P. Fontaine

University of Lille Nord de France, Lille, Nord-Pas-de-Calais, France

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Publications (99)117.54 Total impact

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    ABSTRACT: Introduction/objectives The role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic. The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls. Methods PRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n = 8) at delivery and compared to controls (n = 5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n = 5) or nicotinamide (NCT) plus STZ (n = 9) or vehicle (n = 9). Placental whole-genome gene expression and PRL western blots were performed at birth. Results In human placentas, PRL (p < 0.05) and BMP-1 (p < 0.01) gene expressions were increased with a higher amount of cleaved PRL (p < 0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT–STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p < 0.01) and Bmp-1 (p < 0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p < 0.05) and NCT–STZ (p < 0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women. Conclusions Alterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 09/2014; 1842(9):1783–1793. · 4.91 Impact Factor
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    ABSTRACT: PURPOSE: Aerobic fitness, as reflected by maximal oxygen uptake (VO2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence oxygen supply including oxygen delivery and release, to active muscle during maximal exercise. METHODS: Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n=11 with adequate glycemic control, HbA1c<7.0%; T1D-I, n=12 with inadequate glycemic control, HbA1c>8%) were compared to healthy controls (CON-A, n=11; CON-I, n=12, respectively) matched for physical activity and body composition. Subjects performed an exhaustive incremental exercise to determine VO2max. Throughout exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin (ΔO2Hb), deoxyhemoglobin (ΔHHb), and total hemoglobin (ΔTHb) in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial oxygen transport and factors able to shift the O2Hb dissociation curve. RESULTS: Arterial oxygen content was comparable between groups. However, ΔTHb (i.e., muscle blood volume) was significantly lower in T1D-I compared to CON-I. T1D-I also had impaired ΔHHb levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, VO2max was lower in T1D-I compared to CON-I. No differences were observed between T1D-A and CON-A. CONCLUSION: Poorly controlled patients displayed lower VO2max and a blunted muscle HHb increase. The latter supports the hypotheses of an increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and non-nutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt microangiopathy.
    Medicine and science in sports and exercise. 06/2014;
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    ABSTRACT: The role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic. The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.
    Biochimica et biophysica acta. 06/2014;
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    ABSTRACT: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients.
    Diabetes & metabolism. 06/2014;
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    ABSTRACT: Introduction L’étude DAWN2 révèle une attention insuffisante portée aux aspects psychologiques du vécu du diabète. L’amputation est une des trois complications avec un gros impact sur la qualité de vie des diabétiques. Les études d’évaluation de la qualité de vie observent plus l’état de santé que l’impact d’une amputation. Nous avons cherché à explorer le vécu singulier de la première amputation du point de vue du patient diabétique. Matériels et méthodes Dans une étude qualitative, 12 entretiens semi-directifs ont été menés avec 11 hommes et 1 femme, âgés de 54 à 83 ans, diabétiques depuis 5 à 38 ans, de niveaux d’études variés, non sélectionnés amputés d’orteil depuis au moins 6 mois consultant sur surveillance habituelle. Les discussions ont été retranscrites et soumises à une analyse interprétative avec approche par théorisation ancrée. La saturation des données a été obtenue. Résultats Cinq axes chronologiques ont émergé : un malade sans maladie ; le déclic de la décision d’amputation ; l’amputation ; un geste restant marquant ; un accompagnement dans la crise et vers le changement. L’amputation rend palpable une maladie auparavant silencieuse. C’est un déclic amorcant une modification de comportement sincère mais fragile devant être entretenue. Le vécu de l’amputation est facilité quand cinq critères sont réunis : une annonce convenable, une douleur post-opératoire contrôlée, un moignon d’amputation fermé, un soutien émotionnel et technique effectif ainsi qu’un retour rapide à la marche. Discussion Au quotidien, les soignants pourront, par l’identification des éléments du mauvais vécu de l’amputation, porter une attention particulière aux patients les plus fragiles et adapter leurs actions de santé aux besoins exprimés. En prévention secondaire, la motivation à la modification de comportement amorcée doit être entretenue au long cours par l’équipe médicale mais également par de nouveaux intervenants chargés de l’entretien motivationnel et de l’accompagnement émotionnel.
