Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1–ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1–ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP

Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30 : a combined analysis of two Phase 3a studies in type 2 diabetes

BackgroundInsulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid-acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30). MethodsHypoglycemia data were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal. ResultsOver 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; -31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; -62%; P <0.0001), and 0.16 (95% CI 0.04, 0.59; -84%; P = 0.0061), respectively. ConclusionsCompared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.Peer reviewe

Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity:a cross-sectional study

BACKGROUND: The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extracellular matrix protein, fibulin-1, was recently found in higher concentrations in the arterial wall and in plasma in patients with long duration type 2 diabetes. Furthermore, plasma fibulin-1 independently predicted total mortality and was associated with pulse pressure, an indirect measure of arterial stiffness. Whether plasma fibulin-1 is associated with arterial stiffness at earlier phases of type 2 diabetes has not been determined. METHODS: In this cross-sectional study, we examined 90 patients with recently diagnosed type 2 diabetes (< 5 years) and 90 gender- and age-matched controls. Plasma fibulin-1 was measured immunochemically. Arterial stiffness was assessed by carotid-femoral Pulse Wave Velocity (PWV). Differences in means were assessed by t-tests. Associations were assessed by multivariate regression analyses. RESULTS: Plasma fibulin-1 levels were lower in the diabetic group compared with the control group, 93 ± 28 vs 106 ± 30 μg/mL, p = 0.005. In unadjusted analysis of the total study sample, plasma fibulin-1 was not associated with PWV, p = 0.46. However, with adjustment for the confounders age, gender, mean blood pressure, heart rate, body mass index, diabetes and glomerular filtration rate, a 10 μg/mL increase in plasma fibulin was associated with 0.09 ± 0.04 m/s increase in PWV, p < 0.05. In subgroup analysis, plasma fibulin-1 was associated with PWV in the diabetes group, (0.16 ± 0.07 m/s increase in PWV per 10 μg/mL increase in plasma fibulin-1, p<0.05), but not controls, β = 0.021 ± 0.057 m/s per 10 μg/mL, p = 0.70. The association remained significant in the diabetes group after adjustment for covariates, p < 0.05. CONCLUSIONS: Plasma fibulin-1 is independently associated with PWV. Yet, as the plasma level of fibulin-1 was lower in patients with recently diagnosed type 2 diabetes than in healthy controls, plasma fibulin-1 levels are not a simple marker of the degree of arterial stiffening. Further studies are needed to determine the exact role of fibulin-1 in arterial stiffness and cardiovascular risk in patients with type 2 diabetes

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

Physiotherapists' experiences of physiotherapy interventions in scientific physiotherapy publications focusing on interventions for children with cerebral palsy: a qualitative phenomenographic approach

Background: Physiotherapy research concerning interventions for children with CP is often focused on collecting evidence of the superiority of particular therapeutic methods or treatment modalities. Articulating and documenting the use of theory, instrumentation and research design and the assumptions underlying physiotherapy research interventions are important. Physiotherapy interventions focusing on children with Cerebral Palsy should, according to the literature, be based on a functional and environmental perspective with task-specific functional activity, motor learning processes and Family-Centred Service i.e. to enhance motor ability and improve capacity so that the child can perform the tasks necessary to participate actively in everyday life. Thus, it is important to coordinate the norms and values of the physiotherapist with those of the family and child. The aim of this study was to describe how physiotherapists' experiences physiotherapy interventions for children with CP in scientific physiotherapy publications written by physiotherapists. Methods: A qualitative phenomenographic approach was used. Twenty-one scientific articles, found in PubMed, strategically chosen according to year of publication (2001-2009), modality, journals and country, were investigated. Results: Three qualitatively different descriptive categories were identified: A: Making it possible a functional-based intervention based on the biopsychosocial health paradigm, and the role of the physiotherapist as collaborative, interacting with the child and family in goal setting, intervention planning and evaluation, B: Making it work an impairment-based intervention built on a mixed health paradigm (biomedical and biopsychosocial), and the role of the physiotherapist as a coach, leading the goal setting, intervention planning and evaluation and instructing family members to carry out physiotherapist directed orders, and; C: Making it normal an impairment-based intervention built on a biomedical health paradigm, and the role of the physiotherapist as an authoritative expert who determine goals, intervention planning and evaluation. Conclusions: Different paradigms of health and disability lead to different approaches to physiotherapy which influence the whole intervention process regarding strategies for the assessment and treatment, all of which influence Family-Centred Service and the child's motor learning strategies. The results may deepen physiotherapists' understanding of how different paradigms of health influence the way in which various physiotherapy approaches in research seek to solve the challenge of CP

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH)