Publications by authors named "Gilles Dumoulin"

27 Publications

  • Page 1 of 1

Visceral adiposity in patients with psoriatic arthritis and psoriasis alone and its relationship with metabolic and cardiovascular risk.

Rheumatology (Oxford) 2020 Nov 24. Epub 2020 Nov 24.

Laboratoire de Biochimie Médicale, UF de Biochimie Endocrinienne et Métabolique, CHU de Besançon et EA 3920 Marqueurs pronostiques et facteurs de régulation des pathologies cardiaques et vasculaires, Université de Bourgogne Franche Comté, Besançon, France.

Background: Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO).

Methods: Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin, leptin, resistin and retinol-binding protein-4 (RBP4)] were measured.

Results: Data for 52 patients with PsA and 52 patients with PsO and their respective paired controls were analysed. Android fat and visceral fat were found to be significantly higher in patients with PsO compared with their controls, while these measurements did not differ between patients with PsA and their controls. By multivariate analysis, after adjusting for age, sex and BMI, visceral fat was higher in PsO patients compared with PsA patients (P = 0.0004) and the whole group of controls (P = 0.0013). Insulin levels and HOMA-IR were increased in both PsA and PsO groups. High-molecular-weight/total adiponectin ratio was decreased in patients with PsO. RBP4 was significantly higher in both PsA and PsO patients. In patients with PsO, visceral fat strongly correlated with SCORE (r = 0.61).

Conclusion: Visceral fat accumulates more in PsO alone than in PsA. Visceral adiposity may be a more pressing concern in PsO relative to PsA.

Trial Registration: The ADIPSO study (Évaluation du tissu ADIpeux et des adipokines dans le PSOriasis et le rhumatisme psoriasique et analyse de ses relations avec le risque cardiovasculaire) is a case-control study conducted in Besançon, France, and is registered on ClinicalTrials.gov under the number NCT02849795.
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http://dx.doi.org/10.1093/rheumatology/keaa720DOI Listing
November 2020

Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study.

Arthritis Res Ther 2020 09 29;22(1):224. Epub 2020 Sep 29.

Laboratoire de Biochimie Médicale, UF de Biochimie Endocrinienne et Métabolique, CHU de Besançon; EA 3920 Marqueurs pronostiques et facteurs de régulation des pathologies cardiaques et vasculaires, Université de Bourgogne Franche Comté, Besançon, France.

Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined.

Methods: Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months.

Results: One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up.

Conclusions: Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle.

Trial Registration: The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).
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http://dx.doi.org/10.1186/s13075-020-02297-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523335PMC
September 2020

Beneficial effects of a lifestyle intervention program on C-reactive protein: impact of cardiorespiratory fitness in obese adolescents with sleep disturbances.

Am J Physiol Regul Integr Comp Physiol 2019 04 21;316(4):R376-R386. Epub 2019 Feb 21.

Research unit EA3920, Prognostic Markers and Regulatory Factors of Cardiovascular Diseases and Exercise Performance, Health, Innovation platform, University of Bourgogne Franche-Comté , Besançon , France.

The objectives of this study were to assess the relationship between inflammation and obstructive sleep apnea (OSA) and determine whether the lifestyle program's effects on inflammatory markers are associated with changes in anthropometric parameters, cardiorespiratory fitness, sleep duration, and OSA severity in severely obese adolescents. Participants were aged 14.6 (SD 1.2) yr, with a body mass index (BMI) of 40.2 (SD 6.5) kg/m. Sleep, anthropometric parameters, glucose metabolism, inflammatory profile, and cardiorespiratory fitness [V̇o relative to body weight (V̇o) and fat-free mass (V̇o)] were assessed at admission and at the end of a 9-mo lifestyle intervention program (LIP). Associations between C-reactive protein (CRP) concentrations and BMI, sex, oxygen desaturation index (ODI), sleep fragmentation, total sleep time (TST), and V̇o were assessed via ANCOVA. Twenty-three subjects completed the study. OSA subjects ( n = 13) exhibited higher CRP concentrations and a trend for higher BMI than non-OSA subjects ( P = 0.09) at admission. After intervention, OSA was normalized in six subjects, and CRP significantly decreased in the OSA group and in the whole population. In both groups, leptin levels significantly decreased, whereas adiponectin concentrations increased. At admission, BMI adjusted for sex, arousal index, ODI, TST, and V̇o was associated with CRP levels (adjusted r = 0.32, P < 0.05). The decrease in CRP concentrations postintervention was associated with enhanced V̇o adjusted for sex, weight loss, and changed sleep parameters (adjusted r = 0.75, P < 0.05). Despite higher amounts of CRP in OSA subjects, obesity severity outweighs the proinflammatory effects of OSA, short sleep duration, and low cardiorespiratory fitness. However, enhanced cardiorespiratory fitness is associated with the decrease of inflammation after controlling for the same parameters.
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http://dx.doi.org/10.1152/ajpregu.00309.2018DOI Listing
April 2019

