Cardiometabolic Parameters Research Articles

Abstract 4120229: Shift in body mass index category and associated cardiometabolic risk factors: a post hoc analysis from the SURMOUNT-4 trial

Background: In SURMOUNT-4, participants with obesity demonstrated a mean weight reduction of 21% during the 36-week lead-in with the maximum tolerated dose (MTD) of tirzepatide (TZP). During the 52-week double-blind period, participants who switched to placebo (PBO) experienced a 14% weight regain, while those who continued TZP achieved an additional 6% weight reduction. This post hoc analysis assessed whether participants who shifted to a lower BMI category had improved cardiometabolic factors. Methods: Shift in BMI category (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 , and ≥40 kg/m 2 ) from baseline (week 0) during the lead-in period (week 36) and at the primary endpoint (week 88) and from week 36 to week 88 was assessed in participants from SURMOUNT-4 randomized to TZP MTD (N=332) or PBO (N=329). BMI shifts were grouped into “improved” (shift to ≥1 lower category) or “not improved” (stable/attenuated [no change/shift to a higher category]). Changes from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, vitals and lipid profile were assessed. Results: From weeks 0 to 36, 296 (89%) participants improved in BMI category with TZP, and none had attenuated (Table). From weeks 36 to 88, 130 (39%) participants improved in BMI category with TZP, while the majority (99%) randomized to PBO did not. Overall, from weeks 0 to 88, 304 (92%) vs 189 (57%) participants improved in BMI category with TZP vs PBO, respectively, where the improvements observed in the PBO group originated from the 36-week lead-in period. In general, participants who improved in BMI category at week 88 were noted to have greater improvements in cardiometabolic parameters with TZP vs PBO, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, triglycerides, and cholesterol (total, non-HDL-c, LDL-c, and VLDL-c). Conclusions: In this post hoc analysis of SURMOUNT-4, the majority of TZP-treated participants shifted to lower “improved” BMI categories. Shift to an improved BMI category was accompanied by improved cardiometabolic risk factors, suggesting that TZP treatment may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.

Abstract 4116298: Once Weekly Utreglutide (GL0034), a Glucagon-like Peptide-1 Receptor Agonist, at 4 × 450 µg Doses Reduces Blood Pressure, Lipids, and Body Weight in Post-menopausal Females: A Phase I Study

Background: Utreglutide (GL0034), a novel, once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated significant reductions in body weight (BW) after a single dose ascending study in individuals with obesity . BW reductions after pharmacological treatment of obesity with GLP-1RA is associated with blood pressure (BP) lowering effects. Aim: This phase I study assessed the safety, tolerability, and cardio-metabolic effects of utreglutide after multiple ascending doses in post-menopausal female volunteers with overweight and obesity. Methods: In this randomized, double-blind, placebo-controlled study 12 post-menopausal female volunteers with overweight/obesity, aged 18 to 65 years old with a body mass index (BMI) ≥26 kg/m 2 were randomized (9:3) to subcutaneous utreglutide fixed doses (4 × 450 µg); or placebo once weekly for four weeks. Safety, tolerability, and key cardio-metabolic parameters were assessed. Biomarker measurements included oral glucose tolerance test (OGTT) insulin and glucose area under the curve (AUC), systolic- and diastolic BP, lipid profile (triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL), creatinine, potassium, BW and leptin. Results: Utreglutide was generally well tolerated and related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Reductions in OGTT AUCs of insulin ( p <0.05) and glucose ( p <0.01) were noted on Day 23 after four weeks treatment with Utreglutide. This was accompanied by a decrease ( p <0.001) in mean systolic and diastolic BP on Day 23 from baseline (BL). On Day 23, significant reductions in TC ( p <0.01), LDL ( p <0.05) and non-HDL ( p <0.05) were observed. BW reduction versus BL ( p <0.001) was 2.0 kg and 1.8 kg respectively on Day 29 and End of Study (EoS). Leptin levels significantly reduced from BL on Day 23 ( p< 0.01) and EoS ( p <0.001). No significant changes were observed for TG, creatinine and potassium (Table). Conclusions: Once weekly utreglutide dosing for four weeks at a dose of 450 µg in post-menopausal females with overweight and obesity, demonstrated clinically relevant reductions of systolic and diastolic BP. This was associated with improved performance of OGTT AUC of insulin and glucose, lipids, BW and leptin with an overall good tolerability and with potential to demonstrate cardio-metabolic benefits.

Importance of Return to Usual and School Activities After Social Isolation in Recovering Vitamin D Concentrations, Physical Fitness, and Motor Performance in Adolescents

This study aimed to observe adolescents’ changes and individual responses regarding the anthropometry, cardiometabolic profile, vitamin D concentrations, physical fitness, and motor competence upon immediate return and three months of school activities after lockdown. Methods: The study included 28 adolescents (14.8 ± 0.8 years) of both sexes. Anthropometric measures, body composition, cardiometabolic parameters, physical fitness, and motor competence were assessed. A paired t-test was used to compare the frequencies of respondents and the effect size of the results, considering significant p < 0.05. Results: After three months of school activities, adolescents changed their body composition, reducing % fat mass (p = 0.008) and increasing fat-free mass (p = 0.008). In terms of physical fitness, there was increased abdominal resistance (p < 0.001; ES = −0.42) and motor performance, with reduction in supine-to-stand test time (p < 0.001; ES = 0.53). There were very beneficial effects in reducing resting heart rate (p ≤ 0.001; ES = 0.61) and increasing vitamin D concentrations (p < 0.001; ES = −0.61). After three months of a school routine, the proportions of change in respondents were similar between girls and boys and eutrophic individuals and overweight individuals. Conclusions: Returning to school activities after lockdown was important for the recovery of vitamin D concentrations, physical fitness, and motor competence, whose responses were independent of the level of adiposity and sex of the adolescents.

Are Oxidative Stress Biomarkers Reliable Part of Multimarker Panel in Female Patients with Type 2 Diabetes Mellitus?

Background: Oxidative stress and inflammation are the key features of metabolic diseases, including type 2 diabetes mellitus (T2D). However, studies that explored redox homeostasis parameters in relation to T2D show discrepant results. Accordingly, we aimed to examine the potential reliability of oxidative stress biomarkers [i.e., determined by malondialdehyde (MDA), advanced oxidation protein products (AOPP) and catalase (CAT)] in addition to traditional cardiometabolic parameters in relation to T2D in female cohort. Methods: A total of 214 women (of them 40.6% T2D) were consecutively recruited in the study. Principal component analysis with varimax rotation was performed to determine the adequate number of factors consisting of anthropometric, traditional cardiometabolic and redox status markers. Results: MDA and AOPP concentrations were lower, but CAT activity was higher in T2D group as compared with controls (P < 0.001, P = 0.002, P < 0.001). Traditional markers related factor (i.e., with positive loading of waist circumference, triglycerides, uric acid, high sensitivity C-reactive protein and negative loadings of high-density lipoprotein cholesterol) was found to be independently related with T2D in multivariate binary regression analysis, whereas oxidative stress related factor (i.e., with positive loading of MDA and AOPP) lost its independent prediction after adjustment for confounding factors (i.e., age, menopausal status, antihypertensive, and hypolipemic therapies). Increased Traditional markers related factor was associated with more than three times higher probability for T2D onset (OR = 3.319, p < 0.001). Conclusion: Oxidative stress biomarkers, i.e., MDA, AOPP, and CAT are not superior over traditional cardiometabolic markers in relation to T2D in female population. Future studies with both gender included are needed to confirm such results.

Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.

Aims: To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. Materials and methods: Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. Results: From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. Conclusion: This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.

The role of metformin in modulating cardiometabolic risk in obese pediatric populations with metabolic syndrome: A systematic review

Introduction: Obesity significantly increases the risk of developing cardiometabolic complications, which are precursors to cardiovascular diseases (CVD). In children and adolescents, metabolic dysfunctions such as insulin resistance, dyslipidemia, and hypertension are key contributors to early-onset cardiovascular risk. Metformin, a well-established antidiabetic agent, has shown potential benefits in addressing these metabolic imbalances. However, the long-term impact of metformin on cardiovascular outcomes in obese pediatric patients remains unclear. Aim: This systematic review aims to evaluate the effect of metformin on cardiometabolic parameters in obese children and adolescents with metabolic syndrome, focusing on insulin sensitivity, body mass index (BMI), blood pressure, and lipid profiles. Methods: A systematic review was conducted by searching databases including PubMed, Cochrane Library, Embase, and Web of Science. The inclusion criteria targeted randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses published between 2004 and 2024. Pediatric patients aged 6-18 years with obesity and metabolic syndrome were included. The primary outcomes assessed were BMI, insulin sensitivity, lipid profiles, blood pressure, and cardiovascular outcomes. Results: A total of 23 studies, including 10 RCTs and 1 meta-analysis, were reviewed, involving 777 patients. Metformin demonstrated consistent improvements in insulin sensitivity and BMI in obese children and adolescents. Several studies reported modest reductions in BMI, improved insulin resistance, and better lipid profiles. However, variability in results was observed regarding long-term cardiovascular outcomes. While metformin reduced systolic blood pressure and carotid intimal-medial thickness (CIMT), the long-term impact on preventing major cardiovascular events remained inconclusive. Discussion: Metformin’s benefits on cardiometabolic risk factors in obese children are primarily attributed to its effects on insulin sensitivity, lipid metabolism, and inflammatory pathways. Its ability to activate AMP-activated protein kinase (AMPK) leads to improved metabolic profiles and reduced inflammation and is crucial for mitigating obesity-related cardiovascular risks. Despite these positive effects, the evidence for long-term prevention of cardiovascular events is limited and requires further exploration. Conclusions: Metformin offers significant short-term benefits in improving BMI, insulin sensitivity, and cardiometabolic parameters in obese children and adolescents. However, its long-term efficacy in preventing cardiovascular events remains uncertain. Further studies are necessary to establish its role in long-term cardiovascular protection in pediatric populations

Improvement in Symptoms of Depression and Anxiety and Cardiometabolic Risk Factors in Children and Adolescents with Overweight and Obesity Following the Implementation of a Multidisciplinary Personalized Lifestyle Intervention Program.

