IMPACT OF HYPERGLYCEMIA ON CLINICAL OUTCOME IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION (PCI) FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI)

IMPACT OF HYPERGLYCEMIA ON CLINICAL OUTCOME IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION (PCI) FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI)

Oral Communications / European Journal of Internal Medicine 19S (2008) (2008), S1–S59 S45 FR-58 FR-60 ACTIVATION OF THE ENDOGENOUS CANNABINOID SYS...

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Oral Communications / European Journal of Internal Medicine 19S (2008) (2008), S1–S59

S45

FR-58

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ACTIVATION OF THE ENDOGENOUS CANNABINOID SYSTEM STIMULATES ADIPOGENESIS IN HUMAN ADIPOSE TISSUE

SERUM LIVER ENZYMES IN UNDERWEIGHT PATIENTS WITH EATING DISORDERS

Vettor Roberto, Pagano Claudio, Pilon Catia, Calcagno Alessandra, Urbanet Riccardo, Rossato Marco, Milan Gabriella, Bianchi Katiuscia, Rizzuto Rosario, Bernante Paolo, Federspil Giovanni. Clinica Medica 3, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy

C. Montagnese 2 , A. Signorini 1 , E. De Filippo 1 , C. De Caprio 1 , F. Contaldo 1 , F. Pasanisi 1 , L. Scalfi 2 . CISRO, 1 Departments of Clinical and Experimental Medicine and 2 Food Science, University “Federico II”

The endogenous cannabinoid system participates in the regulation of energy balance, and its dysregulation may be implicated in the pathogenesis of obesity. Adipose tissue endocannabinoids may produce metabolic and endocrine effects, but very few data are available in human adipose tissue. We measured expression of type 1 and type 2 cannabinoid receptors (CB), enzymes of cannabinoids synthesis and degradation in human omental, sc abdominal, and gluteal adipose tissue from lean and obese subjects. Activation of CB1 increases lipoprotein lipase activitiy in adipocytes and this would augment the flux of free fatty acids to adipocytes for triglycerides synthesis. Furthermore, we assessed the effect of CB1 stimulation on glucose uptake and intracellular transduction mechanisms in primary human adipocytes. Then we assessed the reciprocal regulation between CB1 and peroxisome proliferator-activated receptor-gamma (PPAR γ). Finally, we tested whether leptin and adiponectin are regulated by CB1 in human adipocytes. We found that most genes of the endocannabinoid system are down-regulated in gluteal fat and up-regulated in visceral and sc abdominal adipose tissue of obese patients. Treatment of adipocytes with rosiglitazone markedly down-regulated CB1 expression, whereas Win 55,212 increases the mRNA expression of PPARγ. Win 55,212 increased (+50%) glucose uptake, the translocation of glucose transporter 4, and intracellular calcium in fat cells. All these effects were inhibited by SR141716 and wortmannin and by removing extracellular calcium. Win 55,212 and SR141716 had no effect on expression of adiponectin and leptin. These results indicate that CB1 activation by endogenous cannabinoids stimulates PPARγ thus promoting adipogenesis. Local endocannabinoids favour glucose and lipid utilization in human adipocytes thus promoting lipogenesis. These data suggest a role of endocannabinoids-CB1 activation in channeling excess energy fuels to adipose tissue in obese humans.

Background: Data on serum liver enzymes in patients with anorexia nervosa still remain contradictory and inconsistent, whereas no information is available on underweight patients with atypical eating disorders, who may also be considered at risk for poor nutritional status. Subjects and methods: 163 underweight patients were identified among the female subjects aged >17 yrs who consecutively afferred to the outpatient clinic for eating disorders (2000-2004): 97 patients had anorexia nervosa (AN) and 66 patients suffered from atypical eating disorders (AED). An age-matched control group was also studied Fasting blood samples were collected at 08:00-08:30. Haemoglobin, serum albumin, cholesterol, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), and choline esterase (CHE) were all determined using routine laboratory methods. Results: In the AN patients transaminases and GGT were higher while ALP and CHE were lower in comparison to control women. Similar differences were also observed In AED patients for AST, GGT and CHE. Hypertransaminasemia (ALT and/or AST above normal values) occurred in 14.4% of the AN patients and 15.2% of the ATD patients. A high prevalence of abnormal values was also observed in both groups for ALP (15.5 and 22.7%) and CHE (28.2 and 13.6%) In the anorectic group there was a significant association of AST, ALP and GGT with BMI while ALT, AST, GGT, ALP, LDH and CK did not correlate with haemoglobin, albumin, total protein and cholesterol. A relationship with trygliceride levels was found for AST, GGT and LDH while CHE was significantly related to glycaemia and total serum proteins. Conclusion: Serum enzyme abnormalities are quite frequent not only in AN but also in underweight patients with AED. In particular, low CHE values also occur in patients with a relatively small BMI decrease.

