Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06438900
Status:
RECRUITING
Last Update Posted:
2024-06-03
First Post:
2024-05-14
Brief Title:
Investigating the Link Between Advanced Glycation End Products AGEs and Muscle Wasting in Sarcobesity
Sponsor:
Azienda Ospedaliero Universitaria Maggiore della Carita
Organization:
Azienda Ospedaliero Universitaria Maggiore della Carita
Study Overview
Official Title:
Fighting Western-diet Derived AGEs to Mitigate Muscle Wasting in SarcobesityObservational Study on the Relationship Between AGE Levels and Sarcobesity in an Adult Population Affected by Obesity and Type 2 Diabetes Mellitus
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Westernage
Brief Summary:
The study aims to explore whether a high level of AGEs Advanced Glycation end products derived from the diet may mediate diet-related muscle loss in Western-type diet influencing the onset and progression of sarcopenia predisposing to earlier and more severe metabolic consequences including type 2 diabetes T2D
The primary objective of the study is to investigate how the accumulation of AGEs is correlated with muscle loss in adult patients with obesity and type 2 diabetes or lipodystrophy in order to identify possible targets to mitigate the metabolic alterations caused by the Western diet WD Specifically circulating AGEs levels on the skin will be evaluated and correlated with the stage of sarcopenia in a group of patients with obesity and a T2D diagnosis Furthermore the relationship between disease duration and AGE levels will be assessed
A secondary objective will be to analyze the clinical data obtained to identify metabolites and metabolic pathways responsible for the phenotype induced by the WD
The ultimate aim of the study is therefore to verify whether high levels of AGEs are correlated with an early andor more pronounced onset of sarcopenia concurrently with an increase in inflammation and oxidative stress
The primary objective of the study is to investigate how the accumulation of AGEs is correlated with muscle loss in adult patients with obesity and type 2 diabetes or lipodystrophy in order to identify possible targets to mitigate the metabolic alterations caused by the Western diet WD Specifically circulating AGEs levels on the skin will be evaluated and correlated with the stage of sarcopenia in a group of patients with obesity and a T2D diagnosis Furthermore the relationship between disease duration and AGE levels will be assessed
A secondary objective will be to analyze the clinical data obtained to identify metabolites and metabolic pathways responsible for the phenotype induced by the WD
The ultimate aim of the study is therefore to verify whether high levels of AGEs are correlated with an early andor more pronounced onset of sarcopenia concurrently with an increase in inflammation and oxidative stress
Detailed Description:
The study in question is of a cross-sectional observational type The reference population is defined by patients with obesity and a diagnosis of T2D within 15 years of entry into the study or patients with concomitant type 2 diabetes and lipodystrophy syndrome This population was chosen because they are at high risk of sarcopenia
Lipodystrophy includes a heterogeneous spectrum of genetic and acquired diseases characterized by loss of subcutaneous adipose tissue ectopic fat accumulation insulin resistance metabolic and cardiovascular diseases premature aging sarcopenia muscle pain high-grade inflammation epigenetic dysregulation and mitochondrial dysfunction Therefore patients with T2D and lipodystrophy are highly inflamed as they generally present with a more severe T2D phenotype presumed sarcopenic and with a high rate of endogenous AGE production Patients with concurrent lipodystrophy and T2D will be recruited as sarcopenic and obese subjects representing an excellent strategy for comparison with diabetic individuals without lipodystrophy
SUBJECTS AND METHODS A total of 195 consecutive subjects will be enrolled in the study from the Endocrinology Unit of the University of Eastern Piedmont between April 2024 and April 2026 who meet the inclusion criteria
Study duration
The study will last for two years corresponding to the enrollment period given the cross-sectional nature of the study
Statistical Analysis
Descriptive statistics will be used to summarize sociodemographic anthropometric clinical and lifestyle-related information collected Categorical variables will be summarized using absolute frequencies and percentages while numerical variables will be summarized using mean and standard deviation or median and interquartile range if not normally distributed according to the Shapiro-Wilk test and after observation of Q-Q plots quantile-quantile plot
The Pearson correlation coefficient or the corresponding non-parametric Spearman rank correlation coefficient and confidence intervals will be initially calculated to assess the correlation between the levels of individual AGEs and skeletal muscle mass SMM handgrip strength HGS parameters of body composition and functional parameters of skeletal muscle Subsequently linear regression models will be used to evaluate the relationship between AGEs and sarcopenia-defining indices adjusted for age sex duration of diabetes and other potential confounding factors such as inflammation adherence to the Western diet and levels of physical activity The LASSO method will be used for variable selection in multivariable regression models