Background/Objectives: Childhood obesity is one of the most challenging contemporary public health problems. Children and adolescents with obesity experience multiple psychosocial difficulties, such as low self-esteem, depression, anxiety, and behavioral problems, which persist for a long time. The aim of the study was to assess the effect of a multidisciplinary personalized lifestyle intervention for depressive and anxiety symptoms, as evaluated by psychometric questionnaires, and their effect and association with cardiometabolic parameters in children and adolescents with overweight and obesity before and after the intervention. Methods: Six hundred and eleven (n = 611) children and adolescents (mean age ± SE: 10.39 ± 0.10 years; 51.5% females, 46.6% pubertal) were studied prospectively. Subjects were classified as being obese (50.2%), overweight (33.5%), or having a normal BMI (16.2%) according to IOTF criteria. All participants entered a 1-year lifestyle intervention program; laboratory investigations were obtained at the beginning and end of the study and two psychometric questionnaires were completed, the CDI and SCARED, which evaluate symptoms of depression and anxiety, respectively. Results: Following the lifestyle intervention, a significant decrease was noted in anxiety scores in all subjects and in depression scores in youth with obesity, as well as in adolescents with obesity, while females displayed a reduced response to the intervention. Insulin resistance and metabolic syndrome parameters, cortisol, PRL, and LH concentrations were positive predictors for depressive and anxiety symptoms. Conclusions: The implementation of a multidisciplinary personalized lifestyle intervention program in the management of childhood obesity is associated with a significant decrease in cardiometabolic and psychosocial comorbidities in children with and without excess adiposity. The improvement in mental health is likely mediated by an improvement in energy metabolism with subsequent improvement in neuroinflammation owing to lifestyle changes.

Validation of fat mass metrics in pediatric obesity

Introduction Hudda-Index is a prediction model for fat mass (FM) based on simple anthropometric measures., FM is a crucial factor in the development of comorbidities, i.e., type 2 diabetes. Hence, Hudda-Index is a promising tool to facilitate identification of children at risk for metabolic comorbidities. It has been validated against deuterium dilution assessments, however, independent validation against the gold-standard for body composition analysis, magnetic resonance imaging (MRI), is lacking. The aim of this study is to validate FM calculated by Hudda-Index against FM measured by MRI. The secondary aim is to compare Hudda-Index to other anthropometric measures including body mass index (BMI), BMI-standard deviation score (BMI-SDS), waist/hip-ratio, waist circumference (WC) and skinfold thickness. Methods The study cohort consists of 115 individuals between the age of 9 and 15 years, recruited at Paracelsus Medical University Hospital in Salzburg (Austria) and Uppsala University Children's Hospital (Sweden). Anthropometry, blood samples, and oral glucose tolerance tests followed standard procedures. MRI examinations were performed to determine visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Results BMI and WC showed slightly stronger associations with the reference standard VAT (r=0.72 and 0.70, p&lt;0.01, respectively) than Hudda-Index (r= 0.67, p&lt;0.01). There is an almost perfect linear association between BMI and Hudda-Index. Accordingly, BMI and Hudda-Index both showed an acceptable association with cardiometabolic parameters. VAT was strongly associated with markers of liver status (LFF r=0.59, p&lt;0.01) and insulin resistance (HOMA-IR r=0.71, p&lt;0.01) and predicted metabolic dysfunction-associated steatotic liver disease (MASLD). Conclusion BMI, although an imperfect measure, remains the most reliable tool and estimates cardiometabolic risk more reliably than other anthropometry-based measures.

Survodutide, a glucagon receptor/GLP-1 receptor (GCGR/GLP-1R) dual agonist, improves cardiometabolic parameters in adults with obesity: analysis of a placebo-controlled, randomised phase 2 trial

