International Journal of Obesity (2001) 25, Suppl 2, S74±S87 ß 2001 Nature Publishing Group All rights reserved 0307±0565/01 $15.00 www.nature.com/ijo Track 6 Cardiovascular system and obesity P152 P154

Urinary albumin excretion is independently associated with C-reactive Association of early carotid atherosclerosis with hyperinsulinemia and low protein levels in overweight and obese women DHEA(S) in normotensive severe obese women N Pannacciulli1, FP Cantatore2, A Minenna1, M Bellacicco1, R Giorgino1, and S Savastano1, AM Bel®ore2, R Valentino3, M Dorato2, N De Luca4, F Micanti5, G De Pergola1 C Mauriello2, C Falconi2, G Lupoli1, and G Lombardi1 1Department of Emergency and Organ Transplantation - Section of Internal 1Department of Molecular and Clinical Endocrinology and Oncology, University Medicine, Endocrinology and Metabolic Diseases, University of Bari, Bari, Italy; Federico II Medical School Naples, Via S. Pansini n. 5 - 80131 Italy; 2Department of Internal Medicine and Public Health - Section of Rheumatology, 2Department of Neurosciences, Unit of Physiology, University Federico II Medical University of Bari, Bari, Italy School Naples, Via S. Pansini n. 5 - 80131 Italy; 3C.E.O.S., CNR, Department of Cellular and Molecular Biology and Pathology, University Federico II Medical INTRODUCTION: The aim of the present study was to evaluate the possible 4 correlation between urinary albumin excretion (UAE), marker of endothelial School Naples, Via S. Pansini n. 5 - 80131 Italy; Department of Clinical Medicine and Cardiovascular Science, University Federico II Medical School dysfunction, and C-reactive protein (CRP), marker of chronic in¯ammation of 5 the arterial wall, in overweight and obese premenopausal women. Naples, Via S. Pansini n. 5 - 80131 Italy; Unit of Psychotherapy, Department METHODS: CRP levels and UAE rate were measured in 103 overweight (BMI of Psychiatry, University Federico II Medical School Naples, Via S. Pansini n. 25.0 ± 29.9 Kg=m2) and obese (BMI  30.0 Kg=m2) premenopausal women, 5 - 80131 Italy aged 18 ± 45 years. Other measurements included central fat accumulation, as INTRODUCTION: Hypertension, hyperlipemia, smoking, and hyperinsulinae- evaluated by waist circumference, insulin resistance, as calculated by home- mia are well known risk factors in the progression of atherosclerosis. Newer risk ostasis model assessment (HOMAIR), systolic and diastolic blood pressure, and factors, such as hyperandrogenism or DHEAS and DHEA [DHEA(S)] levels have fasting plasma levels of glucose, insulin, and lipids. also been recently suggested, although the direct evidence that hyperinsuli- RESULTS: UAE was positively correlated with BMI (P < 0.01), waist circumfer- naemia or DHEA(S) per se are directly involved has been con¯icting. We ence (P < 0.00l), diastolic blood pressure (P < 0.01), triglyceride (P < 0.01), investigate the cross-sectional association of early carotid atherosclerosis, HOMAIR (P < 0.05), and CRP levels (P < 0.05), and negatively associated with measured as intima-media thickness (IMT), with hyperinsulinaemia, and low HDL-cholesterol (P < 0.001). After multivariate analysis, diastolic blood pres- circulating DHEA(S) levels in 17 normotensive severe obese premenopausal sure, HDL-cholesterol, and CRP levels maintained their signi®cant correlation women and 10 normal-weight age-matched subjects. with UAE (P < 0.05, P < 0.01, and P < 0.01, respectively). Lastly, we observed a METHODS: Oral glucose tolerance test (OGTT), adrenal secretion, carotid gradual increase in CRP plasma levels across the quartiles in which the whole diameter (CD), and left ventricular mass index (LVMi) were determined. population was divided according to UAE levels (F: 5.67, P ˆ 0.001 for linear RESULTS: Impaired glucose tolerance was present in 29% of the obese trend). patients. DHEA(S) levels (P < 0.001) were lower and negatively correlated CONCLUSION: Our study shows a strong relationship between UAE rate and with simulated insulin (r70.7; P < 0.01), in spite of normal values of other CRP concentrations, irrespective of age and other anthropometric and meta- androgens and increased plasma cortisol and urinary free cortisol were found bolic variables. On this basis, it can be argued that in¯ammation of the arterial in 53% of the obese patients, with normal dexamethasone suppression test. wall, as indicated by higher CRP plasma levels, and endothelial dysfunction, as No differences were observed in systolic and diastolic blood pressure, heart shown by higher UAE rate, might represent simultaneous phenomena in the rate, fasting triglycerides, or total cholesterol between the groups. CD, IMT, development of atherosclerosis in overweight and obese premenopausal and LVMi were higher in obese women than in controls (P < 0.05); using women. simple regression analysis, we found that CD was also positively correlated with BMI (r ˆ 0.5; P < 0.05) and fasting insulin (r ˆ 0.6; P < 0.05); a weak positive correlation was present between IMT and LVMi (r ˆ 0.6; P < 0.05), while a strong negative correlation was present between IMT and DHEA(S) P153 (r ˆ 0.9; P < 0.01). The multiple regression analysis, using insulin, BMI, and DHEA(S) as covariates, showed insulin (P < 0.01) and DHEA(S) (P < 0.001) to C-reactive protein is independently associated with total body fat, central be the most powerful predictors for CD and IMT, respectively. fat, and insulin resistance in adult women CONCLUSION: In normotensive severe obese premenopausal women with- G De Pergola1, N Pannacciulli1, FP Cantatore2, A Minenna1, M Bellacicco1, and out hyperandrogenism, hyperinsulinaemia and low DHEA(S) as early carotid R Giorgino1 atherosclerosis can be detected in absence of other covariated risk factors for 1Department of Emergency and Organ Transplantation - Section of Internal cardiovascular disease, suggesting their independent role in atherosclerosis Medicine, Endocrinology and Metabolic Diseases, University of Bari, Bari, Italy; progression. 2Department of Internal Medicine and Public Health - Section of Rheumatology, University of Bari, Bari, Italy P155 INTRODUCTION: The relationship between C-reactive protein (CRP) and atherotrombosis is well established. Moreover, the prevalence of elevated Left ventricular hypertrophy regression: role of weight loss and insulin CRP levels has been shown to be higher in overweight and obese patients than changes in obese normotensive subjects in normal weight subjects. The aim of our study was to investigate whether 1,2 1 1 1 3 3 CRP concentrations are in¯uenced by body composition, insulin resistance F Vetta , S Ronzoni , MR Lupattelli , V Spallone , MG Bendini ,AMeo, 1 1 1 1 1 2 and body fat distribution in apparently healthy women. P Fabbriconi , B Novi , A Pannone , E Cicconetti , C Ficoneri , F Russo , and 1 METHODS: CRP plasma levels, body composition (fat mass, FM, and fat-free MR Bollea 1 mass, FFM), as measured by bioimpedance analysis, central fat accumulation, Department of Internal Medicine, "Tor Vergata" University, Rome, Italy; 2 as evaluated by waist circumference, and metabolic parameters, including Department of Internal Medicine, "SS. Gonfalone" Hospital, Monterotondo, 3 fasting glucose, insulin levels and insulin resistance, as calculated by home- Italy; Institute of Cardiology U.C.S.C. Rome, Italy ostasis model assessment (HOMAIR) have been determined in 201 apparently Obesity and hypertension are the most important determinants of left healthy normal weight, overweight, and obese women, aged 18 ± 60 years. ventricular hypertrophy (LVH). Our previous reports have suggested the RESULTS: CRP was positively correlated with age (P < 0.001), BMI prime role of hyperinsulinism as determinant of LVH independently of blood (P < 0.0001), waist circumference (P < 0.0001), fasting glucose (P < 0.0001), pressure values in obese subjects. fasting insulin (P < 0.000l), HOMAIR (P < 0.000l), FFM (P < 0.0001), and FM Therefore, on the ground of present knowledge, the aim of this study was (P < 0.0001). After multivariate analyses, age, HOMAIR, waist, and FM main- to evaluate, in obese subjects, the in¯uence of weight loss on left ventricular tained their independent association with CRP (P < 0.005, P < 0.00l, P < 0.05, mass (LVM) in relation with changes in glycaemic and insulinemic metabo- and P < 0.05, respectively). Lastly, we observed a gradual increase in CRP lism, 24 h blood pressure values and centripetal adipose tissue distribution. We plasma levels across the quartiles in which the whole population was divided included in our study 24 obese subjects (BMI ˆ 34.3) mean age 38.9 years according to HOMAIR levels (F: 4.83, P ˆ 0.003 for linear trend). and 14 lean subjects (BMI ˆ 23.8) acted as controls age and sex matched. At CONCLUSION: Our study of apparently healthy adult women has shown a enrollment and after a period of at least 6 months ensuing the weight loss strong relationship of total body fat, central fat accumulation, and insulin (74.8 points of BMI), all subjects underwent a 24 h ABPM (Spacelabs 90202), resistance with CRP plasma levels, irrespective of age and other anthropo- a complete anthropoplicometric and bioimpedance analysis (Dietosystem) metric and biochemical variables. Since CRP has been shown to be one of the and biochemical determinations. most powerful predictors of risk of cardiovascular events, it can be hypothe- Areas under glucose and insulin curves were assessed using Haffner's sized that atherogenic mild, chronic in¯ammation may be a further feature of formula by values obtained with OGTT, while insulin resistance was deter- the metabolic syndrome. mined indirectly (HOMAIR). LVM was assessed with ATL Ultramark 8 system, Track 6 Cardiovascular system and obesity

S75 using Devereux and Reichek's formula according to Penn Convention criteria. that was greater than 50% and in the top tertile the increase was 212Æ 49%. Our data, beyond the expected differences between obese and control The respective value after i.v. glucose in the same ®ve subjects was 93Æ 44%. subjects with regard to LVMI (g  m72) and LVMC (g  m72.7) values, There was a signi®cant correlation between peak ATBF in response to the two p < 0.0001 with similar indices of RWT, have shown, in presence of non treatments (Spearman's rs ˆ 0.87, P < 0.001). For both regimens, peak ATBF signi®cative differences in ABPM and AUGC levels, higher values in AUIC was signi®cantly correlated with baseline ATBF (rs ˆ 0.60, P < 0.05 and (p < 0.0001), HOMAIR (p < 0.0001), as well as in centripetal adipose tissue rs ˆ 0.72, P < 0.05 for oral and i.v. glucose respectively). Peak ATBF was distribution parameters (WHR) p < 0.0001 in obese subjects. negatively correlated with BMI (rs ˆ 70.52, P < 0.05 for both treatments). Statistical analysis performed with linear regression method puts in The results show an ATBF response can be elicited either by oral or by i.v. evidence a strict correlation among LVMI, LVMC, RWT and hyperinsulinism, glucose administration, but the effect is greater after oral ingestion. This insulin-resistance, WHR and blood pressure variability (chie¯y systolic values) suggests that factors in addition to an increasing postprandial insulin con- both before and after weight reduction, (p < 0.001) while the same data centration are associated with modulation of postprandial ATBF. Studies such analyzed with multiple regression statistical method suggest the chie¯y role of as this will increase the understanding of the regulation of ATBF in healthy changes in hyperinsulinism and insulin-resistance as determinants of LVM subjects and the implications of dysregulation of ATBF in obesity. modi®cations (p < 0.001). P158 P156 Expression of endothelin-system genes and secretion of endothelin-1 by A speci®c lipolytic defect in visceral fat in polycystic ovary syndrome human adipocytes M RydeÂn1,IEk1, J Hoffstedt1, A ThoÈrne1,CHolm1, H Wahrenberg1, and S Engeli1, J Janke1, K Gorzelniak1, FC Luft1, AM Sharma1, Franz-Volhard- P Arner1 Klinik1, and Max-DelbruÈck1 1Lipidlaboratory, Centre for Metabolism and Endocrinology, Department of 1Center for Molecular Medicine, University Clinic ChariteÂ, Humboldt-University Medicine, Karolinska Institute, Huddinge University Hospital, 141 86, Berlin, Germany Stockholm, Sweden Recent studies have demonstrated that the potent vasoconstrictor peptide INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with insulin endothelin-1 inhibits adipogenesis and activity of lipoprotein lipase activity in resistance, glucose intolerance, dyslipidemia and atherosclerosis, a similar risk rat and human adipocytes via endothelin receptor type A receptors. Further- pro®le as in visceral obesity. The etiology is unknown. In order to study more, endothelin-1 plasma levels have been reported to be higher in obese possible primary defects in omental adipose tissue from subjects with PCOS, individuals. At present, no study has investigated the presence of endothelin we investigated visceral fat cells of 10 young non-obese PCOS women with system components in human adipose tissue. normal metabolic pro®le, except slightly decreased insulin sensitivity and We studied the expression pattern of endothelin system genes in human normal body fat distribution according to computerized tomography. adipose tissue, isolated adipocytes, and cultured preadipocytes by conven- METHODS: Lipolysis was measured in isolated fat cells by standard proce- tional RT-PCR (n ˆ 6 for each sample) and measured secretion of big-endothe- dures. Protein was isolated from omental adipose tissue and separated by SDS- lin-1 into the culture medium of human primary cultured adipocytes by PAGE. Speci®c proteins were detected by Western blot. Speci®c lipolytic radioimmunoassay. We also measured the expression level of the endothe- enzyme activity towards hormone sensitive lipase (HSL) was determined. lin-1 gene in lean and obese subjects by TaqMan-RT-PCR (n ˆ 30). RESULTS: In comparison to 13 control women, inhibition of lipolysis through Expression of the genes for endothelin-1, type A and type B endothelin insulin receptors and Gi receptors was normal but stimulation of lipolysis receptors, and the endothelin-1 regulating transcription factor GATA-2 were through all three beta-adrenergic receptor subtypes was two-fold increased in detected in human adipose tissue as well as in isolated adipocytes and PCOS due to enhanced ability of cyclic AMP to activate lipolysis. Examination preadipocytes. Radioimmunoassay studies revealed secretion of big-endothe- of the lipolytic pathway demonstrated that PCOS cells display several differ- lin-1 by primary cultured human adipocytes into the culture medium. ences at the protein level compared to control cells. The short form of HSL, Endothelin-converting-enzyme, that liberates active endothelin-1 from its which is an enzymatically inactive splice variant, was highly expressed in precursor big-endothelin-1, was not detected in adipose cells. Quantitative control cells while PCOS cells showed a markedly reduced level. The expres- expression of the endothelin-1 gene was higher in obese normotensive sion of the catalytic subunit of protein kinase A (PKA) was increased in PCOS subjects compared to lean normotensive and obese hypertensive subjects. cells. Furthermore, detailed studies on the regulatory PKA subunits demon- Our data point to a potential contribution of adipocytes to increased strated that while Reg IIb was lowered, Regla levels were signi®cantly increased endothelin-1 plasma levels. Further studies must elucidate the regulation of in PCOS cells. This transition in regulatory subunits has been shown to big-endo-thelin-1 secretion by adipocytes and its possible contribution to enhance lipolytic activity in a transgenic animal models. All lipase activity in adipose tissue physiology. visceral fat cells could be attributed to hormone sensitive lipase. CONCLUSION: Young non-obese PCOS women with no apparent metabolic abnormality except slightly decreased insulin sensitivity have a marked P159 increase in the lipolytic function of visceral fat cells due to a superef®cient HSL-PKA complex. This in turn would increase fatty acid delivery to the liver Superoxide dismutase izoenzymes and glutathione peroxidase activity, and be an early and primary defect in the. and malondialdehyde concentration in obese women KZÇ wirska-Korczala1, J Jochem1, R Polaniak2, E Birkner 2, B Rybus-Kalinowska1, P157 and J JagodzinÂska1 1Department of Physiology; 2Department of Biochemistry, Silesian Medical Greater increase in adipose tissue blood ¯ow after oral compared with intravenous glucose University, ul. Jordana 19, 41-808 Zabrze, Poland INTRODUCTION: Obesity is a metabolic disease associated with immunolo- BA Fielding1, F Karpe1, V Ilic1, SM Humphreys1, and KN Frayn1 1 gical complications. It is known that TNF a, pluripotent cytokine secreted in Oxford Lipid Metabolism Group, Oxford Centre for Diabetes, Endocrinology abundance by adipocytes in obesity, stimulates the antioxidant response of and Metabolism, Radcliffe In®rmary, Oxford, OX2 6HE, UK manganese-containing superoxide dismutase (MnSOD). Adipose tissue blood ¯ow (ATBF) increases after meal intake and failure to METHODS: Lipid pro®le and plasma (pl) and erythrocytes (e) activities of regulate ATBF in the postprandial period may be a feature of insulin resistance copper=zinc superoxide dismutase (Cu=ZnSOD), MnSOD and glutathione and obesity. The factors that regulate ATBF in the postprandial period are not peroxidase (GSHpx), and concentration of malondialdehyde (MDA) were well understood, but insulin action is a potential mediator. The aim of this examined in 29 premenopausal obese and 14 lean women (age 34Æ 7.2 vs study was to compare ATBF in subcutaneous abdominal adipose tissue after 27.3Æ 3.2, BMI 38.2Æ 4.5 vs 22.5Æ 1.2 kg=m2, respectively). oral glucose or intravenous glucose=insulin administration. The aim was to RESULTS: Obese women demonstrated in comparison to the control group achieve similar peripheral glucose and insulin concentrations on the two visits. increased levels of total cholesterol (216.0Æ 38.2 vs 166.3Æ 18.4 mg=dl; 15 healthy subjects (8 male) participated in the study after an overnight p < 0.001), LDL-cholesterol (149Æ 28 vs 86Æ 10.1 mg=dl; p < 0.00l) and fast. Their mean age was 35.3 years (23 ± 52) and mean BMI was 23.8 kg=m2 triglicerydes (162.8Æ 21.2 vs 85.5Æ 14.1 mg=dl; p < 0.001), and decreased (19 ± 30). On the ®rst visit, ATBF was measured by 133Xe washout, before and level of HDL-cholesterol (46.3Æ 9.1 vs 60.1Æ 3.2; p < 0.05). In obese women after 75 g oral glucose. On the second, similar concentrations of insulin and Cu=ZnSOD(pl) and Cu=ZnSOD(e) activities were similar to those found in the glucose in plasma were achieved by dynamic i.v. infusions. control group (8.4Æ 3.6 vs 9.8Æ 1.7 NU=g protein and 25.1  1073 Æ 3.8  There was signi®cant heterogeneity in ATBF response between subjects 1073 vs 24.8  1073 Æ 1.2  1073 NU=g protein, respectively). Moreover, we on both days (P < 0.001). The mean peak ATBF was 7.9Æ 1.6 and 4.5Æ found in obese women enhanced activities of MnSOD(pl) (4.3Æ 1.3 vs 0.8 ml=min=l00 g tissue after oral and i.v. glucose respectively (P < 0.05). Nine 2.8Æ 1.7 NU=g protein; p < 0.00l) and PSHpx (40.3Æ 7.1 vs 5.5Æ 3.6 mmol= out of ®fteen subjects exhibited an increase in ATBF in response to oral glucose NADPH2=g protein=min; p < 0.00l), and concentrations of MDA(pl) (2.8Æ 0.3

International Journal of Obesity Track 6 Cardiovascular system and obesity

S76 vs 2.2Æ 0.1 mmol=NADPH2=g protein=min; p < 0.05) and MDA(e) (2.5Æ 0.2 chromaf®n cells, the leptin involment in the overexpression of TH mRNA in the vs 2.1Æ 0.3 mmol=NADPH2=g protein=min; p < 0.05). hypothalamus of cafetria-fed rats remains to be determined. CONCLUSION: Our data reveal the activation of plasma and erythrocytes enzymes involved in oxidative processes, mainly associated with lipid peroxi- dation, in premenopausal obese women with abnormal lipid pro®le. P162

Blood pressure in relation to birth weight and weight history during P160 childhood and adulthood in Danish men Impact of the methylenetetrahydrofolate reductase (MTHFR) 677 C ) T mutation on folate requirements in obese adolescents during weight L Schack-Nielsen1,CHolst1, and TIA Sùrensen1 reduction 1Danish Epidemiology Science Centre, Institute of Preventive Medicine, Kommunehospitalet, DK 1399 Copenhagen K, Denmark ML Frelut1,2, N Emery-Fillon3, JC Guillaud4, V Coppet 2, JP ChristideÁs£, G Potier de Courcy£, and J Navarro1 INTRODUCTION: Obesity is associated with an increased risk of hypertension, 1HoÃpital R. DebreÂ, 48 bd Serurier, 75019 Paris, France; 2CTP 95580 Margency, but whether the duration of obesity has importance for blood pressure is not France; 3HoÃpital de Brabois Nancy, Dijon, France; 4CNRS Dijon, France known. METHODS: 245 obese men (body mass index (BMI)  31 kg=m2) and 236 The 677 C ) T MTHFR mutation increases the folates requirements in humans. random controls were identi®ed retrospectively from draft board examination Low folates in turn lead to increased plasma homocysteine (HCY) levels, an medical records. Weight and height during childhood (7 ± 13 years of age) independant cardiovascular risk factor. The aim of this study is to determine were available from school health records in which birth weight, based on folate requirements, based on HCY plasma concentrations, in obese adoles- mothers recall when the child attended school, was also reported. The cents during weight reduction. subjects were invited to participate in two follow up studies (median age 36 97 obese adolescents (BMI ˆ 36.1Æ 6.0 kg=m2) including 60 girls and 37 years (interval 25; 53 years) and 47 (interval 37; 64 years), respectively), boys, aged 14.1Æ 1.5 yrs were included. 73 completed an inpatient inter- where height, weight and blood pressure were measured. By multiple regres- disciplinary weight (Wt) reduction program during 6 to 12 months, 5 days per sion the importance of BMI and change in BMI in childhood and adolescence week. Wt reduction program included a modertate caloric restriction (720% for blood pressure as adults after taking current weight and age into account of national RDAs) at the expense of sucrose and saturated fat, within a was estimated. balanced diet which provided 400 mg of folate per day. Regular submaximal RESULTS: Current BMI and age were positively associated with systolic and physical training was also included. diastolic blood pressure. While taking these effects into account, BMI during Folate intakes before Wt loss were assessed by mean of adapted food childhood, or change in BMI in childhood or adolescence, had no in¯uence on frequency questionnaire and food composition table. Folates in red blood cells blood pressure. Birth weight was negatively related to systolic blood pressure (EF) were measured by a microbiological assay and plasma homocysteine (regression coef®cient 72.0 mmHg per kg; 95% con®dence interval 74.0; (pHCY) by HPLC. MTHFR polymorphism was assessed by PCR. 70.1 and 72.7 mmHg per kg; 95% con®dence interval 75.3; 0.0 at ®rst and BMI after Wt loss was 27.8Æ 3.8 kg=m2 (p < 0.0001). second follow up, respectively), when adjusting for current BMI and age. Before Wt loss folates intakes were 270Æ 102 mg=d. Folate density in food Further adjustments for BMI measurements in childhood or adolescence did was positively correlated to EF (p < 0.0006) and negatively to pHCY not change these estimates. (p < 0.003). 10% of the subjects are homozygote for the mutation (TT), 47 CONCLUSION: Obesity increases the risk of hypertension, but the duration of are heterozygote (CT) and 44% have the wild type (CC). During Wt loss EF obesity seems not to have an additional in¯uence on blood pressure. This has increase by 9% (p < 0.04) and pHCY by 19% (p < 0.001). pHCY increase is implications for the understanding of the relation between obesity and blood higher in CT ( ‡27%, p < 0.001, n ˆ 35) than in CC ( ‡ 15%, p < 0.05, pressure. However, birth weight was negatively related to blood pressure, only n ˆ 32). In TT, neither pHCY (9.06Æ 2.46 mmol=l, n ˆ 6) nor EF (207Æ 65 mg=l) after taking current BMI into account, indicating an adverse effect of a catch- vary. They remain higher than in CT and CC subjects. up in weight. Since BMI measurements from the age of 7 years and change in Daily folates intakes above 400 mg=d seem to be required to prevent a rise BMI in childhood and adolescence had no in¯uence on blood pressure, this in pHCY in severely obese adolescents during Wt reduction. The increase catch-up in weight has probably taken place before the age of seven. required is proportional to the degree of the mutation (TT > CF > CC).

P161 P163

Potential hypothalamic effects of leptin in cafeteria diet-induced Obesity reduces muscle metabore¯ex control hypertension IC Trombetta1, MM Ribeiro1, LT Batalha2, MUPB Rondon1, T Tinucci3, , C Plut1, C RibieÁre1, Y Giudicelli1, and JP Dausse1 CLM Forjaz3, ACP Barretto1, A Halpern2, SMF Villares2, and CE NegraÄo1 3 1Service de Biochimie et de Biologie MoleÂculaire, Faculte de MeÂdecine de Paris- 1Heart Institute (InCor), University of SaÄo Paulo Medical School, SaÄo Paulo, Brazil; Ouest, France 2Department of Endocrinology, University of SaÄo Paulo, SaÄo Paulo, Brazil; 3School of Physical Education and Sports, University of SaÄo Paulo, SaÄo Paulo, Brazil Obesity is the most common cause of hypertension. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the INTRODUCTION: There is no information about the muscle metabore¯ex hypothalamus may link excess weight gain with increased sympathetic activity control in obese individuals. and elevated blood pressure. In hypothalamus of cafeteria-fed rats, a model of METHODS: In 40 normotensive obese women (OW) and 15 age-matched obesity-induced hypertension, we studied leptin receptor, neuropeptides and lean women (LW), we measured muscle sympathetic nerve activity (MSNA) adrenergic system. After 10 weeks of diet, hyperleptinemia was associated and forearm blood ¯ow (FBF) during static exercise at 10 and 30% of maximal with a decrease in leptin receptor mRNA (735 and 745% for the short and voluntary contraction (MVC). the long isoform respectively). Leptin receptor belongs to cytokine receptor, RESULTS: Baseline MSNA (38Æ 2vs31Æ 1 bursts=min, P ˆ 0.001) and mean we therefore ewamined inhibitors of cytokine signaling. Expressions of CIS and blood pressure (MBP, 100Æ 2vs91Æ 3 mmHg, P ˆ 0.0036) were higher SOCS-3, known modulators of leptin signaling, were unchanged but SOCS-1 in OW compared with LW. FBF was lower (1.90Æ 0.07 vs 2.27Æ 0.15 mL=min= was surprisingly increased. The leptin effect on SOCS-1 increase and its role in 100 g, P ˆ 0.02), while forearm vascular resistance (FVR) was higher in OW the hypothalamic leptin signaling during obesity remain to be determined. A (57Æ 3vs45Æ 3 units, P ˆ 0.03). During 10% MVC, MSNA increased similarly decrease in proopiomelanocortin (POMC) gene expression was also observed in both groups, but during 30% MVC, MSNA increased was higher in LW. The without modi®cation in neuropeptide Y mRNA. The decrease in leptin responses of FBF and FVR during both 10 and 30% MVC were similar between receptor could participate to the state of leptin resistance observed in obesity groups. During post-handgrip circulatory arrest, MSNA remained signi®cantly and contribute to decrease POMC. POMC down-regulation in cafeteria-fed elevated compared with baseline in both groups, but this increase was rats could contribute to the onset of hypertension by a decrease in the signi®cantly lower in OW compared with LW (3.8Æ 0.82 vs 9.4Æ 1.03 hypotensive action of b-endorphin, a POMC product, or by conversion of bursts=min, P ˆ 0.002). Further analysis showed the same results when we this hypotensive response to a contrasting pressor response to b-endorphin compared a subset group 17 OW with similar MBP levels than LW. previously observed in obese rats. On the other band, tyrosine hydroxylase CONCLUSION: Muscle metabore¯ex control of MSNA is blunted in OW. MSNA responses are not augmented during selective activation of central (TH), the rate limiting enzyme in catecholamine synthesis, and a2B-adreno- ceptor were up-regulated. These modi®cations suggest an elevation in sym- command=mechanoreceptors and metaboreceptor, despite increased MSNA pathetic activity and may participate to elavated blood pressure. If leptin has levels in OW. Muscle vasodilatory response during graded handgrip isometric been shown to increase TH mRNA levels in culture porcine adrenal medullary exercise is preserved in OW.