    Diabetes & Metabolism. 01/2014; 40:A7.
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    ABSTRACT: Objectif Évaluer les attitudes et les convictions concernant les hypoglycémies chez les personnes atteintes de diabète (PAD) et leur entourage, i.e. membres de la famille (MF). Matériels et méthodes DAWN2 est une enquête internationale (17 pays) soutenue par Novo Nordisk. En France, les entretiens ont concerné 500 PAD [80 avec un diabète de type 1 (DT1) ; 150 avec un diabète de type 2 (DT2) traités par insuline (DT2 Insuline) ; 170 DT2 non traités par insuline (DT2 Non- Insuline), 100 DT2 sans traitement antidiabétique] et 120 MF [MF de diabétiques traités par insuline (MIT) et MF de diabétiques non traités par insuline (MNIT)]. Résultats 64 % DT1 vs 50 % DT2 déclaraient être inquiets du risque d’hypoglycémie (p < 0,05). 73 % MIT vs 50 % MNIT déclaraient être préoccupés par le risque que la personne avec laquelle elles vivent fasse une hypoglycémie (p < 0,05). 73 % DT1 vs 42 % DT2 Insuline déclaraient traiter eux-mêmes leurs hypoglycémies ≥ 1 fois par semaine ou plusieurs fois par mois (p < 0,05), les deux groupes rapportant une moyenne de 2 épisodes d’hypoglycémie sévère dans l’année précédente. 45 % MIT et 28 % MNIT déclaraient devoir intervenir lors d’une hypoglycémie ≥ 1 fois par semaine ou plusieurs fois par mois. Cependant, 21 % MIT et 33 % MNIT n’étaient pas confiants dans leur capacité à gérer les hypoglycémies. Discussion Les hypoglycémies sont une préoccupation majeure et commune pour les PAD et leur entourage. L’anxiété due aux hypoglycémies pourrait être diminuée par la mise en place de programmes d’éducation, particulièrement pour l’entourage.
    Diabetes & Metabolism. 01/2014; 40:A8.
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    ABSTRACT: Objectif Évaluer l’état émotionnel des personnes atteintes de diabète (PAD) et des membres de leurs familles (MF). Matériels et méthodes DAWN2 est une enquête internationale soutenue par Novo Nordisk conduite dans 17 pays. En France, les entretiens ont concerné 120 MF [MF de diabétiques insulino-traités (MIT) et MF de diabétiques non insulino-traités (MNIT) et 500 PAD [80 avec un diabète de type 1 (DT1) ; 150 avec un diabète de type 2 (DT2) insulino-traité (DT2 Insuline) ; 170 DT2 non insulino-traités (DT2 Non-Insuline), 100 DT2 sans traitement antidiabétique (DT2 Non TT)] Ces deux populations ont complété deux questionnaires : le PAID « Problèmes liés au diabète » – dont la version MF, nouvellement développée pour DAWN2 – et le WHO-5 Well-Being Index. Résultats Parmi les domaines problématiques évalués par les MF (PAID), l’inquiétude de l’avenir et du risque de complications, ainsi que l’anxiété de ne pas aider suffisamment la personne avec laquelle elles vivent, étaient considérées comme des problèmes graves ou très graves respectivement par 53 % et 26 % des MIT. Par ailleurs, 17 % des MIT semblaient être dépressifs (WHO-5). Concernant les PAD, environ la moitié des DT1, DT2 Insuline et DT2 Non TT, et 1/3 DT2 Non-Insuline ressentaient une grande détresse liée au diabète (PAID). 19 % DT1 et 15 % DT2 Insuline se sentaient accablés par leur diabète. 14 % DT1 et 13 % DT2 Insuline semblaient être dépressifs (WHO-5). Conclusion L’anxiété et la détresse des personnes atteintes de diabète sont également éprouvées par les MF. Aussi, il apparaît nécessaire de soutenir aussi bien les personnes atteintes de diabète que leur entourage familial.
    Diabetes & Metabolism. 01/2014; 40:A7–A8.
