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  1. Article ; Online: Validation in type 2 diabetes of a metabolomic signature of all-cause mortality.

    Copetti, Massimiliano / Baroni, Marco Giorgio / Buzzetti, Raffaella / Cavallo, Maria Gisella / Cossu, Efiso / D'Angelo, Paola / Cosmo, Salvatore De / Leonetti, Frida / Morano, Susanna / Morviducci, Lelio / Napoli, Nicola / Prudente, Sabrina / Pugliese, Giuseppe / Savino, Antonio Fernando / Trischitta, Vincenzo

    Diabetes/metabolism research and reviews

    2023  Volume 40, Issue 2, Page(s) e3734

    Abstract: Context: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed.: Objective: To validate in ... ...

    Abstract Context: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high-risk patients for referral to the most aggressive and costly prevention strategies is needed.
    Objective: To validate in type 2 diabetes the association with all-cause mortality of a 14-metabolite score (14-MS) previously reported in the general population and whether this score can be used to improve well-established mortality prediction models.
    Methods: This is a sub-study consisting of 600 patients from the "Sapienza University Mortality and Morbidity Event Rate" (SUMMER) study in diabetes, a prospective multicentre investigation on all-cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high-throughput proton nuclear magnetic resonance metabolomics.
    Results: In type 2 diabetes, the 14-MS showed a significant (p < 0.0001) association with mortality, which was lower (p < 0.0001) than that reported in the general population. This difference was mainly due to two metabolites (histidine and ratio of polyunsaturated fatty acids to total fatty acids) with an effect size that was significantly (p = 0.01) lower in diabetes than in the general population. A parsimonious 12-MS (i.e. lacking the 2 metabolites mentioned above) improved patient discrimination and classification of two well-established mortality prediction models (p < 0.0001 for all measures).
    Conclusions: The metabolomic signature of mortality in the general population is only partially effective in type 2 diabetes. Prediction markers developed and validated in the general population must be revalidated if they are to be used in patients with diabetes.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 2 ; Prospective Studies ; Metabolomics ; Biomarkers
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-10-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1470192-3
    ISSN 1520-7560 ; 1520-7552
    ISSN (online) 1520-7560
    ISSN 1520-7552
    DOI 10.1002/dmrr.3734
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Circadian Genes Expression Patterns in Disorders Due to Enzyme Deficiencies in the Heme Biosynthetic Pathway.

    Savino, Maria / Guida, Claudio Carmine / Nardella, Maria / Murgo, Emanuele / Augello, Bartolomeo / Merla, Giuseppe / De Cosmo, Salvatore / Savino, Antonio Fernando / Tarquini, Roberto / Cei, Francesco / Aucella, Filippo / Mazzoccoli, Gianluigi

    Biomedicines

    2022  Volume 10, Issue 12

    Abstract: Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. ... ...

    Abstract Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5'-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.
    Language English
    Publishing date 2022-12-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10123198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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