International Journal of Obesity Track 6 Cardiovascular system and obesity

S77 P164 to 112.2% (p ˆ 0.01), antithrombin III activity rose from 1.12 to 1.23 u=ml (p ˆ 0.004) and median C-reactive protein rose from 3.8 to 4.2 mg=l Inhibitory effects of anti-diabetic compounds on interleukin-8 production (p ˆ 0.0001). In men, these associations were not statistically signi®cant. in human adipose tissue There was no sex difference in the association of other variables with BMI, so results were combined. JM Bruun1, SB Pedersen1, and B Richelsen1 1 CONCLUSIONS: Increasing BMI is associated with elevation of coagulation Department of endocrinology and metabolism C, Aarhus Amtssygehus, Aarhus factors, inhibitors of ®brinolysis and inhibitors of coagulation. These changes University Hospital and Faculty of Health Sciences, Aarhus University, DK-8000 may partiy explain the increased tendency for thrombosis in obese subjects. Aarhus C, Denmark Explanation for the sex differences requires further investigation. INTRODUCTION: Obesity is known to be strongly associated with an increased risk of developing Type 2 diabetes and cardiovascular disease. Reports have suggested that the chemokine, interleukin-8, may be involved P166 in the development of diabetic macroangiopathy as well as in the pathogen- esis of atherosclerosis, and is has been shown that interleukin-8 is produced Left and right ventricular dysfunction in morbid obesity and released form the human adipose tissue (Bruun et al, J. Clin. Endocrinol. LK Bowles1,TWKoh1, AD Timmis1, and PG Kopelman1 Metab., In press). Two classes of drugs, the biguanides and the insulin- 1 sensitizing thiazolidinediones seem to have additional bene®cial effects on St Bartholomew's and the Royal London School of Medicine, Whitechapel, cardiovascular risk-factors besides their effects on glucose homeostasis. In this London, E1 1BB, United Kingdom study we investigated the effects of the thiazolidinedione, Ciglitazone (a INTRODUCTION: Circulatory volume expansion and increased cardiac output PPARg-agonist), the PPARa-agonist Eicosatetraynoic acid (ETYA) and the accompany increasing body weight. As a consequence, structural changes biguanide, Metformin on interleukin-8 gene expression and production in develop in the heart. Abnormalities of left ventricular (LV) function have been human adipose tissue in vitro. described in obesity, but less is known about alterations in right ventricular METHODS: Adipose tissue obtained from the subcutaneous abdominal region (RV) function. The aim of this study was to assess cardiac adaptation to obesity were incubated up to 24 h together with increasing concentrations of the with particular reference to RV, in 22 young (age 45Æ 11 yrs, 8 female) compounds investigated stimulated with interleukin-1b (2 ng=mL). The con- asymptomatic obese subjects without hypertension using transthoracic echo- centration of IL-8 in the media was measured by ELISA and the gene cardiography (TTE). The results were compared to a control group of 21 expression was determined by real time RT-PCR. The mean stimulated con- normal weight subjects of similar age (40Æ 11 yrs) with structurally normal centration of IL-8 was 42.9Æ 3.1 nM. hearts. RESULTS: The PPARg, Ciglitazone 10 ± 100 mM inhibited interleukin-8 release METHODS: 2-D guided M-mode echocardiographic measurements of the and gene expression by 25 ± 50% (p < 0.05). Metformin 0.1 ± 10 mM inhibi- longitudinal motion of the tricuspid and mitral annulus at the level of the LV ted interleukin-8 release and gene expression by 20 ± 80% (p < 0.05). How- and RV free walls, as well as trans-mitral and trans-tricuspid Doppler in end- ever, the PPARa-agonist, ETYA 1 ± 100 mM did not effect the production of expiration, were recorded by TTE. Pulmonary artery (PA) pressure was interleukin-8 in the adipose tissue. estimated from tricuspid regurgitation. Body weight and BMI for the obese CONCLUSION: We here demonstrate the ability of two anti-diabetic com- group was signi®cantly higher than the control group (150Æ 32 kg vs pounds to decrease the release of interleukin-8 from human adipose tissue in 73Æ 9 kg, 52Æ 10 kg=m2 vs 25Æ 3.0). vitro. These ®ndings could suggest that these anti-diabetic compounds might RESULTS: Our LV observations con®rm previous ®ndings. Short axis measure- have additional bene®cial effects on the atherosclerotic process, besides their ments of the LV showed larger cavity size (LVEDD 5.2Æ 0.6 vs 4.3Æ 0.6 cm), effects on glucose homeostasis through the observed anti-in¯ammatory increased wall thickness (1.3Æ 0.1 vs 1.0Æ 0.1 cm) and greater LV mass (LV mechanism. mass=height index 206Æ 52 vs 96Æ 19 g=m, p < 0.01 for all) in obese vs controls. LV systolic excursion (SE) and shortening rate (SR) were no different P165 to controls, but lengthening rate (LR) was reduced (8.3Æ 2.6 vs Associations of haemostatic variables with body mass index 10Æ 2.5 cm=s), trans-mitral a wave was greater (0.7Æ 0.1 vs 0.5Æ 0.1 m=s)

1 1 1 1 1 1 and e=a ratio was reduced (1.1Æ 0.3 vs 1.4Æ 0.4) in obese vs controls. LK Bowles , PK MacCallum , JA Cooper , DJ Howarth , J Af®eld , TW Meade , (p < 0.05 for all). We report for the ®rst time alterations in RV function. RV and GJ Miller1 1 SE and SR were similar in the obese (2.4Æ 0.3 vs 2.5Æ 0.3 cm, 11.2Æ 2.4 vs MRC Epidemiology and Medical Care Unit, Charterhouse Square, London, 10Æ 2.5 cm=spˆ ns). But LR was reduced in the obese vs controls (8.4Æ 2.4 EC1M 6BQ, United Kingdom vs 10Æ 2.5 cm=s, p < 0.05). Trans-tricuspid a wave was greater (0.5Æ 0.1 vs INTRODUCTION: Obesity is a risk factor for venous and arterial thrombosis 0.2Æ 0.1 m=s), e=a ratio was reduced (0.9Æ 0.2 vs 1.9Æ 0.4), while RV and this may be mediated partly through changes in the haemostatic system. isovolumic relaxation time increased, in obese vs control. (73Æ 22 vs We examined relationships between a range of haemostatic variables, mea- 40Æ 15 s, p < 0.0l for all). PA pressure was similar in obese and controls sured by standard methods, and BMI. (20Æ 5vs18Æ 6 mmHg). METHODS: 150 adults (73 males, 77 females), age range 23 ± 80 years, CONCLUSIONS: Extreme obesity is characterised by alterations in LV and RV identi®ed from a general practise list by strati®ed random sampling within diastolic function. In addition, there are signi®cant alterations in LV mass and gender and decade of age. Correlations with tertiles of BMI were sought after cavity size. These changes contribute to the increased risk of cardiovascular age-adjustment. morbidity and mortality in obese subjects. RESULTS: In women from the lowest to the highest tertile of BMI, ®brinogen rose from 2.66 to 3.24 g=l(pˆ 0.0001), C1-inhibitor antigen rose from 96.2 P167 Tertile of BMI (mean) Sibutramine improves clinical and metabolic parameters in obese patients with polycystic ovary syndrome

1 (21.7) 2 (25.1) 3 (29.3) p value T Sabuncu1, M Harma1, Y Nazligul1, and F Kilic1 1University of Harran, Faculty of Medicine, Research Hospital, 63200, FVIIc1 109.9 (31.7) 124.2 (34.4) 139.8 (30.9) 0.0001 Sanliurfa, Turkey FVIIIc1 108.4 (25.6) 110.2 (31.2) 122.2 (30.2) 0.05 INTRODUCTION: It is known that polycystic ovary syndrome (PCOS) is vWF 95.8 (27.3) 88.1 (26.7) 97.5 (25.7) 0.19 characterized by hyperandrogenemia and may be associated with hyperinsu- FXIIa1 1.69 (0.55) 1.98 (0.71) 2.33 (0.85) 0.0001 linemia, insulin resistance and some other cardiovascular risk factors. Although F1.21 1.32 (0.40) 1.41 (0.38) 1.51 (0.52) 0.12 (0.04)* traditional oral contraceptive use can improve hyperandrogenemia, it is generally inadequate to correct other clinical and metabolic risk factors of t-PA1 2.93 (1.23) 2.30 (1.14) 1.82 (1.22) 0.0002 cardiovascular disease. Therefore, we aimed to evaluate the effectiveness of PAI-1 9.5 (4.6) 10.7 (5.5) 13.6 (7.1) 0.003 sibutramine, an antiobesity drug, alone and combination with ethinyl estra- Plasminogen 102.0 (13.1) 110.2 (11.3) 114.2 (11.4) < 0.0001 diol (35 mg)-cyproterone acetate (2 mg) (EE-CPA) on clinical and metabolic a2-AP 88.4 (10.2) 95.3 (10.6) 99.0 (8.1) 0.0001 parameters of obese (BMI > 30 kg=m2) patients with PCOS. Protein C1 87.9 (12.0) 97.5 (17.6) 105.2 (17.4) < 0.0001 METHODS: Group-1 patients (n ˆ 14) were treated with EE-CPA alone, group- APC1 2.99 (0.35) 2.81 (0.49) 2.61 (0.47) 0.002 2 patients (n ˆ 12) with sibutramine alone (l0 mg=d) and group-3 patients Free PRS1 102.1 (33.3) 115.7 (27.4) 115.2 (28.1) 0.04 (n ˆ 14) with EE-CPA plus sibutramine combination. All three groups of patients were advised to consume a diet of 1200 kcal=d. Body mass index (All values are mean (sd) except, 1geometric mean (approx sd), *test for trend.) (BMI), waist to hip ratio (WHR), systolic blood pressure (sBP), diastolic blood

International Journal of Obesity Track 6 Cardiovascular system and obesity

S78 pressure (dBP), Ferriman-Gallwey hirsutism score (FG), serum levels of total anthropometric parameters were determined and venous blood samples were testosterone (TT), free testosterone (FT), SHBG, DHEAS, total cholesterol (TC), obtained for the measurements of glucose, uric acid, cholesterol, triglyceride, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglyceride, glucose and HDL-cholesterol, and insulin concentrations. Insulin resistance was evaluated by insulin during OGTT, insulin sensitivity index obtained from OGTT (ISI- ``homeostasis model assessment'' (HOMA) formula. Intraabdominal fat area composite), area under the curve for glucose (AUC-glucose) and insulin (IAF) was calculated by a previously validated formula: IAF (cm2) ˆ (waist (AUC-insulin) were measured before and after 6 months of the treatment. circumference  2.57) ‡ (age  0.92) ‡ (suprailiac skinfold thickness  0.69) RESULTS: BMI, FG, serum TT, FT and DHEAS levels signi®cantly decreased and 7188.61. Waist circumference, waist to hip ratio and intraabdominal fat area SHBG signi®cantly increased at the end of the study in all groups. WHIR, dBP were signi®cantly higher in postmenopausai women compared with BMI and serum triglyceride level signi®cantly reduced only in group-2. Both matched-premenopausal women (p < 0.001 for all). Fasting glucose group-2 and group-3 patients had signi®cantly reduction in the levels of (109.6Æ 33.6 vs 99.4Æ 19.1 mg=dL), uric acid (4.78Æ 1.47 vs 4.34Æ AUC-glucose, AUC-insulin and ISI-composite. Group-1 and group-3 patients 1.12 mg=dL), cholesterol (232.2Æ 43.2 vs 202.3Æ 37.0 mg=dL), triglyceride showed signi®cantly increase in the serum level of HDL-C. Serum triglyceride (172.6Æ 79.9 vs 152.2Æ 74.9 mg=dL), systolic blood pressure (148.2Æ 29.7 level signi®cantly increased only in group-1 patients. vs 135.1Æ 26.7 mm Hg) and diastolic blood pressure (91.79Æ 15.7 vs CONCLUSION: This study has showed that treatment with the weight losing 87.7Æ 15.0 mm Hg) were signi®cantly higher (p < 0.001 for all) in postmeno- drug sibutramine may improve hyperandrogenemia, and clinical and meta- pausal women compared with premenopausals. No signi®cant differences were bolic risk factors for cardiovascular disease in obese patients with PCOS. observed with respect to insulin levels and HOMA. Sibutramine combination with EE-CPA may also enhance effectiveness in the It is concluded that an increase in intraabdominal fat accumulation and treatment of hirsutism, and further decrease cardiovascular risk by increasing metabolic consequences of abdominal obesity disturb postmenopausal serum HDL-C level. women even if total body weight and BMI do not change during menopause.

P168 P170 The percentage of body fat and its relationship to age and blood pressure Angiotensiongen expression and angiotensin II secretion are stimulated in men and women without cardiovascular medication by insulin in human abdominal fat A Dzien1, C Dzien-Bischinger1, F Hoppichler 2, and M Lechleitner 3 CL McTernan1, AL Harte1,MCEggo1, AH Barnett1, PG McTernan1, and 1Medical Center Hentschelhof, Innsbruck, Austria; 2Hospital Barmherzige S Kumar1 BruÈder, Salzburg, Austria; 3Department of Internal Medicine, University of 1University of Birmingham, Division of Medical Sciences, Clinical Research Innsbruck, Austria Block, Edgbaston, Birmingham B15 2TH INTRODUCTION: Obesity is associated with a signi®cant increase in overall Hypertension is a common disorder associated with obesity and Type II morbidity and mortality, including an increased risk for hypertension. Adipose diabetes. The reninangiotensin system (RAS) is important for the regulation tissue is known to produce vasoactive substances, but clinical data on the of blood pressure and previous studies have demonstrated the presence of the linkage between the percentage of body fat with blood pressure values is rare. components of an active tissue RAS in human adipose tissue. In this study we METHODS: We have consecutively recruited 355 patients (234 women, 121 investigated the in¯uence of varying insulin doses on both the expression of men; mean age 56.7Æ 17.5 years; mean BMI 25.5Æ 4.4 kg=m2) without angiotensinogen and the secretion of angiotensin II in human subcutaneous cardiovascular medication at a medical outdoor center. Beside laboratory (Sc) abdominal fat. controls, blood pressure measurements and calculation of the body mass Isolated Sc adipocytes (n ˆ 10) were treated with varying doses of insulin index (BMI), the percentage of body fat was determined by a method of (1 nM ± 1000 nM) for 48 hrs. Following treatment, the media from the adipo- bioimpedance applying the OMRON BF 302 body fat monitor. Patients were cytes and the adipocytes were harvested. Western blotting was performed on assigned to a group with normal percentage of body fat (24% and less in the protein extracted from the adipocytes to determine angiotensinogen women; 19% and less in men) and to a group with a more pronounced expression. ELISAs were performed on the collected media to determine the percentage of body fat (25% and more in women; 20% and more in men). secretion of angiotensin II from human adipocytes. Angiotensinogen mRNA RESULTS: The mean age of women in the group with a lower body fat content levels were also assessed. (14.5Æ 4.5%) was 43.4Æ 17.7 years, and thus signi®cantly younger than in Our results demonstrate that increasing doses of insulin (Ins) raised the group with a more pronounced body fat content (30.6Æ 6.9%) with angiotensinogen protein expression in a dose dependent manner (control a mean age of 64.1Æ 12.7 years (p < 0.021). Blood pressure values were 1.0Æ 0.0; (meanÆ SE), protein expression measured relative to control; 1 nM signi®cantly lower in the leaner group (125.0Æ 23.3 mm Hg and Ins: 1.13Æ 0.1; l0 nM Ins: 1.37Æ 0.14:*; l00 nM Ins: 2.1Æ 0.3:**; 500 nM Ins: 78.9Æ 12.6 mm Hg) than in the group with an increased body fat content 4.1Æ 0.83:**; l000 nM Ins: 5.2Æ 8.7:**; *p < 0.05, **p < 0.01). Insulin also (144.5Æ 16.6 mm Hg and 88.0Æ 14.1 mm Hg) (p < 0.050). The results in the raised angiotensin II secretion in a similar pattern to angiotensinogen protein male group were in accordance to the ®ndings obtained in women. Men with expression (control: 155Æ (SEM) 6.4 pg=ml 1 nM Ins: 98Æ 3.6 pg=ml;***; a lower percentage of body fat (15.2Æ 3.4%) were younger (52.7Æ 17.4 l0 nM Ins: 181Æ 2.5 pg=ml:**; l00 nM Ins: 216Æ 8.7 pg=ml:***; 500 nM Ins: years) and revealed lower blood pressure values (130Æ 19.2 mm Hg and 687.3Æ 11.7 pg=ml***; 1000 nM Ins: 1964Æ 18.2 pg=ml***:; ***p < 0.001). 79.7Æ 8.8 mm Hg) than men with a more pronounced percentage of body In conclusion, increasing insulin doses stimulate both angiotensinogen fat (25.7Æ 4.0%) with a mean age of 63.8Æ 12.7 years (146.4Æ 23.5 mm Hg and angiotensin II production in adipocytes showing active regulation of the and 90.7Æ 11.8 mm Hg). Systolic as well as diastolic blood pressure values renin-angiotensin system in fat by insulin. This insulin regulated, adipose showed a strong positive correlation with the percentage of body fat in men tissue-derived angiotensin may be important for obesity related hypertension. (R ˆ 0.35; p < 0.033) and women (R ˆ 0.44; p < 0.015). CONCLUSIONS: Our results suggest that age and blood pressure values are related to the percentage of body fat content also in non-obese patients P171 without cardiovascular medication. P169 LDL phenotype B and triglyceride rich lipoproteins in overweight patients related to platelet adhesion

