Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies

Chung, Yuen‐Li; Rider, Lisa G.; Bell, Jimmy D.; Summers, Ronald M.; Rennebohm, Robert M.; Passo, Murray H.; Hicks, Jeanne E.; Miller, Frederick W.; Scott, David

doi:10.1002/art.21331

Cited by 37 publications

(21 citation statements)

References 29 publications

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“…The creatinine depletion observed in urine from the animal models and T2DM patients may have arisen because of a variety of reasons such as changes in muscle mass, creatinine reabsorption, cell leakage, and changes in caloric intake. However, a decline in the renal glomerular filtration rate (GFR) associated with diabetic nephropathy (8,29,39) would not only explain this observation but also a variety of other metabolite changes. For example, reduced urinary allantoin excretion is also indicative of reduced GFR as allantoin is not reabsorbed across the proximal tubule, and thus its urinary concentration is thought to accurately reflect glomerular filtration (5,19).…”

Section: Discussionmentioning

confidence: 99%

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

Salek

Maguire

Bentley

et al. 2007

Physiological Genomics

371

345

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Type 2 diabetes mellitus is the result of a combination of impaired insulin secretion with reduced insulin sensitivity of target tissues. There are an estimated 150 million affected individuals worldwide, of whom a large proportion remains undiagnosed because of a lack of specific symptoms early in this disorder and inadequate diagnostics. In this study, NMR-based metabolomic analysis in conjunction with multivariate statistics was applied to examine the urinary metabolic changes in two rodent models of type 2 diabetes mellitus as well as unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes. 1H-NMR spectra of urine were used in conjunction with uni- and multivariate statistics to identify disease-related metabolic changes in these two animal models and human sufferers. This study demonstrates metabolic similarities between the three species examined, including metabolic responses associated with general systemic stress, changes in the TCA cycle, and perturbations in nucleotide metabolism and in methylamine metabolism. All three species demonstrated profound changes in nucleotide metabolism, including that of N-methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide unique biomarkers for following type 2 diabetes mellitus progression.

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Section: Discussionmentioning

confidence: 99%

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

Salek

Maguire

Bentley

et al. 2007

Physiological Genomics

371

345

View full text Add to dashboard Cite

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“…Due to limitations in laboratory resources most studies have tested samples from 10-30 patients, with a control or normal group of at least similar size. This limitation in the number of samples is compounded in human studies where subject compliance may be poor (Chung et al 2005). Although reference to Geigy scientific tables is common, the information is based upon limited research with similarly small sample sizes (Geigy 1981(Geigy -1992.…”

Section: Introductionmentioning

confidence: 99%

Variation of metabolites in normal human urine

et al. 2007

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Urine is often sampled from patients participating in clinical and metabolomic studies. Biological homeostasis occurs in humans, but little is known about the variability of metabolites found in urine. It is important to define the inter-and intra-individual metabolite variance within a normal population before scientific or clinical conclusions are made regarding different pathophysiologies. This study investigates the variability of selected urine metabolites in a group of 60 healthy men and women over a period of 30 days. To monitor individual variation, 6 women from the normal population were randomly selected and followed for 30 days. To determine the influence of extraneous environmental factors urine was collected from 25 guinea pigs with similar genetics, diet, and living environment. For both studies, 24 metabolites were identified and quantified using high-resolution 1 H nuclear magnetic resonance spectroscopy (NMR). The data demonstrated large inter and intra-individual variation in metabolite concentrations in both normal human and control animal populations. A defined normal baseline is essential before any conclusions may be drawn regarding changes in urine metabolite concentrations.

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“…Bilgic et al [38•] recently showed a significant correlation between a type I interferon signature and disease activity in adults and children with IIM. Additionally, the ratio between urine creatine and creatinine has been shown to correlate with disease damage [39]. There is considerable optimism that one of these markers (or another related one) will become a useful assessment in children with JIIM in the future.…”

Section: Laboratory Assessmentmentioning

confidence: 99%

Update on the Assessment of Children with Juvenile Idiopathic Inflammatory Myopathy

Huber

2010

Curr Rheumatol Rep

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The availability of validated measurement tools to assess children with juvenile idiopathic inflammatory myopathies is critical to clinical care and to ongoing research into new therapeutic modalities and approaches. Recent work has led to the development of tools for assessment of muscle strength and physical function, skin disease, global disease activity and damage, extramuscular disease, and quality of life. Ongoing work is attempting to integrate these assessments into core sets and definitions of improvement and flare. Future work will refine these assessments and definitions and--where there are multiple choices--determine which tools constitute an optimal assessment.

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Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies

Cited by 37 publications

References 29 publications

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human

Variation of metabolites in normal human urine

Update on the Assessment of Children with Juvenile Idiopathic Inflammatory Myopathy

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