Central regulation of energy homeostasis and the reproductive axis

Alarin is a recently discovered splice variant of the galanin-like peptide (GALP) gene. Alarin is a highly conserved 25 amino acid peptide which shares its first 5 amino acids with GALP, but lacks the galanin receptor binding domain, suggesting that it mediates its biological effects through alternative receptors. Alarin has been detected in the rodent hypothalamus. GALP has a well-characterised role in the integration of energy and reproductive homeostasis. Intracerebroventricular (ICV) alarin increases food intake and plasma luteinising hormone (LH) levels in rats. Alarin stimulates the release of the orexigenic neuropeptide Y (NPY) and gonadotrophin releasing hormone (GnRH) from hypothalamic explants, and GnRH release from an immortalised GnRH releasing cell line. Pre-treatment with a GnRH antagonist blocked the alarin-induced increase in plasma LH levels in vivo. These results suggest that ICV alarin activates the HPG axis via hypothalamic GnRH release. My data also suggests that alarin does not bind to the known galanin receptors. The ventral tegmental area (VTA) is the origin of the mesolimbic dopamine pathway, which mediates the rewarding properties of palatable food. Recent work suggests that the VTA reward pathway is regulated by appetite-regulating signals including leptin and ghrelin. I have shown that intra-VTA melanocortin receptor agonist administration inhibits food intake and administration of an antagonist stimulates food intake in rats, suggesting that the melanocortin system may be involved in hedonic regulation of appetite, in addition to its role in homeostatic regulation of appetite. These studies have elucidated the biological effects of alarin in the regulation of appetite and the HPG axis, and identified a role for the melanocortin system in regulating the central reward circuitry modulating food intake. Further work is required to determine the receptor by which alarin mediates its effect and its precise physiological function, and the physiological importance of the VTA melanocortin system

Closed-loop management of inpatient hyperglycemia.

The prevalence of diabetes in the hospital is increasing and approximately 18-20% of hospital beds are occupied by someone with diabetes [1]. Diabetes disproportionally affects the elderly, with three times greater prevalence in hospitalised people aged over 65 years than in those aged under 45 years [2]. Maintaining near normoglycaemia during hospital admissions can be very challenging. The impact of the current illness, medication changes, alterations to meal timings and intake, and requirement for nutrition support in hospital can all contribute to sub-optimal glucose control. Both hyper- and hypoglycemia in hospital are associated with increased risk of complications, length of stay, admission to the intensive care unit and mortality [3].Diabetes UK (#14/0004878), Swiss National Science Foundation (P1BEP3_165297) and European Foundation for the Study of Diabetes. Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Trust Strategic Award (100574/Z/12/Z)

Correction to: New closed-loop insulin systems.

A Correction to this paper has been published: 10.1007/s00125-021-05443-1</jats:p

New closed-loop insulin systems.

Advances in diabetes technologies have enabled the development of automated closed-loop insulin delivery systems. Several hybrid closed-loop systems have been commercialised, reflecting rapid transition of this evolving technology from research into clinical practice, where it is gradually transforming the management of type 1 diabetes in children and adults. In this review we consider the supporting evidence in terms of glucose control and quality of life for presently available closed-loop systems and those in development, including dual-hormone closed-loop systems. We also comment on alternative 'do-it-yourself' closed-loop systems. We remark on issues associated with clinical adoption of these approaches, including training provision, and consider limitations of presently available closed-loop systems and areas for future enhancements to further improve outcomes and reduce the burden of diabetes management

The changing landscape of automated insulin delivery in the management of type 1 diabetes

Automated insulin delivery systems, also known as closed-loop o r ‘artificial pancreas’ systems, are transforming the management of type 1 diabetes. These systems consist of an algorithm which responds to real-time glucose sensor levels by automatically modulating insulin delivery through an insulin pump. We review the rapidly changing landscape of automated insulin-delivery systems over recent decades, from initial prototypes to the different hybrid closed-loop systems commercially available today. We discuss the growing body of clinical trials and real-world evidence demonst rating their glycaemic and psychosocial benefits. We also address future directions in auto mated insulin delivery such as dual-hormone systems and adjunct therapy as well as the chal lenges around ensuring equitable access to closed-loop technology