FR-61 FR-59 NAFLD ABD TYPE 2 DIABETES: A GENETIC OR METABOLIC ISSUE? L. Carulli, S. Rondinella, A. Rudilosso, D. Ganazzi, M. Bertolotti, P. Loria, N Carulli. University of Modena and Reggio Emilia, Italy Background: Type 2 diabetes (T2D) seems to be a risk factor for the development of Non Alcoholic Fatty Liver Disease (NAFLD) and for its progression to fibrosis. The pathogenesis of the NAFLD-T2D association is not known. Recent data have shown that hyperinsulinemia and insulinresistance (IR) may be the primary phenomenon in NAFLD as well as inflammation. Aim of the study was to evaluate the prevalence of NAFLD in T2D, to correlate NAFLD with the Metabolic Syndrome (MetS) features and with T2D therapy, to evaluate the relation between NAFLD and genetic polymorphisms associated to IR, PC-1 K121Q, and inflammation, IL-6–174 C/G. Methods: 80 diabetic subjects were enrolled and underwent blood sample and medical history to ruled out alcohol consumption and other liver diseases aetiology. Steatosis was defined according to standardized ultrasonographic criteria and a score for each criterion was assigned like indicator of the severity of fatty liver infiltration (Fatty liver indicator, FLI). Results: The subjects studied were overweight with BMI=28.60 (25°÷ 75°=25.35÷ 32.95), had normal lipid profile and uric acid and had higher GPT levels (25–75°; GOT: 7.00–27.25 and GPT: 21.00–38.00). 22.5% subjects had no steatosis whereas 77.5% had different severity of fatty liver infiltration. FLI did correlate significantly with BMI (p< 0.01), total Cholesterol (p<0.01), glycosilated haemoglobin (p<0.05) and TG (p<0.01). No correlation was found between T2D therapy and severity of NAFLD. No significant difference in polymorphisms prevalence was observed when NAFLD subjects were compared to a control group. Discussion: Our data show that T2D patients have a very high prevalence of NAFLD which is probably related to hyperinsulinism and IR. This is further supported by the positive correlation of NAFLD with BMI and TG. The lipogenic effects of insulin may underlie such relationship. In our population NAFLD associates with some features of MetS whereas no significant genetic component is present

IMPACT OF HYPERGLYCEMIA ON CLINICAL OUTCOME IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION (PCI) FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) Ariella De Monte, Andrea Perkan, Giancarlo Vitrella, Serena Rakar, Erica Della Grazia, Alessandro Salvi, Gianfranco Sinagra. Dipartimento di Cardiologia, Azienda Ospedaliero-Universitaria, Trieste. Background and aims: non diabetic patients with STEMI and hyperglycemia at hospital admission have a higher prevalence of cardiac morbidity and mortality, but there are very few data from literature. The aims of this study are to assess the prevalence of acute hyperglycemia in non diabetic patients with STEMI undergoing PCI (primary or rescue) and its prognostic impact on reperfusion and clinical outcome. Methods: 184 patients with STEMI undergone to PCI were enrolled from PCI registry of Trieste (wich contains anamnestic, clinical, angiographic, echocardiographic and therapeutic data) between December 1,2004, and July 31,2006.Follow-up at 1 month is being conducted to quantify patients’postdischarge outcomes. Glycemia was considered 110 mg/dl. The group was divided in 3 subgroups: non diabetic normal if normoglycemic patients (n=22; 12%), non diabetic hyperglycaemic patients (n=104; 57%) and diabetic patients (n=58; 31%). Results: in this study main parameters of hyperglycemic non diabetic patients have a intermediate trend between non diabetic normoglycemic and diabetic groups. The hyperglycemic non diabetic group had a double risk of death compared to normoglycemic one. The group of hyperglycemic non diabetic

Subgroups Age Peripheral vascular disease TIMI Risk Score Ischemia time TIMI post PCI Heart failure 30 days mortality

Normoglycemic

Hyperglycemic

Diabetic

p

62±12 13% 3,2±1,6 91±77 2,9±0,4 17% 4%

64±12 19% 3,9±2,3 134±117 2,8±0,7 21% 10%

69±13 36% 5,0±2,3 197±227 2,6±0,7 38% 15%

<0,05 <0,05 <0,05 <0,05 <0,05 <0,05 NS

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Oral Communications / European Journal of Internal Medicine 19S (2008), S1–S59

subjects had an increased impaired fasting glucose (IFG) at 1 month follow-up compared to non diabetic normoglycemic group (24.8% vs 9.1%, p=0.001). Conclusions: in this study acute hyperglycemia prevalence in non diabetic patients with STEMI is highest of all data from literature (57%). Acute hyperglycemia is associated with a worse outcome also in non diabetic subjects and detects an intermediate risk class between non diabetic and diabetic patients with STEMI, which could benefit by therapy. Acute hyperglycemia is predictive of IFG suggesting a metabolic stadiation in order of a better therapeutic strategy of secondary prevention of ischemic cardiopathy

FR-62 VISCERAL AND SUBCUTANEUS FAT CHANGES FOLLOWING 10% AND 25% WEIGHT LOSS IN SEVERE OBESE PATIENTS TREATED WITH LAPAROSCOPIC GASTRIC BYPASS F. del Genio, I. De Sio, G. del Genio, C. Finelli, F. Pasanisi, F. Contaldo. Dip. Medicina Clinica e Sperimentale Università Federico II & I Div. Chirurgia Generale SUN Bariatric surgery is considered the most effective treatment for reducing excess weight and maintaining weight loss in patients with clinically severe obesity. There are limited data evaluating metabolic and fat changes following bariatric surgery in severely obese patients. We evaluated 22 patients (13 M, 9 F; age 42.6±5.6 years; BMI 49.3±6.0 kg/m2 ), undergoing laparoscopic gastric bypass, before surgery and following 10% and 25% weight loss (WL), obtained on average six and thirty weeks after surgery respectively. Visceral and subcutaneous fat were assessed with ultrasound. Weight (138.5±24.9 vs. 121.8±21.3 vs. 104.6±20.4 kg; p=0.001), BMI (49.3±6.0 vs. 43.4±5.0 vs. 37.1±4.5 kg/m2 ; p=0.001) and waist circumference (142.6±15.5 vs. 133.0±14.1 vs. 117.8±14.1 cm; p=0.001) statistically decreased following 10 and 25% WL. Mean glucose (102.1±25.4 vs. 87.8±8.2 vs. 76.9±7.8 mg/dl; p=0.001), triglyceridemia (174.9±106.3 vs. 130.9±52.7 vs. 103.6±37.7 mg/dl; p=0.005), HDL-cholesterolemia (46.1±11.5 vs. 39.9±8.0 vs. 49.1±9.6 mg/dl; p=NS), AST (22.5±5.3 vs. 29.6±12.1 vs.21.9±9.5 U/ml; p=NS), ALT (33.2±12.9 vs. 34.6±19.2 vs. 20.4±11.2 U/ml; p=0.01), γGT (36.8±29.9 vs. 21.8±11.5 vs. 15.7±8.1 U/ml; p=0.01) and HOMA (6.2±4.0 vs. 2.3±1.2 vs. 1.6±0.8; p=0.001) improved after surgery with significantly reduction at 25% WL. Visceral fat (8.9±3.2 vs. 6.5±2.2 vs. 4.5±1.3 cm; p=0.001) and subcutaneous fat (3.4±1.1 vs. 2.9±0.7 vs. 2.1±0.8 cm; p=0.01 vs. baseline) both significantly decreased following 25% WL after surgery.

Following WL visceral fat thickness progressively decreased paralleling metabolic improvements. Further investigations are needed to evaluate long term effects of metabolic changes in patients undergoing laparoscopic bariatric surgery.

FR-63 THE EFFECT OF PHEOCHROMOCYTOMA TREATMENT ON SUBCLINICAL INFLAMMATION AND ENDOCRINE FUNCTION OF ADIPOSE TISSUE L. Bosanska, O. Petrak, T. Zelinka, M. Mraz, J. Widimsky, M Haluzik. Third Department of Medicine, 1 Faculty of Medicine, Charles University and General University Hosp. Patients with a catecholamine-secreting tumor (e.g. pheochromocytoma) may suffer from early progression of atherosclerosis and higher risk of cardiovascular diseases, although the exact mechanism of accelerated atherosclerosis in these patients is only partially understood. Previous in vitro studies have demonstrated that increased catecholamine levels can markedly modulate the endocrine function of adipose tissue. It is also known, that numerous hormones of adipose tissue such as adiponectin and resistin, may be directly or indirectly involved in the etiopathogenesis of atherosclerosis. The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. 18 patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and 6 months after surgical removal of pheochromocytoma, respectively. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50% 6 months after surgical removal of pheochromocytoma (0.49±0.12 mg/l vs. 0.23±0.05 mg/l, p < 0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by a paradoxical attenuation of subclinical inflammation. We failed to demonstrate an involvement of the changes of circulating leptin, adiponectin or resistin levels in this process. Supported by MZO 000064165 a IGA 8302-5