Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

Ma, Rong

doi:10.3390/cells10112832

Cited by 126 publications

(79 citation statements)

References 172 publications

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“…The poor prognosis of DKD severely reduces the quality of life and imposes a substantial financial burden on patients. The pathogenesis of DKD remains unclear, and there is a lack of comprehensive awareness of the progression of DKD ( Winther et al, 2020 ; Jin and Ma, 2021 ), which severely restricts its prevention and diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

et al. 2022

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Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.

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Section: Introductionmentioning

confidence: 99%

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

et al. 2022

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“…Although the role of circulating amino acids in diabetes complications is unclear, they have been reported to play a vital role in human metabolic pathways including gluconeogenesis (21)(22)(23) and the secretion of insulin and glucagon (24,25). Limited studies on circulating amino acids, and diabetes foot complications are available (10,26). A recent study by Hung et al found an association between DFU healing and plasma levels of four amino acids.…”

Section: Discussionmentioning

confidence: 99%

“…One of the emerging frontiers in prevention and treatment of the diabetic foot complication is metabolomics. Metabolomics has shown promise in identifying pathways and biomarkers associated with risk of developing diabetes (8,9) and its complications (10). We have recently identified circulating risk metabolites and lipids associated with development of various microvascular complications in diabetes including retinopathy (11), renal disease (12)(13)(14), and a severe form of diabetic neuropathy called cardiovascular autonomic neuropathy (15).…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Risk Predictors of Diabetic Foot Complications: a longitudinal observational study in Type 1 Diabetes

Andersen

Suvitaival

Trošt

et al. 2022

Preprint

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Diabetic foot complications is a collective term used for the ailments of the foot that individuals with diabetes incur. The different entities of the term diabetic foot complications are closely linked to each other and several of the other complications of diabetes. Despite implementation of national and international preventive guidelines, diabetic foot complications are still a growing challenge to the individual and society in general. This highlights the need for new strategies in the treatment and prevention of diabetic foot complications. The aim of the study was to investigate associations between plasma metabolites and diabetic foot complications (diabetic foot ulcer (DFU), amputations and Charcot’s Arthropathy) in individuals with diabetes type 1. Non targeted plasma metabolites (n=75) were analyzed using mass spectrometry in a cohort comprising 637 individuals (55% male) with diabetes type 1. Cross sectional associations between metabolites and diabetic foot complications was analysed by linear regression at baseline and by Cox proportional hazards model at follow-up and adjusted for relevant confounders. The median follow up time was 10 years, age 55 (47, 64) years, diabetes duration 35 (25, 44) years and HbA1c 64 (56, 72) mmol/mol. In the adjusted model, four amino acids (proline, threonine, valine, and leucine) were associated with decreased incidence of Charcot’s arthropathy at baseline (padjusted< 0.5). In addition, the plasma levels of ribonic acid was associated with an increased risk of diabetic foot ulcers during follow-up (HR 1.38(1.06-1.8) p<0.05). This study identifies novel circulating metabolites, as potential biomarkers for risk of diabetic foot complications.One Sentence SummarySeveral plasma metabolites show promise as risk markers of diabetic foot complications.

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“…7 Cluster included: 1,2-dipalmitoyl-GPC (16:0/16:0), 1,5-anhydroglucitol (1,5-AG), 2-linoleoylglycerol (18:2), N-acetyltaurine, glycosyl-N-palmitoyl-sphingosine (d18:1/16:0), linoleoylcholine*. 8 Cluster included: eicosenoate (20:1), 3-hydroxybutyrate (BHBA), 3-hydroxydecanoate, docosadienoate (22:2n6), 2-hydroxybutyrate/2-hydroxyisobutyrate, oleate/vaccenate (18:1). 9 Cluster included: maltose, glycerol 3-phosphate, mannitol/sorbitol, beta-citrylglutamate, phosphate.…”

Section: Progression To Type 2 Diabetesmentioning

confidence: 99%

Novel Plasma Metabolomic Markers Associated with Diabetes Progression in Older Puerto Ricans

et al. 2022

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We assessed longitudinal associations between plasma metabolites, their network-derived clusters, and type 2 diabetes (T2D) progression in Puerto Rican adults, a high-risk Hispanic subgroup with established health disparities. We used data from 1221 participants free of T2D and aged 40–75 years at baseline in the Boston Puerto Rican Health and San Juan Overweight Adult Longitudinal Studies. We used multivariable Poisson regression models to examine associations between baseline concentrations of metabolites and incident T2D and prediabetes. Cohort-specific estimates were combined using inverse-variance weighted fixed-effects meta-analyses. A cluster of 13 metabolites of branched chain amino acids (BCAA), and aromatic amino acid metabolism (pooled IRR = 1.87, 95% CI: 1.28; 2.73), and a cell membrane component metabolite cluster (pooled IRR = 1.54, 95% CI: 1.04; 2.27) were associated with a higher risk of incident T2D. When the metabolites were tested individually, in combined analysis, 5 metabolites involved in BCAA metabolism were associated with incident T2D. These findings highlight potential prognostic biomarkers to identify Puerto Rican adults who may be at high risk for diabetes. Future studies should examine whether diet and lifestyle can modify the associations between these metabolites and progression to T2D.

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Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

Cited by 126 publications

References 172 publications

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease

Metabolomic Risk Predictors of Diabetic Foot Complications: a longitudinal observational study in Type 1 Diabetes

Novel Plasma Metabolomic Markers Associated with Diabetes Progression in Older Puerto Ricans

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