Type 2 diabetes mellitus (T2DM) is a leading cause of disability globally. Frailty is a high-impact geriatric condition that increases the risk of negative health outcomes and imposes remarkable health and social burden. Both frailty and T2DM show multifaceted pathophysiology, phenotypic heterogeneity, and fluctuating manifestations that challenge their management, especially when the two conditions co-occur. Muscle wasting and its correlates (e.g., metabolic perturbations and functional decline) that underlie frailty may exacerbates clinical manifestations of T2DM in older people, resulting in worse prognosis. The intrinsic complexity of frailty and T2DM has hampered the identification of clinically meaningful biomarkers to track the clinical progression of the two conditions over time and to monitor the efficacy of pharmacological and lifestyle interventions. Here, we propose an innovative approach for biomarker identification that couples multi-platform analytical determinations with chemometric modeling strategies. This novel multi-marker discovery process is described in the context of the “Metabolic biomarkers of frailty in older people with type 2 diabetes mellitus” (MetaboFrail) study that aimed at identifying metabolic biomarkers of frailty in functionally limited older persons with T2DM.

2型糖尿病（T2DM）是全球残疾的主要原因。衰弱是一种高影响力的老年病，增加了负面健康后果的风险，并给健康和社会带来了沉重负担。体弱和T2DM均表现出多方面的病理生理学，表型异质性和易变的表现，这对他们的管理提出了挑战，特别是当这两种情况同时发生时。虚弱的肌肉消瘦及其相关因素（例如，代谢紊乱和功能下降）可能会加剧老年人中T2DM的临床表现，导致预后更差。身体虚弱和T2DM的内在复杂性阻碍了临床上有意义的生物标志物的鉴定，以追踪两种疾病随时间推移的临床进展并监测药理和生活方式干预措施的有效性。在这里，我们提出了一种创新的生物标志物识别方法，该方法将多平台分析测定与化学计量学建模策略结合在一起。这种新颖的多标记物发现过程是在“ 2型糖尿病老年人体弱的代谢生物标记”（MetaboFrail）研究的背景下进行的，该研究旨在鉴定功能受限的T2DM老年人体弱的代谢生物标记。我们提出了一种创新的生物标志物识别方法，该方法将多平台分析测定与化学计量学建模策略结合在一起。这种新颖的多标记物发现过程是在“ 2型糖尿病老年人体弱的代谢生物标记”（MetaboFrail）研究的背景下进行的，该研究旨在鉴定功能受限的T2DM老年人体弱的代谢生物标记。我们提出了一种创新的生物标志物识别方法，该方法将多平台分析测定与化学计量学建模策略结合在一起。这种新颖的多标记物发现过程是在“ 2型糖尿病老年人体弱的代谢生物标记”（MetaboFrail）研究的背景下进行的，该研究旨在鉴定功能受限的T2DM老年人体弱的代谢生物标记。