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      Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial

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          Objective: Polyamines are naturally occurring cationic molecules present in all living cells. Dysregulation of circulating polyamines has been reported in several conditions, but little is known about the levels of serum polyamines in chronic metabolic disorders such as type 2 diabetes (T2D). Therefore, the aim of this study was to evaluate the polyamine-related metabolome in a cohort of metabolic syndrome individuals with and without T2D. Design and methods: This was a nested case–control study within the PREDIMED-Plus trial that included 44 patients with T2D and 70 patients without T2D. We measured serum levels of arginine, ornithine, polyamines, and acetyl polyamines with an ultra-high performance liquid chromatography tandem mass spectrometry platform. Results: Our results showed that serum putrescine, directly generated from ornithine by the catalytic action of the biosynthetic enzyme ornithine decarboxylase, was significantly elevated in patients with T2D compared to those without T2D, and that it significantly correlated with the levels of glycosylated hemoglobin (HbA1c). Correlation analysis revealed a significantly positive association between fasting insulin levels and spermine. Multiple logistic regression analysis (adjusted for age, gender and body weight index) revealed that serum putrescine and spermine levels were associated with a higher risk of T2D. Conclusions: Our study suggests that polyamine metabolism is dysregulated in T2D, and that serum levels of putrescine and spermine are associated with glycemic control and circulating insulin levels, respectively.

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          Most cited references 37

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          Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.

          A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
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            2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018.

            The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at
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              Modulation of cellular function by polyamines.

              Polyamines (putrescine, spermidine and spermine) are essential for normal cell growth. The polyamine levels in cells are regulated by biosynthesis, degradation, and transport. Polyamines can modulate the functions of DNA, nucleotide triphosphates, proteins, and especially RNA because most polyamines exist in a polyamine-RNA complex in cells. Thus, the major focus on this review is on the role of polyamines in protein synthesis. In addition, effects of polyamines on B to Z conversion of DNA, transcription, phosphorylation of proteins, cell cycle progression, apoptosis and ion channels, especially NMDA receptors, are outlined. The function of eIF5A is also briefly discussed. Finally, a correlation between acrolein, produced from polyamines by polyamine oxidases, and chronic renal failure or brain stroke is summarized. Increased levels of polyamine oxidases and acrolein are good markers of chronic renal failure and brain stroke.

                Author and article information

                [1 ]Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Malaga 29010, Spain; josecarlosfdezgarcia@ (J.C.F.-G.); danie__cc@ (D.C.-C.); aracelimugar@ (A.M.-G.); maribelqo@ (M.I.Q.-O.); fjtinahones@ (F.J.T.)
                [2 ]CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid 28029, Spain; robelopajiju@
                [3 ]Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Sciences (Joint Unit Eurecat-Universitat Rovira i Virgili), Unique Scientific and Technical Infrastructure (ICTS), Reus 43204, Spain; antoni.delpino@ (A.D.-R.); iris.samarra@ (I.S.)
                [4 ]Department of Internal Medicine, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga 29010, Spain
                [5 ]Department of Medical Oncology, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Malaga 29010, Spain
                Author notes
                [* ]Correspondence: fernando.cardona@ (F.C.); bruno.ramos@ (B.R.-M.); Tel.: +34-951-036-2647 (F.C. & B.R.-M.); Fax: +34-951-924-651 (F.C. & B.R.-M.)

                Current address: Laboratory of Biomedical Research-IBIMA, Virgen de la Victoria University Hospital, Campus de Teatinos s/n, Malaga 29010, Spain.

                J Clin Med
                J Clin Med
                Journal of Clinical Medicine
                10 January 2019
                January 2019
                : 8
                : 1
                30634588 6352090 10.3390/jcm8010071 jcm-08-00071
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (


                case-control, polyamines, diabetes, insulin, hba1c


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