Abstract Background Obesity increases the risk of cardiovascular (CV) disease and contributes to CV risk factors, such as hypertension (HTN) and dyslipidaemia. Survodutide is a GCGR/GLP-1R dual agonist in clinical development for obesity. In a phase 2 clinical trial in individuals with obesity without diabetes, survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks (primary endpoint) according to actual treatment.1 Purpose We explored the effect of survodutide on cardiometabolic parameters in this trial cohort. Methods 387 people aged ≥18 to &amp;lt;75 years with body mass index (BMI) ≥27 kg/m2 without diabetes were randomised 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8 mg) or placebo (PBO) for 46 weeks (wk), comprising an initial 20-wk escalation period when the dose could be adjusted for gastrointestinal (GI) tolerability, followed by a 26-wk maintenance period. We evaluated changes from baseline (BL) to wk 46 in waist circumference; lipid parameters (triglyceride [TG], high-density lipoprotein [HDL], very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], total cholesterol [TC], and non-HDL cholesterol [non-HDL-C]); and blood pressure (BP) by presence/absence of HTN before and at screening. Data were analysed descriptively for all participants receiving ≥1 dose of study drug with data for ≥1 efficacy endpoint, i.e. full analysis set (FAS), according to doses received during the maintenance period (actual treatment) and according to doses assigned at randomization (planned treatment) using on-treatment data. Results In the FAS (n=384), BL demographic and clinical characteristics were similar across treatment groups: overall mean age 49.1 years, BMI 37.1 kg/m2, 262 (68.2%) female, 301 (78.4%) White, 40 (10.4%) Asian, and 37 (9.6%) Black. Before and at screening, 133 (34.6%) participants had hypertension and 108 (28.1%) had dyslipidaemia. Waist circumference was reduced in all survodutide doses vs PBO; the largest mean reduction was 16.6 cm (4.8 mg group; actual treatment). Survodutide was associated with reductions of up to 10.2 mmHg in SBP and 4.8 mmHg in DBP from BL to wk 46 by actual treatment; similar reductions were observed for planned treatment, and reductions were comparable with/without HTN before and at screening (Figure 1). A marked decrease in mean TG was observed in all survodutide groups by planned treatment (Figure 2). Mean HDL was relatively unchanged over the period. Small decreases occurred in mean VLDL (all survodutide doses) and mean LDL (2.4 and 3.6 mg doses). Mean TC and non-HDL-C decreased in 0.6, 2.4, and 3.6 mg groups. Conclusion In people living with obesity, the GCGR/GLP-1R dual agonist survodutide was associated with clinically meaningful reductions in waist circumference, BP (with/out HTN before and at screening), and TG.

BMI shift and associated cardiometabolic risk factors in people with type 2 diabetes and obesity and/or overweight: a post hoc analysis from SURMOUNT-2

Abstract In SURMOUNT-2 (SM-2), treatment with once weekly GIP and GLP-1 receptor agonist tirzepatide (TZP) resulted in superior body weight reductions relative to placebo in people living with obesity and T2D. This post hoc analysis assessed whether participants with obesity (body mass index [BMI] ≥30 kg/m2) or overweight (BMI ≥27 kg/m2 with at least one weight-related comorbid condition) who shifted to a lower BMI category had improved cardiometabolic factors. Change in BMI category (&amp;lt;25 kg/m2, 25 to &amp;lt;30 kg/m2, 30 to &amp;lt;35 kg/m2, 35 to &amp;lt;40 kg/m2, and ≥40 kg/m2) from baseline to week 72 was assessed in participants from SM-2 treated with TZP 10 or 15 mg (N=623) or placebo (PBO)(N=315). BMI shifts were grouped into "improved" (shift to lower BMI category) or "non-improved" (stable or shift to a higher BMI category). Cardiometabolic parameters examined included waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, and lipid profile. A mixed model with repeated measures was performed to estimate the mean change from baseline to week 72 for these parameters. In this post hoc analysis a total of 484 (52.1%) participants had improved BMI at week 72. For those whose BMI did not improve, most had stable BMI and only 11 (1.2%) had worsened BMI. Nine participants had no post-baseline BMI measurements and were excluded from analysis. Most participants demonstrated improved BMI with TZP treatment (N=418, 67%) vs PBO (N=66, 21%)(Table). Furthermore, 21% (N=129) of participants on TZP improved by ≥2 BMI categories compared to only 1 participant with PBO. Compared to those with non-improved BMI, participants with improved BMI demonstrated greater improvement in cardiometabolic risk factors, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, systolic and diastolic blood pressure, triglycerides, and cholesterol (non-HDL-c, and LDL-c) and increases from baseline in HDL-c (Figure). Greater improvements to cardiometabolic risk factors were seen in participants on TZP vs PBO. Shifts to lower BMI categories were greater among TZP-treated people living with obesity or overweight and T2D in SM-2 and were associated with improved cardiometabolic risk factors, in this post hoc analysis. SURMOUNT-mortality and morbidity and cardiovascular outcome trials are ongoing to examine the impact of TZP treatment on CVD and mortality.

Cardiometabolic outcomes in patients with overweight and obesity undergoing weight loss trials : a network meta-analysis

