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1.
Diabetes Metab ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032671

RESUMO

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

2.
Eur J Endocrinol ; 182(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652416

RESUMO

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.

3.
Eur J Endocrinol ; 182(1): G1-G32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855556

RESUMO

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.


Assuntos
Índice de Massa Corporal , Hipotireoidismo/diagnóstico , Obesidade/diagnóstico , Comorbidade , Endocrinologia , Humanos , Hipotireoidismo/epidemiologia , Obesidade/epidemiologia , Prevalência , Testes de Função Tireóidea
4.
Nat Commun ; 10(1): 2549, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186409

RESUMO

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45-/CD34+/CD31- progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1-/CD271- and MSCA1-/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFß-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks.


Assuntos
Tecido Adiposo/anatomia & histologia , Tecido Adiposo/citologia , Nicho de Células-Tronco , Células-Tronco/citologia , Adipócitos/metabolismo , Adipogenia , Fosfatase Alcalina , Diferenciação Celular , Matriz Extracelular , Humanos , Gordura Intra-Abdominal/citologia , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Obesidade , Receptores de Fator de Crescimento Neural/metabolismo , Células-Tronco/metabolismo , Gordura Subcutânea/citologia , Fator de Crescimento Transformador beta1/farmacologia
5.
Obes Surg ; 27(4): 902-909, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27664095

RESUMO

BACKGROUND: Super obese patients are recommended to lose weight before bariatric surgery. The effect of intragastric balloon (IGB)-induced weight loss before laparoscopic gastric bypass (LGBP) has not been reported. The aim of this prospective randomized multicenter study was to compare the impact of preoperative 6-month IGB with standard medical care (SMC) in LGBP patients. METHODS: Patients with BMI >45 kg/m2 selected for LGBP were included and randomized to receive either SMC or IGB. After 6 months (M6), the IGB was removed and LGBP was performed in both groups. Postoperative follow-up period was 6 months (M12). The primary endpoint was the proportion of patients requiring ICU stay >24 h; secondary criteria were weight changes, operative time, hospitalization stay, and perioperative complications. RESULTS: Only 115 patients were included (BMI 54.3 ± 8.7 kg/m2), of which 55 underwent IGB insertion. The proportion of patients who stayed in ICU >24 h was similar in both groups (P = 0.87). At M6, weight loss was significantly greater in the IGB group than in the SMC group (P < 0.0001). Three severe complications occurred during IGB removal. Mean operative time for LGBP was similar in both groups (P = 0.49). Five patients had 1 or more surgical complications, all in the IGB group (P = 0.02). Both groups had similar hospitalization stay (P = 0.59) and weight loss at M12 (P = 0.31). CONCLUSION: IGB insertion before LGBP induced weight loss but did not improve the perioperative outcomes or affect postoperative weight loss.


Assuntos
Balão Gástrico , Derivação Gástrica , Obesidade Mórbida/cirurgia , Adulto , Índice de Massa Corporal , Terapia Combinada , Feminino , Derivação Gástrica/métodos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Perda de Peso
6.
Diabetes Metab ; 37(1): 47-51, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21126899

RESUMO

AIM: To describe the clinical presentation and the prognosis of autoimmune type 1 diabetes (T1D) that was first revealed during pregnancy masquerading as gestational diabetes mellitus (GDM). METHODS: We reviewed the files of 21 women in whom diabetes was revealed during a pregnancy ("index pregnancy") and progressed to T1D after delivery, and in whom GAD and/or IA-2 autoantibodies were found. RESULTS: The median age and BMI of the women were 31 years and 19.8 kg/m(2). Eleven women had at least one risk factor for GDM. Eight of the 12 multiparous women had had an abnormal outcome of previous pregnancy, including GDM in five. GDM was diagnosed at week 26 (range: 4-38) of gestation by screening in 18, because of macrosomia in two and during hyperglycaemic crises in three. All were treated with insulin, from the time of diabetes diagnosis in 10 and after 4 weeks (range: 2-15) in 11. Term of delivery was 38 (range: 26-41) weeks. Abnormal outcomes occured in 14 pregnancies, including two fetal deaths, four preterm deliveries and eight macrosomic infants. No congenital malformations were reported. After delivery, insulin therapy was stopped in 18 women for 6 months (range: 2-48). The diagnosis of the autoimmune origin of diabetes was established during the index pregnancy in only eight cases. CONCLUSION: T1D may reveal as GDM in women with or without risk factors for GDM and is associated with a poor prognosis, partly because the correct diagnosis and treatment are delayed. Whether screening for autoimmune markers of T1D should be performed more systematically in women with GDM deserves to be studied.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Gestacional/imunologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Morte Fetal/epidemiologia , Humanos , Gravidez , Prognóstico , Fatores de Risco
7.
Environ Technol ; 28(4): 471-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17500322

RESUMO

The primary driver for efficient biological nutrient removal (BNR) in activated sludge treatment is the sufficient supply of soluble carbon. Several methods have been proposed to increase available carbon sources and enhance BNR. This study examines the effect of ultrasonic equipment and mechanical disintegration technologies on surplus activated sludge (SAS), to release additional soluble chemical oxygen demand (SCOD) and volatile fattty acids (VFA), as a carbon food source for BNR. A laboratory sonicator with a maximum power of 550W, a 3KW SONIX radial horn and a deflaker declared to be used in the paper industry were investigated. All caused significant release of SCOD, up to 48 fold. The maximum concentration of VFA reached (from 0-1 mg 1(-1)), was 530 mg 1(-1). To assess the likely impact to BNR, batch (21) anaerobic lab tests examining the use of disintegrated sludge on phosphorus and nitrogen removal were completed. Phosphorus removal was estimated by observing the phosphate release under anaerobic conditions and up to 460% more release was observed relative to controls. In addition, denitrification rates were improved by over 106%. Ultrasonic and mechanical disintegration technologies have been shown to release soluble carbon for BNR, with subsequent laboratory nitrogen and phosphorus removal efficiencies observed to be comparable to acetate.


Assuntos
Carbono/química , Esgotos , Anaerobiose , Nitratos/química , Fósforo/química
8.
Water Res ; 41(8): 1734-42, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17339046

RESUMO

The primary driver for a successful biological nutrient removal is the availability of suitable carbon source, mainly in the form of volatile fatty acids (VFA). Several methods have been examined to increase the amount of VFAs in wastewater. This study investigates the mechanism of mechanical disintegration of thickened surplus activated sludge by a deflaker technology for the production of organic matter. This equipment was able to increase the soluble carbon in terms of VFA and soluble chemical oxygen demand (SCOD) with the maximum concentration to be around 850 and 6530 mgl(-1), for VFA and SCOD, respectively. The particle size was reduced from 65.5 to 9.3 microm after 15 min of disintegration with the simultaneous release of proteins (1550 mgl(-1)) and carbohydrates (307 mgl(-1)) indicating floc disruption and breakage. High performance size exclusion chromatography investigated the disintegrated sludge and confirmed that the deflaker was able to destroy the flocs releasing polymeric substances that are typically found outside of cells. When long disintegration times were applied (>or=10 min or >or=9000 kJkg(-1)TS of specific energy) smaller molecular size materials were released to the liquid phase, which are considered to be found inside the cells indicating cell lysis.


Assuntos
Carbono/análise , Eliminação de Resíduos Líquidos/instrumentação , Ácidos Graxos Voláteis/análise , Floculação , Tamanho da Partícula , Esgotos , Eliminação de Resíduos Líquidos/métodos
10.
J Anim Sci ; 83(3): 565-78, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15705753

RESUMO

Adiponectin is an adipocyte-derived hormone that plays an important role in lipid metabolism and glucose homeostasis. Objectives of this study were 1) to determine the presence and distribution of adiponectin and its receptors 1 and 2 (adipoR1 and adipoR2) in porcine tissues; 2) to characterize pig adiponectin, adipoR1, and adipoR2 mRNA levels in various fat depots from three different breeds of pigs; and 3) to study, in stromal-vascular cell culture, the effects of leptin and tumor necrosis factor-alpha (TNFalpha) on pig adiponectin, adipoR1, and adipoR2 gene expression. To this end, fat Chinese Upton Meishan (UM, n = 10), lean Ham Line (HL, n = 10), and Large White (LW, n = 10) gilts were used. We report the isolation of partial cDNA sequences of pig adipoR1 and adipoR2. Porcine-deduced AA sequences share 97 to 100% homology with human and murine sequences. Pig adipoR1 mRNA is abundant in skeletal muscle, visceral fat, and s.c. fat tissues, whereas adipoR2 mRNA is predominantly expressed in liver, heart, skeletal muscle, and visceral and s.c. fat tissues. Pig adiponectin mRNA levels in s.c. and visceral fat tissues were not associated with plasma insulin and glucose in fasting animals. Subcutaneous (r = -0.44, P < 0.05), visceral (r = -0.43, P < 0.05), and total body fat (r = -0.42, P < 0.05) weights were negatively correlated with adiponectin mRNA levels measured in visceral, but not s.c., fat. Pig adipoR1 and adipoR2 mRNA levels, in visceral fat, were less expressed in fat UM gilts than in the lean HL gilts (P < 0.05). Inverse associations were found between s.c. (r = -0.57, P < 0.01), visceral (r = -0.46, P < 0.05), and total body fat (r = -0.56, P < 0.01) weights and adipoR2 mRNA levels in visceral fat only. We were unable to find such associations for adipoR1 mRNA levels in the overall gilt population. The current study demonstrated that TNFalpha downregulates adiponectin and adipoR2, but not adi-poR1, mRNA levels in stromal-vascular cell culture. Moreover, leptin significantly decreased adiponectin mRNA levels, whereas there was no effect on adiponectin receptors. We conclude that adiponectin and adi-poR2 mRNA levels, but not adipoR1, are modulated in pig visceral fat tissues. Furthermore, our results indicate that TNFalpha interferes with adiponectin function by downregulation of adipoR2 but not of adipoR1 mRNA levels in pigs.


Assuntos
Adiponectina/biossíntese , Tecido Adiposo/metabolismo , Expressão Gênica/efeitos dos fármacos , Receptores de Adiponectina/biossíntese , Suínos/fisiologia , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/química , Tecido Adiposo/fisiologia , Sequência de Aminoácidos , Animais , Análise Química do Sangue/veterinária , Peso Corporal/genética , Células Cultivadas , Primers do DNA/química , Regulação para Baixo , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Humanos , Leptina/farmacologia , Dados de Sequência Molecular , Receptores de Adiponectina/efeitos dos fármacos , Receptores de Adiponectina/genética , Fator de Necrose Tumoral alfa/farmacologia
11.
Circ Res ; 92(8): 848-55, 2003 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-12663485

RESUMO

Extracellular adenosine production by the glycosyl-phosphatidyl-inositol-anchored Ecto-5'-Nucleotidase plays an important role in the defense against hypoxia, particularly in the intravascular space. The present study was designed in order to elucidate the mechanisms underlying hypoxia-induced stimulation of Ecto-5'-Nucleotidase in endothelial cells. For this purpose, aortic endothelial cells (SVARECs) were submitted to hypoxic gas mixture. Hypoxia (0% O2 for 18 hours) induced a 2-fold increase of Ecto-5'-Nucleotidase activity (Vmax 19.78+/-0.53 versus 8.82+/-1.12 nmol/mg protein per min), whereas mRNA abundance and total amount of the protein were unmodified. By contrast, hypoxia enhanced cell surface expression of Ecto-5'-Nucleotidase, as evidenced both by biotinylation and immunostaining. This effect was accompanied by a decrease of Ecto-5'-Nucleotidase endocytosis, without modification of Ecto-5'-Nucleotidase association with detergent-resistant membranes. Finally, whereas cholesterol content was unmodified, hypoxia induced a time-dependent increase of saturated fatty acids in SVARECs, which was reversed by reoxygenation, in parallel to Ecto-5'-Nucleotidase stimulation. Incubation of normoxic cells with palmitic acid enhanced Ecto-5'-Nucleotidase activity and cell surface expression. In conclusion, hypoxia enhances cell surface expression of Ecto-5'-Nucleotidase in endothelial cells. This effect could be supported by a decrease of Ecto-5'-Nucleotidase endocytosis through modification of plasma membrane fatty acid composition.


Assuntos
5'-Nucleotidase/metabolismo , Membrana Celular/enzimologia , Endotélio Vascular/enzimologia , Hipóxia/fisiopatologia , 5'-Nucleotidase/genética , Monofosfato de Adenosina/farmacologia , Animais , Western Blotting , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Endocitose , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Lipídeos de Membrana/química , Oxigênio/farmacologia , Ácido Palmítico/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
12.
Circ Res ; 90(4): 420-7, 2002 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-11884371

RESUMO

Extracellular adenosine production by the GPI-anchored Ecto-5'-Nucleotidase (Ecto-5'-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5'Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5'-Nu stimulation by HRIs, Ecto-5'-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5'-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5'-Nu and decreased endocytosis of Ecto-5'-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5'-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5'-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5'-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.


