Aims
To investigate the effects of a single dose of 1.2 mg liraglutide, a once‐daily glucagon‐like peptide‐1 (GLP‐1) receptor agonist, on key renal variables in patients with type 2 diabetes.
Methods
...The study was a placebo‐controlled, double‐blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included 51Cr‐EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI‐based renal blood flow (RBF), tissue perfusion and oxygenation.
Results
Liraglutide had no effect on GFR 95% confidence interval (CI) −6.8 to 3.6 ml/min/1.73 m2 or on RBF (95% CI −39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin‐angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines.
Conclusions
Short‐term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short‐term as opposed to long‐term treatment. Catecholamine levels were unchanged and the results did not support a GLP‐1–ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP‐1 receptor agonists.
High altitude (HA) exposure facilitates a rapid contraction of plasma volume (PV) and a slower occurring expansion of hemoglobin mass (Hbmass). The kinetics of the Hbmass expansion has never been ...examined by multiple repeated measurements, and this was our primary study aim. The second aim was to investigate the mechanisms mediating the PV contraction. Nine healthy, normally trained sea-level (SL) residents (8 males, 1 female) sojourned for 28 days at 3,454 m. Hbmass was measured and PV was estimated by carbon monoxide rebreathing at SL, on every 4th day at HA, and 1 and 2 wk upon return to SL. Four weeks at HA increased Hbmass by 5.26% (range 2.5-11.1%; P < 0.001). The individual Hbmass increases commenced with up to 12 days of delay and reached a maximal rate of 4.04 ± 1.02 g/day after 14.9 ± 5.2 days. The probability for Hbmass to plateau increased steeply after 20-24 days. Upon return to SL Hbmass decayed by -2.46 ± 2.3 g/day, reaching values similar to baseline after 2 wk. PV, aldosterone concentration, and renin activity were reduced at HA (P < 0.001) while the total circulating protein mass remained unaffected. In summary, the Hbmass response to HA exposure followed a sigmoidal pattern with a delayed onset and a plateau after ∼3 wk. The decay rate of Hbmass upon descent to SL did not indicate major changes in the rate of erythrolysis. Moreover, our data support that PV contraction at HA is regulated by the renin-angiotensin-aldosterone axis and not by changes in oncotic pressure.
Glucagon-like peptide-1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure (SBP). The aim was to investigate the time course of the anti-hypertensive ...effect of liraglutide treatment and potential underlying mechanisms.
We used an open-label, single-centre trial; 31 participants with Type 2 diabetes and hypertension completed the study. All participants were treated with liraglutide escalated to a maximum dose of 1.8 mg/day for 7 weeks, followed by a 21-day washout period. The primary outcome was a change in 24-h SBP.
Twenty-four-h SBP increased by 10 mmHg on day 3 (P = 0.008) and 7 mmHg on day 7 (P = 0.033, 0.6 mg/day). On day 29, (1.8 mg/day), 24-h SBP was 7 mmHg lower compared with baseline (P = 0.11). Following the treatment period (day 49) and after washout (day 70), 24-h BP was equivalent to baseline. In addition, extracellular volume (ECV) was reduced by 2.0 l 95% confidence interval (CI) = 1.0-3.1 l, P < 0.001 and midregional-pro-atrial natriuretic peptide (MR-proANP) was reduced by 20% (95% CI = 12-28%, P < 0.001). Also, urinary albumin excretion declined by 30% (95% CI = 12-44%, P = 0.003), GFR by 11 ml/min/1.73 m(2) (95% CI = 7.2-14.4 ml/min/1.73 m(2) , P < 0.001) and fractional albumin excretion by 29% (95% CI = 3-48%, P = 0.032).
Liraglutide treatment was associated with an initial increase in 24-h SBP, followed by a 7 mmHg reduction after escalation to 1.8 mg/day. This effect subsided after 4 weeks of maximum dose. Reductions in ECV and MR-proANP may explain the anti-hypertensive potential. Liraglutide treatment was associated with reversible reductions in albuminuria and GFR, which has to be confirmed in randomized trials.
To provide more information about whether sharks benefit from no-take marine reserves, we quantified the relative abundance and biomass of reef sharks inside and outside of Namena, Fiji’s largest ...reserve (60.6 km
2
). Using stereo baited remote underwater video systems (stereo-BRUVs), we found that the abundance and biomass of sharks was approximately two and four times greater in shallow and deep locations, respectively, within the Namena reserve compared to adjacent fished areas. The greater abundance and biomass of reef sharks inside Namena is likely a result of greater prey availability rather than protection from fishing. This study demonstrates that marine reserves can benefit sharks.
