- Email: [email protected]
Sympathetic activation and reflex abnormalities in the metabolic syndrome
204A
POSTERS: Metabolic Syndrome
Material and Methods: N⫽204 patients, aged 35 to 82 years (57 ⫹/12), 108 females, 90 type 2 diabetic patients, 130 hypertensive patients, 85 patients with dyslipidemia and 39 smokers. Group A: N⫽ 74 (C3 ⬎⫽ 120), mean age 59 ⫹-11 years, 30 males. Group B: N⫽ 130 (C3 75-120), mean age 56⫹-12 years, 66 males. BMI(kg/m2). Waist circumference (cm). Glycemia, triglycerides and HDL: HITACHI auto-analyzer. LDL: Friedewald formula. IR: HOMA score: fasting insulin (uU/ml) x fasting plasma glucose (mmol/L)/22.5. C3 (mg/dL) Statistical analysis: t Student, multivariate analysis. Results: 1.Patients in both groups were of similar age and sex gender, but had different BMI (30,03⫹-0,6 vs 26,08⫹-0,39; p⫽0,000), waist circumference (98,5⫹-1,17 vs 92,3⫹-1,02; p⫽0,000), triglyceride levels (175,19 ⫹- 19,95 vs 121,31 ⫹- 11,61; p⫽0,021), HDL levels (50,21⫹1,65 vs 58,31 ⫹- 1,53; p⫽0,000) and degree of IR (3,34 ⫹-0,22 vs 2,61⫹-0,27; p⫽0,04). 2.In the multivariate analysis: BMI: OR 1,13; C I 95 % (1,028;1,24); p⫽0,012; IR: OR 1,24; CI 95 % (0,98;1,56); p⬍0,05. Conclusions: 1.In patients with cardiovascular risk, the BMI is the most important clinical-biochemical parameter of activation of the immune system. 2.High levels of C3 are considered as supportive data of the participation of the immune system in the genesis or the vascular consequences of the metabolic syndrome. Key Words: Activated Immune System, Complement System, Metabolic Syndrome
P-542 SYMPATHETIC ACTIVATION AND REFLEX ABNORMALITIES IN THE METABOLIC SYNDROME Gino L Seravalle, Raffaella Dell’oro, Fosca Quarti Trevano, Guido Grassi, Giuseppe Mancia. Cardiology, St. Luca Hpt, Milan, Italy; Clinica Medica, St. Gerardo Hpt, Monza, Milano, Italy. Background: Previous studies have shown that alterations in vascular, metabolic, inflammatory and hemocoagulative function characterise metabolic syndrome. Whether this is also the case for sympathetic function is not clearly established. Aim of the Study: The present study was aimed at clarifying this issue. It was also designed at determining whether metabolic and reflex mechanisms might be responsible for the possible adrenergic dysfunction. Methods and Results: In 43 healthy controls (age:48.2⫾1.0 years, mean⫾SEM) and in 48 age-matched subjects with metabolic syndrome (ATP III criteria) we measured, along with anthropometric and metabolic variables, arterial blood pressure (Finapres), heart rate (EKG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation induced by intravenous infusion of vasoactive drugs. Compared to controls, body mass index, waist circumference, blood pressure, cholesterol, tryglicerides, insulin and HOMA index values were greater in subjects with metabolic syndrome, whereas HDL cholesterol values were lower. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in controls (61.1⫾2.6 vs 43.8⫾2.8 bursts/100 heart beats, P⬍0.01), the presence of sympathetic activation being detectable also when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic directly and significantly correlated with waist circumference (r⫽0.46, P⬍0.001) and HOMA index (r⫽0.49, P⬍0.001) and it was inversely related to baroreflex sensitivity (r⫽-0.44, P⬍0.001), which was impaired in metabolic syndrome. Conclusions: These data provide the first direct evidence that metabolic syndrome is characterised by sympathetic activation and that this abnormality 1) is detectable also when the metabolic syndrome is not accompanied by hypertension and 2) depends on insulin resistance as well as reflex alterations. Key Words: Baroreceptor, Insulin Resistance, Sympathetic Nervous System
AJH–May 2005–VOL. 18, NO. 5, PART 2
P-543 EFFECT OF PPAR-⌫ AGONIST –ROSIGLITAZONE–ON ADIPONECTIN LEVEL IN THE METABOLIC SYNDROME Yehonatan Sharabi, Irit Avni, Yehuda Kamari, Mor Oron-Herman, Edna Peleg, Ehud Grossman. Hypertension Unit, C.Sheba Medical Center, Tel Hashomer, Israel; Clinical Neurocardiology, National Institutes of Health, Bethesda, MD. Objective: The metabolic syndrome is associated with significant cardiovascular morbidity and mortality. Adiponectin is an adipocytokine that possesses anti-diabetic, anti-atherogenic and anti-inflammatory properties which collectively establish its unique vascular protective role. In addition, thiazolidinediones (TZDs) improve glucose tolerance and insulin sensitivity in animal models of insulin resistance. Therefore we studied the effect of rosiglitazone on adiponectin levels in the fructoseinduced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. Design and Methods: 20 male Sprague-Dawley rats were fed a fructose-enriched diet for 3 weeks.Ten rats continued to consume the Fructose diet for another 2 weeks, while the other 10 received rosiglitazone (10mg/kg) in their drinking water on top of the fructose. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides and adiponectin levels were measured at baseline, after 3 weeks and at the end of the experiment. Visceral fat tissues were taken from all animals after 5 weeks and the expression of adiponectin mRNA was determined by quantitative RT-PCR. Results: Fructose feeding led to significant increase in BP, insulin and triglyceride levels and to impaired OGTT. Adiponectin plasma level did not change significantly. Treatment with rosiglitazone, however, lowered BP, improved OGTT and resulted in significant increase in adiponectin plasma level (from 5.9⫾2.2 to 18.3⫾5g/ml). Adiponectin mRNA expression in visceral fat increased 3.5 fold following rosiglitazone treatment. Conclusion: This study shows for the first time in an animal model which displays most of the metabolic syndrome components, that the insulin sensitizer rosiglitazone induced elevation of plasma level of adiponectin due to an increase in gene expression. Whether this is the mechanism through which rosiglitazone exerts its beneficial effect remains to be studied. Key Words: Adiponectin, Metabolic Syndrome, Thiazolidinediones (TZDs)
P-544 ACCURACY OF THE METABOLIC SYNDROME TO DIAGNOSE INSULIN RESISTANCE Justo Sierra-Johnson, Bruce D Johnson, Kent R Bailey, Gary L Schwartz, Stephen T Turner. Divisions of Hypertension and Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN. The metabolic syndrome (MS) is a cluster of coronary heart disease (CHD) risk factors (high blood pressure, dyslipidemia, glucose intolerance, and central obesity) associated with insulin resistance (IR), which may be responsible for increased CHD risk. A study of selected individuals indicated that MS criteria proposed by the National Cholesterol Education Program 3rd Adult Treatment Panel (ATP-III) may be specific but lack sensitivity to diagnose IR. We assessed accuracy of the component MS measures among asymptomatic adults from the general population. Frequently sampled intravenous glucose tolerance tests were performed in 256 subjects without diagnosed hypertension or diabetes, recruited from the white non-Hispanic population of Rochester MN (123 men and 133 women; ages 19-60 years). The reference standard for IR was determined by Bergman’s minimal model; IR was defined as an insulin sensitivity index ⬍2 x 10 min-1 x mU -1 x ml-1. Component MS
POSTERS: Metabolic Syndrome
Material and Methods: N⫽204 patients, aged 35 to 82 years (57 ⫹/12), 108 females, 90 type 2 diabetic patients, 130 hypertensive patients, 85 patients with dyslipidemia and 39 smokers. Group A: N⫽ 74 (C3 ⬎⫽ 120), mean age 59 ⫹-11 years, 30 males. Group B: N⫽ 130 (C3 75-120), mean age 56⫹-12 years, 66 males. BMI(kg/m2). Waist circumference (cm). Glycemia, triglycerides and HDL: HITACHI auto-analyzer. LDL: Friedewald formula. IR: HOMA score: fasting insulin (uU/ml) x fasting plasma glucose (mmol/L)/22.5. C3 (mg/dL) Statistical analysis: t Student, multivariate analysis. Results: 1.Patients in both groups were of similar age and sex gender, but had different BMI (30,03⫹-0,6 vs 26,08⫹-0,39; p⫽0,000), waist circumference (98,5⫹-1,17 vs 92,3⫹-1,02; p⫽0,000), triglyceride levels (175,19 ⫹- 19,95 vs 121,31 ⫹- 11,61; p⫽0,021), HDL levels (50,21⫹1,65 vs 58,31 ⫹- 1,53; p⫽0,000) and degree of IR (3,34 ⫹-0,22 vs 2,61⫹-0,27; p⫽0,04). 2.In the multivariate analysis: BMI: OR 1,13; C I 95 % (1,028;1,24); p⫽0,012; IR: OR 1,24; CI 95 % (0,98;1,56); p⬍0,05. Conclusions: 1.In patients with cardiovascular risk, the BMI is the most important clinical-biochemical parameter of activation of the immune system. 2.High levels of C3 are considered as supportive data of the participation of the immune system in the genesis or the vascular consequences of the metabolic syndrome. Key Words: Activated Immune System, Complement System, Metabolic Syndrome
P-542 SYMPATHETIC ACTIVATION AND REFLEX ABNORMALITIES IN THE METABOLIC SYNDROME Gino L Seravalle, Raffaella Dell’oro, Fosca Quarti Trevano, Guido Grassi, Giuseppe Mancia. Cardiology, St. Luca Hpt, Milan, Italy; Clinica Medica, St. Gerardo Hpt, Monza, Milano, Italy. Background: Previous studies have shown that alterations in vascular, metabolic, inflammatory and hemocoagulative function characterise metabolic syndrome. Whether this is also the case for sympathetic function is not clearly established. Aim of the Study: The present study was aimed at clarifying this issue. It was also designed at determining whether metabolic and reflex mechanisms might be responsible for the possible adrenergic dysfunction. Methods and Results: In 43 healthy controls (age:48.2⫾1.0 years, mean⫾SEM) and in 48 age-matched subjects with metabolic syndrome (ATP III criteria) we measured, along with anthropometric and metabolic variables, arterial blood pressure (Finapres), heart rate (EKG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation induced by intravenous infusion of vasoactive drugs. Compared to controls, body mass index, waist circumference, blood pressure, cholesterol, tryglicerides, insulin and HOMA index values were greater in subjects with metabolic syndrome, whereas HDL cholesterol values were lower. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in controls (61.1⫾2.6 vs 43.8⫾2.8 bursts/100 heart beats, P⬍0.01), the presence of sympathetic activation being detectable also when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic directly and significantly correlated with waist circumference (r⫽0.46, P⬍0.001) and HOMA index (r⫽0.49, P⬍0.001) and it was inversely related to baroreflex sensitivity (r⫽-0.44, P⬍0.001), which was impaired in metabolic syndrome. Conclusions: These data provide the first direct evidence that metabolic syndrome is characterised by sympathetic activation and that this abnormality 1) is detectable also when the metabolic syndrome is not accompanied by hypertension and 2) depends on insulin resistance as well as reflex alterations. Key Words: Baroreceptor, Insulin Resistance, Sympathetic Nervous System
AJH–May 2005–VOL. 18, NO. 5, PART 2
P-543 EFFECT OF PPAR-⌫ AGONIST –ROSIGLITAZONE–ON ADIPONECTIN LEVEL IN THE METABOLIC SYNDROME Yehonatan Sharabi, Irit Avni, Yehuda Kamari, Mor Oron-Herman, Edna Peleg, Ehud Grossman. Hypertension Unit, C.Sheba Medical Center, Tel Hashomer, Israel; Clinical Neurocardiology, National Institutes of Health, Bethesda, MD. Objective: The metabolic syndrome is associated with significant cardiovascular morbidity and mortality. Adiponectin is an adipocytokine that possesses anti-diabetic, anti-atherogenic and anti-inflammatory properties which collectively establish its unique vascular protective role. In addition, thiazolidinediones (TZDs) improve glucose tolerance and insulin sensitivity in animal models of insulin resistance. Therefore we studied the effect of rosiglitazone on adiponectin levels in the fructoseinduced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. Design and Methods: 20 male Sprague-Dawley rats were fed a fructose-enriched diet for 3 weeks.Ten rats continued to consume the Fructose diet for another 2 weeks, while the other 10 received rosiglitazone (10mg/kg) in their drinking water on top of the fructose. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides and adiponectin levels were measured at baseline, after 3 weeks and at the end of the experiment. Visceral fat tissues were taken from all animals after 5 weeks and the expression of adiponectin mRNA was determined by quantitative RT-PCR. Results: Fructose feeding led to significant increase in BP, insulin and triglyceride levels and to impaired OGTT. Adiponectin plasma level did not change significantly. Treatment with rosiglitazone, however, lowered BP, improved OGTT and resulted in significant increase in adiponectin plasma level (from 5.9⫾2.2 to 18.3⫾5g/ml). Adiponectin mRNA expression in visceral fat increased 3.5 fold following rosiglitazone treatment. Conclusion: This study shows for the first time in an animal model which displays most of the metabolic syndrome components, that the insulin sensitizer rosiglitazone induced elevation of plasma level of adiponectin due to an increase in gene expression. Whether this is the mechanism through which rosiglitazone exerts its beneficial effect remains to be studied. Key Words: Adiponectin, Metabolic Syndrome, Thiazolidinediones (TZDs)
P-544 ACCURACY OF THE METABOLIC SYNDROME TO DIAGNOSE INSULIN RESISTANCE Justo Sierra-Johnson, Bruce D Johnson, Kent R Bailey, Gary L Schwartz, Stephen T Turner. Divisions of Hypertension and Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN. The metabolic syndrome (MS) is a cluster of coronary heart disease (CHD) risk factors (high blood pressure, dyslipidemia, glucose intolerance, and central obesity) associated with insulin resistance (IR), which may be responsible for increased CHD risk. A study of selected individuals indicated that MS criteria proposed by the National Cholesterol Education Program 3rd Adult Treatment Panel (ATP-III) may be specific but lack sensitivity to diagnose IR. We assessed accuracy of the component MS measures among asymptomatic adults from the general population. Frequently sampled intravenous glucose tolerance tests were performed in 256 subjects without diagnosed hypertension or diabetes, recruited from the white non-Hispanic population of Rochester MN (123 men and 133 women; ages 19-60 years). The reference standard for IR was determined by Bergman’s minimal model; IR was defined as an insulin sensitivity index ⬍2 x 10 min-1 x mU -1 x ml-1. Component MS