MECHANISMS IN ENDOCRINOLOGY: Proteomic biomarkers of type 2 diabetes mellitus risk in women with polycystic ovary syndrome

Galazis, Nicolas; Afxentiou, Thalia; Xenophontos, Mikalena; Diamanti-Kandarakis, Evanthia; Atiomo, William

doi:10.1530/eje-12-0718

Cited by 24 publications

(21 citation statements)

References 54 publications

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“…Publications so far in this field have sampled various tissues in small numbers of women and proposed a panel of possible biomarkers. With plasma being the most easily accessible tissue, the early studies have shown altered expression of acute-phase response proteins and markers of inflammation (110,111). From omental adipose tissue, proteins related to intermediate metabolism, oxidative stress and differentiation have been described (111,112).…”

Section: Laboratory and Biomarkersmentioning

confidence: 99%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

European Journal of Endocrinology

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576

492

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Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

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Section: Laboratory and Biomarkersmentioning

confidence: 99%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

European Journal of Endocrinology

Self Cite

576

492

View full text Add to dashboard Cite

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“…Therefore, flotillin overexpression could induce the upregulation of EGFR signaling, thereby leading to disruption of cadherin-mediated intercellular adhesion. Reciprocally, cadherins also exert pro-oncogenic effects, notably in breast tumors, by participating in EGFR activation, either independent (Galazis et al, 2013). Overexpression of flotillins in tumors cells is associated with metastasis formation but the molecular mechanisms involved remain to be determined.…”

Section: Disease Relevance Of Flotillin-mediated Roles At Adhesionsmentioning

confidence: 99%

Flotillins in intercellular adhesion – from cellular physiology to human diseases

Bodin

Planchon

Morris

et al. 2014

Journal of Cell Science

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Flotillin 1 and 2 are ubiquitous and highly conserved proteins. They were initially discovered in 1997 as being associated with specific caveolin-independent cholesterol-and glycosphingolipid-enriched membrane microdomains and as being expressed during axon regeneration. Flotillins have a role in a large number of physiopathological processes, mainly through their function in membrane receptor clustering and in the regulation of clathrinindependent endocytosis. In this Commentary, we summarize the research performed so far on the role of flotillins in cell-cell adhesion. Recent studies have demonstrated that flotillins directly regulate the formation of cadherin complexes. Indeed, flotillin microdomains are required for the dynamic association and stabilization of cadherins at cell-cell junctions and also for cadherin signaling. Moreover, because flotillins regulate endocytosis and also the actin cytoskeleton, they could have an indirect role in the assembly and stabilization of cadherin complexes. Because it has also recently been shown that flotillins are overexpressed during neurodegenerative diseases and in human cancers, where their upregulation is associated with metastasis formation and poor prognosis, understanding to what extent flotillin upregulation participates in the development of such pathologies is thus of particular interest, as well as how, at the molecular level, it might affect cell adhesion processes.

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“…The increase in alpha-1-acid glycoprotein detected by ELISA and suggested by 2DE (although not reaching statistical significance after FDR) has been previously reported in obese adults [28] and T2DM [29], though its biological significance remains uncertain.…”

Section: Discussionmentioning

confidence: 92%

Proteomic analysis allows for early detection of potential markers of metabolic impairment in very young obese children

Martos‐Moreno

Sackmann-Sala

Barrios

et al. 2014

Int J Pediatr Endocrinol

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BackgroundEarly diagnosis of initial metabolic derangements in young obese children could influence their management; however, this impairment is frequently not overt, but subtle and undetectable by routinely used clinical assays. Our aim was to evaluate the ability of serum proteomic analysis to detect these incipient metabolic alterations in comparison to standard clinical methods and to identify new candidate biomarkers.MethodsA cross-sectional study of fasting serum samples from twenty-two prepubertal, Caucasian obese (OB; 9.22 ± 1.93 years; 3.43 ± 1.08 BMI-SDS) and twenty-one lean controls (C; 8.50 ± 1.98 years; -0.48 ± 0.81 BMI-SDS) and a prospective study of fasting serum samples from twenty prepubertal, Caucasian obese children (11 insulin resistant [IR]) before (4.77 ± 1.30 BMI-SDS) and after weight reduction (2.57 ± 1.29 BMI-SDS) by conservative treatment in a reference hospital (Pros-OB) was performed. Proteomic analysis (two-dimension-eletrophoresis + mass spectrometry analysis) of serum and comparative evaluation of the sensitivity of routinely used assays in the clinics to detect the observed differences in protein expression level, as well as their relationship with anthropometric features, insulin resistance indexes, lipid profile and adipokine levels were carried out.ResultsStudy of the intensity data from proteomic analysis showed a decrease of several isoforms of apolipoprotein-A1, apo-J/clusterin, vitamin D binding protein, transthyretin in OBvs. C, with some changes in these proteins being enhanced by IR and partially reversed after weight loss. Expression of low molecular weight isoforms of haptoglobin was increased in OB, enhanced in IR and again decreased after weight loss, being positively correlated with serum interleukin-6 and NAMPT/visfatin levels. After statistical correction for multiple comparisons, significance remained for a single isoform of low MW haptoglobin (OB vs. C and IR vs. non-IR) and Apo A1 (IR vs. non-IR). Assays routinely used in the clinical setting (ELISA/kinetic nephelometry), only partially confirmed the changes observed by proteomic analysis (ApoA1 and haptoglobin).ConclusionProteomic analysis can allow for the identification of potential new candidate biomarkers as a complement to routinely used assays to detect initial changes in serum markers of inflammation and lipid metabolism impairment in young obese children.

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MECHANISMS IN ENDOCRINOLOGY: Proteomic biomarkers of type 2 diabetes mellitus risk in women with polycystic ovary syndrome

Cited by 24 publications

References 54 publications

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Flotillins in intercellular adhesion – from cellular physiology to human diseases

Proteomic analysis allows for early detection of potential markers of metabolic impairment in very young obese children

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