The time course of plasma volume (PV) reduction following an increased training load period is unknown and was investigated. The accompanying fluctuations in Hb and OFF‐hr score were analyzed in the ...Athlete Biological Passport. Further, whether fluctuations in plasma albumin, soluble transferrin receptors (sTfR), and pro‐atrial natriuretic peptide (proANP) concentrations correlate with PV fluctuations was investigated. Eleven high‐level competitive cyclists were investigated for 3 weeks. After initial measurements in week 1, training load was increased ~250% in week 2 followed by a reversion to baseline training load in week 3. PV and hematological variables were determined frequently during all weeks. The higher training load in week 2 increased (P<.001) PV 10%, while Hb and OFF‐hr score decreased ~6% (P<.01) and ~16% (P<.001), respectively. PV and Hb returned to baseline within 2 and 4 days after week 2, respectively, while OFF‐hr score remained reduced for 6 days. Further, one and three atypical blood profiles of the ABP occurred during weeks 2 and 3, respectively. Individual changes in albumin, sTfR, and proANP only correlated weakly (R2<.20) with PV fluctuations. In conclusion, PV and Hb fluctuations caused by an elevated training load period were reverted within 2 and 4 days after returning to baseline training load, respectively, while OFF‐hr remained altered for 6 days. Furthermore, some atypical blood profiles were induced during and subsequent to the increased training load, demonstrating the importance of knowledge on naturally occurring hematological fluctuations. Finally, concentrations of albumin, sTfR, and proANP could not explain PV fluctuations.
To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy.
In ...a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention. Glomerular filtration rates were estimated and measured ((51) Cr-EDTA plasma clearance glomerular filtration rate) after each intervention.
The mean (sd) age of the participants was 57 (9) years, the baseline geometric mean (95% CI) urinary albumin excretion rate was 148 (85-259) mg/24 h, the mean (sd) HbA1c was 70 (9) mmol/mol 8.6 (3)%, the mean (sd) estimated glomerular filtration rate was 47 (15) ml/min/1.73 m(2) and the mean (sd) 24-h blood pressure was 135 (17)/74 (10) mmHg. Compared with placebo therapy, vitamin D analogue therapy had no significant effect on plasma N-terminal probrain natriuretic peptide concentration (P = 0.6), urinary albumin excretion rate was reduced by 18% (P = 0.03 for comparison), estimated glomerular filtration rate was reduced by 5 ml/min/1.73 m(2) (P < 0.001) and measured glomerular filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2).
Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered.
Coronary allograft vasculopathy is a well‐known long‐term complication after cardiac transplantation. Endothelial dysfunction is involved and may be prevented by aerobic exercise. The purpose of this ...study was to examine whether high intensity aerobic exercise improves peak oxygen uptake (VO2 peak) and endothelial function in heart transplant (HT) recipients. Twenty‐seven long‐term HT recipients were randomized to either 8‐weeks high intensity aerobic exercise or no training. Flow mediated dilation of the brachial artery (FMD) was measured by ultrasound and VO2 peak by the analysis of expired air. Blood pressure and biomarkers were measured before and after 8 weeks. VO2 peak increased significantly in the exercise group (VO2 peak 23.9 ± 1.79 to 28.3 ± 1.63 mL/kg/min compared to controls (VO2 peak 24.6 ± 1.38 to 23.4 ± 1.58, p < 0.001 exercise vs. control).FMD increased in the exercise group compared to controls (8.3 ± 1.1% to 11.4 ± 1.2% vs. 5.6 ± 1.0% to 5.3 ± 1.7%, p = 0.024). No increase in nitroglycerin‐induced vasodilation was observed. Systolic blood pressure fell in the exercise group (142 ±4.2 mmHg to127 ± 3.4 mmHg, p = 0.01) and was unchanged in controls (141 ± 4.2 mmHg to 142 ±6.4 mmHg, NS). High intensity aerobic exercise reduces systolic blood pressure and improves endothelial function in HT recipients.
Long‐term heart transplant recipients who perform two months of high intensity exercise training experience increased peak oxygen uptake and endothelial function.
Aims
Erythropoiesis is a tightly controlled biological event, but its regulation under non‐hypoxic conditions, however, remains unresolved. We examined whether acute changes in central venous blood ...pressure (CVP) elicited by whole‐body tilting affect erythropoietin (EPO) concentration according to volume‐regulating hormones.