POWER, INFLUENCE TACTICS, AND INFLUENCE PROCESSES IN VIRTUAL TEAMS

Current studies of power, influence tactics, and influence processes in virtual teams assume that these constructs operate in a similar manner as they do in the face-to- face (FtF) environment. However, the virtual context differs from the FtF environment on a variety of dimensions, such as the availability of status cues. The differences between these contexts may alter how power and influence tactics are expressed in virtual teams. This study examines how power, influence tactics, and influence processes are manifested in virtual teams and which influence tactics are most successful in this context. Twenty-three members of virtual teams were interviewed about their previous attempts to influence team members. The data were coded using a thematic approach. The main findings of the current study were: 1) There is a tendency to use more assertive influence tactics in virtual teams; 2) The success rate of influence tactics varies by the direction of the influence attempt, with lateral influence tactics having the lowest likelihood of success; 3) Specific status characteristics such as knowledge and skills are more relevant for members of virtual teams than diffuse status characteristics; and 4) There is both a relationship orientation and a task orientation in virtual teams. I also present a model for the influence process in virtual teams. First, actors must use technology to get their targets‘ attention. Second, actors should build relationships through getting to know one another and the establishing trust, although this is not a requisite step. Third, actors must choose which influence tactic to use. While many choose to adapt traditional tactics to work in the virtual environment, new influence tactics (e.g., ambiguity reduction techniques) have emerged. Communication technology preferences affect which technologies an actor uses to build relationships and enact influence tactics. The status of the actor and target also affect which influence tactic(s) an actor uses. Recommendations are offered for both low-status members of virtual teams as well as virtual team leaders. Members of virtual teams need to be more assertive in their influence attempts and also need to focus on building relationships with their team members in order to be successful influencers. Future research opportunities are also discussed. Given the growing prevalence of virtual teams, the results of this study are a valuable contribution to both practice and research

Hybrid Closed-loop to Manage Gastroparesis in People With Type 1 Diabetes: a Case Series.

BACKGROUND: Gastroparesis is associated with unpredictable gastric emptying and can lead to erratic glucose profiles and negative impacts on quality-of-life. Many people with gastroparesis are unable to meet glycemic targets and there is a need for new approaches for this population. Hybrid closed-loop systems improve glucose control and quality-of-life but evidence for their use in people with diabetic gastroparesis is limited. METHODS: We present a narrative review of the challenges associated with type 1 diabetes management for people with gastroparesis and present a case series of 7 people with type 1 diabetes and gastroparesis. We compare glycemic control before and during the first 12 months of hybrid closed-loop therapy. Data were analyzed using electronic patient records and glucose management platforms. We also discuss future advancements for closed-loop systems that may benefit this population. RESULTS: Five of 7 patients had data available for time in range before and during hybrid closed-loop therapy, and all had an improvement in percentage time in target glucose range, with the overall mean time in range increasing from 26.0% ± 15.7% to 58.4% ± 8.6% during HCL use, (P = .004). There were significant reductions in HbA1c (83 ± 9 mmol/mol to 71 ± 14 mmol/mol) and mean glucose from 13.0 ± 1.7 mmol/L (234 ± 31 mg/dL) to 10.0 ± 0.7 mmol/L (180 ± 13 mg/dL) with use of a hybrid closed-loop system. Importantly, this was achieved without an increase in time in hypoglycemia (P = .50). CONCLUSION: Hybrid closed-loop systems may represent a valuable approach to improve glycemic control for people with type 1 diabetes and gastroparesis. Prospective studies are required to confirm these findings

Training and Support for Hybrid Closed-Loop Therapy.

Hybrid closed-loop therapy is an emerging technology transforming the management of type 1 diabetes (T1D). Research studies demonstrate glycemic and quality of life benefits of hybrid closed-loop therapy for people with T1D. Translating these outcomes into standard clinical practice is critical for reimbursement and improving access to this technology.High-quality training is essential for achieving optimal outcomes with hybrid closed-loop therapy. Basic diabetes skills and tasks are as important, or even more important, with closed-loop therapy than with standard insulin therapy and need to be reiterated. Establishing expectations of hybrid closed-loop therapy clearly at the outset promotes long-term usage and optimal outcomes.We share key aspects of training and support for users of commercially available hybrid closed-loop systems and consider who may benefit from this technology

CamAPS FX hybrid closed-loop with ultra-rapid lispro compared with standard lispro in adults with type 1 diabetes: a double-blind, randomized, crossover study.

INTRODUCTION To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. MATERIALS AND METHODS In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean±SD: age 44.5±10.7, HbA1c 7.1±0.9% [54±10mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. CamAPS FX closed-loop system was used in both periods. RESULTS In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9 to 10mmol/L; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean±SD: 78.7±9.8% vs. 76.2±9.6%; mean difference 2.5 percentage points [95%CI 0.8 to 4.2]; p=0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9±0.8mmol/L vs. 8.1±0.9mmol/L; p=0.048). The proportion of time with sensor glucose <3.9mmol/L was similar between interventions (median [IQR] ultra-rapid lispro 2.3% [1.3-2.7%] vs. standard insulin lispro 2.1% [1.4-3.3%]; p=0.33). No severe hypoglycemia or ketoacidosis occurred. CONCLUSIONS The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes