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Insulin resistance, the metabolic syndrome and non alcoholic fatty liver disease (NAFLD)
XVII S.I.S.A. National Congress
327
CLINICAL FEATURES AND ESTIMATED CORONARY PATIENTS WITH THE METABOLIC SYNDROME
RISK I N
F Angelico, M Del Ben, MG Cavallo, K Feole, C Alessandri
INSULIN RESISTANCE, THE METABOLIC SYNDROME AND NON ALCOHOLIC FATTY LIVER DISEASE (NAFLD) F Angelico, M Del Ben, R Conti, S Francioso, K Feole, S Fiorello, C Alessandri
IV Division of Internal Medicine, University La Sapienza, Rome IV Division of Internal Medicine, University La Sapienza, Rome Introduction. Aims of the study were to investigate the clinical and metabolic features of the metabolic syndrome (MS) and to assess the contribution of MS to the identification of high CVD risk subjects to address to a more aggressive therapy. Methods. The diagnosis of MS was made in 153 consecutive outpatients according to the definition of the A-I'P I I I Report. Insulin resistance was assessed by the homeostasis model assessment (HOMA). The assignment of patients to the high CVD risk category was made on the presence of an absolute 10-year CHD global risk >20%, according to the Framingham risk scores. Results. Subjects with 0, 1, 2, 3, 4 and 5 risk factors were 3.9%, 19.6%, 20.9%, 34.0%, 15.0% and 6.5% respectively. Prevalence of MS was 55.5%. Among subjects with MS 86.2% had abdominal obesity, 86.4% high blood pressure, 82.1% high TG, 69.0% low HDL-C and 51.2% high fasting glucose. A statistically significant (p<0.001) increase in mean HOMA was observed in subjects with increasing clustering of risk factors (from 3.2±3.1 in subjects without risk factors to 9.74-5.6 in those with 5). Mean estimated 10-year absolute CHD risk significantly increased in subjects belonging to the different quartiles of HOMA (from 9.04-5.3 in the lower quartile to 14.74-13.0 in the upper quartile) and was higher (p<0.001) in subjects with MS, as compared to those without (14.24-10.3 vs 8.14-6.4). However, less than 30% of subjects with MS were classified in the high CVD risk category based on the Framingharn scores. Conclusion. Our findings stress the importance of the identification of subjects with MS as targets of therapy for a more effective prevention of CVD.
CARDIOVASCULAR RISK FACTORS AND THE SYNDROME AFTER LIVER TRANSPLANTATION
The pathogenesis of NAFLD is multifactorial; it has been suggested that this disease might represent the hepatic consequence of the insulin resistance (IR) metabolic syndrome (MS). Methods. Liver steatosis was assessed in 308 consecutive outpatients by US scanning on a 0-3 scale: 0, absent; 1, mild; 2, moderate; 3, severe. HOMA-IR was used as measure of IR. The ratio of early insulin increment to early glucose increment (I 30-0/G 30-0) following oral glucose loading (75 g glucose) was obtained as a surrogate for insulin secretion (IS). Non diabetic subjects were simultaneously categorized by IR and IS status based on HOMA-IR and I 30-0/G 30-0 values above or below median in the non diabetic group. MS was diagnosed following the ATP I I I criteria. Results. According to WHO criteria, 193 subjects had a normal glucose tolerance test, 43 impaired glucose tolerance and 72 type 2 diabetes mellitus. Among the 236 non diabetic subjects, severe steatosis was 45.5% in those with a predominant IR (high HOMA-IR and high I 300/G 30-0), 47.9% in those with IR but decreased IS (high HOMA-IR and low I 30-0/G 30-0) and 35.4% in those with a predominant decreased IS (low HOMA-IR and low I 30-0/G 30-0). IR subjects had higher BMI (p<0.01), waist circumference (p<0.05), and fasting insulin (p<0.001) than those with decreased IS. A positive association (p
METABOLIC
ANTI-ATHEROTHROMBOTIC PROPERTIES OF ROSUVASTATIN I N APO E-DEFICIENT MICE
F Angelico, S Franciomo, MT Antonini, A Petrolati z, C Ciceroni 1, G Tisone 1, M Angelico 1
S Bellosta, M Monetti, M Canadesi, M Camera, R Bonzi, R Paletti, E Tremoli, A Corsini
IV Division of Internal Medicine, University La Sapienza, 1Gastroenterology Unit, Liver Transplantation Center, Tor Vergata University, Rome
University of Milan
Liver transplantation (OLT) is being performed with excellent results in terms of five-year survival rates. However, CVD risk factors are frequently observed and CVD complications are emerging as a potential cause of late morbidity and mortality. Aim of the study was to assess CVD risk factors after OLT and to evaluate their association with pretransplant conditions and current immunosuppression therapy. Methods. The study was performed in 58 consecutive OLT patients with a minimum follow up of 5 years. The metabolic syndrome (MS) was defined according to the ATPIII criteria. Ten-year CHD risk was estimated using the Framingham calculator. Results. Five years after OLT, 22.4% patients were obese, hypertension occurred in 75.9%, diabetes in 27.6%, high l~iglyceride in 24.9%, high total cholesterol in 16.0%. MS was diagnosed in 38.6%. High CVD risk patients (i.e.>20%) were 25.9%. Prevalence of hypertension, high triglyceride, obesity and MS was higher in patients treated with cyclosporine A (81.6%, 27.1% 26.3% and 44.7% vs 50.0%, 15.0%, 8.3% and 25.0%, respectively), while diabetes was as frequent among those treated with cyclosporin A or with tacrolimus (33.3% vs 28.9%). About 50% of hypertensives and diabetics were under current drug treatment, yet most patients did not reach the therapeutic targets. Conclusion. Multi metabolic risk factors after OLT are frequent and poorly controlled and the long term CVD risk is often underestimated. A more intense dietary and drug treatment should be considered in almost half the patients treated with cyclosporine A, who appear to develop over time an iatrogenic metabolic syndrome.
Inflammation plays a key role in the pathogenesis of atherosclerosis and mediates many of the stages of atheroma development from initial leukocyte recruitment to rupture of the unstable plaque leading to thrombosis. We investigated the antiinflammatory and antithrombotic properties of the new statin rosuvastatin on adhesion molecules and tissue factor (TF) expression in vivo. ApoE-deficient female mice were fed a cholesterol-rich diet containing rosuvastatin (0, 1, 2 or 10 mg/kg per day; n=9 mice per group) for 12 weeks. Treatment with rosuvastatin did not significantly alter total cholesterol or triglycerides levels compared to control animals. In addition, the drug did not affect the lipid lesion area either in the valves (V) or in the proximal segment of the ascending aorta (AA). On the contrary, rosuvastatin treatment dose-dependently reduced ICAM-1 expression in the V (up to 40% inhibition, p<0.01) and in the AA (up to 50%, p<0.001) at 10 mg/kg. Similarly, rosuvastatin inhibited VCAM-1 expression in the V (up to 40%, p<0.01) and in the AA (up to 35%, p<0.01) at the 1(1 mg/kg dose. Moreover, rosuvastatin treatment reduced the accumulation of macrophages in the V in a dose-dependent and statistically significant manner (-50%, p<0.001). Finally, TF expression in AA was consistently reduced by rosuvastatin treatment (-71%, p<0.001) even at the lowest dose. Altogether, the data demonstrate that, in the absence of an effect on plasma lipid levels, rosuvastatin attenuated the inflammatory and thrombogenic potential of atherosclerotic lesions of apoE-deficient mice.
327
CLINICAL FEATURES AND ESTIMATED CORONARY PATIENTS WITH THE METABOLIC SYNDROME
RISK I N
F Angelico, M Del Ben, MG Cavallo, K Feole, C Alessandri
INSULIN RESISTANCE, THE METABOLIC SYNDROME AND NON ALCOHOLIC FATTY LIVER DISEASE (NAFLD) F Angelico, M Del Ben, R Conti, S Francioso, K Feole, S Fiorello, C Alessandri
IV Division of Internal Medicine, University La Sapienza, Rome IV Division of Internal Medicine, University La Sapienza, Rome Introduction. Aims of the study were to investigate the clinical and metabolic features of the metabolic syndrome (MS) and to assess the contribution of MS to the identification of high CVD risk subjects to address to a more aggressive therapy. Methods. The diagnosis of MS was made in 153 consecutive outpatients according to the definition of the A-I'P I I I Report. Insulin resistance was assessed by the homeostasis model assessment (HOMA). The assignment of patients to the high CVD risk category was made on the presence of an absolute 10-year CHD global risk >20%, according to the Framingham risk scores. Results. Subjects with 0, 1, 2, 3, 4 and 5 risk factors were 3.9%, 19.6%, 20.9%, 34.0%, 15.0% and 6.5% respectively. Prevalence of MS was 55.5%. Among subjects with MS 86.2% had abdominal obesity, 86.4% high blood pressure, 82.1% high TG, 69.0% low HDL-C and 51.2% high fasting glucose. A statistically significant (p<0.001) increase in mean HOMA was observed in subjects with increasing clustering of risk factors (from 3.2±3.1 in subjects without risk factors to 9.74-5.6 in those with 5). Mean estimated 10-year absolute CHD risk significantly increased in subjects belonging to the different quartiles of HOMA (from 9.04-5.3 in the lower quartile to 14.74-13.0 in the upper quartile) and was higher (p<0.001) in subjects with MS, as compared to those without (14.24-10.3 vs 8.14-6.4). However, less than 30% of subjects with MS were classified in the high CVD risk category based on the Framingharn scores. Conclusion. Our findings stress the importance of the identification of subjects with MS as targets of therapy for a more effective prevention of CVD.
CARDIOVASCULAR RISK FACTORS AND THE SYNDROME AFTER LIVER TRANSPLANTATION
The pathogenesis of NAFLD is multifactorial; it has been suggested that this disease might represent the hepatic consequence of the insulin resistance (IR) metabolic syndrome (MS). Methods. Liver steatosis was assessed in 308 consecutive outpatients by US scanning on a 0-3 scale: 0, absent; 1, mild; 2, moderate; 3, severe. HOMA-IR was used as measure of IR. The ratio of early insulin increment to early glucose increment (I 30-0/G 30-0) following oral glucose loading (75 g glucose) was obtained as a surrogate for insulin secretion (IS). Non diabetic subjects were simultaneously categorized by IR and IS status based on HOMA-IR and I 30-0/G 30-0 values above or below median in the non diabetic group. MS was diagnosed following the ATP I I I criteria. Results. According to WHO criteria, 193 subjects had a normal glucose tolerance test, 43 impaired glucose tolerance and 72 type 2 diabetes mellitus. Among the 236 non diabetic subjects, severe steatosis was 45.5% in those with a predominant IR (high HOMA-IR and high I 300/G 30-0), 47.9% in those with IR but decreased IS (high HOMA-IR and low I 30-0/G 30-0) and 35.4% in those with a predominant decreased IS (low HOMA-IR and low I 30-0/G 30-0). IR subjects had higher BMI (p<0.01), waist circumference (p<0.05), and fasting insulin (p<0.001) than those with decreased IS. A positive association (p
METABOLIC
ANTI-ATHEROTHROMBOTIC PROPERTIES OF ROSUVASTATIN I N APO E-DEFICIENT MICE
F Angelico, S Franciomo, MT Antonini, A Petrolati z, C Ciceroni 1, G Tisone 1, M Angelico 1
S Bellosta, M Monetti, M Canadesi, M Camera, R Bonzi, R Paletti, E Tremoli, A Corsini
IV Division of Internal Medicine, University La Sapienza, 1Gastroenterology Unit, Liver Transplantation Center, Tor Vergata University, Rome
University of Milan
Liver transplantation (OLT) is being performed with excellent results in terms of five-year survival rates. However, CVD risk factors are frequently observed and CVD complications are emerging as a potential cause of late morbidity and mortality. Aim of the study was to assess CVD risk factors after OLT and to evaluate their association with pretransplant conditions and current immunosuppression therapy. Methods. The study was performed in 58 consecutive OLT patients with a minimum follow up of 5 years. The metabolic syndrome (MS) was defined according to the ATPIII criteria. Ten-year CHD risk was estimated using the Framingham calculator. Results. Five years after OLT, 22.4% patients were obese, hypertension occurred in 75.9%, diabetes in 27.6%, high l~iglyceride in 24.9%, high total cholesterol in 16.0%. MS was diagnosed in 38.6%. High CVD risk patients (i.e.>20%) were 25.9%. Prevalence of hypertension, high triglyceride, obesity and MS was higher in patients treated with cyclosporine A (81.6%, 27.1% 26.3% and 44.7% vs 50.0%, 15.0%, 8.3% and 25.0%, respectively), while diabetes was as frequent among those treated with cyclosporin A or with tacrolimus (33.3% vs 28.9%). About 50% of hypertensives and diabetics were under current drug treatment, yet most patients did not reach the therapeutic targets. Conclusion. Multi metabolic risk factors after OLT are frequent and poorly controlled and the long term CVD risk is often underestimated. A more intense dietary and drug treatment should be considered in almost half the patients treated with cyclosporine A, who appear to develop over time an iatrogenic metabolic syndrome.
Inflammation plays a key role in the pathogenesis of atherosclerosis and mediates many of the stages of atheroma development from initial leukocyte recruitment to rupture of the unstable plaque leading to thrombosis. We investigated the antiinflammatory and antithrombotic properties of the new statin rosuvastatin on adhesion molecules and tissue factor (TF) expression in vivo. ApoE-deficient female mice were fed a cholesterol-rich diet containing rosuvastatin (0, 1, 2 or 10 mg/kg per day; n=9 mice per group) for 12 weeks. Treatment with rosuvastatin did not significantly alter total cholesterol or triglycerides levels compared to control animals. In addition, the drug did not affect the lipid lesion area either in the valves (V) or in the proximal segment of the ascending aorta (AA). On the contrary, rosuvastatin treatment dose-dependently reduced ICAM-1 expression in the V (up to 40% inhibition, p<0.01) and in the AA (up to 50%, p<0.001) at 10 mg/kg. Similarly, rosuvastatin inhibited VCAM-1 expression in the V (up to 40%, p<0.01) and in the AA (up to 35%, p<0.01) at the 1(1 mg/kg dose. Moreover, rosuvastatin treatment reduced the accumulation of macrophages in the V in a dose-dependent and statistically significant manner (-50%, p<0.001). Finally, TF expression in AA was consistently reduced by rosuvastatin treatment (-71%, p<0.001) even at the lowest dose. Altogether, the data demonstrate that, in the absence of an effect on plasma lipid levels, rosuvastatin attenuated the inflammatory and thrombogenic potential of atherosclerotic lesions of apoE-deficient mice.