| 1. |
- Ahren, Bo, et al.
(författare)
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Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes : The adjunct two randomized trial
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:10, s. 1693-1701
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c ) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6mmol/mol]; 1.2mg: -0.22% [2.4mmol/mol]; 0.6 mg: -0.23% [2.5mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2mg vs. placebo and of hyperglycemia with ketosis >1.5mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
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| 2. |
- Petersen, Astrid H., et al.
(författare)
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The effect of exercise on the absorption of inhaled human insulin via the AERx insulin diabetes management system in people with type 1 diabetes
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:10, s. 2571-2576
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - This study investigated the effect of moderate exercise on the absorption of inhaled insulin via the AERx insulin diabetes management system (iDMS). RESEARCH DESIGN AND METHODS - in this randomized, open-label, four-period crossover, glucose clamp study 23 nonsmoking subjects with type I diabetes received a dose of 0.19 units/kg inhaled human insulin followed in random order by either 1) no exercise (NOEX group) or 30 min exercise starting, 2) 30 min after dosing (EX30), 3) 120 min after dosing (EX120), or 4) 240 min after dosing (EX240). RESULTS - Exercise changed the shape of the free plasma insulin curves, but compared with the NOEX group the area under the curve for free plasma insulin (AUC(ins)) for the first 2 h after the start of exercise was unchanged for EX30 and EX240, while it was 15% decreased for EX120 (P < 0.01). The overall insulin absorption during 6 and 10 h after dosing was 13% decreased for EX30 (P < 0.005), 11% decreased for EX120 (P < 0.01), and unchanged for EX240. Exercise.), while the time to C-max was 22 min did not influence the maximum insulin concentration (C-max) earlier for EX30 (P = 0.04). The AUC for the glucose infusion rate (AUC(GIR)) for 2 h after the start of exercise increased by 58% for EX30, 45% for EX120, and 71% for EX240 (all P < 0.02) compared with the NOEX group. CONCLUSIONS - Thirty minutes of moderate exercise led to unchanged or decreased absorption of inhaled insulin via AERx iDMS and faster C-max for early exercise. Thus, patients using AERx iDMS can adjust insulin dose as usual independent of time of exercise, but they should be aware of the faster effect if exercising early after dosing.
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| 3. |
- Petersen, Astrid H., et al.
(författare)
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The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma
- 2010
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 69:3, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- center dot People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects. center dot In people with moderate asthma, the administration of a bronchodilator before inhalation of insulin has been shown to lead to increased uptake of inhaled insulin compared with no prior administration of bronchodilator. WHAT THIS STUDY ADDS center dot This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin. center dot This study illustrates that due to the effect of terbutaline on glucose metabolism, the effect of insulin on plasma glucose is complex when terbutaline is administered concomitantly. AIM To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids. METHODS A single-centre, randomized, open-label, two-period cross-over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n = 25) or without reversible bronchoconstriction (Rev-; n = 16). A dose of 0.10 U kg-1 inhaled human insulin was administered on each dosing day with or without prior administration of the bronchodilator terbutaline (in random order). RESULTS Prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the Rev+ group compared with no prior administration of bronchodilator [ratio (95% confidence interval) 1.44 (1.13, 1.82), P = 0.004], whereas no effect was seen for the Rev- or the whole group. The maximum insulin concentration (C-max) increased by 34% for the Rev+ group (P = 0.018) and 17% for the whole group (P = 0.046), whereas no significant effect of prior terbutaline administration was seen for Rev-. The time to C-max was not significantly different for the Rev+ group, whereas it was approximately 30% longer after bronchodilator administration for the Rev- group (P = 0.044) and the whole group (P = 0.032). CONCLUSIONS In people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be detected.
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| 4. |
- Eisenberg, Tobias, et al.
(författare)
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Cardioprotection and lifespan extension by the natural polyamine spermidine
- 2016
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 22:12, s. 1428-1438
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.
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| 5. |
- Petersen, Astrid H, et al.
(författare)
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The impact of large tidal volume ventilation on the absorption of inhaled insulin in rabbits.
- 2007
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 1879-0720 .- 0928-0987. ; 30:3-4, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that ventilation patterns affect absorption of inhaled compounds. Thus, the aim of this study was to investigate the effect of large tidal volume ventilation (LTVV) on the absorption of inhaled insulin in rabbits. Mechanically ventilated rabbits were given human insulin via a nebuliser system, and plasma insulin was measured for the following 120 min. Ventilation was adjusted to (1) normal tidal volume ventilation (NTVV) for the entire period after dosing (NTVV group), to (2) LTVV for the entire period after dosing (LTVV group), to (3) NTVV except for 15 min LTVV immediately after dosing (Early LTVV group), or to (4) NTVV except for 15 min LTVV starting at 60 min after dosing (late LTVV group). Insulin absorption (AUC(ins(0-120min))) was increased by 149% for the LTVV group compared to NTVV group (p < 0.01) with increased maximal insulin concentration (106%, p = 0.03). The Early LTVV group showed a changed absorption profile. For the late LTVV group an increase in insulin levels was observed after the LTVV period (not significant compared to the NTVV group). These data could potentially have implications for patients using inhaled insulin in situations where a change in breathing pattern is seen, such as exercise.