Paradoxical elevation of serum TRACP5b levels despite increase in lumbar spine bone mineral density during anti-TNFα therapy in patients with inflammatory rheumatic disease: a 2-year prospective assessment of bone mass, bone metabolism, and the trabecular bone score.

Eur J Rheumatol 2017 Sep 1;4(3):189-193. Epub 2017 Sep 1.

Department of Endocrine and Metabolic Biochemistry, University Hospital of Besançon, Besançon, France.

Objective: To examine the impact of long-term anti-TNFα therapy on bone mass, bone metabolism, and the trabecular bone score (TBS) in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS).

Material And Methods: In eight patients with RA and 12 with AS, bone mineral densities (BMDs) of the lumbar spine (LS), left and right femoral neck, and total skeleton were measured using dual X-ray absorptiometry at baseline and then at 6, 12, and 24 months after anti TNFα therapy. The TBS was also calculated. At baseline and at 1, 3, 6, 12, 18, and 24 months, bone metabolism was assessed by measurements of pro-collagen-I carboxyterminal propeptide (PICP), osteocalcin, and bone alkaline phosphatase levels in the serum, which are indicative of bone formation and β-isomerized carboxy-terminal telopeptide of type-I collagen (β-CTX-I) and serum isoform 5b of tartrate-resistant acid phosphatase (TRACP5b) levels in the serum, which are indicative of bone resorption.

Results: In patients with RA, the LS T-score increased (3.2%, p<0.001) and the TBS progressively decreased (-3.9%, p=0.03). In patients with AS, the LS BMD and T-score increased (4.3% and 6.2%, respectively; p<0.001) with no significant change in the TBS. Serum TRACP5b levels dramatically increased in both groups (227% in patients with RA and 150% in those with AS, p<0.001), while β-CTX-I levels did not change. Serum osteocalcin and PICP levels showed a transitory increase in patients with AS.

Conclusion: Long-term anti-TNFα therapy increased LS bone mass and affected bone quality (TBS) with little impact on bone remodeling. Conversely, TRACP5b levels dramatically increased during anti-TNFα therapy but without any detrimental effect on bone mass.
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http://dx.doi.org/10.5152/eurjrheum.2017.17006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685278PMC
September 2017

Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis.

Clin Rheumatol 2017 Nov 22;36(11):2531-2539. Epub 2017 Aug 22.

Endocrine and Metabolic Biochemistry, University Hospital of Besançon, F-, 25000, Besançon, France.

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS (p < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group (p = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.
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http://dx.doi.org/10.1007/s10067-017-3789-0DOI Listing
November 2017

A phase 2 randomized trial to evaluate the impact of a supervised exercise program on cardiotoxicity at 3 months in patients with HER2 overexpressing breast cancer undergoing adjuvant treatment by trastuzumab: design of the CARDAPAC study.

BMC Cancer 2017 Jun 19;17(1):425. Epub 2017 Jun 19.

UPFR des Sports, Université de Franche-Comté, 31 chemin de l'Epitaphe, 25000, Besançon, France.

Background: The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is a poor prognosis. Trastuzumab improves overall survival but is associated with cardiotoxicity, especially a decline in left ventricular ejection fraction (LVEF). In addition, chemotherapy and radiotherapy increase fatigue and pain, decrease physical capacity and health-related quality of life. To date, no study has evaluated the benefits of physical activity on the side effects of treatment in patients with HER2 positive breast cancer. The aim of this study is to evaluate the impact of 3 months' exercise intervention on myocardial function and in particular on the rate of cardiotoxicity.

Methods: This multicenter, randomized clinical trial will include 112 patients treated by adjuvant trastuzumab for HER2 positive breast cancer to investigate the effects of a 3 months' supervised exercise program (intermittent exercise, combining moderate and high intensities; 55 minutes duration, 3 times per week), on the rate of cardiotoxicity [defined by either a decrease of the LVEF under 50% or an absolute drop of LVEF of 10%] between baseline and at 3 months and on strength, aerobic capacity, metabolic, inflammatory and hormonal parameters. Health-related quality of life, fatigue, pain and level of physical activity will also be assessed. Participants are randomly allocated to one of the two groups ("training group" vs "standard oncological care"). Performance-based and self-reported outcomes are assessed at baseline, at the end of supervised exercise program and at six months follow-up.