Methods
Plasma EPO, angiotensin II (ANGII), aldosterone, pro‐atrial natriuretic peptide (proANP) and copeptin concentrations were measured at supine rest and up to 3 h during 30° head‐up (HUT) and head‐down tilt (HDT) in ten healthy male volunteers. Plasma albumin concentration was used to correct for changes in plasma volume and CVP was estimated through the internal jugular vein (IJV) aspect ratio with ultrasonography.
Results
From supine rest, the IJV aspect ratio was decreased and increased throughout HUT and HDT respectively. Plasma EPO concentration increased during HUT (13%; P = 0.001, P for linear component = 0.017), independent of changes in albumin concentration. Moreover, ANGII and copeptin concentrations increased during HUT, while proANP decreased. The increase in EPO concentration during HUT disappeared when adjusted for changes in copeptin. During HDT, EPO, ANGII and copeptin concentrations remained unaffected while proANP increased. In regression analyses, EPO was positively associated with copeptin (β = 0.55; 95% CI = 0.18, 0.93; P = 0.004) irrespective of changes in other hormones and albumin concentration.
Conclusion
Reduction in CVP prompts an increase in plasma EPO concentration independent of hemoconcentration and hence suggests CVP per se as an acute regulator of EPO synthesis. This effect may be explained by changes in volume‐regulating hormones.
Periodically harvested closures (PHCs) have become the most common form of spatial management in Melanesia. Despite their popularity, their effectiveness to sustain local fish stocks remains largely ...unknown. Here we test the ability of non-destructive sampling techniques to detect the impacts of fishing in a PHC where harvest catch data provide an impact of known magnitude. We compared the ability of three commonly used techniques (underwater visual census, UVC; diver operated stereo-video, stereo-DOV; and baited remote underwater stereo-video, stereo-BRUV) to detect the impact of a harvest on fish assemblages within a PHC in Fiji. The technique stereo-DOV recorded a significant decrease in harvested individuals at both the assemblage and species level (primarily herbivorous species). The technique stereo-BRUV also recorded an impact at the assemblage level, but only for carnivorous fishes, which were less numerous in the catch. UVC did not detect an impact of the harvest at the assemblage or species level. We conclude that stereo-DOV is the most suitable technique for detecting the impacts of harvests and monitoring the effectiveness of PHCs as a fisheries management strategy, especially in areas where herbivorous fish are targeted. However, stereo-BRUV may be more appropriate where strong gradients in the abundance of carnivorous species or behavioural responses to divers are expected.
•Periodically harvested closures (PHCs) can be used to compare methods.•Diver operated video accurately detects the impacts of fishing during harvests.•Baited video is useful for carnivorous species and avoiding behavioural bias.•Underwater visual census did not detect the impacts of fishing during harvests.•Diver operated video should be used to assess PHCs as a management strategy.
Protection from fishing generally results in an increase in the abundance and biomass of species targeted by fisheries within marine reserve boundaries. Natural refuges such as depth may also protect ...such species, yet few studies in the Indo Pacific have investigated the effects of depth concomitant with marine reserves. We studied the effects of artisanal fishing and depth on reef fish assemblages in the Kubulau District of Vanua Levu Island, Fiji, using baited remote underwater stereo-video systems. Video samples were collected from shallow (5–8 m) and deep (25–30 m) sites inside and outside of a large old marine reserve (60.6 km
2
, 13 years old) and a small new marine reserve (4.25 km
2
, 4 years old). Species richness tended to be greater in the shallow waters of the large old reserve when compared to fished areas. In the deeper waters, species richness appeared to be comparable. The difference in shallow waters was driven by species targeted by fisheries, indicative of a depth refuge effect. In contrast, differences in the abundance composition of the fish assemblage existed between protected and fished areas for deep sites, but not shallow. Fish species targeted by local fisheries were 89% more abundant inside the large old reserve than surrounding fished areas, while non-targeted species were comparable. We observed no difference in the species richness or abundance of species targeted by fisheries inside and outside of the small new reserve. This study suggests that artisanal fishing impacts on the abundance and species richness of coral reef fish assemblages and effects of protection are more apparent with large reserves that have been established for a long period of time. Observed effects of protection also vary with depth, highlighting the importance of explicitly incorporating multiple depth strata in studies of marine reserves.
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