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| 2. |
- Rosenstock, Julio, et al.
(författare)
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Advancing Basal Insulin Replacement in Type 2 Diabetes Inadequately Controlled With Insulin Glargine Plus Oral Agents: A Comparison of Adding Albiglutide, a Weekly GLP-1 Receptor Agonist, Versus Thrice-Daily Prandial Insulin Lispro.
- 2014
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 37:8, s. 2317-2325
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Tidskriftsartikel (refereegranskat)abstract
- GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine.RESEARCH DESIGN AND METHODS: Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26.RESULTS: At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).CONCLUSIONS: Weekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.
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| 4. |
- de Witte, L. C., et al.
(författare)
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Nitrogen deposition changes ectomycorrhizal communities in Swiss beech forests
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 605-606, s. 1083-1096
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric pollution has implications for the health and diversity of temperate forests covering large parts of central Europe. Long-term elevated anthropogenic deposition of nitrogen (N) is driving forest ecosystems from the limitation by N to other nutrients and is found to affect tree health and ectomycorrhizal fungi (EMF), which most trees depend on for nutrient uptake. However, the consequence of EMF community changes for trees remains unclear. Therefore, we investigated changes in EMF communities on root tips and in soil of beech forests along a N deposition gradient ranging between 16 and 33 kg N ha− 1 a− 1, where high N deposition was found to negatively affect tree growth and nutrient levels. The most important factors significantly explaining variation in root tip and mycelium EMF community composition in both root tips and mesh bags were increased N deposition, base saturation, growing season temperature and precipitation. With increasing N deposition, fine root length, EMF root colonization, EMF diversity on root tips and in soil, and production of extramatrical mycelium decreased significantly. Foliar P and potassium (K) were positively associated with increasing EMF diversity and we found EMF community composition to be associated with foliar P and N:P ratio. The decrease in root colonization, mesh bag ingrowth and abundance of the important species Cenococcum geophilum as well as high biomass species with increasing N availability clearly indicate repercussions for belowground carbon allocation, although some indicator species for high N deposition and low foliar P have long mycelia and may reflect a potential optimization of host P uptake. Our study supports the hypothesis that the decrease in nutrient uptake in beech forests across Europe is related to changes in EMF communities and suggests that continued high N deposition changes soil carbon and nutrient cycles, thereby affecting forest ecosystem health.
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| 5. |
- Jendle, Johan, 1963-, et al.
(författare)
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Better glycaemic control and less weight gain with once weekly dulaglutide vs bedtime insulin glargine, both combined with thrice daily lispro, in type 2 diabetes (AWARD-4)
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:Suppl 1, s. S23-S24
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: This 52 week, parallel-arm, open-label, phase 3 study compared two doses of the once weekly GLP-1 receptor agonist dulaglutide (DU) versus bedtime insulin glargine, all combined with pre-meal insulin lispro with or without metformin, in patients with type 2 diabetes mellitus inadequately controlled on conventional insulin therapy. Insulin glargine and insulin lispro were titrated to attempt to reach glycaemic targets.Materials and methods: Patients (N = 884; mean baseline characteristics: age 59.4 years; duration of diabetes 12.7 years; HbA1c 8.5%; body weight 91.1 kg; BMI 32.5 kg/m2; total daily insulin dose 56 U) were randomised (1:1:1) to once weekly DU 1.5 mg, DU 0.75 mg, or bedtime insulin glargine titrated-to-target. The primary objective was to compare the change in HbA1c from baseline of DU 1.5 mg with insulin glargine at 26 weeks for noninferiority (margin 0.4%) and if met, then superiority was tested.Results: At 26 and 52 weeks, both DU doses were statistically superior to insulin glargine for HbA1c change from baseline. Insulin glargine was associ-ated with greater fasting serum glucose reduction compared with both DU doses. The mean prandial insulin doses at 26 weeks were 93 U for DU 1.5 mg, 97 U for DU 0.75 mg, and 68 U for insulin glargine. The insulin glargine dose was 65 U. Similar insulin doses were observed at 52 weeks. Body weight decreased with DU 1.5 mg and increased with DU 0.75 mg and insulin glar-gine at 52 weeks. The rate of documented symptomatic hypoglycaemia (≤3.9 mmol/L) at 52 weeks was 31.0, 35.0,and 39.9 events/patient/year for DU 1.5 mg, DU 0.75 mg, and insulin glargine, respectively. The number of severe hypoglycaemia events was 11 for DU 1.5 mg, 15 for DU 0.75 mg, and 22 for insulin glargine. Nausea, diarrhoea, and vomiting were more common with DU 1.5 mg (25.8%, 16.6%, and 12.2%, respectively) and DU 0.75 mg (17.7%, 15.7%, and 10.6%) versus insulin glargine (3.4%, 6.1%, and 1.7%).Conclusion: DU compared to insulin glargine, both combined with insu-lin lispro, resulted in better glycaemic control, less body weight gain, no in-creased risk of hypoglycaemia, and more common reporting of gastrointes-tinal adverse events.
