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Frontiers in Endocrinology 2024Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and... (Review)
Review
Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively.
Topics: Humans; Diabetic Retinopathy; Animals; Molecular Targeted Therapy; Cell- and Tissue-Based Therapy; Vascular Endothelial Growth Factor A
PubMed: 38948520
DOI: 10.3389/fendo.2024.1416668 -
Integrative Medicine Research Jun 2024Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes...
BACKGROUND
Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension.
METHODS
Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined.
RESULTS
The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT.
CONCLUSIONS
The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.
PubMed: 38948488
DOI: 10.1016/j.imr.2024.101041 -
Frontiers in Pharmacology 2024Tetrandrine (Tet) is the main pharmacological component of S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive...
INTRODUCTION
Tetrandrine (Tet) is the main pharmacological component of S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses and .
METHODS
The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.
RESULTS
Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.
DISCUSSION
This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.
PubMed: 38948468
DOI: 10.3389/fphar.2024.1387756 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024To investigate the effects of intraoperative intravenous administration of dexmedetomidine (DEX) on the recovery quality of donors undergoing pure laparoscopic donor... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effects of intraoperative intravenous administration of dexmedetomidine (DEX) on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy.
METHODS
A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups, a DEX group ( =28) and a control group ( =28). Donors in the DEX group received DEX infusion at a dose of 1 μg/kg over 15 minutes through a continuous pump, which was followed by DEX at 0.4 μg/(kg·h) until the disconnection of the portal branch. Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group. The primary outcome was the incidence of emergence agitation (EA). The Aono's Four-point Scale (AFPS) score was used to assess EA. The secondary observation indicators included intraoperative anesthesia and surgery conditions, spontaneous respiration recovery time, recovery time, extubation time, scores for the Ramsay Sedation Scale, the incidence of chills, numeric rating scale (NRS) score for pain, and blood pressure and heart rate after extubation.
RESULTS
The incidence of EA was 10.7% and 39.3% in the DEX group and the control group, respectively, and the incidence of EA was significantly lower in the DEX group than that in the control group ( =0.014). The APFS scores after extubation in the DEX group were lower than those in the control group (1 [1, 1] vs. 2 [1, 3], =0.005). Compared to the control group, the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group ( <0.05). During the recovery period, the number of donors requiring additional boluses of analgesia, the blood pressure, and the heart rate were all lower in the DEX group than those in the control group ( <0.05). No significant differences between the two groups were observed in the spontaneous respiration recovery time, recovery time, extubation time, the incidence of chills, NRS score, scores for the Ramsay Sedation Scale, and the length-of-stay in postanesthesia care unit (PACU) ( >0.05).
CONCLUSION
DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.
Topics: Dexmedetomidine; Humans; Hepatectomy; Laparoscopy; Male; Female; Adult; Living Donors; Liver Transplantation; Hypnotics and Sedatives; Anesthesia Recovery Period
PubMed: 38948292
DOI: 10.12182/20240560603 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Prior studies have established a connection between albuminuria and various inflammatory reactions, highlighting that an increase in C-reactive protein by 1 mg/L...
OBJECTIVE
Prior studies have established a connection between albuminuria and various inflammatory reactions, highlighting that an increase in C-reactive protein by 1 mg/L increases the likelihood of albuminuria by 2%. Recent investigations indicate a positive correlation between the systemic immune-inflammation index (SII) and increased urinary protein excretion. In addition, elevated levels of the systemic inflammatory response index (SIRI) also correlate with a higher prevalence of albuminuria. The aggregate index of systemic inflammation (AISI) offers a more comprehensive indicator of inflammation, providing an extensive assessment of systemic inflammatory status compared to SII and SIRI. Yet, the specific relationship between AISI and albuminuria remains unclear. This study aims to explore this association in U.S. adults.