Discussion: Although physical exercise is recommended to reduce the side effects of adjuvant treatments in breast cancer patients, no randomized study has been conducted to assess the benefits of a physical training program in patients with HER2 overexpressing breast cancer. Cardiac toxicity of trastuzumab may be minimized with an exercise program combining high and moderate intensities. This type of program may be safe, feasible and effective but also increase cardiorespiratory fitness and improve health-related quality of life. If these benefits are confirmed, this exercise intervention could be systematically proposed to patients during the course of treatment by trastuzumab in addition to standard oncological care.

Trial Registration: National Clinical Trials Number ( NCT02433067 ); Registration 28 april 2015.
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http://dx.doi.org/10.1186/s12885-017-3420-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480259PMC
June 2017

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol.

Dig Liver Dis 2015 Sep 22;47(9):783-9. Epub 2015 May 22.

Hepatology and Digestive Intensive Care Unit, University Hospital of Besançon, France; EA UPRES 3186 « Agents Pathogènes et Inflammation » of Franche-Comté University, France. Electronic address:

Background: Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol.

Aims: Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis.

Methods: 43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured.

Results: T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001).

Conclusions: In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.
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http://dx.doi.org/10.1016/j.dld.2015.05.016DOI Listing
September 2015

The role of leptin in the pathophysiology of rheumatoid arthritis.

Life Sci 2015 Nov 27;140:29-36. Epub 2015 May 27.

University Hospital of Besançon, Endocrine and Metabolic Biochemistry, 25000 Besançon, France; University of Franche Comté, UPRES EA 3920 "Cardiovascular Pathophysiology and Prevention", SFR FED 4234, Besançon, France.

The past 20 years of research on leptin has provided important insights into its role in rheumatoid arthritis (RA). Leptin is one of the different adipokines produced by the adipose tissue that influences the endocrine system, energy homeostasis and the immune response in several ways. Leptin is known to have predominantly pro-inflammatory effects, especially in the setting of chronic inflammation. Animal models of arthritis have illustrated well the participation of leptin in the inflammatory response within the joints. In patients with RA, numerous studies have evaluated the concentrations of leptin in the bloodstream and/or the joint cavity, showing higher levels compared to control populations. Leptin has also been found to correlate with clinical or biological measurements of disease activity of RA. Conversely, the relationship between serum leptin and joint structural damage is less evident. Leptin may also promote the development of atherosclerosis in RA and may contribute to the cardiovascular consequences of the metabolic syndrome that coexists with RA. Indeed, leptin could be a link between inflammation, metabolic risk factors and cardiovascular diseases in RA. Finally, due to abnormal body composition phenotypes with an increased prevalence of obesity in RA, the therapeutic response to traditional DMARDs and/or biological agents may be attenuated. This review discusses the multiple interplays that have been described between leptin and the clinical, radiographic and therapeutic aspects of RA.
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http://dx.doi.org/10.1016/j.lfs.2015.05.001DOI Listing
November 2015

Effects of TNF-α inhibitors on abdominal adiposity in patients with inflammatory rheumatic diseases.

J Rheumatol 2014 Dec;41(12):2491

University Hospital of Besançon, Endocrine and Metabolic Biochemistry, and University of Franche Comté, Besançon, France.

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http://dx.doi.org/10.3899/jrheum.140912DOI Listing
December 2014

Relationships between Adipose Tissue and Psoriasis, with or without Arthritis.

Front Immunol 2014 12;5:368. Epub 2014 Aug 12.

Endocrine and Metabolic Biochemistry, University Hospital of Besançon , Besançon , France ; UPRES EA 3920 "Cardiovascular Pathophysiology and Prevention", University of Franche Comté , Besançon , France.

