The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

Objective: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. Design: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5 mg CGP-12177 or 5 mg norepinephrine (NE) and were immediately placed at 4°C for 24 h. Other SX groups were injected with CGP-12177 or NE 1 mg/kg BW i.p. and placed in the cold for 4 h. The latter group was injected, in addition, with prazosin 0.4 mg/100 g BW i.p. or propranolol 0.5 mg/100 g BW i.p. 15 min before and 2 h after the administration of CGP-12177 or NE. Methods: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500g for 10min at 4°C. The infranatants were incubated during 60min in the presence of dithiothreitol and 1 μCi [125I]T4. Aliquots were chromatographed on paper for the measurement of [125I]T4 and its deiodinated subproducts. Results: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. Conclusions: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.Fil: Hofer, Dietmar. Karl-Franzens-Universität Graz; AustriaFil: Raices, Marilina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; ArgentinaFil: Schauenstein, Konrad. Karl-Franzens-Universität Graz; AustriaFil: Porta, Sepp. Karl-Franzens-Universität Graz; AustriaFil: Korsatko, Wolfgang. Karl-Franzens-Universität Graz; AustriaFil: Hagmüller, Karl. Karl-Franzens-Universität Graz; AustriaFil: Zaninovich, Angel Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

BACKGROUND: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. METHODS: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,τ,SS)) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,τ,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)). RESULTS: Total exposure (AUC(IDeg,τ,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,τ,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC(IDeg,0–12h,SS)/AUC(IDeg,τ,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,τ,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,τ,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. CONCLUSIONS: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT0096441

Use of PaQ®, a Simple 3-Day Basal/Bolus Insulin Delivery Device, Reduces Barriers to Insulin Therapy in Patients With Type 2 Diabetes

PaQ (CeQur SA) is a simple to use patch-on device which provides set basal rates and bolus insulin on demand. PaQ was designed to minimize barriers to insulin therapy. In addition to feasibility of use, safety and effi cacy (reported elsewhere), this study analyzed the impact of the use of PaQ on patient reported outcomes (PRO) including; barriers against insulin treatment, diabetes related distress and negative attitudes towards insulin therapy in twenty patients with type 2 diabetes (T2D) on a stable multiple daily injections (MDI) insulin regimen. This single center, open label, single arm study was comprised of three 2-week periods; baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Three validated questionnaires were completed at the end of the baseline and PaQ treatment periods; Barriers to Insulin Treatment - Questionnaire (BIT), Problem Areas In Diabetes -Scale (PAID) and Insulin Treatment Appraisal Scale (ITAS). Nineteen patients (age 59 ±5 y, T2D duration 15±7 y, 21% female, A1C 7.7 ±0.7%) completed the questionnaires at the two measurement points. There was a strong and signifi cant effect of PaQ in the mean BIT total score (2.5 to 2.1, difference (D)=0.4 ±0.6; p = .01, effect size (d) = 0.70). Patients perceived less hardship from insulin therapy (overall improvement d = 0.35), less stigmatization by insulin injection (overall improvement d=0.28) and less fear of hypoglycemia (overall reduction d=0.29). Diabetes related distress was slightly reduced (PAID 21.7 to 21.0, D=0.7 ±6.7, p = 0.79, d= 10). A non-signifi cant reduction was also seen in the mean ITAS score (42.80 to 40.80, D=2.0 ±6.5, p = .20, d= 31). The study is limited by both the uncontrolled design and small sample size, however, the results and the moderate to large effect sizes suggest that the use of PaQ has benefi cial and clinically relevant effects to overcome barriers to and negative appraisal of insulin treatment, without increasing other diabetes related distress

The impact of patient-centred versus didactic education programmes in chronic patients by severity: the case of type 2 diabetes mellitus

Background Education leads to better health-related decisions and protective behaviors, being especially important for patients with chronic conditions. Self-management education programs have been shown to be beneficial for patients with different chronic conditions and to have a higher impact on health outcomes than does didactic education. Objective To investigate improvements in glycemic control (measured by glycated hemoglobin A1c) in patients with type 2 diabetes mellitus. Methods Our comparative trial involved one group of patients receiving patient-centered education and another receiving didactic education. We dealt with selection bias issues, estimated the different impact of both programs, and validated our analysis using quantile regression techniques. Results We found evidence of better mean glycemic control in patients receiving the patient-centered program, which engaged better patients. Nevertheless, that differential impact is nonmonotonic. Patients initially at the healthy range at the patient-centered program maintained their condition better. Patients close to, but not within, the healthy range benefited equally from attending either program. Patients with very high glycemic level benefited significantly more from attending the patient-centered program. Finally, patients with the worst initial glycemic control (far from the healthy range) improved equally their diabetic condition, regardless of which program they attended

Evaluation of educational needs in patients with diabetes mellitus in respect of medication use in Austria