METHODS
We analyzed data from the National Health and Nutrition Examination Survey (NHANES) for 2007-2018, excluding pregnant women and individuals under 18. Cases with missing data on AISI, urinary albumin concentration, and other covariates were also excluded. AISI was computed using the formula: AISI=(platelet count×neutrophil count×monocyte count)/lymphocyte count. Albuminuria was defined as the urinary albumin-to-creatinine ratio exceeding 30 mg/g. Continuous variables were presented in the form of the mean±standard error, and categorical variables in percentages. We utilized weighted -tests and chi-square tests for baseline comparisons. We applied weighted multivariable logistic regression and generalized additive models (GAM) to explore the association between AISI and albuminuria and to assess potential nonlinear relationships.
RESULTS
The study included 32273 participants, with an average age of (46.75±0.24) years old. The cohort comprised 48.73% males and 51.27% females. The prevalence of albuminuria was 9.64%. The average logarithmic value of logAISI was 7.95±0.01, and were categorized into tertiles as follows: Quartile 1 (Q1) (4.94 to 7.49), Q2 (7.49 to 8.29), and Q3 (8.29 to 10.85). As logAISI increased, so did the prevalence of hypertension, diabetes, congestive heart failure, and albuminuria, all showing statistically significant increases (<0.001). Similarly, the use of antihypertensive, lipid-lowering, and hypoglycemic drugs was also more prevalent (<0.001). Statistically significant differences were observed across the three groups concerning age, race and ethnicity, formal education, alcohol consumption, smoking status, systolic and diastolic blood pressures, body mass index, estimated glomerular filtration rate, HbA1c, alanine aminotransferase, aspartate aminotransferase, albumin, creatinine, uric acid, and high-density lipoprotein cholesterol (<0.05). However, no significant differences were noted in the total cholesterol or the sex ratios among the groups. The association between logAISI and albuminuria was assessed using weighted multivariable logistic regression, and the detailed results are presented in Table 2. In model 1, without adjusting for covariates, each unit increase in logAISI was associated with a 32% increase in the risk of albuminuria (odds ratio [OR]=1.32, 95% confidence interval [CI]: 1.27-1.38, <0.001). Model 2 was adjusted for age, gender, race, and education level, and showed a similar trend, with each unit increase in logAISI associated with a 31% increased risk (OR=1.31, 95% CI: 1.26-1.37, <0.001). Model 3, which was further adjusted for all covariates, revealed that each unit increase in logAISI was associated with a 20% increase in the risk of albuminuria (OR=1.20, 95% CI: 1.15-1.26, <0.001). The study also transformed logAISI from a continuous to a categorical variable for analysis. Compared with Q1, the risk of albuminuria in Q3, after adjusting for all covariates, significantly increased (OR=1.37, 95% CI: 1.22-1.55, <0.001). Q2 also demonstrated a higher risk compared with Q1 (OR=1.13, 95% CI: 1.06-1.36, =0.004). The trend test indicated a dose-effect relationship between increasing logAISI and the rising risk of albuminuria. GAM revealed a nonlinear relationship between logAISI and albuminuria, with distinct trends noted between sexes. Segmented regression based on turning points showed significant effects among women, although the slope difference between the segments was not significant. In men, a significant threshold effect was observed; below the logAISI of 7.25, increases in logAISI did not enhance the risk of albuminuria, but above this threshold, the risk significantly increased. As part of a sensitivity analysis, weighted multivariable logistic regression was performed by changing the outcome variable to macroalbuminuria and adjusting for all covariates. The analysis showed that for every unit increase in logAISI, the risk of developing macroalbuminuria increased by 31% (OR=1.31, 95% CI: 1.15-1.49, <0.001). Compared with Q1, the risk of albuminuria in Q3 increased by 69% (OR=1.69, 95% CI: 1.27-2.25, <0.001), and in Q2, it increased by 40% (OR=1.40, 95% CI: 1.03-1.92, =0.030). Subgroup analysis and interaction results showed that the positive association between AISI and proteinuria risk was stronger in men than in women. Similarly, the association was stronger in people with hypertension compared with those with normal blood pressure, and higher in overweight people compared with those of normal weight. Furthermore, smokers and drinkers showed a stronger positive association between AISI and the risk of proteinuria than non-smokers and non-drinkers do. These results suggest that sex, blood pressure, body mass index, smoking, and alcohol consumption interact with AISI to influence the risk of proteinuria.