Psoriasis (Pso) is a common chronic cutaneous inflammatory disease involving the skin that is associated with serious comorbidities. Comorbidities in Pso include psoriatic arthritis (PsA), reduced quality of life, malignancy, depression, but also a constellation of associated conditions that enhance the cardiovascular (CV) risk. Indeed, obesity is common in patients with Pso or PsA and is considered to be a risk factor for the onset of these diseases. Patients with Pso and PsA share common obesity-related complications such as metabolic syndrome (MetS), dyslipidemia, diabetes or insulin resistance, and CV diseases. Chronic inflammation in Pso and PsA partially explains the development of atherosclerosis and CV diseases. In parallel, body composition is disturbed in patients with Pso or PsA, as suggested by anthropometric measurements, while an excess of abdominal adiposity is observed in PsA, enhancing the risk of MetS and CV diseases. Adipokines may link the adipose tissue to the obesity-related complications of Pso and PsA. Indeed, altered circulating levels of the adipokines leptin, adiponectin, visfatine, and resistin have been found in patients with Pso or PsA. In addition, an excess of adipose tissue may compromise the therapeutic response to traditional drugs or biological agents in Pso and PsA. This paper reviews the comorbidities that contribute to enhanced CV risk, the body composition results, and the potential role of adipokines in systemic inflammation and energetic balance in Pso and PsA.
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http://dx.doi.org/10.3389/fimmu.2014.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129363PMC
August 2014

Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study.

Front Immunol 2013 13;4:453. Epub 2013 Dec 13.

University Hospital of Besançon, Endocrine and Metabolic Biochemistry , Besançon , France ; University of Franche Comté, UPRES EA 3920 "Cardiovascular Pathophysiology and Prevention", SFR FED 4234 , Besançon , France.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These results confirm that body composition was altered in RA and AS, affecting distinct soft tissue compartments. The effect of the increased visceral adipose tissue on cardiovascular risk is presumably attenuated by the favorable cardiometabolic profile in women with RA, as suggested by the normal HOMA-IR and atherogenic index.
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http://dx.doi.org/10.3389/fimmu.2013.00453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861781PMC
December 2013

TNFα blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study.

Eur J Nutr 2014 Apr 31;53(3):951-61. Epub 2013 Oct 31.

Clinical Investigation Center for Biotherapy (INSERM CBT-506), University Hospital of Besançon, Bâtiment St Joseph, 2 Place St Jacques, 25000, Besançon, France,

Purpose: To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS).

Methods: Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed.

Results: There was a significant gain in body mass index (p = 0.05) and a tendency for weight (p = 0.07), android fat (p = 0.07), and visceral fat (p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased (p = 0.02) with a parallel weight gain (p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9%; p = 0.003), body mass index (+2.5%; p = 0.004), total fat mass (+11.1%; p = 0.007), and fat in the android region (+18.3%; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3%; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (-15.2%, p = 0.057 and -9.3%, p = 0.067, respectively). Resistin decreased significantly (-22.4%, p = 0.01).

Conclusions: Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments.
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http://dx.doi.org/10.1007/s00394-013-0599-2DOI Listing
April 2014

Impact of diet and exercise training-induced weight loss on myocardial mechanics in severely obese adolescents.

Obesity (Silver Spring) 2013 Oct;21(10):2091-8

EA 4278, Laboratoire de Pharm-Ecologie Cardiovasculaire, University of Avignon, F-84000, Avignon, France.

Objective: Recent findings indicated silent incipient myocardial dysfunction in juvenile obesity despite normal global cardiac function. The present study investigated whether lifestyle intervention is able to favorably impact these obesity-related myocardial abnormalities and whether improvements are related to changes in insulin resistance and cardiac remodeling.

Design And Methods: Twenty-eight severe obese adolescents (OB) participated in a 9 month lifestyle intervention program (LIP) based on aerobic exercise and diet. Twenty healthy adolescents (CG) served as controls. Conventional echocardiography and myocardial mechanics were obtained at baseline and follow-up along with insulin resistance.

Results: Insulin sensitivity improved (P < 0.001) and body weight decreased (P < 0.001) consecutive to LIP. At baseline, OB had depressed longitudinal (L) strain (CG: -18.3 ± 2.6, OB: -14.2 ± 3.6%, P < 0.001) and enhanced twist compared to controls. The LIP in OB restored L strain to normal values (-16.9 ± 3.5%, NS), whereas it did not affect twist mechanics. From stepwise multiple regression analysis, only baseline L strain and changes in BMI Z-score (r(2) -adjusted = 0.49, P < 0.001) emerged as independent predictors of L strain changes.

Conclusions: Juvenile obesity is associated with myocardial mechanic abnormalities that can be partly corrected by lifestyle intervention. Restoration of longitudinal myocardial function occurs in the absence of left ventricular remodeling changes and is not associated with insulin resistance improvements.
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http://dx.doi.org/10.1002/oby.20495DOI Listing
October 2013

Plasma copeptin, a possible prognostic marker in cirrhosis.