Effective control of diabetes mellitus type 1 (DM1) and type 2 (DM2) can reduce the development and progression of diabetic complications. Therefore, patient education should be considered as an integral part of diabetes management. Objective The aim of the study was to assess DM patients’ perception of knowledge for their medication and attitude towards self management and pharmacist’s role. Setting The study was conducted at the diabetes out-patient clinic at the Vienna General Hospital (AKH), Division of Endocrinology and Metabolism, Department of Internal Medicine III, Austria. The study was a cross sectional survey using patient data from a validated patient questionnaire and medical records. Medical records were evaluated by applying a medication assessment tool. Main outcome measure To assess the quality of diabetes self management the following outcome measures are considered: HbA1c levels, pre- and post-prandial blood glucose levels, prevention of acute episodes of hypo- and hyperglycaemia, reduction of macrovascular risk factors, short term quality of life, adverse effects and treatment tolerance. Results The present study comprised 225 patients with DM1 and 201 patients with DM2, respectively. In comparison to DM2 patients, cardio- and cerebrovascular diseases were diagnosed very rarely in patients with DM1. The risk for these diseases was higher in patients with other factors of the metabolic syndrome, in addition. Overall, 118 of these patients participated in the questionnaire. The level of positive response on diabetes self-care and knowledge with respect to medication for the prevention of diabetes complications, glycaemic control, and treatment goals in diabetes was 81.8 %. The comparison of patients’ perceptions of diabetes self-care and knowledge showed differences among subgroups. Higher perceived knowledge and selfcare apparently was associated with DM1. Additional findings of this study indicate that patients do not expect community pharmacists to be integrated in a multidisciplinary diabetes care team. Although the level of positive response was found to be high there is still a minority of patients whose level of comprehension appears to be insufficient. Intense pharmaceutical care including patients’ education within a multidisciplinary team could contribute to improvements in those patients

International recommendations for glucose control in adult non diabetic critically ill patients

The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishedPour la Société Française d'Anesthésie-Réanimation (SFAR); Société de Réanimation de langue Française (SRLF) and the Experts grou

A rapid synthesis of the evidence on interventions supporting self-management for people with long-term conditions. (PRISMS Practical systematic RevIew of Self-Management Support for long-term conditions)

Background: Despite robust evidence concerning self-management for some long-term conditions (LTCs), others lack research explicitly on self-management and, consequently, some patient groups may be overlooked. Aim: To undertake a rapid, systematic overview of the evidence on self-management support for LTCs to inform health-care commissioners and providers about what works, for whom, and in what contexts. Methods: Self-management is ‘the tasks . . . individuals must undertake to live with one or more chronic conditions . . . [including] . . . having the confidence to deal with medical management, role management and emotional management of their conditions’. We convened an expert workshop and identified characteristics of LTCs potentially of relevance to self-management and 14 diverse exemplar LTCs (stroke, asthma, type 2 diabetes mellitus, depression, chronic obstructive pulmonary disease, chronic kidney disease, dementia, epilepsy, hypertension, inflammatory arthropathies, irritable bowel syndrome, low back pain, progressive neurological disorders and type 1 diabetes mellitus). For each LTC we conducted systematic overviews of systematic reviews of randomised controlled trials (RCTs) of self-management support interventions (‘quantitative meta-reviews’); and systematic overviews of systematic reviews of qualitative studies of patients’ experiences relating to self-management (‘qualitative meta-reviews’). We also conducted an original systematic review of implementation studies of self-management support in the LTCs. We synthesised all our data considering the different characteristics of LTCs. In parallel, we developed a taxonomy of the potential components of self-management support. Results: We included 30 qualitative systematic reviews (including 515 unique studies), 102 quantitative systematic reviews (including 969 RCTs), and 61 studies in the implementation systematic review. Effective self-management support interventions are multifaceted, should be tailored to the individual, their culture and beliefs, a specific LTC and position on the disease trajectory, and underpinned by a collaborative/communicative relationship between the patient and health-care professional (HCP) within the context of a health-care organisation that actively promotes self-management. Self-management support is a complex intervention and although many components were described and trialled in the studies no single component stood out as more important than any other. Core components include (1) provision of education about the LTC, recognising the importance of understanding patients’ pre-existing knowledge and beliefs about their LTC; (2) psychological strategies to support adjustment to life with a LTC; (3) strategies specifically to support adherence to treatments; (4) practical support tailored to the specific LTC, including support around activities of daily living for disabling conditions, action plans in conditions subject to marked exacerbations, intensive disease-specific training to enable self-management of specific clinical tasks; and (5) social support as appropriate. Implementation requires a whole-systems approach which intervenes at the level of the patient, the HCP and the organisation. The health-care organisation is responsible for providing the means (both training and time/material resources) to enable HCPs to implement, and patients to benefit from, self-management support, regularly evaluating self-management processes and clinical outcomes. More widely there is a societal need to address public understanding of LTCs. The lack of public story for many conditions impacted on patient help-seeking behaviour and public perceptions of need. Conclusions: Supporting self-management is inseparable from the high-quality care for LTCs. Commissioners and health-care providers should promote a culture of actively supporting self-management as a normal, expected, monitored and rewarded aspect of care. Further research is needed to understand how health service managers and staff can achieve this culture change in their health-care organisations. Study registration: This study is registered as PROSPERO CRD42012002898. Funding: The National Institute for Health Research Health Services and Delivery Research programme