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Biomedical subjects

Gianluca Iacobellis

Publications and source records attributed to Gianluca Iacobellis.

At least 19 recordsLinked to original sources

Aminotransferase activity in morbid and uncomplicated obesity: predictive role of fasting insulin.

BACKGROUND AND AIMS: An elevation in liver enzymes and, most notably, high serum alanine aminotransferase (ALT) activity, has been correlated with metabolic syndrome and obesity. However, whether obesity per se or obesity-related co-morbidities affect aminotransferase activity is still unclear. In this study we sought to evaluate serum aminotransferase activity in morbid and uncomplicated obese subjects METHODS: In this cross-sectional study, serum aminotransferase activity, anthropometric and metabolic parameters were assessed in 290 morbid and 105 uncomplicated consecutive obese subjects matched for body mass index (BMI) (40.1+/-6.8 vs. 39.9+/-8.3 kg/m(2), respectively), age (35.9+/-10 vs. 34.8+/-9.6 years, respectively), sex distribution and duration of obesity. RESULTS: Uncomplicated obese subjects showed significantly lower serum ALT activity (17.58+/-6.3 (range 10-39) vs. 23.43+/-16 (range 12-89) U/l, (p<0.001)), and lower aspartate aminotransferase (AST), AST/ALT ratios and gamma-glutamyltranspeptidase (gammaGT) (p<0.01 for all) than morbid obese subjects. Only 11% women and 19% men in the uncomplicated obese group showed high ALT levels, while ALT activity was high in 48% women and 51% men in the morbid obese group. Fasting insulin was the best correlate of ALT activity (R(2)=0.21, p=0.003). CONCLUSIONS: Our findings show that elevated ALT and AST activity are associated with increased fasting insulin and not with obesity per se, suggesting that the presence of insulin resistance, rather than BMI alone, plays a role in mediating the increased aminotransferase activity.

Adult↗

Different "weight" of cardiac and general adiposity in predicting left ventricle morphology.

Excess adiposity has been widely related to cardiac morphological changes. Nevertheless, the mechanistic link between increased adiposity and left ventricular (LV) morphology is controversial and not completely understood. In this context, several authors have recently debated the different "weight" of BMI as an index of general adiposity vs. the importance of the epicardial fat depot as a marker of local visceral adiposity in obesity-related LV changes. Studies in uncomplicated obesity suggest that the role of BMI in predicting LV abnormalities remains rather doubtful. In contrast, several lines of evidence suggest that cardiac adiposity could play an important part in the development of cardiac modifications. Epicardial fat as an index of cardiac adiposity could have a functional and mechanical role in obesity-related LV abnormalities. Epicardial fat is clinically correlated with LV mass, atrial dimensions, and diastolic function, but a causal effect of epicardial adipose tissue on cardiac chamber modifications remains to be demonstrated. Nevertheless, the close anatomical and functional relationship of epicardial adipose tissue to the adjacent myocardium should readily allow local, paracrine interactions between these tissues.

Adiposity↗

Left ventricular mass and +276 G/G single nucleotide polymorphism of the adiponectin gene in uncomplicated obesity.

The single nucleotide polymorphism at position 276 in the adiponectin gene (APM1/ACDC +276 G>T) and left ventricular mass (LVM) have been associated with increased cardiovascular risk. We sought to evaluate whether +276 G>T variants in the adiponectin gene are correlated with LVM in uncomplicated obese subjects. APM1/ACDC +276 G>T single nucleotide polymorphism, echocardiographic indexed LVM (LVM/body surface area and LVM/height(2.7)), insulin sensitivity by euglycemic clamp, and plasma adiponectin levels were analyzed in 62 obese subjects without complications (51 women and 11 men; mean age, 34.2 +/- 10.2 years; BMI, 38.6 +/- 9.1 kg/m2). Forty lean subjects formed the control group for LVM evaluation. We found 23 (37%) uncomplicated obese subjects with the APM1/ACDC +276 G/G genotype, 25 (40%) with the G/T genotype, and 14 (23%) with the T/T genotype. G/G uncomplicated obese subjects showed significant higher LVM/body surface area and LVM/height(2.7) (within the normal range in the majority of them) than uncomplicated obese subjects carrying the G/T and T/T genotypes (p < 0.01 and p < 0.05, respectively). This study showed that LVM is significantly higher in uncomplicated obese subjects carrying the G/G genotype at position 276 of the human adiponectin gene.

Adiponectin↗

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype.

Cholesterol, LDL↗

Treatment of obesity: a challenging task.

BACKGROUND: Obesity is a chronic and heterogeneous medical condition. Weight loss is clearly the most desirable goal in obese subjects management. Successful obesity treatment should be defined as long-term weight loss maintenance. In this chapter, we briefly review the current evidences regarding the treatment of obesity. METHODS: We searched MEDLINE and PubMed for original articles published between 1995 and 2006, focusing on obesity treatment. The search terms we used, alone or in combination, were 'obesity', 'lifestyle changes', 'diet', 'exercise', 'pharmacological treatment', 'surgical treatment'. CONCLUSIONS: The conventional management of obese patients involves weight reduction with lifestyle changes, including dietary therapy and increased physical activity, or a combined approach with lifestyle changes and pharmacological or surgical interventions. Exercise appears crucial in the successful maintenance of weight loss and in fostering cardiovascular health in obese patients. Some anti-obesity drugs, such as sibutramine and orlistat, have been shown to induce a significant weight loss and long-term weight loss maintenance. Surgical therapy is often necessary in morbidly obese patients and generally results in more significant and long-lasting weight loss than other treatments.

Anti-Obesity Agents↗

Cardiomyocyte apoptosis in cocaine-induced myocarditis with involvement of bundle of His and left bundle branch.

Cocaine abuse can cause degenerative and inflammatory alterations of the myocardium. Cocaine-induced myocarditis has been previously described, but mostly in chronic cocaine addicts. Among several pathogenetic mechanisms of cocaine-related myocardial damage, the myocardial adrenergic stress and cardiomyocytes apoptosis have been recently proposed. We report an unusual case of myocarditis involving the bundle of His and left bundle branch and cardiac myocytes apoptosis in otherwise healthy occasional cocaine abuser.

Adult↗

Normal serum alanine aminotransferase activity in uncomplicated obesity.

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3+/-9.6 years, BMI 39.9+/-8.3 kg/m(2)) were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73+/-6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m(2)) and those with BMI <40 kg/m(2) (18.63+/-6.25 vs 17.26+/-6.02 U/L). ALT was significantly correlated with fasting insulin (r = 0.485, P = 0.02) and triglycerides (r = 0.358, P = 0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesity-related comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.

Adiponectin↗

Epicardial adipose tissue and insulin resistance in obese subjects.

CONTEXT: Epicardial adipose tissue has been recently recognized as a source of bioactive molecules as well as free fatty acids, adiponectin, and inflammatory cytokines. Epicardial fat reflects intraabdominal visceral fat, and the echocardiographic assessment of this tissue is an easy and reliable marker of visceral adiposity. OBJECTIVE: In this study we evaluated whether epicardial adipose tissue is related to insulin sensitivity and glucose metabolism in obese subjects. PATIENTS: Thirty obese subjects (20 women and 10 men; mean age, 40.8 +/- 11.5 yr; body mass index, 43 +/- 9.1 kg/m2) were included in this study. No subject was taking drugs or had a history or evidence of metabolic, cardiovascular, respiratory, or hepatic disease. MAIN OUTCOME MEASURES: Each subject underwent a transthoracic echocardiogram to evaluate epicardial adipose tissue thickness, a euglycemic hyperinsulinemic clamp to estimate insulin sensitivity, and an oral glucose tolerance test to evaluate glucose tolerance. RESULTS: The thickness of the epicardial adipose tissue on the right ventricle varied between 4 and 17.4 mm. Echocardiographic epicardial adipose tissue was significantly correlated with whole-body glucose uptake index from the clamp and with all indices of insulin resistance and glucose intolerance measured, except the 120-min plasma glucose level after an oral glucose tolerance test. CONCLUSIONS: Our study showed that the epicardial fat is significantly related to obesity-related insulin resistance. This finding could be of potential interest in clinical practice and research of obesity-related risk stratification.