Abstract Objective Cardiometabolic outcomes are intrinsically linked with obesity. According to a study by Jayedi A et al. a 5kg weight gain could increase CVD mortality and MI risk by 11% and 18% respectively, with most overweight and obese patient also suffering from cardiometabolic derangements. This network meta-analysis evaluates cardiometabolic effects bought about by glucagon-like peptide 1 receptor agonists (GLP-1 RA) and other weight loss drugs in an overweight and obese population. Methods Cochrane CENTRAL, Embase and Medline were searched for randomised clinical trials (RCTs) on GLP-1 RA and United States Food and Drug administration weight loss drugs. A network meta-analysis was performed, using risk ratios(RR) to compare the efficacy of the interventions against one another. Network diagrams and surface under the cumulative ranking curve analysis were generated for the following cardiometabolic outcomes ( LDL, HDL, TC, TG, HbA1c, FPG, SBP and DBP). Results Among the cardiometabolic outcomes analysed, the GLP-1RA’s consistently ranked on top, with tirzepatide followed by semaglutide and then liraglutide. In terms of glycaemic control, tirzepatide 15, 10 and 5mg ranked first in a dose dependent manner(SUCRA = 0.8480, 0.8410, 0.6725) followed by semaglutide1.7mg(SUCRA= 0.6232). Tirzepatide 15mg did not achieve statistical significance compared to semaglutide 1.0mg (MD: -0.77, 95%CI: -2.04 to 0.50) or liraglutide1.8mg (MD: -0.64, 95%CI: -1.68 to 0.41). In reducing blood pressure, tirzepatide exhibiting a dose dependent reduction with Tirzepatide 15mg, (SUCRA =0.9457),10mg(SUCRA=0.9069)and 5mg(SUCRA=0.8419) followed by semaglutide 1.7mg (SUCRA =0.7415) then liraglutide 1.8mg(SUCRA = 0.5521).Tirzepatide 15mg demonstrated statistical significance compared to semaglutide 1.0mg (MD: -3.53, 95%CI: -6.78 to -0.27) and liraglutide 3.0mg (MD: -3.47, 95%CI: -5.59 to -1.36). The GLP-1RA’s also exhibited superiority in lipid reduction for TC and TG, with tirzepatide reducing TC (SUCRA = 0.7867) and TG(SUCRA = 0.9843) followed by semaglutide 1.7 mg (SUCRA = 0.7796) for TC and tirzepatide 10 mg (SUCRA = 0.9018) for TG. Orlistat 120mg(SUCRA =0.8789) and 60mg(SUCRA= 0.8458) were superior in reducing LDL, with tirzepatide 15mg(SUCRA =0.7806) and then semaglutide 2.4mg(SUCRA=0.7260) coming in behind. Naltrexone 32mg/Bupropion 360mg(SUCRA = 0.8757) ranked first followed by tirzepatide(SUCRA=0.8593) in increasing HDL, however the increase was not statistically significant (MD: 0.00, 95%CI: -0.04 to 0.05). Conclusion GLP-1 RAs’ superiority in addressing cardiometabolic parameters that are often deranged in patients with overweight and obesity highlights the need for weight lost medication transitioning from one that decreases and suppresses appetite or prevent the absorption of lipids to one that targets the altered metabolic mileu of patients with overweight and obesity, highlighting the multipronged approach needed to treat this metabolic disease.

The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

Health concerns about excess dietary salt have traditionally focused on its relationship with hypertension and the increased risk of cognitive impairment. However, research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, particularly regarding disease prevention and treatment strategies for women. The present study examined aged female rats over 12 weeks, using control, low, and high salt diets to mimic the post-menopausal phase in human females when cardiovascular risks typically increase. Cardiometabolic parameters and cognition were monitored. The findings revealed the impact of varying salt diets on blood lipids, blood pressure (BP) and heart rate (HR) levels and variability, anxiety, and cognition. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Aged female rats exhibited increased anxiety on the low-salt diet at the fourth week, but the anxiety began to improve starting from the eighth week. Additionally, a trend suggested that the low salt intake worsened short-term memory while improving long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on a high-salt diet compared to those on a low-salt diet. The study provides valuable insights into the effects of salt intake on cardiometabolic parameters and cognitive function in aged female rats, highlighting the importance of considering sex-specific dietary guidelines for cardiometabolic and cognitive health.

Effects of an Exercise and Lifestyle Education Program in Brazilians living with prediabetes or diabetes: study protocol for a multicenter randomized controlled trial.

Patient education is a crucial strategy for promoting prevention and diabetes self-management since glycemic control achievement involves taking medications, medical nutrition therapy, physical exercise, and behavior changes. However, patient education programs are still barely implemented in low- and middle-income countries. This trial aims to investigate whether a lifestyle education intervention added to physical exercising is superior to sole physical exercising regarding functional capacity, disease-related knowledge, health behaviors, cardiometabolic health parameters, quality of life, depression, and diet quality in individuals with prediabetes or diabetes. Multicenter double-blinded randomized controlled trial with two parallel arms involving 12-week intervention and 6-month follow-up. The eligible individuals (≥ 18years, living with prediabetes or diabetes, literate, no clinical decompensation and/or physical and/or mental limitations that contraindicate physical exercising, written physician permission for exercise, no cognitive impairment, no vision limitations for reading, no confirmed diagnosis of unstable coronary disease or heart failure, no pacemaker and/or implantable cardioverter-defibrillator, no complex ventricular arrhythmias, no intermittent claudication, no recent cardiovascular event or cardiac surgery, and no currently enrolled in a structured exercise program) were recruited from two Brazilian cities and randomized to either (1) an Exercise and Lifestyle Education Program (ExLE) or (2) an Exercise Program (Ex), which can be delivered on-site or remotely based on the participants' internet access and technology literacy. The primary outcomes will be changes in functional capacity and disease-related knowledge. The secondary outcomes will involve changes in health behaviors (health literacy, physical activity level, exercise self-efficacy, and medication adherence) and cardiometabolic health parameters (glycemic control, anthropometric measures, and cardiac autonomic control). Program adherence, satisfaction with the program, diabetes-related morbidity, and changes in quality of life, depression, and diet quality will be the tertiary outcomes. Assessments will occur at baseline, post-intervention, and after 6-month follow-up. If superior effectiveness of ExLE compared to Ex program to improve the outcomes measures is found, this program could be delivered broadly in the Brazilian health system, especially in the primary care facilities where most individuals living with prediabetes and diabetes in our country are assisted. ClinicalTrials.gov, NCT03914924 . Registered on April 16, 2019.

