Changes in attitudes to awareness of hypoglycaemia during a hypoglycaemia awareness restoration programme are associated with avoidance of further severe hypoglycaemia episodes within 24 months: the A2A in HypoCOMPaSS study

Aims/hypothesis: The aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months). Methods: This analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring. Results: The age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier hyperglycaemia avoidance prioritised (2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in asymptomatic hypoglycaemia normalised from baseline (2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for asymptomatic hypoglycaemia normalised, reduced change in asymptomatic hypoglycaemia normalised scores at 24 weeks, and lower baseline hypoglycaemia concern minimised scores (all p<0.05). Conclusions/interpretation: Participation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with hyperglycaemia avoidance prioritised most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition asymptomatic hypoglycaemia normalised. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes. Clinical trials registration: www.isrctn.org: ISRCTN52164803 and https://eudract.ema.europa.eu: EudraCT2009-015396-27. Graphical abstract: [Figure not available: see fulltext.]. (c) 2022, The Author(s)

Satisfaction with the Use of Different Technologies for Insulin Delivery and Glucose Monitoring Among Adults with Long-Standing Type 1 Diabetes and Problematic Hypoglycemia: 2-Year Follow-Up in the HypoCOMPaSS Randomized Clinical Trial

Background In the HypoCOMPaSS trial, adults with long-standing type 1 diabetes and problematic hypoglycaemia were randomised to compare insulin pump (CSII) vs multiple daily injections (MDI) and real-time continuous glucose monitoring (RT-CGM) vs conventional self-monitoring (SMBG). Our aim was to investigate participants\u27 satisfaction with these technologies at 6-month RCT endpoint and at 2-year follow-up. Methods Participants completed the Insulin Treatment Satisfaction Questionnaire (ITSQ) subscales \u27device delivery\u27 and \u27hypoglycaemia control\u27; and Glucose Monitoring Experience Questionnaire (GME-Q), assessing \u27convenience\u27, \u27effectiveness\u27, \u27intrusiveness\u27 and \u27total satisfaction\u27. We assessed change over time and between group differences by insulin and monitoring modalities. Results Participants (N=96) were: 64% women, aged 49\ub112 years, diabetes duration 29\ub112 years. At 6 months, participants reported improvements compared to baseline (all p&lt;0.001) in satisfaction with insulin \u27delivery device\u27 (r=0.39) and \u27hypoglycaemia control\u27 (r=0.52), and trends towards significance in perceived \u27effectiveness\u27 (r=0.42) and \u27intrusiveness\u27 (r=0.27) of monitoring device (but not \u27convenience\u27, p=0.139). All improvements were sustained at 2 years. At 6 months, the only difference between arms was that greater satisfaction with insulin \u27delivery device\u27 was reported in the CSII group compared to MDI (p&lt;0.001, r=0.40). No between-group differences were observed at 2 years. Conclusions Overall, significant improvements in participant satisfaction with diabetes technologies were observed over the 6-month RCT, in all domains except \u27convenience\u27, maintained at 2 years. While HypoCOMPaSS demonstrated non-inferiority of SMBG versus CGM, and MDI versus CSII in terms of biomedical outcomes, detailed assessments confirm participants\u27 satisfaction with delivery device was greater in those allocated to CSII than MDI

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins