An observational study in Sarcopenia and Obesity, sponsored by Azienda Ospedaliero Universitaria Maggiore della Carita. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-01.
Sponsored by Azienda Ospedaliero Universitaria Maggiore della Carita · Observational
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 and/or more pronounced onset of sarcopenia, concurrently with an increase in inflammation and oxidative stress.
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 (e.g., 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.
1,208 studies on the registry are indexed under Sarcopenia; 402 are open to participants now.
This study's planned enrollment of 195 is above the median of 120 across 419 observational studies indexed under Sarcopenia.
Browse Sarcopenia studies →Azienda Ospedaliero Universitaria Maggiore della Carita is the lead sponsor of 54 studies on the registry; 20 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Given a type I error rate (α) of 0.05 and a power of 80%, 195 subjects will be needed to observe a significant correlation between AGE levels and sarcobesity indices of at least 0.2. Considering the low prevalence of lipodystrophy and a recruitment duration of one year, approximately 35 subjects with this condition are expected to be included. The remaining 160 subjects will have diabetes and obesity. Furthermore, considering that the duration of diabetes may influence AGE levels and sarcobesity, both subjects with long-standing diabetes (80 patients) and those with less than one year of diagnosis (80 patients) will be selected, which can be considered comparable to subjects in pre-diabetes.
Exclusion Criteria:
Skeletal mass functionality for sarcopenia definition
Functional parameters of skeletal muscle defined by muscle strength measured through hand grip strength (HGS) The test requires the patient to tighten the handle the dynamometer with the maximum possible force, then maintaining the contraction for at least 5 seconds; you should repeat the test on the other hand (it is normal that the dominant expresses a higher force) and possibly repeat the test 2-3 times, with a break between different attempts, then going to calculate the average oh the kg moved with the dynamometer
Time frame: evaluation of sarcopenia state through study completion, an average of 1 year
Skeletall mass fuctionality for sarcopenia definition
Functional parameters of skeletal muscle defined by the chair test: five-times sit-to-stand test; time duration 30-second chair stand test. You measure by considering the ability in seconds to get up and sit down from the chair properly
Time frame: evaluation of sarcopenia state through study completion, an average of 1 year
Skeletall mass calculation for sarcopenia definition
The percentage of skeletal muscle mass relative to body mass will be considered. Skeletal mass will be calculated as follows: SM(Kg)=\[(h\^2/(BIA resistance)0.401)+(gender3.825)+(age\*0.071)\]+5.102 Where h indicates height measured in cm, gender is a dichotomous variable taking a value of 1 for males and 0 for females, and age is measured in years. From this measurement, the percentage of skeletal muscle mass (%SMM) will be calculated: %SMM=(SM (Kg))/(Body mass (Kg))\*100
Time frame: evaluation of sarcopenia state through study completion, an average of 1 year
Number of participants with sarcopenia
According to consensus statement of European Society for Clinical Nutrition and Metabolism (ESPEN) and dell' European Association for the Study of Obesity (EASO) guidelines, individuals with altered skeletal muscle functionality parameters (HGS \< 16 kg for females and \< 27 kg for males or chair test \>15 seconds for both males and females \[27\]), altered %BF(body fat) (≥ 25% for males and ≥35% for females \[28\]), and altered %SMM (\<35.6% (≤28.7% severe sarcopenia) for males, \<28.4% (≤23% severe sarcopenia) for females) will be defined as sarcopenic.
Time frame: evaluation of sarcopenia state through study completion, an average of 1 year
Advanced glycation end products quantification
AGE levels will be measured using skin fluorescence, using the "AGE reader mu" device (range from 1.3 to 5 level of AGEs respect to the patient's age).
Time frame: evaluation of AGEs through study completion, an average of 1 year
Endogenous and exogenous AGEs plasma quantification
AGEs will also be assessed at the plasma level in free form (ELISA, fluorescence assay) or bound to hemoglobin (HbA1c clinical practice test), both measured in pg/mL
Time frame: evaluation of AGEs through study completion, an average of 1 year
With questionnaires assessment of socio-demographic characteristics
Gender, date of birth, date of diabetes diagnosis (for diabetic subjects) are assessed through questionnaires and medical record
Time frame: evaluation of socio-demographic characteristics through study completion, an average of 1 year
Anthropometric measurements
weight is assessed in Kg with the use of the bioimpedance balance
Time frame: evaluation of weight and body composition through study completion, an average of 1 year
Anthropometric measurements
the height is measured in cm through a wall altimeter
Time frame: evaluation of height through study completion, an average of 1 year
Anthropometric measurements
the BMI (body mass index) is calculated by making the ratio of the weight to the square of the height
Time frame: evaluation of BMI (body mass index) through study completion, an average of 1 year
Anthropometric measurements
waist, hip, arm, and calf circumference are measured using an anelastic meter
Time frame: evaluation of circumferences through study completion, an average of 1 year
Dietary Inflammatory Index (DII)
Calculated using Alternative Healthy Eating Index-2010 (AHEI-2010) derived from basal metabolism assessment through fasting morning indirect calorimetry.
Time frame: evaluation of DII through study completion, an average of 1 year
Adherence level to the Western diet with European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaires
Assessed with the use of questionnaire. EPIC is used for the bromatology evaluation of the diet, so there aren't scales but only indication about the macro and micronutrient composition. This is a qualitative questionnaires and not quantitative.
Time frame: evaluation of DII through study completion, an average of 1 year
Adherence level to the Western diet with 24h recall questionnaires
Assessed with the use of questionnaires. 24h recall questionnaire is used for the bromatology evaluation of the diet, so there aren't scales but only indication about the macro and micronutrient composition. This is a qualitative questionnaires and not quantitative.
Time frame: evaluation of DII through study completion, an average of 1 year
Level of physical activity, related to sarcopenia,using a questionnaire
Physical activity is assessed using the International Physical Activity Questionnaire (IPAQ), which provides results in Metabolic Equivalent of Tasks (METs). The questions refer to activities over the past 7 days, including work, transportation, and leisure time. Moderate physical activity: Requires moderate effort and a slightly higher breathing rate than normal. One can speak but not sing during this activity. Intense physical activity: Requires significant effort and a much higher breathing rate, causing sweating and making it difficult to talk. The METs scale is as follows: Less than 700 METs: Inactive 700 to 2519 METs: Sufficiently active More than 2520 METs: Active
Time frame: evaluation of METs through study completion, an average of 1 year
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Azienda Ospedaliero Universitaria Maggiore della Carita