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| 6. |
- Pieber, Simone M., et al.
(författare)
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Analysis of regional CO2contributions at the high Alpine observatory Jungfraujoch by means of atmospheric transport simulations and δ13C
- 2022
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:16, s. 10721-10749
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated the regional contributions of carbon dioxide (CO2) at the location of the high Alpine observatory Jungfraujoch (JFJ, Switzerland, 3580ĝ€¯mĝ€¯a.s.l.). To this purpose, we combined receptor-oriented atmospheric transport simulations for CO2 concentration in the period 2009-2017 with stable carbon isotope (δ13C-CO2) information. We applied two Lagrangian particle dispersion models driven by output from two different numerical weather prediction systems (FLEXPART-COSMO and STILT-ECMWF) in order to simulate CO2 concentration at JFJ based on regional CO2 fluxes, to estimate atmospheric δ13C-CO2, and to obtain model-based estimates of the mixed source signatures (δ13Cm). Anthropogenic fluxes were taken from a fuel-type-specific version of the EDGAR v4.3 inventory, while ecosystem fluxes were based on the Vegetation Photosynthesis and Respiration Model (VPRM). The simulations of CO2, δ13C-CO2, and δ13Cm were then compared to observations performed by quantum cascade laser absorption spectroscopy. The models captured around 40ĝ€¯% of the regional CO2 variability above or below the large-scale background and up to 35ĝ€¯% of the regional variability in δ13C-CO2. This is according to expectations considering the complex Alpine topography, the low intensity of regional signals at JFJ, and the challenging measurements. Best agreement between simulations and observations in terms of short-term variability and intensity of the signals for CO2 and δ13C-CO2 was found between late autumn and early spring. The agreement was inferior in the early autumn periods and during summer. This may be associated with the atmospheric transport representation in the models. In addition, the net ecosystem exchange fluxes are a possible source of error, either through inaccuracies in their representation in VPRM for the (Alpine) vegetation or through a day (uptake) vs. night (respiration) transport discrimination to JFJ. Furthermore, the simulations suggest that JFJ is subject to relatively small regional anthropogenic contributions due to its remote location (elevated and far from major anthropogenic sources) and the limited planetary boundary layer influence during winter. Instead, the station is primarily exposed to summertime ecosystem CO2 contributions, which are dominated by rather nearby sources (within 100ĝ€¯km). Even during winter, simulated gross ecosystem respiration accounted for approximately 50ĝ€¯% of all contributions to the CO2 concentrations above the large-scale background. The model-based monthly mean δ13Cm ranged from -ĝ€¯22ĝ€¯‰ in winter to -ĝ€¯28ĝ€¯‰ in summer and reached the most depleted values of -ĝ€¯35ĝ€¯‰ at higher fractions of natural gas combustion, as well as the most enriched values of -ĝ€¯17ĝ€¯‰ to -ĝ€¯12ĝ€¯‰ when impacted by cement production emissions. Observation-based δ13Cm values were derived independently from the simulations by a moving Keeling-plot approach. While model-based estimates spread in a narrow range, observation-based δ13Cm values exhibited a larger scatter and were limited to a smaller number of data points due to the stringent analysis prerequisites.
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| 7. |
- Wollmer, Per, et al.
(författare)
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Delivering needle-free insulin using AERx (R) iDMS (Insulin Diabetes Management System) technology
- 2007
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 9, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- Background and Methods: Inhaled insulin has recently emerged as an alternative to subcutaneous insulin administration. One inhaled insulin device, AERx (R) (a registered trademark of Aradigm Corp., Hayward, CA, or its affiliates in the United States and other countries) insulin diabetes management system (iDMS) (Novo Nordisk A/S, Bagsvoerd, Denmark), uses a unique liquid human insulin strip to deliver an aerosol of insulin to the lungs. AERx iDMS enables 1-unit increment dosing, and the device ensures that the insulin dose is released at the optimal point of inhalation for delivery to the lungs. Results: Compared with subcutaneous human insulin, the pharmacokinetic and pharmacodynamic profile of inhaled insulin with AERx iDMS is similar, but with a more rapid onset of action. Data from these pharmacokinetic studies have also demonstrated that inhaled insulin dosing with AERx iDMS is as consistent and reproducible as subcutaneous human insulin. Conclusions: In individuals with diabetes prandial inhaled insulin with AERx iDMS is as effective and well tolerated as subcutaneous prandial human insulin or insulin aspart in terms of glycemic control and overall hypoglycemia. No major safety concerns have been raised with respect to pulmonary function tests. Other clinical studies using AERx iDMS in special populations, such as smokers, people with asthma, or people suffering from upper respiratory tract infections, have provided important information regarding the use of inhaled insulin in these circumstances. Overall, pulmonary insulin delivery with the AERx iDMS device appears to be a promising safe and efficacious alternative to subcutaneous insulin injections.
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