Liver Int 2013 Jul 7;33(6):843-51. Epub 2013 Apr 7.

Service d'Hépatologie et de Soins Intensifs Digestifs, Hôpital Jean Minjoz, Besançon, France.

Background & Aim: Copeptin, secreted stoichiometrically with vasopressin, demonstrated its prognostic role in various diseases other than cirrhosis.

Methods: We investigated the association between severity of cirrhosis and plasma concentrations of copeptin, and the prognostic value of copeptin in 95 non-septic cirrhotic patients (34 Child-Pugh A, 29 CP-B, 32 CP-C), 30 septic patients with a Child-Pugh >8 ('group D'), and 16 healthy volunteers. Patients were followed for at least 12 months to assess the composite endpoint death/liver transplantation.

Results: Median copeptin concentrations (interquartile range) increased through healthy volunteers group [5.95 (3.76-9.43) pmol/L] and 'group D' patients [18.81 (8.96-36.66) pmol/L; P < 0.001)]. During a median follow-up of 11.0 ± 6.1 months, 28 non-transplanted patients died and eight were transplanted. In receiver operated characteristic curves analysis, the area under the curve values were as follows: Child-Pugh score 0.80 (95% CI: 0.71-0.86), model of end-stage liver disease (MELD) score 0.80 (0.70-0.86), C-reactive protein (CRP) 0.71 (0.60-0.80) and copeptin 0.70 (0.57-0.79). By stratifying the values of these variables into tertiles, the risk of death/liver transplantation for patients belonging to the highest tertile of copeptin (>13 pmol/L) was high (Log-rank test: P = 0.0002) and 2.3-fold higher than for patients with lower concentrations after adjusting for MELD score (>21) and CRP (>24 mg/L) in a Cox model. Other potential predictors (age, total cholesterol, natraemia and serum free cortisol) did not reach a significant level.

Conclusion: In cirrhotic patients, copeptin concentrations increased along with the severity of liver disease. In our cohort, the 1-year mortality or liver transplantation was predicted by high MELD score and high concentrations of CRP and copeptin.
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http://dx.doi.org/10.1111/liv.12175DOI Listing
July 2013

Two-dimensional strain and twist by vector velocity imaging in adolescents with severe obesity.

Obesity (Silver Spring) 2012 Dec 7;20(12):2397-405. Epub 2012 May 7.

EA 4278, "Laboratoire de Pharm-Ecologie Cardiovasculaire", Faculty of Sciences, University of Avignon, Avignon, France.

The prevalence of severe obesity is increasing worldwide in adolescents. Whether it is associated with functional myocardial abnormalities remains largely unknown, potentially because of its frequent association with other cardiovascular risk factors and also use of insensitive techniques to detect subclinical changes in myocardial function. We used 2D vector velocity imaging (VVI) to investigate early changes in left ventricular (LV) myocardial function in youths with isolated severe obesity. Thirty-seven asymptomatic severely obese adolescents free of diabetes and hypertension, and 24 lean controls were enrolled. LV longitudinal, basal, and apical circumferential strain, strain rate (SR), rotations, and LV twist were measured. Obese adolescents had greater LV mass and reduced systolic and early diastolic tissue Doppler imaging (TDI) velocities than lean counterparts. L strain (-24%) and systolic and early diastolic SR were also diminished in the obese, whereas no intergroup differences existed for the circumferential deformation indexes. LV twist was more pronounced in the obese (+1.7°, P < 0.01) on account of greater apical rotation only (4.1 ± 0.9 vs. 5.2 ± 1.2°, P < 0.01), potentially compensating for the loss in longitudinal function. Systolic-diastolic coupling, an important component of early filling and diastolic function, was maintained with severe obesity. No intergroup differences were reported regarding time to peak values for all VVI indexes highlighting that dynamics of strain and twist/untwist along the cardiac cycle was preserved with severe obesity. Isolated severe obesity in adolescents, at a preclinical stage, is associated with changes in myocardial deformation and torsional mechanics that could be in part related to alterations in relaxation and contractility properties of subendocardial fibers.
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http://dx.doi.org/10.1038/oby.2012.111DOI Listing
December 2012

Effects of an in-patient treatment program based on regular exercise and a balanced diet on high molecular weight adiponectin, resistin levels, and insulin resistance in adolescents with severe obesity.