8073 Association Between Serum GDF15 Level And Metabolic Parameters in Severely Obese Men Undergoing Weight Loss From Lifestyle Intervention

Abstract Disclosure: S. Bathina: None. V. Fuenmayor Lopez: None. M. Prado: None. G. Colleluori: None. D.T. Villareal: None. R.C. Villareal: None. Background: Growth Differentiation factor (GDF-15), member of TGF-β superfamily was identified as marker of aging, frailty, and metabolic disorders. Several clinical studies demonstrated an association between GDF15 with obesity and cardiovascular disease. However, information on the changes in GDF15 and its relationship to changes in metabolic and body composition parameters in the population of severely obese subjects undergoing weight loss (WL) remains lacking. Objective: The objective of this study is to evaluate the influence of WL on serum GDF15 level and its relationship to glucometabolic parameters in severely obese hypogonadal men. Method: Data from 116 severely obese (BMI ≥35 kg/m2) hypogonadal men participating in an ongoing clinical trial of WL from lifestyle intervention±anastrozole, aged 35-65 years old (NCT03490513) were analyzed. Hemoglobin A1C (A1C) was measured by HPLC, lipid profile by colorimetric method (except LDL was calculated), testosterone (T) and estradiol (E2) LC-MS and GDF-15 by ELISA. Body composition was measured by DXA. Results: The mean age of the participants was 51.4±7.6 years with mean BMI 41.8 ±5.4 kg/m2. At baseline, serum GDF15 positively correlated with age (r=0.25, p=0.01), fasting blood glucose (r=0.29, p=0.004) and A1C (r=0.39, p&amp;lt;0.001) but no correlation was found for lipid parameters and with T and E2. GDF15 was negatively correlated with total lean mass (r= -0.23, p=0.03), appendicular lean mass (r= -0.30, p=0.02), and fat-free mass (r= -0.22, p=0.03), but positively correlated with visceral adipose tissue volume (r=0.22, p=0.03). Average WL was 4.2±4.7% and 5.8±8.5% at 6months (6M) and 12 months (12M), respectively. Overall GDF15 levels increased by 9.4±84.7% at 6M and 18.4±128.0% at 12M. At 12M, changes in GDF15 levels positively correlated with changes in A1C (r= 0.26, p&amp;lt;0.05), and negatively with changes in total cholesterol ( r= -0.30, p=0.05), Triglycerides (r= -0.35, p=0.02) and E2 (r=-0.31, p=0.028). For LDL cholesterol changes, a negative correlation with GDF15 changes was observed at 6M (r= -0.27, p=0.047). There was no correlation between changes in GDF15 with changes in body weight and changes in body composition parameters. A comparison for those with significant WL (≥5%) vs. those with less WL showed that at 6M, GFD15 levels were reduced among those with WL of ≥5% (-19.5±42.3%) vs &amp;lt;5% (+19.8±93.9%), p=0.07, and at 12M (≥5% (-29.5±38.7) vs &amp;lt;5% (+0.61±69%), p&amp;lt;0.1). Conclusion: We demonstrated that changes in serum GDF15 in severely obese men undergoing WL was associated with alteration in cardiometabolic parameters. Our results show a new perspective on the potential role of GDF15 in cardiometabolic disorders associated with severe obesity. Aside from GDF15 used as a biomarker for health, it may also be used as target for drug development in modifying potential cardiometabolic complications in severe obesity. Presentation: 6/1/2024

8068 Beneficial Effects of a Personalized Exercise Program for Patients with Cushing's Disease and Acromegaly After Biochemical Control

