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Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury.
Zhao, M, Sun, S, Huang, Z, Wang, T, Tang, H
Clinical journal of the American Society of Nephrology : CJASN. 2020;(1):70-78
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Abstract
BACKGROUND AND OBJECTIVES Little is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials. RESULTS In the 18 trials with a total of 2051 AKI events (range: 1-300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis. CONCLUSIONS Current evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.
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Comparison of High-Intensity Interval Training and Moderate-to-Vigorous Continuous Training for Cardiometabolic Health and Exercise Enjoyment in Obese Young Women: A Randomized Controlled Trial.
Kong, Z, Fan, X, Sun, S, Song, L, Shi, Q, Nie, J
PloS one. 2016;(7):e0158589
Abstract
OBJECTIVE The aim of this study was to compare the effects of 5-week high-intensity interval training (HIIT) and moderate-to-vigorous intensity continuous training (MVCT) on cardiometabolic health outcomes and enjoyment of exercise in obese young women. METHODS A randomized controlled experiment was conducted that involved thirty-one obese females (age range of 18-30) randomly assigned to either HIIT or MVCT five-week training programs. Participants in HIIT condition performed 20 min of repeated 8 s cycling interspersed with 12 s rest intervals, and those in MVCT condition cycled continuously for 40 min at 60-80% of peak oxygen consumption ([Formula: see text]O2peak), both for four days in a week. Outcomes such as [Formula: see text]O2peak, body composition estimated by bioimpedance analysis, blood lipids, and serum sexual hormones were measured at pre-and post-training. The scores of Physical Activity Enjoyment Scale (PAES) were collected during the intervention. RESULTS After training, [Formula: see text]O2peak increased significantly for both training programs (9.1% in HIIT and 10.3% in MVCT) (p = 0.010, η2 = 0.41). Although MVCT group had a significant reduction in total body weight (TBW, -1.8%, p = 0.034), fat mass (FM, - 4.7%, p = 0.002) and percentage body fat (PBF, -2.9%, p = 0.016), there were no significant between-group differences in the change of the pre- and post-measures of these variables. The HIIT group had a higher score on PAES than the MVCT group during the intervention. For both conditions, exercise training led to a decline in resting testosterone and estradiol levels, but had no significant effect on blood lipids. CONCLUSION Both HIIT and MVCT are effective in improving cardiorespiratory fitness and in reducing sexual hormones in obese young women; however, HIIT is a more enjoyable and time-efficient strategy. The mild-HIIT protocol seems to be useful for at least maintaining the body weight among sedentary individuals.
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Collagen Type III and VI Turnover in Response to Long-Term Immobilization.
Sun, S, Henriksen, K, Karsdal, MA, Byrjalsen, I, Rittweger, J, Armbrecht, G, Belavy, DL, Felsenberg, D, Nedergaard, AF
PloS one. 2015;(12):e0144525
Abstract
BACKGROUND Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. METHODS In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. RESULTS Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. CONCLUSION The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.
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Salt loading and potassium supplementation: effects on ambulatory arterial stiffness index and endothelin-1 levels in normotensive and mild hypertensive patients.
Liu, Z, Peng, J, Lu, F, Zhao, Y, Wang, S, Sun, S, Zhang, H, Diao, Y
Journal of clinical hypertension (Greenwich, Conn.). 2013;(7):485-96
Abstract
The authors investigated effects of excessive salt intake and potassium supplementation on ambulatory arterial stiffness index (AASI) and endothelin-1 (ET-1) in salt-sensitive and non-salt-sensitive individuals. AASI and symmetric AASI (s-AASI) were used as indicators of arterial stiffness. Plasma ET-1 levels were used as an index of endothelial function. Chronic salt-loading and potassium supplementation were studied in 155 normotensive to mild hypertensive patients from rural northern China. After 3 days of baseline investigation, participants were maintained sequentially for 7 days each on diets of low salt (51.3 mmol/d), high salt (307.7 mmol/d), and high salt+potassium (60 mmol/d). Ambulatory 24-hour blood pressure (BP) and plasma ET-1 were measured at baseline and on the last 2 days of each intervention. High-salt intervention significantly increased BP, AASI, s-AASI (all P<.001); potassium supplementation reversed increased plasma ET-1 levels. High-salt-induced changes in BP, s-AASI, and plasma ET-1 were greater in salt-sensitive individuals. Potassium supplementation decreased systolic BP and ET-1 to a significantly greater extent in salt-sensitive vs non-salt-sensitive individuals (P<.001). Significant correlations were identified between s-AASI and ET-1 change ratios in response to both high-salt intervention and potassium supplementation (P<.001). Reducing dietary salt and increasing daily potassium improves arterial compliance and ameliorates endothelial dysfunction.
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A randomized controlled study comparing once-weekly to every-2-week and every-4-week dosing of epoetin alfa in CKD patients with anemia.
Pergola, PE, Gartenberg, G, Fu, M, Sun, S, Wolfson, M, Bowers, P
Clinical journal of the American Society of Nephrology : CJASN. 2010;(4):598-606
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Abstract
BACKGROUND AND OBJECTIVES Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment. RESULTS Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects. CONCLUSIONS Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.