Assuntos
5'-Nucleotidase/metabolismo , Membrana Celular/metabolismo , Endotélio Vascular/metabolismo , Lovastatina/farmacologia , beta-Ciclodextrinas , Proteínas rho de Ligação ao GTP/metabolismo , 5'-Nucleotidase/genética , Animais , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Colesterol/metabolismo , Ciclodextrinas/farmacologia , Relação Dose-Resposta a Droga , Endocitose/efeitos dos fármacos , Endotélio Vascular/citologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Ácido Mevalônico/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Fosfatos de Poli-Isoprenil/farmacologia , Prenilação de Proteína/efeitos dos fármacos , RNA Mensageiro/biossíntese , Ratos
13.
J Am Acad Child Adolesc Psychiatry ; 40(9): 1070-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11556631

RESUMO

OBJECTIVE: To compare phenomenology, psychosocial correlates, and treatment seeking in DSM-Itt-R major depression and dysthymia among adolescents diagnosed as cases in a community-based study. METHOD: A self-report questionnaire, including psychosocial data, life events, eating behaviors, depressive symptoms, substance use, pathological behaviors, and family and school functioning was administered to a nonselected sample (N = 3,287, 93.2% of targeted population) of adolescents aged 11 to 20 years from several Haute-Marne communities in France in 1988-1989. Subgroups of subjects (n = 205, 84.7% of eligible subjects) were interviewed with a structured diagnostic schedule, and adolescents with major depression (n = 49), dysthymia (n = 21) and controls (n = 135) were compared. RESULTS: Nearly 30% of controls had at least one current symptom of depression. Patterns of affective symptoms were similar in major depression and dysthymia, but significant differences emerged in comorbid conditions (more anxiety disorders, suicidal behaviors, and alcohol intoxications associated with major depression) and stressor at onset (more severe in major depression). Experiences of loss during the prior 12 months were associated with both forms of affective disorder, while poor family relationships were specific correlates of dysthymia. In contrast, peer relationships and pathological behaviors did not differ between depressed subjects and controls. Although psychosocial functioning was significantly impaired in both groups of depressed adolescents, treatment seeking was limited to 34.7% for major depressive subjects and 23.8% for dysthymic subjects. CONCLUSION: The results provide evidence that major depression and dysthymia in adolescence are equally severe but may have distinct patterns in associated factors. Despite free access to health care, the rate of treatment seeking for mood disorders in France is similar to that reported in U.S. studies.


Assuntos
Serviços de Saúde do Adolescente/estatística & dados numéricos , Transtorno Depressivo/psicologia , Transtorno Distímico/psicologia , Comportamentos Relacionados com a Saúde , Adolescente , Adulto , Comorbidade , Transtorno Depressivo/terapia , Transtorno Distímico/terapia , Relações Familiares , Feminino , França , Humanos , Masculino , Serviços de Saúde Mental/estatística & dados numéricos , Cooperação do Paciente , Grupo Associado , Fatores de Risco
15.
Arch Mal Coeur Vaiss ; 94(8): 775-8, 2001 Aug.
Artigo em Francês | MEDLINE | ID: mdl-11575202

RESUMO

In diabetes, endothelium-dependent dilation of large and small coronary arteries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an iron chelator that inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold pressor test and flow increase in angiographically normal epicardial coronary arteries of diabetic patients. This result suggests that nitric oxide could be inactivated by reactive oxygen species. The aim of this study was to assess the effects of deferoxamine on coronary microcirculation vasomotion when myocardial oxygen demand is increased by sympathetic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without any other coronary risk factors, coronary blood flow has been measured using quantitative angiography and intracoronary Doppler at baseline and during a cold pressor test, before and after intravenous administration of 500 mg deferoxamine. Increase in rate-pressure product, an estimate of myocardial metabolic demand, was similar before and after deferoxamine (+21.1 +/- 8.7% vs +20.5 +/- 8.9%, respectively), but coronary blood flow increase was significantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%, respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation between coronary blood flow and rate-pressure product changes before deferoxamine (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary microcirculation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matching between myocardial oxygen demand and coronary blood flow.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Coração/fisiologia , Ferro/farmacologia , Estresse Oxidativo , Adulto , Quelantes/administração & dosagem , Quelantes/farmacologia , Vasos Coronários/fisiologia , Desferroxamina/administração & dosagem , Desferroxamina/farmacologia , Diabetes Mellitus Tipo 2/patologia , Endotélio/fisiologia , Feminino , Hemodinâmica , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio , Fluxo Sanguíneo Regional
16.
Rev Mal Respir ; 18(3): 289-96, 2001 Jun.
Artigo em Francês | MEDLINE | ID: mdl-11468590

