Fighting Western-diet Derived AGEs to Mitigate Muscle Wasting in Sarcobesity:Observational Study on the Relationship Between AGE Levels and Sarcobesity in an Adult Population Affected by Obesity and Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 195
- 试验地点
- 1
- 主要终点
- Number of participants with sarcopenia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients of both sexes.
- •BMI compatible with obesity and a diagnosis of type 2 diabetes under good metabolic control (HbA1c < 7.5%) within 15 years of entry into the study or diagnosis of lipodystrophy (included in the European Consortium of Lipodystrophies (ECLip) Registry (eclip-web.org))
排除标准
- •Age under 18 years.
- •Secondary obesity or genetic diseases (Prader-Willi Syndrome, Down Syndrome); metabolic and endocrine disorders (Cushing's syndrome, hypothyroidism).
- •Subjects with: Inflammatory Bowel Disease (IBD), cancer.
- •Confirmed or planned pregnancy during the study participation months.
结局指标
主要结局
Number of participants with sarcopenia
时间窗: evaluation of sarcopenia state through study completion, an average of 1 year
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.
Skeletal mass functionality for sarcopenia definition
时间窗: evaluation of sarcopenia state through study completion, an average of 1 year
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
Skeletall mass fuctionality for sarcopenia definition
时间窗: evaluation of sarcopenia state through study completion, an average of 1 year
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
Advanced glycation end products quantification
时间窗: evaluation of AGEs through study completion, an average of 1 year
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).
Endogenous and exogenous AGEs plasma quantification
时间窗: evaluation of AGEs through study completion, an average of 1 year
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
Skeletall mass calculation for sarcopenia definition
时间窗: evaluation of sarcopenia state through study completion, an average of 1 year
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
次要结局
- Dietary Inflammatory Index (DII)(evaluation of DII through study completion, an average of 1 year)
- Level of physical activity, related to sarcopenia,using a questionnaire(evaluation of METs through study completion, an average of 1 year)
- Adherence level to the Western diet with European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaires(evaluation of DII through study completion, an average of 1 year)
- Anthropometric measurements(evaluation of circumferences through study completion, an average of 1 year)
- Adherence level to the Western diet with 24h recall questionnaires(evaluation of DII through study completion, an average of 1 year)
- With questionnaires assessment of socio-demographic characteristics(evaluation of socio-demographic characteristics through study completion, an average of 1 year)
研究者
Flavia Prodam
Professor
Azienda Ospedaliero Universitaria Maggiore della Carita