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    ABSTRACT: Obesity, characterized by low grade inflammation, induces adipose tissue macrophage (ATM) infiltration in white adipose tissue (AT) in both humans and rodents, thus contributing to insulin resistance. Previous studies have shown altered prolactin secretion in obesity, however, studies linking ATM infiltration and prolactin (PRL) secretion to the pathogenesis of the metabolic syndrome, obesity and diabetes are lacking. In vivo, qPCR and Western blot analysis demonstrated that prolactin expression was increased in AT of obese rats and also in human AT from obese, obese pre-diabetic and obese diabetic compared to lean counterparts. Immunohistochemistry of obese rat and human AT sections demonstrated a specific expression of prolactin in macrophages. In vitro, we demonstrated that hyperglycemia and inflammation stimulated macrophages (human THP-1 cell line and sorted rat ATM) to express PRL, when challenged with different glucose concentrations with or without IL1β. In in vivo and in vitro experiments, we assessed the expression of Pit-1 (PRL-specific transcription factor) and found that its expression was parallel to PRL expression. In this study, we show that rodent and human macrophages synthesize prolactin in response to inflammation and high glucose concentrations. Our data shed new light on the potential role of macrophages in the physiopathology of diabesity via the PRL expression and on its expression mechanism and regulation.
    Biochimica et Biophysica Acta 12/2013; · 4.66 Impact Factor
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    ABSTRACT: Growing evidence indicates that maternal pathophysiological conditions, such as diabetes, influence fetal growth and could program metabolic disease in adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are placental macrophages characterized by an anti-inflammatory profile (M2), can sense the modified maternal environment. The goal of this study was to investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in placentae from control and diabetic patients to assess the balance between pro- and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been observed in humans. We used pregnant rats, receiving a single injection of streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1 macrophage unbalance as we observed in human. An in vitro model of isolated rat HBCs was used to identify the direct effects of high glucose. We found that high glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)-dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose switched their M2 profile towards M1, with increased expression of pro-inflammatory cytokines and markers. We also noticed that the oxidative-stress pathway was activated in response to high glucose driven by Hif-1α. In this study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory profile of HBCs, by stimulating these cells to acquire an inflammatory profile leading adverse consequences for the fetal-placental-maternal axis.
    Biochimica et Biophysica Acta 07/2013; · 4.66 Impact Factor
  • P. Fontaine, S. Halimi
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    ABSTRACT: The study Diabetes Attitudes, Wishes, and Needs 2 (DAWN2™) reveals a deficit of the quality of information, support and consideration of the emotional factors and the wishes of the patient. It shows the necessity of a coordination between the actors and the partners of the patients and the strengthening of information and support about long term. These inadequacies are related to the organization of care. Current developments or upcoming can improve the course of care and support for patients. The national orientations incite to favour the preventive action, the coordinated action of the professionals and the emergence of new jobs. Concrete actions concern the new modes of liberal exercise, the professional cooperation and delegation of tasks, the therapeutic education in primary care and the motivational and emotional support. The improvement of the organization of the care is a continuous process based on a pragmatic and concrete approach of the problems to be solved involving the professionals and the patients.
    Médecine des Maladies Métaboliques 01/2013; 7:S53–S57.
  • Annales d'Endocrinologie. 09/2012; 73(4):251.
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    ABSTRACT: Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP participation early in the trial. Based on our questionnaire response rates, we found that one in two GPs were willing to participate in our hospital-led study, regardless of their initial attitudes.
    BMC Family Practice 06/2012; 13:63. · 1.61 Impact Factor
  • Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).
  • Journal Des Maladies Vasculaires - J MAL VASCUL. 01/2011; 36(5):314-315.
  • Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).
  • Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).
  • Diabetes & Metabolism - DIABETES METAB. 01/2011; 37(1).