Univariable and multivariable Poisson regression models with robust variance will be used to estimate relative prevalence risks for the association between AGEs and patient characteristics with sarcopenia presence and the corresponding confidence intervals
An integration of clinical data biochemical data AGE levels and patient omic signatures will be performed to develop a multifactorial diagnostic model using multivariate statistical analysis eg factor analysis principal component analysis cluster analysis discriminant analysis partial least squares analysis logistic regression and data-driven approaches Machine learning algorithms will be applied to prioritize and weigh risk factors These analyses will be conducted with internal statistical consultation already utilized by the group
Expected Results
With this study the investigators expect to obtain further information and correlations between nutritional assessment and its impact on inflammation sarcopenia definition and progression obesity and T2D based on body measurements and clinical parameters Through biochemical hormonal and metabolomic analyses conducted on biological samples te investigators expect to identify possible markers related to the presence of AGEs In conclusion the primary expected outcome would be to identify a positive correlation between AGE accumulation in at least one compartment skin plasma urine and the severity of sarcopenia thus obtaining a rapid and non-invasive method to identify individuals at high risk of developing muscle wasting MW and identify correlations between AGE levels and other metabolic characteristics even in lipodystrophic pathology
Lipodystrophy includes a heterogeneous spectrum of genetic and acquired diseases characterized by loss of subcutaneous adipose tissue ectopic fat accumulation insulin resistance metabolic and cardiovascular diseases premature aging sarcopenia muscle pain high-grade inflammation epigenetic dysregulation and mitochondrial dysfunction Therefore patients with T2D and lipodystrophy are highly inflamed as they generally present with a more severe T2D phenotype presumed sarcopenic and with a high rate of endogenous AGE production Patients with concurrent lipodystrophy and T2D will be recruited as sarcopenic and obese subjects representing an excellent strategy for comparison with diabetic individuals without lipodystrophy
SUBJECTS AND METHODS A total of 195 consecutive subjects will be enrolled in the study from the Endocrinology Unit of the University of Eastern Piedmont between April 2024 and April 2026 who meet the inclusion criteria
Study duration
The study will last for two years corresponding to the enrollment period given the cross-sectional nature of the study
Statistical Analysis
Descriptive statistics will be used to summarize sociodemographic anthropometric clinical and lifestyle-related information collected Categorical variables will be summarized using absolute frequencies and percentages while numerical variables will be summarized using mean and standard deviation or median and interquartile range if not normally distributed according to the Shapiro-Wilk test and after observation of Q-Q plots quantile-quantile plot
The Pearson correlation coefficient or the corresponding non-parametric Spearman rank correlation coefficient and confidence intervals will be initially calculated to assess the correlation between the levels of individual AGEs and skeletal muscle mass SMM handgrip strength HGS parameters of body composition and functional parameters of skeletal muscle Subsequently linear regression models will be used to evaluate the relationship between AGEs and sarcopenia-defining indices adjusted for age sex duration of diabetes and other potential confounding factors such as inflammation adherence to the Western diet and levels of physical activity The LASSO method will be used for variable selection in multivariable regression models
Univariable and multivariable Poisson regression models with robust variance will be used to estimate relative prevalence risks for the association between AGEs and patient characteristics with sarcopenia presence and the corresponding confidence intervals
An integration of clinical data biochemical data AGE levels and patient omic signatures will be performed to develop a multifactorial diagnostic model using multivariate statistical analysis eg factor analysis principal component analysis cluster analysis discriminant analysis partial least squares analysis logistic regression and data-driven approaches Machine learning algorithms will be applied to prioritize and weigh risk factors These analyses will be conducted with internal statistical consultation already utilized by the group
Expected Results
With this study the investigators expect to obtain further information and correlations between nutritional assessment and its impact on inflammation sarcopenia definition and progression obesity and T2D based on body measurements and clinical parameters Through biochemical hormonal and metabolomic analyses conducted on biological samples te investigators expect to identify possible markers related to the presence of AGEs In conclusion the primary expected outcome would be to identify a positive correlation between AGE accumulation in at least one compartment skin plasma urine and the severity of sarcopenia thus obtaining a rapid and non-invasive method to identify individuals at high risk of developing muscle wasting MW and identify correlations between AGE levels and other metabolic characteristics even in lipodystrophic pathology
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None