| 1. |
- 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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| 2. |
- 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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| 3. |
- Clauson, Per
(författare)
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Secondary drug failure in non insulin dependent diabetes : on causes and aspects of treatment
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non Insulin Dependent Diabetes (NIDDM) represents a major health problem with increased risk of atherosclerotic disease and early death. The grave consequences of NIDDM are partly due to inadequate and insufficient treatment. The purpose of the present study was to study the causes of treatment failure and evaluate new strategies of treatment. The main aims were 1) to study the prevalence of secondary failure (to sulphonylurea drugs) in an area-based NIDDM population (where diabetes of autoimmune origin had been excluded) and the relationship of secondary failure to pancreatic beta-cell function; 2) to study reversibility of decreased beta-cell function by short term correction of hyperglycemia; 3) to evaluate a combination treatment with sulphonylurea and insulin versus insulin alone; 4) to study insulin absorption kinetics in NIDDM patients. The results of this thesis indicate 1) that diabetes duration associates with deterioration of metabolic control and a decrease in endogenous insulin secretion; 2) that short term correction of hyperglycemia improves insulin secretion to a variable extent; 3) that a combination of daytime sulphonylurea and bedtime insulin in secondary failure in NIDDM is as efficient as intensive insulin treatment in improving metabolic control. One advantage of the combination treatment is that it leads to a lesser degree of weight gain after one year compared to intensive insulin treatment; 4) that the absorption rate of rapid acting insulin in NIDDM subjects is decreased between 15 and 45% compared to insulin dependent diabetes mellitus (IDDM) patients. Altogether, the study shows that NIDDM is a progressive disease using the present therapeutic strategy. New treatment alternatives are needed as well as better use of existing alternatives.
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| 4. |
- Petersen, AH, et al.
(författare)
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The effect of exercise on the absorption of inhaled human insulin in healthy volunteers
- 2008
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 65:2, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- What is already known about this subject * Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans. What this paper adds * This report is the first to investigate the effect of exercise on the absorption of inhaled insulin. * In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via a nebulizer and followed in random order by either 1) no exercise (NOEX), 2) 30 min exercise starting immediately after dosing (EX0), or 3) 30 min exercise starting 30 min after dosing (EX30). The study was carried out as a 10 h euglycaemic glucose clamp (90 mg dl(-1) (5.0 mmol l(-1))). Results The absorption of insulin over the first 2 h after start of exercise was 16% increased for EX0 (ratio (95%CI) 1.16 (1.04, 1.30), P = 0.01) and 20% increased for EX30 (1.20 (1.05, 1.36), P < 0.01), both compared with NOEX; the overall insulin absorption during 6 h and 10 h after dosing was not influenced by exercise. The maximum insulin concentration (C(max)) increased by 32% for EX0 and 35% for EX30 (both P < 0.01) compared with NOEX, while the time to C(max) was 31 min faster for EX0 (P < 0.01), but not significantly different after EX30, compared with NOEX. Conclusions A significant and clinically relevant increase of insulin absorption over the first 2 h after the beginning of exercise was observed. Until data from studies using the specific insulin inhalers exists, patients using inhaled insulin should be made aware of a potential increased absorption and higher concentration of insulin in connection with exercise.
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