Plasma leptin level mirrors metabolome alterations in young adults

Kumar, Ashok; Satheesh, Gopika; Vijayakumar, G.; Chandran, Mahesh; Prabhu, Priya R.; Simon, Leena; Kutty, V. Raman; Cc, Kartha; Jaleel, Abdul

doi:10.1007/s11306-020-01708-9

Cited by 4 publications

(3 citation statements)

References 65 publications

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“…The evidence supports the role of leptin as a mediator of energy and hormone metabolism. [ 160 ] BCAAs and LysoPC The role of BCAAs and LysoPCs in the progression from prediabetes to T2DM was evaluated using a targeted metabolomic approach. It was demonstrated that BCAAs (isoleucine, leucine, and valine) and LysoPCs, especially LysoPCs acyl C28:1, contribute to the progression of diabetes.…”

Section: Clinically Validated Biomarkersmentioning

confidence: 99%

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

et al. 2022

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Purpose of Review Diabetes mellitus is a complex, chronic illness characterized by elevated blood glucose levels that occurs when there is cellular resistance to insulin action, pancreatic β-cells do not produce sufficient insulin, or both. Diabetes prevalence has greatly increased in recent decades; consequently, it is considered one of the fastest-growing public health emergencies globally. Poor blood glucose control can result in long-term micro- and macrovascular complications such as nephropathy, retinopathy, neuropathy, and cardiovascular disease. Individuals with diabetes require continuous medical care, including pharmacological intervention as well as lifestyle and dietary changes. Recent Findings The most common form of diabetes mellitus, type 2 diabetes (T2DM), represents approximately 90% of all cases worldwide. T2DM occurs more often in middle-aged and elderly adults, and its cause is multifactorial. However, its incidence has increased in children and young adults due to obesity, sedentary lifestyle, and inadequate nutrition. This high incidence is also accompanied by an estimated underdiagnosis prevalence of more than 50% worldwide. Implementing successful and cost-effective strategies for systematic screening of diabetes mellitus is imperative to ensure early detection, lowering patients' risk of developing life-threatening disease complications. Therefore, identifying new biomarkers and assay methods for diabetes mellitus to develop robust, non-invasive, painless, highly-sensitive, and precise screening techniques is essential. Summary This review focuses on the recent development of new clinically validated and novel biomarkers as well as the methods for their determination that represent cost-effective alternatives for screening and early diagnosis of T2DM.

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Section: Clinically Validated Biomarkersmentioning

confidence: 99%

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

et al. 2022

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“…Most studies included in the SLR were in exclusively adult study populations. Three studies studied children 53 , 61 , 62 and two studies 52 , 57 adolescents and young adults. Age is another influential factor in the composition of the metabolome that may need additional adjustment strategies in the long term 63 .…”

Section: Discussionmentioning

confidence: 99%

“…Because of the large number of associations usually present in metabolomics studies, this would greatly increase the possibility for future studies to build on. Another important observation in the SLR is that only four out of 50 studies 43,52,57,58 stratified by sex, with two additional studies having cohorts restricted to either males 59 or females 60 , though many additional studies adjusted for or matched by sex. Given how strong the influence [11][12][13]15,16,30,31,52 of sex is on many different aspects of the metabolome, a better and ideally unified strategy to account for these influences in future studies is needed.…”

Section: Discussionmentioning

confidence: 99%

Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study

Brachem

Weinhold²,

Alexy³

et al. 2023

Sci Rep

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Metabolomics-derived metabolites (henceforth metabolites) may mediate the relationship between modifiable risk factors and clinical biomarkers of metabolic health (henceforth clinical biomarkers). We set out to study the associations of metabolites with clinical biomarkers and a potential mediation effect in a population of young adults. First, we conducted a systematic literature review searching for metabolites associated with 11 clinical biomarkers (inflammation markers, glucose, blood pressure or blood lipids). Second, we replicated the identified associations in a study population of n = 218 (88 males and 130 females, average age of 18 years) participants of the DONALD Study. Sex-stratified linear regression models adjusted for age and BMI and corrected for multiple testing were calculated. Third, we investigated our previously reported metabolites associated with anthropometric and dietary factors mediators in sex-stratified causal mediation analysis. For all steps, both urine and blood metabolites were considered. We found 41 metabolites in the literature associated with clinical biomarkers meeting our inclusion criteria. We were able to replicate an inverse association of betaine with CRP in women, between body mass index and C-reactive protein (CRP) and between body fat and leptin. There was no evidence of mediation by lifestyle-related metabolites after correction for multiple testing. We were only able to partially replicate previous findings in our age group and did not find evidence of mediation. The complex interactions between lifestyle factors, the metabolome, and clinical biomarkers warrant further investigation.

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A new statistical workflow (R-packages based) to investigate associations between one variable of interest and the metabolome

Ferrario,

Bub,

Frommherz

et al. 2023

Metabolomics

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Introduction In metabolomics, the investigation of associations between the metabolome and one trait of interest is a key research question. However, statistical analyses of such associations are often challenging. Statistical tools enabling resilient verification and clear presentation are therefore highly desired. Objectives Our aim is to provide a contribution for statistical analysis of metabolomics data, offering a widely applicable open-source statistical workflow, which considers the intrinsic complexity of metabolomics data. Methods We combined selected R packages tailored for all properties of heterogeneous metabolomics datasets, where metabolite parameters typically (i) are analyzed in different matrices, (ii) are measured on different analytical platforms with different precision, (iii) are analyzed by targeted as well as non-targeted methods, (iv) are scaled variously, (v) reveal heterogeneous variances, (vi) may be correlated, (vii) may have only few values or values below a detection limit, or (viii) may be incomplete. Results The code is shared entirely and freely available. The workflow output is a table of metabolites associated with a trait of interest and a compact plot for high-quality results visualization. The workflow output and its utility are presented by applying it to two previously published datasets: one dataset from our own lab and another dataset taken from the repository MetaboLights. Conclusion Robustness and benefits of the statistical workflow were clearly demonstrated, and everyone can directly re-use it for analysis of own data.

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Plasma leptin level mirrors metabolome alterations in young adults

Cited by 4 publications

References 65 publications

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study

A new statistical workflow (R-packages based) to investigate associations between one variable of interest and the metabolome

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