Abstract
Regulation of blood glucose requires precise coordination between different endocrine systems and multiple organs. Type 2 diabetes mellitus (T2D) arises from a dysregulated response to elevated glucose levels in the circulation. Globally, the prevalence of T2D has increased dramatically in all age groups. T2D in older adults is associated with higher mortality and reduced functional status, leading to higher rate of institutionalization. Despite the potential healthcare challenges associated with the presence of T2D in the elderly, the pathogenesis and phenotype of late-onset T2D is not well studied. Here we applied untargeted metabolite profiling of urine samples from people with and without late-onset T2D using ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS) to identify urinary biomarkers for late-onset T2D in the elderly. Statistical modeling of measurements and thorough validation of structural assignment using liquid chromatography tandem mass-spectrometry (LC-MS/MS) have led to the identification of metabolite biomarkers associated with late-onset T2D. Lower levels of phenylalanine, acetylhistidine, and cyclic adenosine monophosphate (cAMP) were found in urine samples of T2D subjects validated with commercial standards. Elevated levels of 5′-methylthioadenosine (MTA), which previously has only been implicated in animal model of diabetes, was found in urine of older people with T2D.
Highlights
Diabetes mellitus is a highly prevalent chronic disorder characterized by complex changes of metabolism in the body systems
29.5% were on statins, while none were treated with metformin[22]
Namely phenylalanine and acetylhistidine, were found to be reduced in urine samples of late-onset Type 2 diabetes mellitus (T2D) subjects. This is in agreement with the majority of the studies in younger-onset T2Ds that reported perturbations in urinary amino acids in the context of chronic hyperglycemia
Summary
Diabetes mellitus is a highly prevalent chronic disorder characterized by complex changes of metabolism in the body systems. Metabolomics study involves the use of high-throughput technologies, e.g. liquid chromatography tandem mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR), to comprehensively identify and quantify all or selected groups of endogenous small molecule metabolites[14] This new approach has been successfully applied to describe metabolic phenotypes in T2D15. In the light of getting a better insight into the complex age-associated changes in fuel metabolism and regulation related to diabetes, we have studied a cohort of community-dwelling older people from the Southern part of Germany. In this case-control study, untargeted urine metabolomics was performed on a cohort of older people aged 70 years and older with late-onset type 2 diabetes mellitus and respective controls[20]. Data obtained were used to compare with the already published results from metabolomics studies in T2D subjects where the disease onset has been before 70 years of age
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