Body fat distribution and cardiovascular risk factors in pre- and 1 1 1 1 1 J Hartwich , I LeszczynÂska-Gol--bek , M KwasÂniak , A Gruca , M Motyka , postmenopausal obese women with similar body mass index 1 1 L-- Partyka , and A DembinÂska-Kiec N Ozbey1, M Taskale1, S Molvalilar1, E Sencer1, and Y Orhan1 1Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian 1Department of Internal Medicine, Division of Endocrinology, Istanbul Faculty University, Krakow, Kopernika 15A str., Poland of Medicine, Capa, 34390, Istanbul, Turkey INTRODUCTION: The genetically determined and environmentally in¯u- An increase in the incidence of atherosclerotic cardiovascular disease is enced LDL pattern B (atherogenic lipid pro®le ALP) and triglyceride rich observed in women after menopause. An increase in intraabdominal fat and lipoproteins have recently been recognised as an important risk factor of a more atherogenic lipid pro®le might-in part-be operative for this observa- CAD. The nongenetic factors shown to in¯uence LDL density include intra- tion.The aim of this study is to determine the body fat distribution and abdominal fat accumulation, exercise and diet. Blood platelet adhesion cardiovascular risk factors in pre- and post menopausal obese women contributes to pathomechanism of atherosclerosis. The aim of the study was matched for weight, height and body mass index (BMI). to determine the in¯uence of lipoprotein composition on platelet adhesion in Study group consisted of 405 premenopausal obese (BMI > 27 kg=m2, relation to obesity. mean BMI 37.8Æ 6.9 kg=m2) and 405 postmenopausal obese METHODS: Lipoproteins (VLDL, LDL, HDL) were isolated from fasting plasma (BMI > 27 kg=m2), BMI-matched (mean BMI 37.7Æ 6.8 kg=m2) women. None of overweight subjects (BMI > 25 kg=m2). VLDL after standard fat meal were of the women were on hormone replacement therapy. After an overnight fast, also used. The particle distribution pro®le (LDL, HDL), apoE phenotype, a

International Journal of Obesity Track 6 Cardiovascular system and obesity

S79 tocopherol and b carotene contents, susceptibility to oxidation and reactive predict the probability of a CHD within a speci®ed time frame. As recent lysine amino groups (R-Lys) were estimated. Adhesion of human washed results indicated that sibutramine signi®cantly reduces the probability of a platelets to native and oxidized lipoproteins immobilized in microtiter wells CHD within 10 years we investigated whether this reduction is dose-related. was examined. The total number of adhered platelets was measured as the METHODS: We applied the Whitehead and Whitehead meta-analysis techni- platelet acid phosphatase activity. que and the Framingham risk equation on data from 5612 patients from 26 RESULTS: Platelet adhesion was activated by all the lipoproteins tested. VLDL, studies. We compared patients receiving 10 mg or 15 mg sibutramine once small dense LDL and oxidized lipoproteins were the most potent adhesion daily with all placebo patients. activators. Platelet adhesion to VLDL was in¯uenced by apoE phenotype and RESULTS: Treatment difference in 10-year CHD-risk change1 R-Lys content. The standard fat meal augmented platelet adhesion to VLDL. 1sibutramine minus placebo; Whitehead and Whitehead meta-analysis tech- Adhesion to LDL and HDL was related to antioxidant content, particle density, nique; sibutramine categorical analysis vs all placebo. oxidative susceptibility and R-Lys level. High antioxidant content in LDL and HDL strongly limited platelet activation. Enrichment of LDL and oxLDL in oxidatively modi®ed lipids: 7-ketocholesterol and lyso-PC increased platelet adhesion. BMI correlated with platelet adhesion to VLDL (r ˆ‡0.55, p. < 0.05) and to dense LDL (r ˆ‡0.48, p. < 0.05). CONCLUSION: Particle distribution pro®le, apoE phenotype and antioxidant contents strongly in¯uenced platelet adhesion to lipoproteins in overweight patients. Fasting and postprandial VLDL, small, dense LDL, native antioxidant- poor and oxidized lipoproteins were the most potent adhesion activators.

P172

Cardiac autonomic neuropathy in obese children CONCLUSION: The results indicate that sibutramine signi®cantly reduces the KToÈroÈk1, I Wittmann2, and D MolnaÂr1 risk of CHD in a dose-dependent manner. 1Department of Paediatrics, University of PeÂcs, Hungary; 2Second Department of Medicine, University of PeÂcs, Hungary INTRODUCTION: Obesity is associated with an increased incidence of hyper- P174 tension, unexplained death, as well as an overall increase in mortality rate. The An anthropometric index of obesity-linked risk factors based on the autonomic nervous system is involved in the regulation of energy metabolism combination of body weight and waist circumference values and cardiovascular system activity. Obese persons often have an alteration in their autonomic nervous system, accounting for several clinical consequences F Bel®ore1, S Iannello1, and M Prestipino1 of obesity. Silent myocardial infarction and myocardial ischemia seem to be 1Department of Internal Medicine, University of Catania Medical School, associated with cardiac neuropathy in some cases. Long before the appear- Ospedale Garibaldi, 95123 Catania, Italy ance of clinical signs of autonomic neuropathy, subclinical signs can be INTRODUCTION: We propose an anthropometric index of obesity-linked risk, detected. It has been suggested that subclinical signs of cardiovascular resulting from the combination of the body weight and waist circumference autonomic neuropathy appear in obese children and adolescents. values, and compare this Index with the body mass index (BMI) and the METHODS: To evaluate the alterations in cardiac autonomic function, sub- Waist=Hip ratio (W=H). Our index is obtained with a formula similar to that clinical signs of autonomic neuropathy were investigated in 47 obese children one previously described (Bel®ore et al Mol Gen Metab 1998; 63: 134 ± 141; (age: 13.4Æ 2.53 years, body weight: 81.64Æ 16.3 kg, body fat: 32.9Æ 8.1 kg Diabetes Care 23: 1595 ± 1596, 2000) to calculate an insulin sensitivity Index. [meanÆ SD]) with different cardiovascular risk factors. Resting heart rate, heart METHODS: The commonly used indicators of obesity risk, the BMI and the rate variation to deep breathing, heart rate response to standing from a lying W=H, are based on four anthropometric measures: body weight (WE), height position, fall in systolic blood pressure on standing, and rise in diastolic blood (HE), waist circumference (WA) and the hip circumference (HI). We combined pressure during sustained handgrip were measured, by means of standardized the WE and WA values into a single index, that we named WE 7 WA, through tests. the following formula: WE 7 WA ˆ 2=[(rWEp  rWAp) ‡ 1], where rWEp and RESULTS: Using reference ranges obtained in normal weight controls (Barkai rWAp are the ``reciprocal'' values of WE and WA of the person studied. Both et al, Arch Dis Child 1995; 73: 515 ± 518), 19 obese children (40%) had 2 or WE and WA are expressed by taking their ``mean normal value'' (MNV) as 1, more abnormal autonomic test results (Table). i.e. by dividing the value recorded in the person studied by the MNV. The CONCLUSION: Cardiovascular autonomic dysfunctions are detectable in ``reciprocal values'' (i.e., rWEp and rWAp) are calculated by dividing the MNV obese children. According to the preliminary results further investigations by the value measured in the person studied. In normal subjects WE 7 WA is are needed to clarify subgroups being at risk of autonomic dysfunctions. always close to 1, with maximal variations between 0 and 2. The MNV of WE Table Abnormal autonomic test results in our patients and WA needs not be strictly de®ned or related to sex or groups. Rather, a ``general mean normal value'' can be selected, leaving sex or group variations Obese children (n ˆ 47) to be re¯ected by small variations of the WE 7 WA obtained. We selected as mean normal values 70 (Kg) for WE and 80 (cm) for WA. We studied 95 Abnormal autonomic test results n % subjects (25 male and 70 female), age 18 ± 71 years, BMI 24.07 ± 52.76 and W=H 0.76 ± 1.13, and analyzed the correlations with several risk factors. 3 5 10.6 RESULTS: In our study population, WE 7 WA ranged from 0.86 to 1.50, and was signi®cantly correlated with an index of insulin sensitivity deduced from 2 14 29.8 the OGTT data, triglycerides, uric acid and diastolic blood pressure 1 22 46.8 (r ˆ 0.40 7 0.45, p < 0.001 in all instances). BMI and W=H (as well as the 0 6 12.8 combination of 3 or all the 4 anthropometric measures mentioned above) showed only  3 of these correlations with weaker ``r'' and ``p'' values. CONCLUSION: WE 7 WA seems as a promising risk index in obese patients.

P173 P175

Is the reduction of coronary heart disease risk by sibutramine Increased arterial pulse pressure in subjects with moderate obesity but dose-related? not in those with simple overweight KW Lauterbach1, and T Evers1 AJ Scheen1, I Geronooz1, Ph Ernest1, and M Marchand1 1Institute of Health Economics and Clinical Epidemiology, Gleueler Str. 1Department of Medicine, CHU Sart Tilman LieÁge, Belgium 176 ± 178, D-50935 Cologne INTRODUCTION: The study aimed at comparing the changes in mean arterial INTRODUCTION: The additive nature and direct relationship between inde- pressure (PAM) and pulse pressure (PP) in obese, overweight and lean subjects pendent risk factors and the probability of CHD is well established. On the submitted to an orthostatic test (``squatting'') and continuous cardiovascular basis of these risk factors equations have been developed which allow to monitoring.

International Journal of Obesity Track 6 Cardiovascular system and obesity

S80 METHODS: 30 obese subjects (BMI: 33.5Æ 2.6 kg=m2 ± meanÆ SD ± ), 30 ities for at least 3 months prior to inclusion and during the study. Patients were overweight individuals (BMI: 26.7Æ 1.4 kg=m2) and 30 lean controls (BMI: randomized to orlistat 120 mg t.i.d. (O) or placebo (P) combined with a mildly 22.2Æ 1.6 kg=m2) were submitted to an active orthostatic test (1 min stand- reduced-calorie and fat diet. ing ± 1 min squatting ± 1 min standing). The three groups were matched for At baseline there were no signi®cant difference between O and P. The sex (11 women and 19 men) and age (around 42 years), and no subjects took variations of the primary endpoints are shown below: medication interfering with cardiovascular regulation. Systolic, diastolic, mean and pulse arterial blood pressure were continuously monitored with a Fina- Weight (Kg) LDL-C (mM=l) HbA1c(%) presR device (Ohmeda, USA). RESULTS: PAM (p ˆ 0.06) and heart rate (p ˆ 0.08) tended to be higher in Pooled population Hypercholesterolemics Diabetics obese vs lean subjects when averaged during the whole test. During squat- ting, PAM was higher in obese subjects (95.7Æ 13.6 vs 84.9Æ 16.0 mm Hg, Orlistat Placebo Orlistat Placebo Orlistat Placebo p ˆ 0.007) while it was intermediate in overweight subjects (n ˆ 499) (n ˆ 505) (n ˆ 98) (n ˆ 99) (n ˆ 97) (n ˆ 96) (92.9Æ 15.8 mm Hg, p ˆ 0.06 vs lean; NS vs obese). Heart rate during squat- ting was higher in overweight (85Æ 14 beats=min; p ˆ 0.005) and in obese M0 93.2 Æ 14.2 92.5 Æ 13.7 4.4 Æ 0.6 4.2 Æ 0.6 7.6 Æ 0.7 7.7 Æ 0.9 (83Æ 13 beats=min; p ˆ 0.035) subjects than in lean controls M6 88.0 Æ 14.3 90.8 Æ 13.9 3.8 Æ 0.8 4.0 Æ 0.7 7.1 Æ 17.6Æ 1.1 (76Æ 9 beats=min). Average PP was similar in overweight and lean subjects D 7 5.6 Æ 5# 7 1.9 Æ 4.2 7 11.7 Æ 16.1# 7 4.5 Æ 14.9 7 0.54 Æ 1*# 7 0.18 Æ 0.9* (46.4Æ 15.8 vs 45.7Æ 10.6 mm Hg, NS), whereas it was markedly increased in

obese subjects (53.8Æ 12.2 mm Hg, p ˆ 0.009 vs controls and p < 0.05 vs # overweight subjects). Such a difference was observed throughout the test and D: %M6 7 M0, *:D:M6 7 M0; :p< 0.005 vs placebo (ANCOVA adj.) in each posture condition (standing or squatting). In hypertensive patients, DBP changes (77.5Æ 10.6 mmHg) did not differ CONCLUSION: Increased heart rate, mean arterial pressure and pulse pressure in O and P. In diabetics, HbA1c levels decreased  1% in 34% vs 21% and levels were observed in obese middle-aged subjects. Because high pulse  1.5% in 19% vs 4% of O and P patients respectively (p < 0.005). In pressure has been shown to be associated with a higher risk, such an increase hypercholesterolemics, LDL-C levels decreased  20% in 31% and 13% of may contribute to the higher cardiovascular rnortality of obese patients. O and P patients (p < 0.005). These results show that orlistat treatment in overweight and obese patients with comorbidities is able to further improve cardiovascular risk P176 factors, especially in those with type 2 diabetes and hypercholesterolemia.

