Metabolomics in diabetic complications

Filla, Laura A.; Edwards, John A.

doi:10.1039/c6mb00014b

Cited by 79 publications

(63 citation statements)

References 121 publications

(181 reference statements)

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“…Given the imperfections in the armamentarium of conventional biomarkers for diagnosis, prognosis, or risk prediction and disease prevention at the individual patient level, there is an ongoing effort using novel high-precision laboratory techniques to discover new biomarkers that will increase the sensitivity and specificity above current clinical tests [1][2][3][4]. Glycoproteins play key roles in inflammatory and pathological processes [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Connelly

Gruppen

Otvos

et al. 2016

Clinica Chimica Acta

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The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity.

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Section: Introductionmentioning

confidence: 99%

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Connelly

Gruppen

Otvos

et al. 2016

Clinica Chimica Acta

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“…Macrovascular complications [5,11], which represent the leading cause of death in DM2 [7,12], have been associated with poor glycemic control [13] and blood oxidative stress (BLOS) [14]. This happens because of the induction of superoxide release due to changes in the electron transport chain of mitochondria [15] and increased activity of NADPH oxidase [14].…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

Dries¹,

Soares

Ziulkoski

et al. 2017

Sci Med

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AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up. METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients' questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson's correlation and Spearman's correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and end of the study was evaluated using Student's t-test or Wilcoxon U test. The significance level was set at 5%. RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m 2 , who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient. CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.KEY WORDS: diabetes mellitus; oxidative stress; superoxide dismutase; malondialdehyde; metformin; diabetic complications. RESUMOOBJETIVOS: Avaliar parâmetros de estresse oxidativo em pacientes com diabetes mellitus tipo 2 em uso de metformina, relacionando estes valores a seus efeitos adversos, níveis plasmáticos, controle glicêmico, complicações diabéticas, perfil lipídico, e a influência do acompanhamento farmacoterapêutico. MÉTODOS: Foram avaliados pacientes com diabetes mellitus tipo 2, em uso de metformina, em acompanhamento farmacoterapêutico por quatro meses. O acompanhamento farmacoterapêutico consistiu na prestação de informações e no esclarecimento de dúvidas dos pacientes sobre a medicação e a doença. Além disto, foram verificados os horá...

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“…Therefore, we chose a follow-up chart of the cross-sectional urine analysis of T2D patients with MA for this study. In our analysis we used untargeted metabolomics with the ability to uncover novel and potentially relevant metabolites, combined with targeted metabolomics, as commercially available standards can be used as calibrants to establish quantitation [35]. …”

Section: Discussionmentioning

confidence: 99%

5-Hydroxyhexanoic Acid Predicts Early Renal Functional Decline in Type 2 Diabetes Patients with Microalbuminuria

Tang

You

Liu

et al. 2019

Kidney Blood Press Res

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Background/Aims: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Microalbuminuria (MA) is widely used to predict early progressive renal function decline (ERFD) of DN in type 2 diabetes mellitus (T2D) patients, but the sensitivity and specificity of MA have been questioned. Here, we determined the urine metabolites differences between T2D patients with MA who maintained stable renal function and those who progressed to ERFD in order to identify specific biomarkers of the progression of renal dysfunction. Methods: A total of 102 T2D patients with MA and normal renal function at baseline were followed up for 5–6 years. Of these, 52 patients were selected and classified into two groups according to the later renal function; 25 patients who experienced ERFD were regarded as the progressive group, while 27 patients who maintained stable renal function were considered as the stable group. In the pilot study, untargeted, broad-spectrum urine metabolomics was performed on the urine of 12 subjects from the progressive group (5 patients as “progressors”) and stable group (7 patients as “non-progressors”) to discover candidate markers. We then used a targeted metabolomics analysis to identify the selected markers in the urine of an additional 40 patients (20 from the progressive group as cases, and 20 from the stable group as controls) in the validation study. Results: A total of 318 known metabolites were detected in the pilot study and 6 metabolites with significant difference between progressors and non-progressors were identified. The levels of 4 metabolites, including azelaic acid, adipic acid, 5-hydroxyhexanoic acid, and L-tryptophan decreased significantly, while levels of L-pyroglutamic acid and D-norvaline increased observably in the progressors compared with non-progressors. Furthermore, in the validation study, 6 metabolites were confirmed by quantitative measurements and their concentrations were consistent with the changes in the pilot study. Concentrations of L-pyroglutamic acid and D-norvaline still increased in the cases, but were not statistically significant. Of the 4 metabolites with decreased concentrations among the cases, only 5-hydroxyhexanoic acid remained statistically significant while the other 3 metabolites did not differ between cases and controls. Conclusion: We have identified urine metabolites and shown that 5-hydroxyhexanoic acid can be used as a predictor of progression of ERFD in T2D patients with MA. This finding provides the new perspective that 5-hydroxyhexanoic acid may be useful to identify T2D patients with MA who are at risk of ERFD.

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Metabolomics in diabetic complications

Cited by 79 publications

References 121 publications

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

5-Hydroxyhexanoic Acid Predicts Early Renal Functional Decline in Type 2 Diabetes Patients with Microalbuminuria

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