CONCLUSION
There is a robust positive association between AISI and increased risks of albuminuria in US adults. As logAISI increases, so does the risk of albuminuria. However, further validation of this conclusion through large-scale prospective studies is warranted.
Topics: Humans; Albuminuria; Nutrition Surveys; Cross-Sectional Studies; Inflammation; Female; Male; Adult; Middle Aged; C-Reactive Protein; Platelet Count
PubMed: 38948283
DOI: 10.12182/20240560108 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women...
OBJECTIVE
Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy, revealing a potential association between hyperandrogenism in women and PE. To explore the causal relationship between hyperandrogenism and PE, this study selected total testosterone (TT), bioavailable testosterone (BIOT), and sex hormone binding globulin (SHBG) as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes. Two-sample Mendelian randomization (MR) analyses were used to genetically dissect the causal relationships between the three exposure factors (TT, BIOT, and SHBG) and the outcomes of PE and chronic hypertension with superimposed PE.
METHODS
Two independent genome-wide association study (GWAS) databases were used for the two-sample MR analysis. In the GWAS data of female participants from the UK Biobank cohort, single nucleotide polymorphisms (SNPs) associated with TT, BIOT, and SHBG were analyzed, involving 230454, 188507, and 188908 samples, respectively. GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP, involving 3556 PE cases and 114735 controls, as well as 38 cases of chronic hypertension with superimposed PE and 114735 controls. To meet the assumptions of instrumental relevance and independence in MR analysis, SNPs associated with exposure were identified at the genome-wide level (<5.0×10), and those in linkage disequilibrium interference were excluded based on clustering thresholds of <0.001 and an allele distance greater than 10000 kb. Known confounding factors, including previous PE, chronic kidney disease, chronic hypertension, diabetes, systemic lupus erythematosus, or antiphospholipid syndrome, were also identified and the relevant SNPs were removed. Finally, we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS, integrating exposure and outcome data, and removing palindromic sequences. Five genetic causal analysis methods, including inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method, were used to infer causal relationships. In the IVW, it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect. IVW was consequently used as the primary analysis method in this study. Considering the potential heterogeneity among the instrumental variables, random-effects IVW was used for MR analysis. The results were interpreted using odds ratios (OR) and the corresponding 95% confidence interval (CI) to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE. If the CI did not include 1 and had a value less than 0.05, the difference was considered statistically significant. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Heterogeneity was examined using Cochran's test, and pleiotropy was assessed using MR-Egger intercept analysis. Additionally, leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations. To further validate the findings, MR analyses were performed using the same methods and outcome variables, but with different exposure factors, including waist-to-hip ratio adjusted for BMI (WHRadjBMI) and 25-hydroxyvitamin D levels, with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.
RESULTS
According to the criteria for selecting genetic instrumental variables, 186, 127, and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT, BIOT, and SHBG. MR analysis did not find a causal relationship between the TT, BIOT, and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE. The IVW method predicted that genetically predicted TT (OR [95% CI]=1.018 [0.897-1.156], =0.78), BIOT (OR [95% CI]=1.11 [0.874-1.408], =0.392), and SHBG (OR [95% CI]=0.855 [0.659-1.109], =0.239) were not associated with PE. Similarly, genetically predicted TT (OR [95% CI]=1.222 [0.548-2.722], =0.624), BIOT (OR [95% CI]=1.066 [0.242-4.695], =0.933), and SHBG (OR [95% CI]=0.529 [0.119-2.343], =0.402) were not significantly associated with chronic hypertension with superimposed PE. Additionally, MR analysis using the MR-Egger method, weighted median method, simple mode method, and weighted mode method yielded consistent results, indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE. Heterogeneity was observed for SHBG in the analysis with PE (Cochran's test, =0.01), and pleiotropy was detected for BIOT in the analysis with PE (MR-Egger intercept analysis, =0.014), suggesting that the instrumental variables did not affect PE through BIOT. Other instrumental variables did not show significant heterogeneity or pleiotropy. Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables. Consistent with previous MR studies, the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.