Low-fat, high-carbohydrate diets do not inevitably lead to P178 hrypertriglyceridaemia Effects of one year weight loss obtained by laparoscopic gastric banding on QTc interval and QT dispersion in morbid obesity KS Culling1, KN Frayn1, F Karpe1, and HAW Neil2 1Oxford Lipid Metabolism Group, Oxford Centre for Diabetes, Endocrinology A Saibene1, A Girola1, P Pizzocri1, P Vedani1, M Marchi1, M Paganelli1, and Metabolism, Radcliffe In®rmary, Oxford, OX2 6HE, UK; 2Division of M Giacomelli1, G Ferla1, and AE Pontiroli1 Public Health and Primary Health Care, Institute of Health Sciences, University 1H San Raffaele and UniversitaÁ degli Studi, Via Olgettina 60, 20132 Milano, Italy of Oxford, Old Road, Headington, Oxford, OX3 7LF, UK INTRODUCTION: A prolonged QTc interval at ECG, and a high QT dispersion, INTRODUCTION: Low-fat diets are established as the best way to lose weight are regarded as a risk factor for ventricular arrhythmias and consequently and maintain weight loss. Reducing dietary fat usually leads to an increase in sudden death. Furthermore obesity per se is considered to be a risk factor for the carbohydrate (CHO). Recently, concern has been expressed that these sudden death. Nevertheless the relationships between obesity and QTc and low-fat, high-CHO diets cause hypertriglyceridaemia (HTG), a known risk improvement of the latter after weight loss are not yet well established. Aim of factor for coronary heart disease. The objective of this study was to discover this study was to evaluate the effects of a substantial weight loss in morbid if the type of carbohydrate consumed had any effect on the degree of HTG obesity (BMI > 35 Kg=m2) on QTc interval and on QT dispersion (QTd). observed. METHODS: l00 patients (BMI 44.5Æ 0.63 kg=m2) underwent laparoscopic METHODS: Five normal-weight, normolipaemic subjects (3 female, 2 male) gastric banding (LAGB) and received low calorie diet (900 ± 1100 Kcal=day) were recruited. Each followed 3 different 3-day, isoenergetic, weight main- for one year. QT intervals were measured on 12-lead resting electrocardio- tenance diets. Each diet was separated by at least one month. These consisted grams and were adjusted for heart rate according to Bazett's formula. QTd was of one high-fat diet (50% fat, 35% CHO, 15% protein), a `high-sugar' diet expressed as the difference between the maximum and the minimum QTc in (70% CHO, 40% as sucrose, 30% as complex-CHO, 15% fat, 15% protein), any of the 12 electrocardiographic leads. Patients using drugs known to affect and a `high-starch' diet (70% CHO, 40% as complex-CHO, 30% as sucrose, QTc interval or patients with heart diseases were excluded. 15% fat, 15% protein). Each diet was followed by a study-day, where fasting RESULTS: BMI dropped to 36.4Æ 0.55 Kg=m2 (p < 0.001); QTc changed from and postprandial triacylglycerol (TG) concentrations were measured. Subjects 412.5Æ 2.67 ms to 399.2Æ 2.77 (p < 0.001) and QTd from 37.9Æ 3.8 to all received an identical mixed-meal. 35.3Æ 1.6 ms (p < 0.001). RESULTS: There was a signi®cant effect of diet on fasting TG (p < 0.0001 by CONCLUSION: These data indicate that a signi®cant weight loss is accom- repeated measures ANOVA). Post-hoc tests with Bonferroni correction showed panied by a signi®cant decrease of both QTc and QTd. that fasting TG was signi®cantly higher after the high-sugar diet compared REFERENCES: 1) Algra A, Tijssen JGP, Roelandt JRTC, Pool J, Lubsen J ``QTc with the high-fat (p < 0.005) and high-starch diet (p < 0.008). There was no prolongation measured by standard 12 lead electrocardiogram is an indipen- signi®cant difference between fasting TG concentration on the high-starch dent risk factor for sudden death due to cardiac arrest'' Circulation 83: 1888 ± compared to the high-fat diet. The high-sugar diet signi®cantly increased 1894, 1991 plasma TG compared with the high-starch diet (p < 0.03) and high-fat diet 2) Sagie A, Larson MG, Goldberg RJ, Bemgston JR, Levy D ``An improved (p < 0.05). However, there was no signi®cant difference between TG concen- method for adjusting the QT interval for heart rate (The Framingham Heart trations on the high starch compared with the high-fat diet. Study)'' Arn J Cardiol 70: 797 ± 801, 1992 CONCLUSION: A low-fat diet need not result in increased fasting and 3) Seim HC, Mitchell JE, Pomeroy C, De Zwaan M, ``Electrocardiographic postprandial TG concentrations if dietary fat is replaced with complex carbo- ®ndings associated with very low calorie dieting'' Int J Obes 19: 817 ± 819, 1995 hydrate rather than sugar. 4) Carella MJ, Mantz SL, Rovner DR, Willis PW, Gossain VV, Bouknight RR, Ferenchick GS ``Obesity, adiposity, and lengthening of the QT interval: P177 improvement after weight loss'' Int J Obes 20: 938 ± 942, 1996 Improvement of cardio-vascular risk factors with a six months orlistat P179 treatment in overweight and obese patients with comorbidities Tilt table testing in obesity B Guy-Grand1,HGin1,PDrouin1, E Eschwege1, and P Valensi1 1Depts of Nutrition, Paris, Bordeaux, Nancy, INSERM U258 Villejuif, Bondy, K Mizia-Stec1, B Zahorska-Markiewicz1, T Mandecki1, E J astrzeÎbska-Maj1, France A Szulc1, L SzymanÂski1, and T Majewski1 1 A six month multicenter double blind study was conducted in 1004 over- 2nd Department of Pathophysiology, 2nd Department of Cardiology, Silesian weight and obese outpatients with comorbidities (18 ± 65 y., BMI 28 ± University, Medical Faculty, Katowice, Poland 40 Kg=m2): 197 patients with hypercholesterolemia (LDL-C 3.4 ± 5.8 mM), INTRODUCTION: The symphatetic-parasymphatetic disbalance has been 193 with type 2 diabetes (HbA1c 7 ± 9%), 614 with hypertension (Diastolic suggested in obesity. The aim of this study was to estimate the results of tilt BP 90 ± 110 mmHg). Patients had to be stable on therapy for their comorbid- table testing (TT) in obese patients (pts).

International Journal of Obesity Track 6 Cardiovascular system and obesity

S81 METHODS: We examined 59 pts with simplex obesity (F=M:50=9; BMI ± METHODS: Pooled data of two randomized, parallel groups, double blinded, 36.9Æ 3.9 kg=m2) ± group A and 19 healthy persons as control group multicenter clinical trials. 514 patients with BMI  27 kg=m2 were randomized (F=M:16=3; BMI ± 24.7Æ 4.3 kg=m2) ± group C. Additionally TT was per- (261 Orlistat, 253 placebo) after 4 weeks of placebo run-in and hypocaloric formed in 11 pts from group A after 3-months of weight reducing treatment. diet (30% of calories from fat). Cardiovascular risk at 10 years was computed The cardiovascular reactions to tilting were determined by the measurements using Framingham algorithm assuming all patients were smokers. of HR, SBP and DBP. We assessed: baseline values, values after tilting, RESULTS: Baseline cardiovascular risk was similar for Orlistat (ORL) and difference between maximal and minimal values during TT (A), and index placebo (PLA) (14.45% vs 13.36%). The change in predicted 10-year cardi- of change (%D ˆ D=baseline value  100%). ovascular risk after 6 months treatment was threefold for Orlistat than for RESULTS: Positive TT was observed in 10 obese pts (17%), and none of the placebo (71.43% vs 70.53%, p ˆ 0.063). Greater risk reduction was controls. The comparison of HR, SBP and DBP between groups A and C observed among hypercolesterolemic patients (73.02%) than diabetic revealed higher DHR in group of obese pts (23.9Æ 13.7 vs 17.87Æ 8.9) only. In patients (71.46%). Signi®cant mean weight loss was achieved with Orlistat pts with positive TT results signi®cant higher HR after tilting, DHR, and %DHR when pooling data from diabetic and non diabetic patients (77.1% vs were noted in comparison to pts with negative TT and to group C. Pts after 73.46%, p < 0.001). Diabetic mellitus group lost less weight than non weight reducing treatment were characterised by: higher %DHR than group diabetic mellitus, consistent with previous reports than weight loss is more A, and lower baseline HR, SBP, DBP in comparison both to group A and to their dif®cult for DM. Orlistat achieved a higher reduction of mean waist perimeter results before treatment. (76.36 vs 74.2 cm, p < 0.001) and BMI (72.66 vs 71.37, p < 0.001). CONCLUSION: The positive results of TT are observed in 17% pts with 31.5% and 38.3% of patients normalized total cholesterol and LDL choles- simplex obesity. Different HR reaction to tilting (increased HR ¯uctuation) is terol, respectively with ORL in comparison with 22.5% and 26.1% with present in obese pts, especially in pts with positive TT. The 3-months weight placebo (p ˆ 0.018 and p ˆ 0.003). Greater reduction of plasma glucose reducing treatment decreases HR, SBP and DBP, but does not normalize the was achieved with ORL than with placebo (1.59 vs 0.79, p < 0.001). cardiovascular reaction to tilting. Our results can support the hypothesis of CONCLUSION: Orlistat produces a signi®cant weight loss as well as a reduc- autonomic disbalance in obesity. tion of cardiovascular risk through decreases of total and LDL cholesterol and Supported by KBN grant C008=P05=2000 an improvement of metabolic control of type 2 diabetes in overweight or obese patients with additional risk factors. P180 6 Mo high protein diet does not increase P-homocysteine in obese P182

1 1 1 1 1 Sex hormone ± binding globulin levels and cardiovascular risk in morbidly N Haulrik , S Toubro , S Stender , AR Skov , and A Astrup obese subjects before and after diet or biliopancreatic diversion 1The Research Department of Human Nutrition, RVAU, Rolighedsvej 30, DK-1958 Frederiksberg, Denmark A Scarfone1, A Giancaterini1, AV Greco1, M Castagneto1, and G Mingrone1, 1 Replacing carbohydrate with protein in ad lib fat-reduced diets increases fat Institute of Internal Medicine, Catholic University, Rome, Italy loss without adverse effects on blood lipids and renal function1±2 Several studies showed that in obese subjects low plasma SHBG levels were Plasma homocysteine (Hcy) is a risk factor for cardiovascular disease and is associated with high fasting insulin concentrations and with an altered lipid- thought to be increased by a high protein intake. We studied the effect of lipoprotein pro®le, including reduced HDL cholesterol and an increased protein intake in obese subjects in a 6 mo randomized intervention study atherogenic index. A cross-sectional study was conducted to verify the comparing two ad lib fat reduced diets (30% of total energy): Low-protein (LP, changes of SHBG and lipid pro®le in 79 morbidly obese subjects, 27 men 12 energy-%) or high-protein (HP, 22 energy-%). 65 overweight and obese and 52 women (age: 30 ± 45yrs), randomly assigned to the diet protocol subjects were randomly assigned to LP (n ˆ 25), HP (n ˆ 25) or a control (20 kcal=kgFFM, 55% carbohydrates, 30% fat, and 15% proteins) or to BPD group (C, n ˆ 15). All food was provided by self selection in a shop at the procedure. We investigated the modi®cation of Coronary Heart Disease (CHD) department. Compliance to the diet composition was evaluated by urinary risk in morbidly obese subjects after weight reduction treatment, either diet or nitrogen excretion.The protein intake was increased in the HP group mainly biliopancreatic diversion (BPD), and to evaluate whether SHBG changes might by lean meat and low fat dairy products. Folate intake nearly doubled in the LP play any pathogenetic or diagnostic role. group and increased by 60% in the HP group (LP vs HP; P < 0.05). It remained Fatness parameters by dual-energy X-ray absorptiometry (Fat Mass and unchanged in the C group (LP & HP vs C; P ˆ 0.0001). B12 intake decreased in Fat-Free Mass), SHBG and sex hormones plasma levels and lipid pro®le at the LP and increased by 80% in the HP (P < 0.0001), whereas B6 intake baseline and 1 year after the beginning of the study has been evaluated. increased by 70 ± 90% in LP and HP groups with no change in the C group Pre-Post weight loss differences in SHBG plasma levels were signi®cantly (P < 0.0001). Plasma Hcy did not change in the LP or C groups, but there was higher in the BPD group compared to the dieting group (84.0Æ 25.2 nM=lvs a non-signi®cant 20% decrease in the HP group. Fat loss was 4.3 kg in LP and 143.4Æ 23.4, P < 0.0001). Furthermore, surgical treated subjects largest 7.6 kg in HP (P < 0.0001), with no change in the C group. In multiple linear changes in insulin, total cholesterol, HDL-cholesterol and tryglicerides after regression analyses plasma Hcy after 3 mo intervention was determined by weight loss compared to the diet-group. (P < 0.0001). The main result was the baseline Hcy (r ˆ‡0.34, P ˆ 0.0001), folate intake (r ˆ 70.003, P ˆ 0.0350), signi®cant decrease of the atherogenic risk observed in BPD patients dietary protein content (r ˆ 70.17, P ˆ 0.0007), and by weight change (6.58Æ 3.33 vs 2.90Æ 0.58 after the treatment; P < 0.0001), while no differ- (r ˆ 70.12, P ˆ 0.0350). After 6 mo the same trends were seen (baseline ences were found in dieting patients. Hcy P ˆ 0.0001; protein content P ˆ 0.09). This study shows that increasing A step-down regression analysis showed that FFM and SHBG were the the dietary protein from 12 to 22 energy-% does not increase plasma most powerful independent variables for predicting HDL-cholesterol levels; homocysteine levels. By contrast, animal protein, independent of intake of B while insulin did not in¯uence signi®cantly HDL-CH changes. The positive vitamins and weight loss, may actually decrease plasma homocysteine con- relationship between low SHBG levels and increased CHD risk appears to be centrations in obese subjects. mediated, to a large extent, by concomitant variation in body fatness 1. Skov AR et al. Randomized trial on protein versus carbohydrate in ad libitum measured directly. In this regard, SHBG level may be viewed as a re¯ection fat reduced diet for the treatment of obesity. It J Obes 1999;23:528 ± 536. of total adiposity rather than a predictor of an altered insulin=glucose home- 2. Skov AR et al. Changes in renal function during weight loss induced by ostasis. high vs low-protein low-fat diets in overweight subjects. It J Obes 1999;23: 1170 ± 1177. P183 Autonomic nervous system activity in obese subjects and during weight P181 reduction

Orlistat reduces cardiovascular risk in overweight or obese patients with 1 1 1 1 1 other risk factors J Chaloupka ,PHluÂbik , L Opltova ,HMala , and S PelcaÂk 1Purkyne Military Medical Academy, TrÏebesÏska 1575, 500 01 Hradec KraÂloveÂ, D Bellido1, JL Herrera-Pombo2, F Armero3, and M GenõÂs3 Czech Republic, [email protected] 1 2 Hospital Naval (El Ferrol); FundacioÂn JimeÂnez Diaz (Madrid) on behalf of the Power spectral analysis of heart rate variability during modi®ed orthostatic test Research group on Orlistat in diabetic and hypercholesterolemic patients (Spain); 3 is the non-invasive method used for the evaluation of autonomic nervous Roche Farma Spain SA system (NS) activity. INTRODUCTION: The present study was designed to evaluate the impact of In the groups of 82 healthy volunteers (BMI 24.9Æ 2.7 kg=m2) and 37 treatment for weight loss with 120 mg orlistat (Xenical1) t.i.d. versus placebo on healthy obese subjects (BMI 36.1Æ 4.9 kg=m2) some of the vegetative NS cardiovascular risk in overweight or obese patients with other cardiovascular risk parameters have been compared. In the group of 16 volunteers we measured factors (type 2 diabetic and non diabetic patients with hypercholesterolemia). the vegetative NS activity changes during the weight reduction regimen