RESUMO

Clinical data support the hypothesis that aggressivity is inhibited amongst asthmatics. The relationship of violence, as a marker of aggressiveness, to asthma was examined in a population-based sample of 12.466 students of secondary schools in France (Enquête sur la Santé de l'adolescent 1993/1994) using an epidemiological questionnaire on health status, life events, potential risk factors and disease management. Twelve percent of the students reported having had at least one episode of asthma, 4% had asthma attacks, and 1% had severe asthma at the time of the survey. Asthma had been confirmed by a physician in 81% of the cases. Acts of violence [fits of violence (21%), screaming when angry (30%), hitting when angry (45%), 'racketeering' (1%)] or sustained violence [physical aggressions (15%) and rape (4%)] were significantly related to asthma in past year when applying a logistic model including age, sex, ethnic group, socioeconomical status, geographical zone, and type of school as potential confounders (adjusted odds-ratios ranging from 1.26 to 1.87 and from 1.44 to 3.48 respectively). Similarly, violence was related to severe asthma. Results persisted after exclusion of individuals for whom asthma had not been confirmed by a physician. These findings strongly challenge the current hypothesis according to which aggressiveness is inhibited in asthmatic adolescents.


Assuntos
Comportamento do Adolescente , Agressão , Asma/psicologia , Violência , Adolescente , Estudos Epidemiológicos , Feminino , França/epidemiologia , Humanos , Masculino
18.
Diabetes ; 50(5): 1180-5, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11334424

RESUMO

Coronary microcirculation dysfunction may be associated with myocardial perfusion defects on thallium imaging in diabetic patients without coronary artery stenosis. Microvascular coronary adaptation to increased myocardial oxygen demand in response to sympathetic stimulation evoked by the cold pressor test was examined in 22 type 2 diabetic patients with thallium imaging defects and in 15 control subjects. Both the diabetic patients and control subjects had angiographically normal coronary arteries and no other risk factors. Despite a similar increase in the rate-pressure product in the two groups (22.6 +/- 12.4% in diabetic patients and 31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in the left anterior descending artery (mean flow velocity measured by intracoronary Doppler multiplied by the cross-sectional area measured by digital angiography) was significantly lower in diabetic patients than in control subjects (14.7 +/- 19.8 vs. 75.5 +/- 13.5%, respectively; P = 0.0001). In addition, when there was a positive correlation between the two parameters in control subjects (r = 0.651, P < 0.01), there was no relationship in diabetic patients (r = 0.054). In conclusion, vasodilation of the coronary microcirculation in response to sympathetic stimulation evoked by the cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilation during current life stress episodes such as exercise, mental stress, or cold exposition.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hemodinâmica/fisiologia , Microcirculação/fisiologia , Vasodilatação/fisiologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Temperatura Baixa , Angiografia Coronária , Vasos Coronários/fisiologia , Feminino , Frequência Cardíaca , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Fatores de Risco
19.
Diabetes Metab ; 27(5 Pt 3): S23-7, 2001 Nov.
Artigo em Francês | MEDLINE | ID: mdl-11910976

RESUMO

Most patients with type 2 diabetes gain weight when treated with insulin. Weight gain is observed when insulin is introduced after oral agents have failed, but also when insulin is introduced shortly after the diagnosis of diabetes. The mechanisms of this weight gain are incompletely understood, but reduction of energy lost by glucosuria and reduction of energy needed for glucose production are main determinants. The same reasons apply to the weight gain observed at the beginning of treatment with sulfonylureas, even though patients usually gain less weight with sulfonyulreas than with insulin. In the UKPDS, at 10 years of the study, patients treated with insulin gained 2 kg more, i.e. 2.5% of the average weight of patients included in the trial, than patients treated with sulfonylureas. The reasons of the excess of weight gain with insulin as compared with sulfonylureas remain unclear. Patients with type 2 diabetes treated with insulin gain weight only during the first 2-3 years after insulin introduction. The weight stabilizes thereafter. Type 2 diabetes usually remains unknown for years before diagnosis and patients may lose weight during this long period of time preceding diagnosis. It is hypothesized that the weight gain observed after the introduction of insulin may simply correspond to the reexpression of the physiologically controlled body weight.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/efeitos adversos , Ganho de Peso/efeitos dos fármacos , Metabolismo Energético , Humanos , Hipoglicemiantes/efeitos adversos
20.
Arch Mal Coeur Vaiss ; 93(8): 937-41, 2000 Aug.
Artigo em Francês | MEDLINE | ID: mdl-10989733

RESUMO

A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Adaptação Fisiológica , Angiografia Digital , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Temperatura Baixa , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Exposição Ambiental , Feminino , Frequência Cardíaca/fisiologia , Humanos , Análise dos Mínimos Quadrados , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Miocárdio/metabolismo , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Ultrassonografia Doppler , Vasodilatação/fisiologia
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