Abstract Disclosure: E. Valassi: None. L. Martel-Duguech: None. H. Bascuñana: None. V. Priego-Corredor: None. J. Viñals-Ribé: None. O. González-Viñuela: None. T. Caparrós-Pons: None. S.M. Webb: None. Background: Patients with Cushing’s disease (CD) in remission and controlled acromegaly (ACRO) present with residual metabolic derangements, muscle dysfunction, and poor quality of life (QoL). Although exercise is known to exert positive effects on psychophysical health in several conditions, evidence demonstrating its potential benefits in pituitary diseases is scanty. Main hypothesis: A personalized program of combined (aerobic and resistance training) exercise lasting 12 weeks improves cardiometabolic parameters, body composition, physical performance and QoL in patients with CD in remission and controlled ACRO. Methodology: Ten female patients with CD in remission [mean (±SD) age, 59±4 years, mean (±SD) BMI, 35±2 Kg/m2, median (IQR) duration of remission, 5(4) years] and 10 male patients with controlled ACRO [mean (±SD) age, 53±9 years, mean (±SD) BMI, 27±4 Kg/m2, median (IQR) duration of control, 6(3) years] underwent a 12-week, structured, personalized program of combined aerobic and resistance exercise, under the supervision of professional trainers. We evaluated the following parameters at baseline and within 72 hours after the completion of the exercise program: blood pressure (BP), BMI, waist and neck circumferences; physical performance (gait speed, hand grip strength, 30-Second Chair Stand; Timed “Up and Go”); lumbar and femoral bone mineral density (BMD) and body composition, using dual x-ray absorptiometry (DXA); muscle thickness (cm) at the middle and distal third of rectus femoris (RF) and vastus intermedius (VI) on both sides, using muscle ultrasound scans in the transverse plane (Philips Affiniti 70; The Netherlands); quality of life (QoL), using the questionnaires CushingQoL in CD patients and AcroQoL in ACRO patients. Major results: After completion of the exercise program, CD patients had lower diastolic BP and waist circumference as compared with baseline (p&amp;lt;0.05). Physical performance globally improved (p&amp;lt;0.01 for all function tests). Femoral BMD was higher, percentage of lean mass increased while trunk fat decreased (p&amp;lt;0.01). RF and VI muscle thickness was greater at both the middle and distal third on the right side (p&amp;lt;0.01), and at the distal third on the left as compared with baseline (p&amp;lt;0.05). ACRO patients had a lower systolic BP as compared with baseline. Gait speed and hand grip strength increased while performance on the 30-Second Chair Stand improved (p&amp;lt;0.05). Muscle thickness at the middle third of the right RF was greater as compared with baseline (p&amp;lt;0.05). QoL was unchanged in both CS and ACRO patients at the end of the program. Conclusions: A customized exercise program promotes beneficial cardiometabolic and muscle changes in patients with CD and ACRO and, therefore, should be offered in a specialized pituitary clinic, within an integrated multidisciplinary team approach. Study financed by ISCIII research project number FIS PI21/01223 Presentation: 6/1/2024

Is High Intensity Interval Training (HIIT) a feasible method for improving anthropomorphic and cardiometabolic parameters in preschool children?

Is High Intensity Interval Training (HIIT) a feasible method for improving anthropomorphic and cardiometabolic parameters in preschool children?

The EAT-Lancet diet associated cardiovascular health parameters: evidence from a Brazilian study

BackgroundThe EAT-Lancet diet is a diet aimed at promoting population and planetary health from the perspective of sustainable diets in terms of environmental and health aspects. This study aimed to assess the association between adherence to the EAT-Lancet diet and cardiometabolic risk factors among adults and elderly individuals in a capital city in the northeastern region of Brazil.MethodsThis is an analytical cross-sectional observational study from a population-based sample conducted between 2019 and 2020, involving 398 non-institutionalized adults and elderly people, of both sexes from “Brazilian Usual Consumption Assessment” study (Brazuca-Natal). There was a 38% response rate due to the suspension of data collection due to the covid-19 pandemic, but According to the comparative analysis of socioeconomic and demographic variables between the surveyed and non-surveyed sectors, losses were found to be random (p = 0.135, Little’s MCAR test). Socioeconomic and lifestyle data, anthropometric measurements, and dietary consumption were collected. We used the Planetary Health Diet Index (PHDI) and the Cardiovascular Health Diet Index (CHDI) for cardiovascular health to assess adherence to the diet’s sustainability. The evaluated cardiometabolic parameters included fasting blood glucose, triglycerides, total cholesterol, HDL-C, LDL-C, and systolic and diastolic blood pressure measurements. We also assessed the presence of type 2 diabetes mellitus, arterial hypertension, and dyslipidemia. For the data analyses, sample weights and the effect of the study design were taken into account. Pearson’s chi-square test was used to evaluate the statistical significance of frequencies. Multiple linear regression models assessed the associations between PHDI and CHDI and its components and the cardiometabolic parameters.ResultsThe mean PHDI was 29.4 (95% CI 28.04:30.81), on a total score ranging from 0 to 150 points and the mean CHDI was 32.63 (95% CI 31.50:33.78), on a total score ranging from 0 to 110 points. PHDI showed a significant positive association with the final CHDI score and components of fruits, vegetables, and legumes, and a negative association with Ultra-processed Food (UPF) (p < 0.05). Notably, among the most consumed UPF, the following stand out: “packaged snacks, shoestring potatoes, and crackers” (16.94%), followed by margarine (14.14%). The PHDI exhibited a significant association with diabetes and dyslipidemia, as well as with systolic blood pressure, total cholesterol, and LDL-C.ConclusionsThe results suggest that adopting the EAT-Lancet diet is associated with the improvement of key cardiovascular health indicators.