International Journal of Obesity Track 6 Cardiovascular system and obesity

S82 (10 day's hospitalisation, daily energy intake 3300 kJ, weight before p ˆ 0.012) and to the compliance to the diet (r ˆ 70.48, p ˆ 0.018). In 101.5Æ 18.1 kg, after 97.5Æ 17.1 kg, p < 0.0001). Acute reactions to the stepwise multiple regression, changes in SMC proliferation could be explained energy restriction were evaluated in the groups of 10 volunteers during 3 by changes in HDLc (step 1: 23%) and by compliance to the diet (step 2: days of energy intake 3200, 6600 a 13 400 kJ. 16%). Obese persons show a slight decrease of both sympathetic and parasym- In conclusion, during the early weight loss, diets enriched in olive oil could pathetic NS activities. In the supine position, only few changes in the have a protective effect on SMC proliferation and therefore on atherosclerosis. sympathetic=parasympathetic NS activity ratio were observed. In the standing position, in the obese group, a decrease of sympathetic=parasympathetic NS activity ratio was described. Signi®cant correlations between sympathetic NS P186 activity and lipid oxidation (r ˆ 0.329, p < 0.01) as well as saccharide oxida- The effects of symptomatic and asymptomatic left ventricular systolic tion (r ˆ 70.258, p < 0.05) were observed. dysfunction on effort capacity and quality of life in 55 to 75 year olds During the weight reduction, a slight increase of the parasympathetic NS obese patients activity and a higher increase in the sympathetic NS activity were measured. D Rosu1, V Ivan1, and M Bordea1 Acute reaction to the low-energy diet was observed in a few days. Relative 1 increase mainly in the sympathetic NS activity doesn't depend on the degree Academic Hospital Department of Cardiology Timisoara Romania of energy de®ciency only, but some subjective factors may play a signi®cant The effects of left ventricular systolic dysfunction (LVSD) in asymptomatic role. form, are less known as contributor to the disabling condition in chronic heart In the group of obese persons non-speci®c changes of the vegetative NS failure. activity were observed. They are modulated by some behavioural factors. The METHODS: We studied 69 obese patients aged 55 to 74 years, randomly tendency to the higher parasympathetic NS activity con®rms the MONA LISA selected from hospitalized patients. Cardiovascular risk factors were observed. theory of the origin of obesity. The return of the indexes after overweight Each patient completed questionnaires regarding medical history, the symp- reduction is an important information. tom of breathlessnes, quality of life, current medication. Echocardiograms and maximal exercise tests were performed. Left ventricular mass (LVM, Penn formula) and left ventricular ejection fraction (LVEF, Simpson's method) were P184 calculated. Data was compared with the same parameters in 30 nonobese Cardiac morphology and left ventricular function in children with simplex patients, with the same age and chronic heart failure. obesity RESULTS: LVM in obese patients was 145Æ 25 g=m2, more then 2 1 1 1 115Æ 15 g=m which was found in nonobese patients (p < 0.01). The E Sadurska , L Szewczyk , and D Witkowski median LVEF was 46.7% in 7 (10%) asymptomatic obese patients and 1Dept. of Paediatric Cardiology, Medical Academy, University Children's 2 50.9% in 5 (18%) nonobese patients (p < 0.05). The median LVEF of 35%, Hospital in Lublin, Poland; Dept. of Peadiatric Endocrinology and Neurology, vs 42% was found in symptomatic patients, obeses and nonobeses. The Medical Academy, University Children's Hospital in Lublin, Poland median exercise time was lower in obese then nonobese patients (302.3 s vs The purpose of this study was to assess left ventricular (LV) structure, systolic 380.0 s, p < 0.001). Regarding asymptomatic patients, median exercise time and diastolic function in obese children. The study group consist of 25 young was also lower in obese then non obese patients (324.0 s v 456.0 s p < 0.001) patients (aged 12 ± 17) with body mass index (BMI) above 30 kg=m2.The The multivariate analysis showed that for obese and nonobese patients, LVEF results were compared with those in a control group of 15 healthy children was the signi®cant determinant of exercise time. In symptomatic and asymp- without overweight. tomatic obese patients LVM was also the signi®cant determinant of exercise Echocardiography was performed and echocardiographic measurements time. The comparison of asymptomatic obese patients with asymptomatic were obtained in accordance with the recommendations of the American nonobese patients showed lower LEVF, higher LVM and also lower quality of Society of Echocardiography with the exception of data for LV mass, which life in obeses. was derived using Penn convention methodology. LV diastolic ®lling was CONCLUSION: The comparison between obese and nonobese patients assessed using pulsed-wave Doppler echocardiography, in accordance with showed a less number of asymptomatic patients with chronic heart failure, the methods of Nishimura at all. and lower quality of life between obeses. Apparently asymptomatic, obese It was established that LV mass, LV mass corrected for body surface and LV patients presented a signi®cant decrease of LVEF. The increase of LVM in obese mass corrected for height were signi®cantly higher in obese children. The patients is an independent factor in the evolution of chronic heart failure. In prevalence of LV hypertrophy in children with obesity (using LV mass=height de®ning asymptomatic cardiac heart failure, we should include the quality of index) was almost 78%. life and the response to exercise tests, especially in obese pacients. The tested parameters of the left ventricle systolic function: shortening fraction (%SF), ejection fraction (%EF) were within normal values and there were no signi®cant differences when compared to controls with normal P187 weight. The date obtained from pulsed ± Doppler echocardiography indicate Gender-speci®ic associations of leptin and body composition in liver that left ventricular ®lling pattern in obese children also was no signi®cantly cirrhosis

disturb. Peak early (MVE) left ventricular ®lling velocity, peak atrial (MVA) 1 1 1 1 1 1 velocity, MVE=MVA velocities ratio were similiar in both groups. M Riedl , B Tribl ,CMuÈller , P Georg , D David , G Tappeiner , W WaldhaÈusl1, and B Ludvik1 1Department of Internal Medicine III, Waehringer Guertel 18-20, 1090 Vienna P185 INTRODUCTION: Data on leptin levels and their association with body MUFA enriched hypocaloric diet: effect on weight loss and on composition in patients with liver cirrhosis are controversial, potentially due atherosclerosis to ignoring gender-speci®c differences. METHODS: We therefore measured leptin, body composition (BIA) and C Mary1, C Colette1, N Pares-Herbute1, TC Pham1, and L Monnier1 1 insulin sensitivity (HOMA-Analysis) in 51 patients with liver cirrhosis (22 Laboratoire de Nutrition et AtheÂrogeneÂse, IURC, 641 avenue du doyen Giraud, females (LF) and 29 males (LM)) and in 55 healthy sex, age and BM1-matched 34093 Montpellier Cedex 5, France control subjects (CF, CM). In 23 obese patients, we compared the effects of 2 hypocaloric diets (730% RESULTS: Compared o controls, patients with liver cirrhosis exhibited of total energy expenditure) on weight loss rate, on smooth muscular cell decreased insulin sensitivity (l.9Æ 0.2 vs 4.4Æ 0.4, p < 0.001) and increased (SMC) proliferation and on blood cardiovascular risk factors : TG, TC, HDLc, insulin levels (50.4Æ 4.2 vs 120.0Æ 11.7 pmol=L, p < 0.001). In both groups, LDLc, ®brinogen, Lp(a), insulin resistance (HOMA). leptin levels were increased in female vs male subjects (17.0Æ 0.3 vs In % of total energy intakes, the composition of the 2 diets (pro- 4.3Æ 0.5 ng=mL, LF vs LM, p < 0.001, and I3.8Æ 3.3 vs 6.4Æ 0.9 ng=mL, CF teins=fats=CHO) was 20=25=55 (diet A, n ˆ 11) vs 20=40=40 (diet B, vs CM, p < 0.001). Leptin levels were higher (p < 0.05) in male, however not n ˆ 12). 65% of total energy intake was brought by CHO and MUFA in in female cirrhotic patients when compared to controls. FFM was slightly both diets: 55 ‡ 10 (diet A) and 40 ‡ 25 (diet B enriched in olive oil). Biology reduced in LM (57.1Æ 1.9 kg vs 57.8Æ 1.2 kg, LM vs CM, p < 0.05). In was evaluated at days 0 and 60. Weight was measured at days 0, 30 and 60. contrast to CM, CF and to LM patients, plasma leptin concentrations did Neither at day 30 nor at day 60 was the weight loss dependent on the not correlate with FM (r ˆ 0.4, p ˆ 0.08), insulin levels (r ˆ 0.2, p ˆ 0.44) or type of the diet. At day 60, insulin resistance and plasma concentrations of TG, insulin sensitivity (r ˆ 0.1, p ˆ 0.65) in LF. TC and LDLc were signi®cantly diminished independently of the type of the CONCLUSION: In conclusion, only male, but not female cirrhotic patients diet. HDLc, Lp(a) and ®brinogen remained unchanged. SMC proliferation was exhibit increased leptin levels when compared to controls. Circulating leptin is enhanced with type A diet ( ‡ 3.67%, p ˆ 0.025). Changes in SMC prolifera- not correlated to fat mass, insulin levels and insulin sensitivity in female tion (%) were negatively correlated to changes in HDLc (r ˆ 70.51, cirrhotic patients. These data point towards a gender-speci®c difference in

International Journal of Obesity Track 6 Cardiovascular system and obesity

S83 P190 the regulation of circulating leptin and the association of leptin with para- meters of body composition and glucose metabolism in cirrhotic patients. Reduction of smooth muscle cell contraction by perivascular adipose tissue G Dubrovska1,MLoÈhn1, B Lauterbach1, FC Luft1, M Gollasch1, AM Sharma1, Franz-Volhard-Klinik1, and Max-DelbruÈck1 P188 1Center for Molecular Medicine, University Clinic ChariteÂ, Humboldt-University Berlin, Germany MUFA enriched hypocaloric diet: effect on weight loss and on atherosclerosis In earlier studies, perivascular adipose tissue was shown to in¯uence the underlying blood vessel contraction. We have pursued this intriguing notion. C Mary1, C Colette1, N Pares-Herbute1, TC Pham1, and L Monnier 1 We measured contraction of male Sprague-Dawley rat (200 ± 300 g) aortic 1Laboratoire de Nutrition et AtheÂrogeneÂse, IURC, 641 avenue du doyen Giraud, rings in a Schuler organ bath system. Vessels were either stripped of surround- 34093 Montpellier Cedex 5, France ing adipose tissue or were left intact and were incubated with several During hypocaloric diets, weight loss but also the dietary composition can substances in¯uencing vascular contraction. contribute to the cardiovascular risk modi®cation. The aim of the study was to Contractile responses to KCI were not different between stripped or intact compare the effects of 2 hypocaloric diets (730% of total energy expendi- vessels. However, a signi®cant reduction of smooth muscle cell contraction to ture) on weight loss rate, on smooth muscular cell (SMC) proliferation and on serotonin and phenylephrine was measured in intact vessels. Dose-response blood cardiovascular risk factors: TG, TC, LDLc, ®brinogeÁne, Lp(a). insulino- curves for serotonin and phenylephrine in intact vessels showed a signi®cantly reÂsistance (HOMA). rightward shift. The reduction of contraction response of intact vessels to 23 obese patients were included. In % of total energy intakes, the serotonin and phenylephrine was abolished by preincubation of the vessels composition of the 2 diets (proteins=fats=CHO) was 20=25=55 (diet A, with glybenclamide. Application of cromakalim to stripped vessels resulted in n ˆ 11) vs 20=40=40 (diet B, n ˆ 12). Monounsaturated fatty acids were a reduction of the contractile response to serotonin and phenylephrine. Other 10% of calories in diet A and 25% in diet B. 65% of total energy intake was potassium channel blockers did not modulate the reduced response of intact brought by CHO and monounsaturated fats in both diets: 55 ‡ 10 (diet A) and vessels to serotonin or phenylephrine. Additionally, vessels with perivascular 40 ‡ 25 (diet B enriched in olive oil). Patients were asked to prepare their adipose tissue were either denuded of endothelium or were left intact to rule meals at home from pre-established menus, during 60 days. Biology was out an involvement of endothelium. No signi®cant differences were measured evaluated at days 0 and 60. Weight was measured at days 0, 30 and 60. in endothelium-denuded or endothelium-intact vessels with perivascular Neither at day 30 (74.6 kg) nor at day 60 (77 kg) was the weight loss adipose tissue. (adjusted on mean basal weight) dependent on the type of the diet. At day We conclude that perivascular adipose tissue exhibited a signi®cant effect 60, insulinoresistance and plasma concentrations of TG, TC and LDLc were on rat aortic smooth muscle cell contraction. This modulation did not depend signi®cantly diminished independently of the type of the diet. HDLc, Lp(a) and on the endothelium. We suggest that perivascular adipose tissue affects ®brinogen remained unchanged. SMC proliferation was enhanced with type B smooth muscle cell ATP-dependent potassium channels and thereby reduces diet ( ‡ 3.6%, p ˆ 0.025). Changes in SMC proliferation (%) were negatively serotonin or phenylephrine-evoked rat aortic smooth muscle cell contractions. correlated to changes in HDLc (r ˆ 70.51, p ˆ 0.012) and to the compliance to the diet (r ˆ 70.48, p ˆ 0.018). In stepwise multiple regression, changes in SMC proliferation (%) could be explained by changes in HDLc (step 1:23%) and by compliance to the diet (step 2 : 16%). In conclusion, during the early weight loss, neither weight loss nor lipid metabolism were dependent on dietary composition. However, during this period, diets enriched in olive oil seem to have a protective effect on SMC proliferation and therefore on atherosclerosis. P191 Biochemical markers of patients with type 2 diabetes and orlistat induced weight loss CW le Roux1, J Alaghband-Zadeh1, J Suttard1, G Frost1, and JF Laycock1 P189 1Departments of Metabolic Medicine, Dietetics and Neuroendocrinology, Imperial College School of Medicine, Charing Cross Hospital, London, UK Effects of weight loss induced by gastric surgery on blood pressure levels and metabolic parameters BACKGROUND: Obesity, insulin resistance, hypercholesterolaemia, Lp(a) and