Appl Physiol Nutr Metab 2012 Aug 11;37(4):672-9. Epub 2012 May 11.

Université de Franche-Comté, Besançon, France.

Adiponectin, the most abundant hormone produced by adipose tissue, circulates in 3 isoforms, including high molecular weight (HMW) adiponectin. The latter has been suggested to be a better predictor of metabolic disturbances and insulin resistance associated with obesity. This study investigated changes in total and HMW adiponectin, resistin, and homeostasis model assessment (HOMA) during a 9-month in-patient treatment program based on physical exercise and a balanced diet in 32 severely obese adolescents. Total and HMW adiponectin, resistin, and HOMA were measured at baseline (month 0) and during the program (months 3, 6, 9). In addition, a control group of 15 teenagers served as a reference for the baseline assessments. At baseline, HMW adiponectin was more markedly decreased in obese adolescents than total adiponectin, and both were lower than in controls. Conversely, resistin and HOMA were higher in obese adolescents. During the program, there was a significant change in body composition and improved insulin sensitivity among obese teenagers. In addition, HMW adiponectin and the ratio of HMW-to-total adiponectin increased throughout the study, whereas total adiponectin only increased up until the sixth month. On the contrary, resistin did not show any significant change. In obese adolescents, a long-term combination of aerobic exercise and a balanced diet, inducing change in body composition and improved insulin sensitivity, markedly increased HMW adiponectin compared with total adiponectin, without any change in resistin concentrations. Our results thus suggest that the determination of HMW adiponectin could be more useful than measurement of total adiponectin in clinical settings.
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http://dx.doi.org/10.1139/h2012-045DOI Listing
August 2012

Ghrelin and PYY levels in adolescents with severe obesity: effects of weight loss induced by long-term exercise training and modified food habits.

Eur J Appl Physiol 2012 May 11;112(5):1797-805. Epub 2011 Sep 11.

Université de Franche-Comté, 25000 Besançon, France.

This study investigated (a) changes in ghrelin and peptide YY (PYY) concentrations during a weight reduction programme and (b) baseline ghrelin and PYY levels as predictors of weight loss in 32 severely obese adolescents (BMI z score = 4.1). Subjects spent an academic year in an institution for childhood obesity. Fasting ghrelin and PYY, leptin, insulin levels and insulin resistance were measured at baseline (month 0) and during the programme (months 3, 6, 9). In addition, 15 normal-weight teenagers served as reference for the baseline assessments. At baseline, obese teenagers had lower ghrelin and PYY concentrations than normal-weight adolescents (P < 0.05). Moreover, they showed significantly higher leptin, insulin levels and homeostasis model assessment (HOMA) (P < 0.0001). During the lifestyle modification, there was a significant decrease in body weight among obese teenagers, associated with an increase in ghrelin (apparent from month 6; P < 0.05), a decrease in leptin (from month 3; P < 0.05) and a decrease in insulin and HOMA (from month 3; P < 0.0001), without any significant change in PYY. Anthropometrical changes were correlated neither with baseline ghrelin levels nor with changes in ghrelin and PYY after the lifestyle modification. However, higher baseline PYY tended to correlate with greater anthropometrical changes (P < 0.1). In adolescents with severe obesity, a long-term combination of supervised aerobic exercises and a balanced diet led to weight reduction and increased ghrelin concentrations, without any change in PYY concentrations. Moreover, baseline PYY concentrations might be considered as predictors of weight loss.
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http://dx.doi.org/10.1007/s00421-011-2154-2DOI Listing
May 2012

Influence of the consumption pattern of magnesium from magnesium-rich mineral water on magnesium bioavailability.

Br J Nutr 2011 Aug 8;106(3):331-4. Epub 2011 Apr 8.

Nestlé Research Center, Lausanne, Switzerland.

It is generally considered that the absorption of Mg is inversely related to the ingested dose. The objective of the present study was to determine if the mode of administration (bolus v. consumption throughout the day) could influence Mg bioavailability from Mg-rich natural mineral water comparing the same nutritional Mg amount (126 mg). Using a 2 d cross-over design, twelve healthy men were asked to drink 1·5 litres Mg-rich mineral water either as 2 × 750 ml or 7 × 212 ml throughout the day. Two stable isotopes ((25)Mg and (26)Mg) were used to label the water in order to distinguish both regimens. Fractional apparent Mg absorption was determined by faecal monitoring and Mg retention was determined by measuring urinary excretion of Mg isotopes. Higher Mg absorption (50·7 (SD 12·7) v. 32·4 (SD 8·1) %; P = 0·0007) and retention (47·5 (SD 12·9) v. 29·0 (SD 7·5) %; P = 0·0008) from Mg-rich mineral water were observed when it was consumed in seven servings compared with larger servings. Thus, regular water consumption throughout the day is an effective way to increase Mg bioavailability from Mg-rich mineral water.
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http://dx.doi.org/10.1017/S0007114511001139DOI Listing
August 2011

Elevated adiponectin serum levels in women with systemic autoimmune diseases.