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| 9. |
- Rubino, Domenica, et al.
(författare)
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Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity The STEP 4 Randomized Clinical Trial
- 2021
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 325:14, s. 1414-1425
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. OBJECTIVE To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or 7 , -27 with >1 weight-related comorbidity) and without diabetes. INTERVENTIONS A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). RESULTS Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741(92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3,3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
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| 10. |
- Sheldrake, Merlin, et al.
(författare)
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A phosphorus threshold for mycoheterotrophic plants in tropical forests
- 2017
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1848
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Tidskriftsartikel (refereegranskat)abstract
- The majority of terrestrial plants associate with arbuscular mycorrhizal (AM) fungi, which typically facilitate the uptake of limiting mineral nutrients by plants in exchange for plant carbon. However, hundreds of non-photosynthetic plant species—mycoheterotrophs—depend entirely on AM fungi for carbon as well as mineral nutrition. Mycoheterotrophs can provide insight into the operation and regulation of AM fungal relationships, but little is known about the factors, fungal or otherwise, that affect mycoheterotroph abundance and distribution. In a lowland tropical forest in Panama, we conducted the first systematic investigation into the influence of abiotic factors on the abundance and distribution of mycoheterotrophs, to ask whether the availability of nitrogen and phosphorus altered the occurrence of mycoheterotrophs and their AM fungal partners. Across a natural fertility gradient spanning the isthmus of Panama, and also in a long-term nutrientaddition experiment, mycoheterotrophs were entirely absent when soil exchangeable phosphate concentrations exceeded 2 mg P kg21. Experimental phosphorus addition reduced the abundance of AM fungi, and also reduced the abundance of the specific AM fungal taxa required by the mycoheterotrophs, suggesting that the phosphorus sensitivity of mycoheterotrophs is underpinned by the phosphorus sensitivity of their AM fungal hosts. The soil phosphorus concentration of 2 mg P kg21 also corresponds to a marked shift in tree community composition and soil phosphatase activity across the fertility gradient, suggesting that our findings have broad ecological significance.
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| 11. |
- Sheldrake, Merlin, et al.
(författare)
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Arbuscular mycorrhizal fungal community composition is altered by long-term litter removal but not litter addition in a lowland tropical forest
- 2017
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 214:1, s. 455-467
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forest productivity is sustained by the cycling of nutrients through decomposing organic matter. Arbuscular mycorrhizal (AM) fungi play a key role in the nutrition of tropical trees, yet there has been little experimental investigation into the role of AM fungi in nutrient cycling via decomposing organic material in tropical forests. We evaluated the responses of AM fungi in a long-term leaf litter addition and removal experiment in a tropical forest in Panama. We described AM fungal communities using 454-pyrosequencing, quantified the proportion of root length colonised by AM fungi using microscopy, and estimated AM fungal biomass using a lipid biomarker. AM fungal community composition was altered by litter removal but not litter addition. Root colonisation was substantially greater in the superficial organic layer compared with the mineral soil. Overall colonisation was lower in the litter removal treatment, which lacked an organic layer. There was no effect of litter manipulation on the concentration of the AM fungal lipid biomarker in the mineral soil. We hypothesise that reductions in organic matter brought about by litter removal may lead to AM fungi obtaining nutrients from recalcitrant organic or mineral sources in the soil, besides increasing fungal competition for progressively limited resources.
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| 12. |
- Sheldrake, Merlin, et al.
(författare)
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Responses of arbuscular mycorrhizal fungi to long-term inorganic and organic nutrient addition in a lowland tropical forest
- 2018
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Ingår i: ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12:10, s. 2433-2445
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Tidskriftsartikel (refereegranskat)abstract
- Improved understanding of the nutritional ecology of arbuscular mycorrhizal (AM) fungi is important in understanding how tropical forests maintain high productivity on low-fertility soils. Relatively little is known about how AM fungi will respond to changes in nutrient inputs in tropical forests, which hampers our ability to assess how forest productivity will be influenced by anthropogenic change. Here we assessed the influence of long-term inorganic and organic nutrient additions and nutrient depletion on AM fungi, using two adjacent experiments in a lowland tropical forest in Panama. We characterised AM fungal communities in soil and roots using 454-pyrosequencing, and quantified AM fungal abundance using microscopy and a lipid biomarker. Phosphorus and nitrogen addition reduced the abundance of AM fungi to a similar extent, but affected community composition in different ways. Nutrient depletion (removal of leaf litter) had a pronounced effect on AM fungal community composition, affecting nearly as many OTUs as phosphorus addition. The addition of nutrients in organic form (leaf litter) had little effect on any AM fungal parameter. Soil AM fungal communities responded more strongly to changes in nutrient availability than communities in roots. This suggests that the ‘dual niches’ of AM fungi in soil versus roots are structured to different degrees by abiotic environmental filters, and biotic filters imposed by the plant host. Our findings indicate that AM fungal communities are fine-tuned to nutrient regimes, and support future studies aiming to link AM fungal community dynamics with ecosystem function.
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