, by examining various circulating biomarkers. RESULTS: Our results show that many biomarkers, across TEG, cytokine and lipid groups, were greatly dysregulated in the T2DM sample. Furthermore, our T2DM sample's coagulation profiles were significantly more hypercoagulable when compared to our heathy sample, and ultrastructural analysis confirmed a matted and denser clot structure in the T2DM sample. CONCLUSIONS: We suggest that dysregulated circulating molecules may in part be responsible for a hypercoagulable state and vascular dysfunction in the T2DM sample. We propose further that a personalized approach could be of great value when planning treatment and tracking the patient health status after embarking on a treatment regimes, and that looking to novel inflammatory and vascular biomarkers might be crucial.

Serum amyloid A binds to fibrin(ogen), promoting fibrin amyloid formation.

Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer's disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation. To study the role of SAA in coagulation and thrombosis, in vitro experiments were performed where purified human SAA, in concentrations resembling a modest acute phase response, was added to platelet-poor plasma (PPP) and whole blood (WB), as well as purified and fluorescently labelled fibrinogen. Results from thromboelastography (TEG) suggest that SAA causes atypical coagulation with a fibrin(ogen)-mediated increase in coagulation, but a decreased platelet/fibrin(ogen) interaction. In WB scanning electron microscopy analysis, SAA mediated red blood cell (RBC) agglutination, platelet activation and clumping, but not platelet spreading. Following clot formation in PPP, the presence of SAA increased amyloid formation of fibrin(ogen) as determined both with auto-fluorescence and with fluorogenic amyloid markers, under confocal microcopy. SAA also binds to fibrinogen, as determined with a fluorescent-labelled SAA antibody and correlative light electron microscopy (CLEM). The data presented here indicate that SAA can affect coagulation by inducing amyloid formation in fibrin(ogen), as well as by propelling platelets to a more prothrombotic state. The discovery of these multiple and complex effects of SAA on coagulation invite further mechanistic analyses.

Platelet activity and hypercoagulation in type 2 diabetes.

BACKGROUND: A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines. METHODS: The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1ß, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1ß, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay. RESULTS: In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM. CONCLUSIONS: Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.