1 1 1 1 1 elevated homocysteine are all independent cardiovascular risk factors. The AN Faria , KMB Carvalho , CH Arasaki , JC Del Grande ,ABeaniJr, and interaction between these factors, enhances the relative risk of cardiovascular MT Zanella1 1 disease. Presently the reduction of weight through medical intervention has Universidade Federal de SaÄo Paulo, SP-Brasil not yet been demonstrated to have cardiovascular mortality bene®ts. This INTRODUCTION: Gastric surgery has been indicated to treat obese patients study aimed to evaluate biochemical risk factors for cardiovascular disease in with body mass index above 40 kg=m2, mostly of them with associated patients with type 2 diabetes undergoing orlistat induced weight loss. morbidity, as hypertension, diabetes or dislipemia, which augment their METHODS: 7 patients (6 females, 1 male) with type 2 diabetes were followed cardiovascular risk. as part of an on going Lifestyle clinic. A dietician followed patients monthly METHODS: In this study 15 severe obese patients (12F, 3M), aged 38Æ 10 and measured their body mass index (BMI) and hypoglycaemic agent years old and BMI of 50Æ 6kg=m2, were submitted to gastric surgery (band ‡ requirement. After 2.5 kg initial weight loss in 4 weeks, they were started on by-pass) and evaluated for BMI, blood pressure (BP), fasting glucose (GLU), orlistat 120 mg tds. Fasting blood samples were obtained before any weight tryglicerides (TG) and cholesterol (CHOL) levels, before and after 6Æ 3 loss and 6 months after orlistat therapy. Plasma was analysed for insulin, months. A 24 hour report of food ingestion was used to calculate the total glucose, fasting insulin resistance index (FIRI ˆ glucose  insulin=25), total energy consumed (TEC) after surgery. cholesterol, triglycerides, high density lipoprotein (HDL), calculated low RESULTS: A reduction of 23.6Æ 6.0% (p < 0.01) in BMI correlated with period density lipoprotein (LDL), Lp(a), HbAlc and homocysteine. after surgery. The TEC ranged from 220 to 1400 kcal with a positive correla- RESULTS: The BMI of the patients decreased signi®cantly from tion with the time after surgery (r ˆ 0.79; p < 0.01), indicating an adaptative 40.2Æ 3.23 kg=m2 (meanÆ SEM) to 37.8Æ 3.23 kg=m2 (p < 0.001). However process. Systolic and diastolic BP (SBP=DBP) fell from 136Æ 12=78Æ 8to the majority of biochemical markers did not show any signi®cant change: 123Æ 17=71Æ 12 mm Hg (p < 0.05),TG levels from 151Æ 85 to 106Æ 64 FIRI (4.1Æ 1.2 to 5.6Æ 1.3), total cholesterol (4.8Æ 0.15 mmol=Lto (p < 0.01) GLU levels from 101Æ 19 to 93Æ 7mg=dl (p ˆ 0.06) without 4.8Æ 0.18 mmol=L), triglycerides (1.4Æ 0.19 mmol=Lto1.5Æ 0.23 mmol=L), changes in CHOL. No correlation was found between changes in BP and Lp(a) (284Æ 87 mg=L to 258Æ 82 mg=L), homocysteine (8.6Æ 0.9 mmol=Lto changes in BMI. 8.4Æ 0.5 mmol=L). The only signi®cant improvements were HbAlc CONCLUSION: We concluded that the weight loss consequent to bariatric (8.7Æ 0.59% to 6.9Æ 0.29%, p ˆ 0.01) and LDL=HDL ratio (2.88Æ 0.3 to surgery is effective in reducing blood pressure and, tryglicerides levels, 2.32Æ 0.3, p ˆ 0.01) indicating a reduced cardiovascular risk. tending also to diminish glucose levels in severe obese patients, contributing CONCLUSIONS: It was disappointing that the signi®cant weight reduction to a decrease of the cardiovascular risk of these patients. The increase in TEC, did not translate into reductions in all of the individual biochemical markers of an expected adaptative behavior, probably responsible for the weight stabi- cardiovascular risk. It could be postulated that a certain amount of weight loss lization after an year of the procedure, otherwise may compromise the results needs to be achieved over a longer follow up period, before reduction of of the surgery during long term follow-up and needs further evaluation. cardiovascular risk will be realised.

International Journal of Obesity Track 6 Cardiovascular system and obesity

S84 P192 category. An AI higher than 3,5 a.u. was found in 61% of males with normal weight, in 79% of overweight males and in 90% of obese males. A statistically Effect of body fat and fat distribution on cardiovascular risk factors signi®cant decrease in comparison with the normal weight category was

1 1 1 1 1 1 found in the HDL-chol serum levels of both the overweight and obesity F Magri , B Pontiggia , A Rebesco , L Busconi , D Camozzi , S Precerutti , categories. In the same way, an increase in Tchol and LDL-chol, TAG serum and E Ferrari1 1 concentrations and AI values in higher CVD category (according to the waist Dept. of Int. Medicine and Med. Therapy, Chair of Geriatrics, University of circumference value: 94 ± 102 cm) and high risk CVD category (waist circum- Pavia, Italy ference value > 102 cm) was found in comparison with the low CVD risk INTRODUCTION: It is well known that an excess of body fat is associated with category (waist circumference value < 94 cm). alterations in metabolism homeostasis. In particular, changes in lipid metabo- lism are associated with central fat or visceral fat and there is a close correlation between fat distribution and cardiovascular risk. P194 The aim of this study was to evaluate the relationship between the supine sagittal abdominal diameter and others indicators of body fat distribution with Estimation of visceral fat in obese patients with DEXA compare with CT cardiovascular (CVD) risk factors, such total cholesterol, HDL-cholesterol, scan triglycerides and blood pression, giving a particular attention to the gender D Bellido1, J Carreira1, A Bouza1, B RodriÂguez1, V Blay2, A Becerra3, differences. 4 5 6 METHODS: One hundred and seventy eight obese women (BMI 34.4Æ 0.41 D De Luis , G Piedrola , and A HernaÂndez 1  2 SE; age 41.2Æ 1.12 ES) and 49 obese men (BMI 34.7Æ 0.68 ES; age Servicio de Endocrinologia y NutricioÂn. H. Naval Ferrol; H. Militar Zaragoza; 3H. Ramon y Cajal Madrid; 4H. Rio Hortega Valladolid; 5Virgen de las Nieves 40.9Æ 2.02 ES) were studied. In each subjects we evaluated: degree of 6 overweight (BMI), fat distribution (waist and hip circumference and abdom- Granada; Dr. Peset Valencia inal sagittal diameter by a sliding-beam abdominal calliper), body composi- INTRODUCTION: Computarized tomography (CT) scan is considered as gold tion (bioelectric impedance measure), systolic and diastolic blood pressure, standard technique in estimation of visceral fat in obese patients, correlation of total and HDL cholesterol and tryglicerides. this technique with abdominal circumference, sagital diameter and cardio- RESULTS: Both in women and in men, age was signi®cantly related to the vascular risk factors has been demonstrated. However estimation of visceral fat decrease of height and the increase of waist circumference or of the waist to volumen need a lot of CT scan slides, with low ef®cciency in clinical practice. hip ratio. In women BMI was signi®cantly correlated with systolic pressure, PATIENTS AND METHODS: Fifty three patients (100% women) were studied, total and HDL cholesterol and tryglicerides. On the contrary, BMI was with a mean body mass index (BMI) 32,05 (5,28) Kg=m2, and a mean age 32 signi®cantly related only with systolic pressure in men. In the group of (10) years. Total abdominal fat, intra-abdominal fat mass, and subcutaneous obese women, but not in the one of obese men, waist circumference and fat mass were determined in all patients (LUNARR DPX). Datas were compared the waist to hip ratio were signi®cantly related to systolic and diastolic blood with estimation of visceral fat from obese patients that previously has been pressure and blood lipid parameters. A signi®cant association was also found, reported by our group (Int J Obes 2000; 24 (1): VF (cm2) ˆ 764.5 ‡ in women, between abdominal sagittal diameter, measured with sliding beam (33.47  SD) 7 (7.15  A) 7 4.51  H) 7 (49  S): VF visceral fat, SD sagital abdominal calliper, and blood arterial pressure, but this relation was not diameter, A abdominal circumference, H height in cm, S sex: male ˆ 1, pointed in the group of men; in obese men the abdominal sagittal diameter female ˆ 2. was signi®cantly related only to total cholesterol. In women there was a Linear correlation of Pearson were used in quantitative variables, with correlation between fat mass (FM) and fat free mass (FFM) and systolic blood STATISTICAR for WINDOWS. pressure and cholesterol. RESULTS AND CONCLUSIONS: A signi®cative correlation were obtained CONCLUSION: Among the different measures of fat distribution, the sagittal among between visceral fat estimated with our equation and intrabdominal abdominal diameter was very useful for the prediction of cardiovascular fat mass determined by DEXA (r ˆ 0.73; p < 0.0001). Estimation of visceral fat disease risk factors both in obese women (signi®cant relationship with systolic in obese patients is an interesting area of investigation, although Ct scan is the and diastolic blood pressure) and in obese men (signi®cant relationship with gold standard technique, datas are correlated with DEXA results. total cholesterol). These results showed that aplication of DEXA in clinical practice is easy, and could be a good reference technique. P193

Obesity and risk of cardiovascular disease development P195

1 1 1 1 1 The bene®ts of very low calorie diet (VLCD) in the treatment extremely PHluÂbik ,SByÂma , J Chaloupka , L Opltova , and V BlaÂha obese persons 1Purkyne Military Medical Academy, TrÏebesÏska 1575, 500 01 Hradec KraÂloveÂ, Czech Republic E Stokic1, and T Ivkovic-Lazar1 1 The Czech Republic ranks among the countries with highest prevalence of Dept. of Endocrinology, Medical Faculty H.Veljkova 1-3, 21000 Novi Sad, overweight and obesity. It is important to recognize obesity as a serious Yugoslavia disorder associated with several chronic deseases. The study provides exten- Obesity is associated with a number of disorders such as glucose tolerance sive information on selected anthropometncal and biochemical parameters, disturbances, insulin resistance, hyperinsulinaemia, hypertension, dyslipidae- especially on those, which are generally used as risk indices for the origin and mia, impaired ®brinolysis, accelerated atherosclerosis which all lead to cardi- development of cardiovascular disease (CVD): body mass index (BMI), body ovascular disease. VLCD therefore bene®ts the individual by reducing health fat percentage (b.fat), waist circumference (waist), serum concentrations of risks and improving the quality of life. total cholesterol (Tchol), HDL- and LDL-cholesterol (HDL-chol, LDL-chol), In order to assess the in¯uence of VLCD on lipids, insulin, glucose, triacylglyceroles (TAG) and the atherogenic index (AI). ®brinogen and blood pressure, we have evaluated 36 extremely obese females The nutritional status of a selected population ± 6267 male members of (age 32,06 ‡ =7 6.64 years), in whom, apart from standard measures (body the Czech Army ± was assessed in 2000. The results of the study proved the weight, BMI, systolic and diastolic blood pressure), subcutaneous (SAT) and considerable prevalence of the overweightness and obesity in the male visceral adipose tissue (VAT) had been measured by ultrasound. Patients were population group that was followed: according to the calculated BMI, 52% treated with VLCD (1254 kJ) for 30 days. As for physical activities, during this of volunteers were estimated to be overweight and 15% to be obese. As far as period only the light walking has been practiced. At the end of the study BMI lipid parameters were concerned, increased serum levels were estimated in signi®cantly decreased (42.06 ‡ =77.64 to 37.58 ‡ =76.44 kg=m2,p< 0.05). 34% (TAG), 58% (Tchol) and 41% (LDL-chol) of volunteers. Decreased serum VAT has been reduced signi®cantly (34.10 ‡ =73.25 to 24.78 ‡ =72.50 mm, levels of HDL-chol were found in 17% of volunteers. An AI higher than 3,5 a.u. p < 0.05), while SAT has been reduced but only on the edge of signi®cance was calculated for 73% of all subjects in study. The study concept made it (p ˆ 0.05). The signi®cant improvement of the lipid parameters was observed: possible to reveal the relationships among the anthropometrical and bio- total cholesterol (Ch) (5.68 ‡ =71.02 to 4.2 ‡ =70.84 mmol=l, p < 0.001), chemical parameters followed. The regression analysis results document a triglycerides (2.25 ‡ =71.34 to 1.30 ‡ =70.59 mmol=l, p < 0.001), LDL-Ch statistically signi®cant positive dependence among the BMI or waist values (3.37 ‡ =71.23 to 2.68 ‡ =70.86 mmol=l, p < 0.05). The study has shown and the serum concentrations of Tchol, LDL-chol, TAG and AI. A signi®cant that the decrease of HDL-Ch happened on the bene®t of HDL3 subfraction. negative correlation was found between the HDL-chol serum concentration After weight reduction the level of ®brinogen and fasting insulin statistically and the BMI or waist values. signi®cantly decreased. The variance analysis results (the estimated lipid parameter values were These results suggest that VLCD decreases signi®cantly body weight, divided into groups according to the BMI and waist categories) document a mainly by reducing the VAT and improves the metabolic pro®le of extremely statistically signi®cant increase of serum Tchol, LDL-chol, TAG and AI in both obese persons. Also, this treatment is associated with reducing in ®brinogen the overweight and obese categories in comparison with the normal weight level.

International Journal of Obesity Track 6 Cardiovascular system and obesity

S85 P196 P198 The blood leptin concentrations are not corelated with trigliceride and Is leptin affect arterial hypertension in obesity Ð in¯uence of insulin and glucose levels after functional tests in obese families from South Poland different methods of obesity assessment