Adipose Tissue↗

Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease.

BACKGROUND: Intra-peritoneal adipose tissue is recognized as a predictor of metabolic syndrome and may contribute to the risk for cardiovascular disease by the production of adipocytokines, including adiponectin. Nevertheless, there is no knowledge on whether other visceral depots of adipose tissue, including the epicardial fat, have any metabolically active role, including production of adiponectin. AIM OF THE STUDY: We sought to evaluate adiponectin protein expression in epicardial adipose tissue in vivo both in patients with severe coronary artery disease (CAD) and in subjects without CAD. METHODS: Twenty-two patients were enrolled for the study. We selected 16 patients who underwent elective coronary artery bypass graft surgery for critical CAD, 5 who underwent surgery for valve replacement and 1 for correction of an interatrial defect. Epicardial adipose tissue biopsy samples were obtained before the initiation of cardiopulmonary bypass. Adiponectin protein level in epicardial adipose tissue was evaluated by Western blotting. RESULTS: Adiponectin protein value, expressed as adiponectin/actin ratio, in epicardial adipose tissue was significantly lower in patients with severe CAD than in those without CAD (1.42 +/- 0.77 vs 2.36 +/- 0.84 p = 0.02, 95% CI 0.64-1.74). CONCLUSIONS: This study showed for the first time that human epicardial adipose tissue expresses adiponectin. Adiponectin expression is significantly lower in epicardial fat isolated from patients with CAD.

Adiponectin↗

Effect of acute hyperinsulinemia on ventricular repolarization in uncomplicated obesity.

BACKGROUND: Acute hyperinsulinemia has been shown to increase QTc interval in lean subjects, but data on obese subjects are still unclear. Aim of this study was to evaluate the effect of acute hyperinsulinemia on QTc interval and QTc dispersion in uncomplicated obesity. METHODS: We calculated QTc duration and QTc dispersion in 30 uncomplicated obese subjects (mean age 32.2 +/- 7, BMI 36.7 +/- 9.4 kg/m(2)) by measurements of 12-lead ECG recording during a euglycemic hyperinsulinemic clamp. RESULTS: Insulin infusion during the clamp did not significantly modify QTc interval and QTc dispersion in uncomplicated obese subjects (401.5 +/- 29.2 vs. 413.7 +/- 30.5; 35.4 +/- 10.5 vs. 38.7 +/- 14.5, respectively). CONCLUSIONS: Acute hyperinsulinemia seems to no significantly affect ventricular repolarization in uncomplicated obesity. Insulin resistance and the absence of diabetes and hypertension could explain, at least in part, this finding.

Acute Disease↗

Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart.

A growing amount of evidence suggests that regional fat distribution plays an important part in the development of an unfavorable metabolic and cardiovascular risk profile. Epicardial fat is a metabolically active organ that generates various bioactive molecules, which might significantly affect cardiac function. This small, visceral fat depot is now recognized as a rich source of free fatty acids and a number of bioactive molecules, such as adiponectin, resistin and inflammatory cytokines, which could affect the coronary artery response. The observed increases in concentrations of inflammatory factors in patients who have undergone coronary artery bypass grafting remain to be confirmed in healthy individuals. Furthermore, epicardial adipose mass might reflect intra-abdominal visceral fat. Therefore, we propose that echocardiographic assessment of this tissue could serve as a reliable marker of visceral adiposity. Epicardial adipose tissue is also clinically related to left ventricular mass and other features of the metabolic syndrome, such as concentrations of LDL cholesterol, fasting insulin and adiponectin, and arterial blood pressure. Echocardiographic assessment of epicardial fat could be a simple and practical tool for cardiovascular risk stratification in clinical practice and research. In this paper, we briefly review the rapidly emerging evidence pointing to a specific role of epicardial adipose tissue both as a cardiac risk marker and as a potentially active player in the development of cardiac pathology.

Adipose Tissue↗

Prevalence of uncomplicated obesity in an Italian obese population.