Mediators Inflamm 2010 26;2010:938408. Epub 2010 Dec 26.

Department of Rheumatology, University Hospital Jean Minjoz, Bd Fleming, 25030 Besançon Cedex, France.

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.
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http://dx.doi.org/10.1155/2010/938408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017955PMC
April 2011

Whole body immersion and hydromineral homeostasis: effect of water temperature.

Eur J Appl Physiol 2010 Jan 16;108(1):49-58. Epub 2009 Sep 16.

Human Factor Department, French Army Health Center, La Tronche Cedex, France.

This experiment was designed to assess the effects of prolonged whole body immersion (WBI) in thermoneutral and cold conditions on plasma volume and hydromineral homeostasis.10 navy "combat swimmers" performed three static 6-h immersions at 34 degrees C (T34), 18 degrees C (T18) and 10 degrees C (T10). Rectal temperature, plasma volume (PV) changes, plasma proteins, plasma and urine ions, plasma osmolality, renin, aldosterone and antidiuretic hormone (ADH) were measured. Results show that compared to pre-immersion levels, PV decreased throughout WBI sessions, the changes being markedly accentuated in cold conditions. At the end of WBI, maximal PV variations were -6.9% at T34, -14.3% at T18, and -16.3% at T10. Plasma osmolality did not change during and after T34 immersion, while hyperosmolality was present at the end of T18 immersion and began after only 1 h of T10 immersion. In the three temperature conditions, significant losses of water (1.6-1.7 l) and salt (6-8 g) occurred and were associated with similar increases in osmolar and free water clearances. Furthermore, T18 and T10 immersions increased the glomerular filtration rate. There was little or no change in plasma renin and ADH, while the plasma level of aldosterone decreased equally in the three temperature conditions. In conclusion, our data indicate that cold water hastened PV changes induced by immersion, and increased the glomerular filtration rate, causing larger accumulated water losses. The iso-osmotic hypovolemia may impede the resumption of baseline fluid balance. Results are very similar to those repeatedly described by various authors during head-out water immersion.
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http://dx.doi.org/10.1007/s00421-009-1187-2DOI Listing
January 2010

Pretransplant serum vitamin D levels and risk of cancer after renal transplantation.

Transplantation 2008 Jun;85(12):1755-9

Inserm, U645 Besançon, University of Besançon, Besançon, France.

Background: Serum levels of 25-OH-D3 inversely correlate with the incidence of various types of cancers in the general population. Because risk factors and incidence of cancer in renal transplant recipients (RTRs) are different from the general population, this study was designed to determine whether pretransplant 25-OH-D3 levels could be predictive of cancer risk in RTRs.

Methods: Pretransplant 25-OH-D3 levels were reviewed in 363 consecutive RTRs. The impact of 25-OH-D3 levels on the development of cancer was then analyzed with respect to other known risk factors.

Results: One hundred twenty-four patients (34.2%) showed vitamin D deficiency, 185 (51%) vitamin D insufficiency, and 54 (14.8%) with normal vitamin D levels. Thirty-two cancers (8.8%) occurred in 32 patients. A higher incidence of cancer was observed in patients with vitamin D deficiency (13.7% vs. 7% for patients with vitamin D insufficiency [P=0.068] and 3.7% for those with normal vitamin D levels [P=0.007]). 25-OH-D3 levels were lower in patients who developed cancer after transplantation (13.7+/-6 vs. 18.3+/-17.8 ng/mL, P=0.022). Age (hazard ratio, 1.06; 95% confidence interval, 1.02-1.11, for each 1 year increase; P=0.009) and low 25-OH-D3 levels (hazard ratio, 1.12; 95% confidence interval, 1.04-1.23, for every 1 ng/mL decrease; P=0.021) were independent risk factors for development of cancer.