1 1 1 1 1 1 1 1 M Malczewska-Malec , I WybranÂska , I LeszczynÂska-Golabek , S Niedbal , ML--uczak , P BogdanÂski , W Bryl , and D Musialik 1 1 2 1 A Zdzienicka , T Krzeszowska , F Pietri-Rouxel , and A DembinÂska-Kiec 1Department of Internal Diseases, University of Medical Sciences, PoznanÂ, 1 Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian Poland, [email protected] University, KrakoÂw, Kopernika 15a, Poland; 2Institut Cochin de Genetique Moleculaire, Laboratoire d'ImmunoPharmacologie Moleculaire, CNRS UPR INTRODUCTION: Hyperinsulinemia is regarded as one of most important 0415 and Universite de Paris VII 22, rue Mechain, 75014, Paris, France pathogenetic factors in obesity-related hypertension. Leptin, a peptide pro- duced in adipocite tissue, regulates food intake and energy expenditure. It is INTRODUCTION: Leptin acts as a regulator of lipid reserves through changes also considered to participate in development of arterial hypertension mainly in food intake, energy expenditure and fuel selection, and its direct effects on cellular lipid and carbohydrate metabolism is suggested. Table METHODS: The blood leptin, blood lipids (cholesterol, high-density lipopro- tein [HDL]- and low-density lipoprotein [HDL]-cholesterol, and triglycerides) Group 1 Group 2 Control were determined in 68 women and men from obese families from South Poland Glucose and insulin concentrations in the blood were measured before WHR 0.92Æ 0.09 0.84Æ 0.06* 0.77Æ 0.05* and 30, 60, 90 and 120 minutes after oral glucose (75 g) tolerance test Fat % 44.4Æ 5.4 43.1Æ 5.1 22.3Æ 3.2* (OGTT) according to WHO guidelines. The postprandial trigliceride levels Fat kg 42.3Æ 11.7 40.3Æ 10.7 16.8Æ 6.1* were determined after oral lipid tolerance test. SBP mmHg 154.2Æ 10.1 133.8Æ 5.3* 128.4Æ 7.5* RESULTS: The mean body mass index of study group was 33,2 kg=m2. Leptin DBP mmHg 101.9Æ 6.7 85.6Æ 4.9* 78.9Æ 6.4* level was strongly associated with percentage body fat (r ˆ 0.63; p < 0.001), fat mass (r ˆ 0.60; p < 0.001), and body mass index (r ˆ 0.38; p ˆ 0.04). Leptin ng=ml 56.4Æ 13.7 41.6Æ 10.9* 13.3Æ 12.4* However any correlation with basal metabolic rate (BMR) (r ˆ 0.02; Insulin mI=ml 29.4Æ 11.9 22.5Æ 7.8* 11.2Æ 6.3* p ˆ 0.93) was observed. The occurrence of arterial hypertension in the group of highest values of BMI and leptin was 38% compared to reference * p < 0.05 vs group 1 2 group (BMI < 30 kg=m ; leptin < 10 ng=ml) 10%. There was no correlation through sympathetic activation and mitogenic action. between blood leptin level and parameters of lipid and carbohydrate METHODS: 45 untreated obese hypertensives (group 1) aged 40.7Æ 7.5 metabolism. years, BMI 35.4Æ 4.9 kg=m2 were compared to 40 obese normotensives CONCLUSION: These ®ndings con®rm the associations between leptin and (group 2) aged 37.9Æ 6.9 years, BMI 36.3Æ 5.8 kg=m2. 20 lean normoten- body fat content and suggest the lack of direct relationship between serum sives matched for age constituted the control group. We measured systolic leptin and triglicerides and glucose concentration in healthy humans. and diastolic blood pressure (SBP, DBP), waist to hip ratio (WHR), fasting serum insulin and leptin (by RIA). Adipocite tissue content was assessed by bioelectrical impedance. Results were analysed by multivariate analysis method. RESULTS: In group 1 we found signi®cantly elevated WHR values, serum leptin and P197 insulin. In both groups leptin signi®cantly correlated positively with BMI, fat content, SBP, DBP and insulin. In group 1 after adjustment for BMI and insulin, Blood pressure in relation to body fat distribution: gender differences leptin remained independent predictor of DBP, but this association disap- BZ Beleslin1, S Vujovic1, Z Penezic1, M Zarkovic1, B Trbojevic1, and M Drezgic1 peared after adjustment for adipocite tissue content as a measure of fatness. 1Institute of Endocrinology, Diabetes and Metabolic Diseases, 13 Dr Subotica, CONCLUSIONS: we did not con®rm direct relationship between serum leptin Belgrade, Yugoslavia and arterial hypertension. Insulin, degree of obesity and fat distribution remain most important factors in¯uencing obesity-related hypertension. Several prospective studies have shown that the selective accumulation of adipose tissue in the central or abdominal region is associated with an increased risk for development of cardiovascular diseases. The aim of this study was to asses gender differences in blood pressure (BP) in relation to body fat distribution in extreme obese patients (pts). The study population consisted of 56 extremely obese patients with no signs of endocrine, cardiovascular and renal disease, divided according to P199 body fat distribution to lower-body (LB) obese men (7 pts; 39Æ 4years, BMI 52Æ 14 kg=m2), upper-body (UB) obese men (11 pts; 36Æ 10 years, BMI Ad libitum intake of a low-fat diet fails to reduce blood pressure in 47Æ 5kg=m2), LB obese women (19 pts; 33Æ 7 years; BMI 43Æ 5kg=m2), overweight adults and UB obese women (19 pts; 35Æ 8 years; BMI 45Æ 6kg=m2). Patients JM Moesenender1, and HJF Zunft1 underwent 21 days of very low calorie diet. Results are presented in the 1 following Table including systolic (SBP) and diastolic (DBP) BP before and after German Institute of Human Nutrition & University of Potsdam, D-14558 the diet. Bergholz-Rehbruecke INTRODUCTION: Aim of the study was to investigate whether the result of Table the DASH study can be con®rmed by (i) using a German hypertensive population and (ii) replacing the well-controlled feeding design by allowing UB obese women LB obese women ad libitum intake according to dietary advices. METHODS: 53 overweight subjects from Potsdam with borderline hyperten- before after before after sion and without medication were randomly assigned to either a combination diet low in fat and rich in dairy products, fruits and vegetables (I-group) or a SBP(mmHg) 141Æ 22 132Æ 13 134Æ 9 126Æ 10 habitual diet as control (C-group). During 5 weeks the subjects were provided DBP(mmHg) 92Æ 17 89Æ 10 83Æ 883Æ 9 50% of their daily intake for free according to their dietary pattern. Single and 24 h blood pressure measurements, dietary and physical activity records, UB obese men LB obese men blood and urine samples and anthropometnc measurements were collected before after before after before, during and 5 weeks after the intervention period. SBP(mmHg) 146Æ 26 131Æ 8 154Æ 15 143Æ 15 RESULTS: No reduction of blood pressure could be observed in the I-group of DBP(mmHg) 93Æ 18 84Æ 798Æ 10 89Æ 9 our trial. No change of body weight was observed during the whole study period. CONCLUSION: Even convincing results of a controlled trial cannot be simply In conclusion, signi®cant reduction of BP (p < 0.05) during very low calorie transferred into dietary advices for the general public. For addressing food- diet was observed in all groups except for DBP in LB obese women. In based dietary guidelines to reduce the risk of hypertension it is necessary to addition, BP was similar in both UB obese women and men, whereas both consider carefully (i) the genetic background, (ii) the dietary and (iii) lifestyle SBP and DBP was signi®cantly (p < 0.05) higher in LB obese men then women. situation of the target population.

International Journal of Obesity Track 6 Cardiovascular system and obesity

S86 P200 P202

Waist=hip circumference=height ratio and its relationship to athero- Association of fasting serum insulin, proinsulin and leptin levels with sclerotic risk factors in obese women hypertension in obesity subjects N Ozbey1, M Taskale1, S Molvalilar1, E Sencer1, and Y Orhan1 X Gao1, SF Jiang1, NQ Zhao1, and ZQ Lu1 1Department of Internal Medicine, Division of Endocrinology, Istanbul Faculty 1Department of endocrinology, Zhongshan, Hospitai, Shanghai Medical of Medicine, Capa, 34390, Istanbul, Turkey University, Shanghai 200032 P.R.China Anthropometric parameters can predict cardiovascular risk status in epide- PURPOSE: To investigate the association of fasting serum insulin, proinsulin miological studies. Waist girth and waist=hip ratio are known to be related to and leptin levels with hypertension in obesity subjects. metabolic derangement induced by visceral obesity. Recently Asayama and METHODS: 152 obesity or overweight subjects (BMI 29.5(28.2 ± 31.6) and Hayashi used waist=hip circumference =height ratio (WHRH) standart devia- 28.8(27.9 ± 30.6), p ˆ 0.072, aged 20 to 65 years were selected. The demo- tion scores as an index of body fat distribution in children. The aim of this graphic parameters and metabolic pro®le in 78 subjects were compared with study is to determine the validity of WHRH as a risk factor predictor in obese 74 normotesives. Fasting serum insulin proinsulin and leptin were mesured by women. RIA. Study group is composed of 1940 obese (BMI > 27 kg=m2,meanage RESULTS: Two groups had the same BMI, it was 29.5(28.2 ± 31.6) in hyper- 37.1Æ 11.7 years) women. Fasting serum glucose level > 126 mg=dL, cho- sives and 28.8(27.9 ± 30.6) in normotesives, p ˆ 0.072. Hypertensives (Bp lesterol and triglyceride levels > 200 mg=dL, HDL-cholesterol level < 133=90 mmHg) had signi®cantly higher W, WHR and fasting glucose and 45 mg=dl, blood pressure > 140=90 mm Hg, serum uric acid level > 5.5 mg=dL triglyceride levels than normotesives (BP 118=77 mmHg). The groups did not and fasting serum insulin level > 13 mU=mL are considered as risk factors. differ in fasting serum insulin, leptin, and HOMA . In the hypertensive group, WHRH were signi®cantly higher in women with risk factors than without fasting serum proinsulin level was signi®cantly increased comparaed with it in risk factors (p < 0.001 for all). WHRH correlated positively with age (r ˆ 0.32, the normotesive group, it was 22.87 (8.99 ± 44.40) pmol=l and 14.90(8.27 ± p > 0.001), BMI (r ˆ 0.33, p < 0.001), systolic and diastolic blood pressure 25.45) pmol=l, respectively, p ˆ 0.0322. Proinsulin=insulin ratio was 18.0 (r ˆ 0.24, p < 0.001 and r ˆ 0.21, p < 0.001 respectively), uric acid (r ˆ 0.13, (9.0 ± 30.5) and 14.4 (7.2 ± 22.2) respectively in hypertensives and normote- p < 0.001), glucose (r ˆ 0.20, p < 0.001), insulin (r ˆ 0.14, p < 0.001), HOMA sives, p ˆ 0.0087. Age, waist-to-hip ratio, proinsuim level, hyperglycemia and (r ˆ 0.17, p < 0.001), cholesterol and triglyceride (r ˆ 0.20, p < 0.001 and dyslipidemia were associated with hypertension. But, after adjusted by BMI, r ˆ 0.26, p < 0.001 respectively) and negatively with HDL-cholesterol those associations did not existence. (r ˆ 70.06, p ˆ 0.01). According to receiver operating characteristics (ROC) CONCLUSIONS: Hypertensive and normotensive subjects with obesity had analysis, a WHRH > 0.70 indicated increased likelihood of presence of one or the same insulin sensitivity level. Hypertensive subjects had more visceral fat more risk factors and a WHRH < 0.5 indicated low likelihood of presence of risk and higher glucose and triglyceride levels than normotensive ones. b cell factors. dysfunction were present in hypertensive patients, probably mediated It is concluded that WHRH can be used as an indicator for cardiovascular through dyslipidemia. Leptin seems not a major factor to cause hypertension. risk status in obese women.

P201 P203

The incidence of cardiovascular complications in the obese before and Obesity and cardiovascular risk in persons with newly diagnosed 6 months after hypocaloric diet and physical exercise diabetes mellitus (``EPIDIAB'' study in Romania ± 2000) C Tudor1, Jeberean Rorica1, Danciu Simina1, V Lungu1, Vizman Carmen1, and NHaÃncu1, G Roman1,ACif1, IA Veresiu1, A cerghizan1, and S Cernea1 C Vizman1 1Clinical Center of Diabetes, Nutrition, Metabolic Diseases, 2 Clinicilor st., 1First Medical Clinic - University of Medicine and Pharmacy, B-dul Tudor 3400 Cluj-Napoca, Romania Vladimirescu Nr.16, ap.2, 1900 Timisoara, Romania INTRODUCTION: Obesity alone or associated with other components of the Android obesity generates cardiovascular complications (increased blood ``X metabolic syndrome'' is frequent met in diabetes. Its presence increases pressure, ischaemic cardiac disease, strokes and peripheral arteriopathy). both global and cardiovascular risk, either by itself or by associated comor- Their incidence is directly related to the weight excess and to the metabolic bidity. Intensive care should be addressed to screen, evaluate and control disorders evolution (glucose intolerance, diabetes mellitus, hyperlipoprotei- obesity and other risk factors in people with diabetes. nemias and hyperuricemias). The metabolic disorders appear early during the OBJECTIVE: The study intended to evaluate the presence of obesity, other obesity evolution representing major risk factors to the cardiovascular system. cardiovascular risk factors (CVRF) and the obesity-induced risk classes in These require from practitioners to establish as soon as possible a hypocaloric persons with newly diagnosed diabetes. diet in order to bring back the metabolic parameters to normal values thus METHOD: Data regarding the prevalence of CVRF: overweight, obesity, waist diminishing the cardiovascular risk. circumference, dyslipidemia, blood pressure, lifestyle and familial history, have The authors analyze the incidence of cardiovascular complications in 350 been recorded and assessed in 890 patients with newly diagnosed diabetes obese patients, 156 males with BMI ˆ 35,3Æ 5kg=m2 and mean age 48Æ 12 mellitus (DM) last year in Cluj-Napoca. This is a section of a larger study years, and 144 females with BMI ˆ 37,4Æ 4kg=m2 and mean age 44,6Æ 11 (EPIDIAB- epidemic of diabetes), including 12 counties, which aims to years. The incidence of cardiovascular complications was 43% and after 6 evaluate the prevalence of diabetes and its medical and socio-economic months it decreased signi®cantly. 210 (60%) obese patients were given impact. Patients have been selected in clinical risk classes according to Body 1000 kcal=24 h for 6 months, together with dosed physical exercise, according Mass Index (BMI) adjustment with other risk factors (waist, hypertension, to their cardiovascular and articular tolerance. 130 (40%) lost weight only by dyslipidemia) (D.H. Ryan, G. Bray, 1998). means of hypocaloric diet, being unable of physical efforts. RESULTS: The prevalence of overweight=obesity in Type 1 DM patients is The weight loss was bigger in the group that exercised than in the other 0.7%=0.3% and in Type 2 DM is 34.3%=51.2%. High waist circumference group, getting to a BMI ˆ 30,4Æ 3 and the incidence of cardiovascular ( > 80 cm for females and > 92 cm for males) has been found in 91.3% Type 2 complications was 12%, versus the group that couldn't afford the physical DM patients. A subgroup of 590 patients have been selected in clinical risk exercises, which got to a BMI ˆ 32,2Æ 4kg=m2 and incidence of cardiovas- classes, according to adjusted BMI, as follows: cular complications of 28,2% (p < 0.001). 5% at low risk (BMI ˆ 25 ± 29.9 kg=m2), 27.2% at moderate risk In the time with the weight loss, the plasmatic lipids values and glucose ((BMI ˆ 30 ± 35 kg=m2) and 67.47% at high risk (BMI > 30 kg=m2). tolerance improved signi®cantly. In conclusion the authors consider the CONCLUSION: As we expected, the prevalence of overweight and obesity is hypocaloric diet and the dosed physical effort as the best therapeutical very high in newly diagnosed Type 2 DM patients mainly represented by method in the improvement of cardiovascular and osteoarticular perfor- abdominal fat distribution. When assessing the prevalence of the other mance. The returnal to normal values of metabolic parameters signi®cantly cardiovascular risk factors among newly diagnosed Type 2 DM patients the reduces the cardiovascular risk. global obesity-induced risk is extremely high. As a practical consequence intensive weight management should be started from the moment of diabetes diagnosis, in association with all CVRFs control. KEYWORDS: EPIDIAB, obesity, cardiovascular risk

International Journal of Obesity Track 6 Cardiovascular system and obesity

S87 P204

Negative correlation between fat free mass and 24 hour heart rate S Toubro1, H Hausner1, NF Johnsen1, and A Astrup1 1Royal Vet & Agri University, 1958- Frederiksberg, Denmark INTRODUCTION: A positive correlation between resting heart rate and mortality has been observed. Weight gain increase resting heart rate and in¯uence the balance of the autonomic nervous system. METHODS: A sibling cohort of 7l (27 male and 43 femals) healthy mainly lean (BMI: 23.7Æ 4.1 (range 16.9 ± 38.8 kg=m2) subjects aged 29.1Æ 4.5 years, had their body composition estimated by bioimpedance and 24-hour energy expenditure (24-h EE) and heart rate (24-h HR) measured under standardised low physical activity conditions in open-circuit respiration chambers. Cate- cholamines and thyroid hormones assessed fasting after the stay. The day to night decrease in heart rate were also tested for differences between lean and obese. RESULTS: The variation in heart rate correlated primarily with lean body mass (r ˆ 70.35, p < 0.01). The following prediction equations for 24-h HR was found by backward elimination: 24-h HR ˆ 71.7 ± 1.13 x FFM ‡ 0.15 x 24 hour EE(r ˆ 0.57, p ˆ 0.01). No difference in delta 24-h HR was found between obese and lean. CONCLUSION: On a low physical activity level lean body mass together with 24-h EE are the best predictors of 24-h HR. There was no difference in day to night drop in heart rate between lean and obese.

International Journal of Obesity