CONCLUSION
The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT, BIOT, and SHBG levels and the development of PE and chronic hypertension with superimposed PE. This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.
Topics: Humans; Female; Polymorphism, Single Nucleotide; Pregnancy; Pre-Eclampsia; Genome-Wide Association Study; Hyperandrogenism; Sex Hormone-Binding Globulin; Mendelian Randomization Analysis; Testosterone; Hypertension
PubMed: 38948277
DOI: 10.12182/20240560106 -
PeerJ 2024Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study.
BACKGROUND
Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated.
METHODS
A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study.
RESULTS
The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure ( < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like and which might have a beneficial role in the current context and a similar decrease in species like and which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.
Topics: Humans; Male; Hypertension; Female; Middle Aged; Gastrointestinal Microbiome; Prospective Studies; Diabetes Mellitus, Type 2; Hyperglycemia; Precision Medicine; Inflammation; Proof of Concept Study; Glycated Hemoglobin; Aged; Hyperlipidemias; Adult; C-Reactive Protein
PubMed: 38948211
DOI: 10.7717/peerj.17583 -
The Lancet Regional Health. Western... Jun 2024Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous,...
Efficacy and safety of visepegenatide, a long-acting weekly GLP-1 receptor agonist as monotherapy in type 2 diabetes mellitus: a randomised, double-blind, parallel, placebo-controlled phase 3 trial.
BACKGROUND
Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous, glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection without the requirement of dose titration that has shown glycaemic control and safety profile in two phase 2 studies conducted in China and the United States, respectively. The aim of this study was to evaluate the efficacy and safety of visepegenatide as a monotherapy in treatment-naïve patients with T2DM.
METHODS
This was a multicentre, double-blind, parallel, placebo-controlled, phase 3 trial conducted in 30 centres in China. Adult participants (aged 18-75 years) with T2DM, glycated haemoglobin (HbA1c) of 7.5%-11.0% [58.47-96.73 mmol/mol], body mass index (BMI) of 18-40 kg/m, and who had been treated with diet and exercise alone for at least 8 weeks before the screening visit were eligible for enrolment. After a 4-week placebo injection run-in period, participants with HbA1c of 7.0%-10.5% [53.0-91.3 mmol/mol] and fasting plasma glucose (FPG) < 15 mmol/L were randomised in a ratio of 1:1 to receive visepegenatide (150 μg) or placebo subcutaneous injections once a week for 24 weeks. The treatment was extended to another 28 weeks during which all participants received visepegenatide. The primary outcome was a change in HbA1c from baseline to week 24. This study was registered with ClinicalTrials.gov, as NCT04504370.
FINDINGS
Between November 2, 2020, and November 2, 2022, we randomly assigned 273 adult participants to the visepegenatide (n = 137) and placebo (n = 136) groups. In total, 257 (94.12%) participants, 131 (95.6%) on visepegenatide, and 126 (92.6%) on placebo, completed the double-blinded treatment period. At baseline, the mean (SD) HbA1c was 8.47% (0.81) [69.07 [8.81] mmol/mol], which rapidly decreased to 7.63% (0.80) [59.94 [8.70] mmol/mol] with visepegenatide by week 4 of treatment, and the change from baseline was significantly greater than that in the placebo group (-0.82% [-0.90 to -0.74]; [-8.99 [-9.89 to -8.10] mmol/mol] -0.30% [-0.41 to -0.19]; [-3.30 [-4.50 to -2.09] mmol/mol]). At week 24, when evaluating the effects of treatment with treatment policy estimand, the least square mean (LSM change in HbA1c from baseline was -1.36 (95% confidence interval [CI] -1.52 to -1.20) [-14.84 [-16.60 to -13.08] mmol/mol] in the visepegenatide group -0.63 (-0.79 to -0.46) [-6.84 [-8.61 to -5.07] mmol/mol] in the placebo group. The reduction in HbA1c was significantly greater with visepegenatide than placebo (LSM difference -0.73, 95% CI -0.96 to -0.50; p < 0.001). When evaluating the treatment estimand with hypothetic