Correlation of body mass index, with cardiometabolic and cardiorespiratory fitness in health care professionals of Multan.

The current study was conducted at Ali-Ul-Murtaza Department of Rehabilitation Sciences, Muhammad Institute of Medical and Allied Sciences, Multan, Pakistan, from October to December 2022 to explore the correlation of body mass index with cardiometabolic and cardiorespiratory parameters in 393 male and female healthcare professionals, including physiotherapists, pharmacists and medical laboratory technicians, aged 22- 40 years. The evaluation was on the basis of the Physical Activity Readiness Questionnaire, body mass index, lipid profile, body fat and correlation of blood pressure, temperature, oxygen saturation, respiration rate and heart rate with cardiorespiratory fitness assessed through shuttle-run test, step test and treadmill test. Data was analysed using SPSS 25. Of the 393 subjects, 140(35.62) were underweight, 140(35.62) were overweight and 113(28.75) were obese. Of the total, 153(38.93) were pleased with their general health, while 240(61.06) had a history of cardiovascular and metabolic conditions. There was a highly significant correlation between lipid profiles and the subjects' quality of life (p<0.05).

Lipid profile is similar in both subjects with high 1-hour postload glucose and 2-hour postload glucose and is related to cardio-metabolic profile in prediabetes

AimThe study aimed to investigate a lipid profile in people with normal glucose tolerance (NGT), NGT and 1hrOGTT > 8.6 mmol/l, and impaired glucose tolerance (IGT); and to assess its association with some cardio-metabolic parameters. Material and methodsA total of 90 subjects, of mean age 46.7 ± 10.5 years and mean BMI of 32.0 ± 6.3 kg/m2 were enrolled. They were divided into 3 groups: 19 with NGT, 22 with NGT and 1hrOGTT > 8.6 mmol/l, and 49 with IGT; and subdivided into 2 subgroups according to HOMA-IR: 40 with HOMA-IR < 2.5 and 50 with HOMA-IR ≥ 2.5. Body composition (Inbody 720) and advanced glycation end products (AGE Reader) were assessed. Two functional tests (OGTT; MMTT) were performed and AUC for glucose, insulin and triglycerides were calculated. ResultsThere was no difference across the glucose tolerance groups for all evaluated lipids. The results showed higher AUCinsulin during OGTT (p = 0.037 and 0.020), AUCtriglycerides during MMTT (p = 0.048) and triglycerides/HDL ratio (p = 0.064 and 0.016) in the 1hrOGTT and IGT subgroups with HOMA-IR ≥ 2.5 in comparison to those with HOMA-IR < 2.5. AUCtriglycerides during OGTT is independently related to body composition, b-cell function and insulin sensitivity; and AUCtriglycerides during MMTT is independently related to blood pressure and hsCRP in prediabetes. Triglycerides/HDL-C ratio emerged as an independent contributor to glycaemia and insulinemia. ConclusionOur results demonstrate a similar lipid profile in subjects with 1hrOGTT > 8.6 mmol/l and IGT, whereas increased AUCtriglycerides during OGTT, AUCtriglycerides during MMTT and triglycerides/HDL-C ratio have been found in the subgroups with insulin resistance. The triglycerides/HDL-C ratio outlined as an independent predictor of insulin secretion and action, and postload triglycerides appear to be independently related to most of the metabolic parameters.

Semaglutide: A revolution in the treatment of obesity and prevention of cardiovascular disease

Introduction and Objective: Obesity represents a significant public health concern in the 21st century, with a substantial burden of disease attributable to its complications, including type 2 diabetes, hypertension, and cardiovascular disease. The objective of this review is to evaluate the efficacy and safety of semaglutide, a GLP-1 receptor agonist, in the treatment of obesity and its impact on cardiometabolic risk factors. The Review and Methods: This review is based on an analysis of the scientific literature, including meta-analyses and clinical trials. The PubMed, Scopus and Web of Science databases were searched for publications up to 2023. Abridged Description of the State of Knowledge: The efficacy of semaglutide in reducing body weight in patients with obesity is supported by evidence from clinical trials. Its mechanism of action includes the delay of gastric emptying and the reduction of hunger. The drug has been demonstrated to exert a beneficial effect on the lipid profile and blood pressure, thereby reducing the risk of cardiovascular disease. The adverse effects, which are primarily gastrointestinal in nature, are typically mild and resolve with treatment. Summary: Semaglutide represents a promising therapeutic option for obese patients, offering an effective means of reducing body weight and improving cardiometabolic parameters. However, further studies are required to evaluate the long-term effects of this therapy and its application in different patient populations. Keywords: Semaglutide, obesity, weight reduction, GLP-1, cardiometabolic risk factors, drug treatment.