OBJECTIVE: The existence of healthy obese subjects has been suggested but not clearly reported. We sought to address the prevalence of uncomplicated obesity and adverse risk factors in a large Italian obese population. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of a population of consecutive Italian obese subjects. We studied 681 obese subjects (514 women and 167 men), with a mean age of 41.1+/-13.9 years (range, 16 to 77 years), mean BMI of 40.2+/-7.6 kg/m2 (range, 30 to 89.8 kg/m2), and a history of obesity for 20.5+/-7 years (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity-related risk factors were evaluated. RESULTS: The prevalence of uncomplicated subjects was 27.5%, independent of BMI and duration of obesity. The youngest group of obese subjects showed a higher, but not statistically significantly higher, prevalence of uncomplicated obesity. No statistical difference for the prevalence of impaired fasting glucose, glucose intolerance, high triglycerides, high total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol among BMI categories (from mild to extremely severe obesity degree) was found. Obese subjects with BMI>50 kg/m2 showed a higher prevalence of high blood pressure only when they were compared with the group with a BMI of 30 to 35 kg/m2 (p<0.01). Obese subjects with BMI>40 kg/m2 showed a higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m2 (p<0.01). DISCUSSION: This study shows that a substantial part of an Italian obese population has uncomplicated obesity, and the prevalence of adverse risk factors in this sample is unexpectedly low and partially independent of obesity degree. Uncomplicated obesity could represent a well-defined clinical entity.

Adolescent↗

Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women.

BACKGROUND: A possible relationship between thyroid hormones and adipose tissue metabolism in humans has been suggested. Aim of the study We sought to evaluate thyroid function and its possible relationship with body mass index (BMI), leptin, adiponectin and insulin sensitivity in euthyroid obese women. MATERIALS AND METHODS: Eighty-seven uncomplicated obese women (mean age 34.7 +/- 9 years, mean BMI 40.1 +/- 7 kg/m(2)) were studied. Levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3), plasma adiponectin and leptin were evaluated. Insulin sensitivity was assessed by euglycaemic hyperinsulinaemic clamp (M index), fasting insulin and HOMA-IR. RESULTS: Uncomplicated obese women with BMI > 40 kg/m(2) showed higher serum TSH than obese subjects with BMI < 40 kg/m(2) (P < 0.01). TSH was correlated with BMI (r = 0.44, P = 0.01) leptin (r = 0.41, P = 0.01), leptin/BMI ratio (r = 0.33, P = 0.03), body surface area (r = 0.26, P = 0.05), HOMA-IR (r = 0.245, P = 0.05) and inversely with adiponectin (r = -0.25, P = 0.05) and M index (r = -0.223 P = 0.05). CONCLUSIONS: Our data show that, although thyroid function was normal in the studied obese population, TSH and BMI were positively related. TSH has been found to be correlated also with leptin adjusted for BMI. TSH could represent a marker of altered energy balance in severe, but uncomplicated obese women.

Adiponectin↗

Prevalence of cancer in Italian obese patients referred for bariatric surgery.

BACKGROUND: An association between obesity and cancer has been shown in large epidemiological studies. The aim of this study was to evaluate the prevalence and types of malignancies in an Italian cohort of obese patients referred to a bariatric center. METHODS: A retrospective, observational study was conducted. Between Jan 1996 and Dec 2004, 1,333 obese patients (M=369, F=964) were seen in the center for minimally invasive treatment of morbid obesity. Morbid obesity were considered as BMI >40 kg/m(2) or BMI >35 kg/m(2) with at least one co-morbidity. Obese and morbidly obese patients who suffered any form of cancer were reviewed. RESULTS: 43 patients (3.2%) presented various malignancies, with 88.3% in females. The prevalence of cancer in the younger group (21-46 years) was higher than in the older group (47-70 years), 2.1% vs 1.1%. 26 obese patients out of the 43 (60.5%) (age 41+/-7.9 years, BMI 38.2+/-9.9) presented hormone-related tumors. The most frequent site of cancer was breast (20.9%), followed closely by thyroid. CONCLUSION: This is the first Italian report on prevalence of cancer in a homogeneous obese population attending an academic bariatric center. The morbidly obese patients appear to have a higher risk of developing cancer, with a higher prevalence of hormone-related tumors. The predominant gender affected by both obesity and cancer was female. Thus, a preoperative work-up for cancer screening is indicated in this group of patients.

Adolescent↗