policy, the LSM change in HbA1c from baseline in the visepegenatide group (-1.37 [-1.53 to -1.20]) [-14.95 [-16.76 to -13.14] mmol/mol] was significantly greater than the placebo group (-0.63 [-0.81 to -0.45]) [6.90 (-8.89 to -4.90) mmol/mol]. The LSM difference was (-0.74, 95% CI -0.98 to -0.49; [-8.00 [-10.50 to -5.50] mmol/mol]; p < 0.001]. A significantly greater proportion of the visepegenatide group achieved a target HbA1c level of <7% (<53 mmol/mol) than the placebo (50.4% 14.2%; p < 0.05) and stringent HbA1c level of ≤6.5% (≤48 mmol/mol) (26.7% 7.9%), respectively. There was also a significantly greater improvement in FPG, 2-h postprandial glucose, homeostasis model assessment (HOMA) of beta cell function, post-prandial insulin, fasting, and post-prandial C-peptide level (p < 0.05) with visepegenatide treatment. The number (3 [2.2%]) of participants who received rescue therapy in the visepegenatide group was remarkably lower compared with those (17 [12.5%]) in the placebo group (p < 0.05). During the extended treatment period, visepegenatide consistently maintained the efficacy till week 52 confirmed by all the above endpoints. The reduction in HbA1c at week 52 was -1.39% (-1.58 to -1.19) [-15.14 [-17.28 to -13.01] mmol/mol], which was even greater than that at week 24. There was also a significant improvement in HOMA-insulin resistance (p = 0.004) at week 52 compared with the baseline value. For the placebo→visepegenatide group, which received visepegenatide in the extended treatment period, a notable decrease in HbA1c at week 52 compared to baseline was observed. The change from baseline in HbA1c was -1.49% (-1.68 to -1.30) [-16.27 [-18.37 to -14.16] mmol/mol]. The outcome was in the same direction as the visepegenatide group from the double-blind treatment period. Comprehensive benefits of visepegenatide including weight loss, improvement in lipid profile, and reduction in blood pressure have been demonstrated in this study. Visepegenatide reduced the body weight in a BMI-dependent manner that was prominent in BMI ˃32 kg/m with a mean (SD) reduction of -4.77 (13.94) kg at week 52 (p < 0.05). Incidences of gastrointestinal adverse events were less common than other weekly GLP-1 RA in the market, and most of the adverse events were mild and moderate in nature, occurring in the first weeks of the treatment, and were transient. No serious hypoglycaemia or grade 2 hypoglycaemia (blood glucose: ≤3 mmol/L) was reported during the study.
INTERPRETATION
As a monotherapy, visepegenatide provided rapid without the risk of hypoglycaemia, significant, and sustainable glycaemic control by improving islet β-cell function and insulin resistance. Treatment with visepegenatide induced early treatment response in reducing HbA1c and maintaining glycaemic control for 52 weeks. Meanwhile, visepegenatide provided a comprehensive benefit in body weight loss, lipids, and blood pressure reduction. Visepegenatide had a better safety profile than other weekly GLP-1 RA in participants with T2DM even without the requirement of dose titration. Visepegenatide would provide an optimal treatment approach with its high benefit and low-risk balance.
FUNDING
PegBio Co., Ltd.
PubMed: 38948164
DOI: 10.1016/j.lanwpc.2024.101101 -
Frontiers in Physiology 2024The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems.
UNLABELLED
The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems.
METHODS
A total of 33 individuals completed this study. On visit 1, arterial occlusion pressure (AOP, mm Hg), cardiovascular responses, and discomfort (RPE-D) were measured with each BFR system at rest. On visit 2, unilateral bicep curls were completed [30% one-repetition maximum; 50% AOP] with one system per arm. Muscle thickness (MT, cm) and maximal force (N) were assessed before (pre), immediately (post-0), 5 min (post-5), and 10 min (post-10) post-exercise. Ratings of perceived exertion (RPE-E) and ratings of perceived discomfort (RPE-D) were assessed throughout the exercise. AOP and repetitions were compared with Bayesian paired t-tests. Other outcomes were compared with Bayesian RMANOVAs. BF represents the likelihood of the best model vs. the null. The results are presented as mean ± SD.