Conclusion: Pretransplant level of 25-OH-D3 is an important determinant for subsequent development of cancer after transplantation. Future studies should examine whether 25-OH-D3 supplementation can effectively decrease the incidence of cancer in RTRs.
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http://dx.doi.org/10.1097/TP.0b013e318172cb2cDOI Listing
June 2008

Cardiovascular autonomic control during short-term thermoneutral and cool head-out immersion.

Aviat Space Environ Med 2008 Jan;79(1):14-20

Université de Franche Comté, Physiologie, Faculté de Médecine, Besançon, France.

Background: Moderately cold head-out water immersion stimulates both baro- and cold-receptors, and triggers complex and contradictory effects on the cardiovascular system and its autonomic nervous control.

Objectives: To assess the effects of water immersion and cold on cardiovascular status and related autonomic nervous activity.

Methods: Hemodynamic variables and indexes of autonomic nervous activity (analysis of heart rate and blood pressure variability) were evaluated in 12 healthy subjects during 3 exposures of 20 min each in the upright position, i.e., in air (AIR, 24-25 degrees C), and during head-out water immersion at 35-36 degrees C (WIn) and 26-27 degrees C (WIc).

Results: Plasma noradrenaline, systolic and diastolic blood pressure, and total peripheral resistances were reduced during WIn compared to AIR (263.9 +/- 39.4 vs. 492.5 +/- 35.7 pg x ml(-1), 116.5 +/- 3.7 and 65.4 +/- 1.7 mmHg vs. 140.8 +/- 4.7 and 89.8 +/- 2.8 mmHg, 14.1 +/- 1.0 vs. 16.3 +/- 0.9 mmHg x L(-1) x min, respectively) while they were increased during WIc (530.8 +/- 84.7 pg ml(-1), 148.0 +/- 7.0 mmHg, 80.8 +/- 3.0 mmHg, and 25.8 +/- 1.9 mmHg x L(-1) x min, respectively). The blood pressure variability was reduced to the same extent during WIc and Win compared to AIR. Heart rate decreased during WIn (67.8 +/- 2.7 vs. 81.2 +/- 2.7 bpm during AIR), in parallel with an increased cardiac parasympathetic activity. This pattern was strengthened during WIc (55.3 +/- 2.2 bpm).

Conclusions: Thermoneutral WI lowered sympathetic activity and arterial tone, while moderate whole-body skin cooling triggered vascular sympathetic activation. Conversely, both WI and cold triggered cardiac parasympathetic activation, highlighting a complex autonomic control of the cardiovascular system.
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http://dx.doi.org/10.3357/asem.2147.2008DOI Listing
January 2008

Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis.

Metabolism 2007 Oct;56(10):1383-9

Department of Rheumatology, University hospital Jean Minjoz, Bd Fleming, F-25030 Besançon, Cédex, France.

Adipokines such as leptin and adiponectin are involved in the regulation of inflammation. Ghrelin, a gastric peptide playing a role in the appetite regulation, possesses anti-inflammatory properties. In this study, we evaluated the circulating levels of adipokines (leptin as potential proinflammatory and adiponectin as anti-inflammatory marker) and ghrelin and the fat mass in patients with ankylosing spondylitis (AS). Serum leptin, adiponectin, and ghrelin were evaluated in 53 AS patients with active disease (mean Bath Ankylosing Spondylitis Disease Activity Index >40) and 35 controls. Fat and lean masses were determined using dual-energy x-ray absorptiometry. Fat and lean masses did not differ between patients and controls. Ankylosing spondylitis patients had lower leptin levels compared with controls, even after adjustment for fat mass (AS vs controls: leptin, 7.6 +/- 1.3 ng/mL vs 10.3 +/- 1.5 ng/mL; leptin [in nanograms per milliliter]/fat mass [in kilograms], 0.28 +/- 0.04 vs 0.44 +/- 0.04; P = .006 and P = .0003, respectively). Serum adiponectin did not differ between patients and controls, whereas circulating ghrelin was higher in AS patients (1354.6 +/- 70.5 pg/mL vs 1008.0 +/- 82.5 pg/mL; P = .001). However, all these results were significant only for male patients. No correlation was found between leptin and adiponectin, and erythrocyte sedimentation rate, C-reactive protein levels, tumor necrosis factor alpha, or Bath Ankylosing Spondylitis Disease Activity Index. Ankylosing spondylitis patients had no changes in fat mass. Leptin production was reduced in contrast with normal levels of adiponectin. These adipokine results, together with high serum ghrelin levels, may influence the inflammatory response in AS.
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http://dx.doi.org/10.1016/j.metabol.2007.05.009DOI Listing
October 2007