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    ABSTRACT: Vascular accelerated aging represents the major cause of morbidity and mortality in subjects with diabetes mellitus. In the present study, our aim was to compare premature functional and morphological changes in the arterial wall resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a short-term period with those that develop during physiological aging. The effect of aminoguanidine (AG) on the prevention of these alterations in the diabetic group was also analyzed. The vascular relaxation response to acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine (Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and compare to 12- and 84-wk-old mice. Aortic structural changes were investigated, and receptor for AGE (RAGE) aortic expression was quantified by western blot. Compared to the 12-wk control group (76 ± 5%), significant endothelium-dependant relaxation (EDR) impairment was found in the group of 12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD) (52 ± 4%; P < 0.01) and was yet more apparent in the group of 16-wk-old mice, which underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34 ± 4%; P < 0.001). The alteration in EDR was relatively comparable between the diabetic 12wk-4WD group and the 84-wk-old group (52.7 ± 4 vs. 48 ± 4%). Intima/media aortic thickening and aortic structural changes were significantly increased in the diabetic 12wk-4WD group and were even more apparent in the 84-wk group compared to the 12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly improved EDR, decreased RAGE expression and showed an aging preventive effect on the structural changes of the arterial wall. Our study compared EDR linked to physiological aging with that observed in the case of STZ-induced diabetes over a short-term period, and demonstrated the beneficial effect of AG.
    Diabetes & Metabolism 12/2010; 37(2):106-11. · 2.39 Impact Factor
  • G. Prévost, E. Boulanger, P. Fontaine
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    ABSTRACT: Epidemiologic and pathologic data have demonstrated that diabetic patients are prematurely exposed to atherosclerotic lesions thus it has been suggested that diabetes confers an equivalent risk to ageing 15 years more. Ageing and diabetes share common vascular abnormalities. Structural modifications include intima-media thickness, matrix remodeling, and calcifications. Functional changes are representated by arterial stiffness and endothelial dysfunction. Common pathophysiologic mechanisms including advanced glycation endproducts (AGEs) and oxidative stress are also described and suggest novel therapeutic targets.
    Médecine des Maladies Métaboliques 09/2010; 4(4):402–406.
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    ABSTRACT: The long-term outcome of type 2 diabetes mellitus after laparoscopic adjustable gastric banding (LAGB) is unknown. A longitudinal cohort study was undertaken of patients with grade 3 obesity and type 2 diabetes or impaired fasting glucose (IFG) undergoing LAGB. Metabolic outcomes and quality of life (QoL) were assessed before and 5 years after LAGB. At 5 years, data for 22 out of 23 patients with type 2 diabetes and 51 out of 53 with IFG were available. Mean(s.d.) excess weight loss was 41(25) and 41(27) per cent in patients with type 2 diabetes and IFG respectively, and was associated with a significant decrease in haemoglobin (Hb) A1c, fasting and postprandial blood glucose, insulin and triglyceride levels, and in liver steatosis. There were significant increases in insulin sensitivity, beta-cell function, disposition index, high-density lipoprotein-cholesterol and QoL (Nottingham Health Profile). Good metabolic control (HbA1c 7 per cent or less) was obtained in 13 diabetic patients, but complete diabetes remission was maintained in only four. Longer duration of diabetes, and poor preoperative glucose control and beta-cell function at baseline were associated with a less favourable outcome. LAGB improved metabolic outcomes and QoL in patients with grade 3 obesity with IFG or type 2 diabetes but rarely led to prolonged remission in long-standing diabetes.
    British Journal of Surgery 06/2010; 97(6):884-91. · 4.84 Impact Factor

Publication Stats

595 Citations
117.54 Total Impact Points

Institutions

  • 2010–2014
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 1997–2014
    • Centre Hospitalier Régional Universitaire de Lille
      • • General and Endocrine Surgery Service
      • • Division of Neurology
      Lille, Nord-Pas-de-Calais, France
  • 2008–2010
    • Université du Droit et de la Santé Lille 2
      • Faculty of Medicine
      Lille, Nord-Pas-de-Calais, France
    • Centre hospitalier Gustave Dron
      Tourcoing, Nord-Pas-de-Calais, France
  • 2009
    • Hôpital Bichat - Claude-Bernard (Hôpitaux Universitaires Paris Nord Val de Seine)
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 2002
    • CHRU de Strasbourg
      Strasburg, Alsace, France