RESULTS
Supine cardiovascular responses and RPE-D were similar for manual and automated (all BF ≤ 0.2). Supine AOP for manual (157 ± 20) was higher than that of automated (142 ± 17; BF = 44496.0), but similar while standing (manual: 141 ± 17; automated: 141 ± 22; BF = 0.2). MT (time, BF = 6.047e + 40) increased from Pre (3.9 ± 0.7) to Post-0 (4.4 ± 0.8; BF = 2.969e + 28), with Post-0 higher than Post-5 (4.3 ± 0.8) and Post-10 (4.3 ± 0.8; both BF ≥ 275.2). Force (time, BF = 1.246e + 29) decreased from Pre (234.5 ± 79.2) to Post-0 (149.8 ± 52.3; BF = 2.720e + 22) and increased from Post-0 to Post-5 (193.3 ± 72.7; BF = 1.744e + 13), with Post-5 to Post-10 (194.0 ± 70.6; BF = 0.2) being similar. RPE-E increased over sets. RPE-D was lower for manual than automated. Repetitions per set were higher for manual (Set 1: 37 ± 18; Set 4: 9 ± 5) than automated (Set 1: 30 ± 7; Set 4: 7 ± 3; all BF ≥ 9.7).
CONCLUSION
Under the same relative pressure, responses are mostly similar between BFR systems, although a manual system led to lower exercise discomfort and more repetitions.
PubMed: 38948082
DOI: 10.3389/fphys.2024.1409702 -
International Journal of Hypertension 2024Cardiovascular risk factors such as obesity, type 2 diabetes, hypertension, smoking, and dyslipidemia enfold heart disease morbimortality. Diagonal earlobe crease has...
Traditional Cardiovascular Risk Factors Associated with Diagonal Earlobe Crease (Frank Sign) in Mexican Adults: Aging, Obesity, Arterial Hypertension, and Being Male Are the Most Important.
INTRODUCTION
Cardiovascular risk factors such as obesity, type 2 diabetes, hypertension, smoking, and dyslipidemia enfold heart disease morbimortality. Diagonal earlobe crease has been proposed as a prognostic marker of extension and severity of illness in patients with acute coronary syndrome. But its usefulness remains unclear in patients with or without coronary disease.
METHODS
A case-control study was carried out on a total of 805 patients with and without cardiovascular risk factors or acute coronary syndrome. Univariate and multivariate binary logistic regression analyses were used to determine the probability of having diagonal earlobe crease with the presence of cardiovascular risk factors and acute coronary syndrome. Data were summarized as odds ratio with 95% confidence intervals and values.
RESULTS
An unadjusted (univariate) analysis showed that being male, being older than 55 years, obesity, type 2 diabetes mellitus, arterial hypertension, smoking, and dyslipidemia, as well as having acute coronary syndrome, were associated with the presence of diagonal earlobe crease. The multivariate analysis showed that men (OR 1.6, 95% IC 1.1-2.4, =0.007), being over 55 years old (OR 4.8, 95% IC 3.2-7.2, < 0.001), being obese (OR 2.1, 95% IC 1.4-3.1, < 0.001), having arterial hypertension (1.5, 95% IC 1.1-2.3, =0.025), or suffering from acute coronary syndrome (OR 5.3, 95% IC 2.5-11.1, < 0.001), were independent factors associated with diagonal earlobe crease. The rest of cardiovascular risk factors were not relevant in the multivariate model.
CONCLUSIONS
In Mexican adults, having an acute coronary syndrome is not the only factor associated with diagonal earlobe crease but also being a man, older than 55 years, having high blood pressure and obesity. Diagonal earlobe crease may simply be caused by changes in the skin and connective tissues of the ears because of the aging process, obesity, and/or being male. These factors, by themselves, enfold cardiovascular risk due to well-known pathophysiological causes.
PubMed: 38948003
DOI: 10.1155/2024/5598134