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Background: Physical activity (PA)/exercise have become an integral part of the management of type 2 diabetes mellitus (T2DM). However, current guidelines are difficult to put into action in this population due to a number of barriers, especially the lack of acceptable, feasible, and validated behavioral intervention strategies. The present manuscript reports the rationale, study design and methods, and design considerations of the Italian Diabetes and Exercise Study (IDES)-2, a randomized controlled trial testing the efficacy of a behavior change strategy in increasing total daily PA and reducing sedentary time (SED-time) in patients with T2DM., Methods/design: Starting 7 January 2014, the IDES_2 began enrolling 300 patients with known T2DM of at least 1-year duration in three tertiary referral outpatient Diabetes Clinics in Rome. Additional requirements are age 40 to 80 years, body mass index 27 to 40 kg/m(2), sedentary lifestyle, and physically inactive for at least 6 months, ability to walk 1.6 km without assistance, and eligibility after cardiovascular evaluation. Patients are randomized by center and within each center, by age and type of diabetes treatment to either the intervention or the control group. Patients in the intervention (INT) group (n = 150) receive theoretical and practical exercise counseling consisting of aggregated behavior change techniques (one individual theoretical counseling session plus eight twice-a-week individual theoretical and practical exercise counseling sessions) once a year for 3 years. Patients in the control (CON) group (n = 150), receive standard care, including general physician recommendations for daily PA. The primary outcomes are total daily PA and SED-time, as measured objectively by the use of an accelerometer. Secondary outcomes include physical fitness, modifiable cardiovascular risk factors, musculoskeletal disturbances, well-being/depression, and health-related quality of life., Discussion: The behavioral intervention strategy tested in the IDES_2 is based on solid theoretical grounds and uses several behavioral change techniques, two factors which were found to improve effectiveness of behavioral intervention. In addition, physicians and exercise specialists have been specifically trained for counselling/prescribing and supervising PA/exercise, respectively, in subjects suffering from metabolic disorders. Finally, the large sample size, the long study duration, and the objective measurement of PA allow statistically significant and scientifically robust conclusions to be drawn on the feasibility and efficacy of this intervention in T2DM patients., Trial Registration: ClinicalTrials.gov; NCT01600937 ; 10 October 2012.

Background: Very few studies have reported results of the BioEnterics Intragastric Balloon (BIB) at > or =12 months follow-up. The aim of this study is the retrospective evaluation of the results of BIB placement compared to diet regimen alone., Methods: From January 2005 to June 2006, 130 outpatients underwent a structured diet plan with simple behavioral modification at our institutions. Controls (n = 130) were selected from the charts of patients who, during the same period, underwent BIB treatment. Patients in the outpatient group were given a structured balanced diet with a caloric intake between 1,000 and 1,200. The approximate macronutrient distribution, according the "Mediterranean diet," was 25% protein (at least 60 g/day), 20-25% lipids, and 50-55% carbohydrates. In the BIB group, patients received generic counseling for eating behavior. In both groups, we considered weight loss parameters (kilograms, percentage of excess weight loss [%EWL], body mass index [BMI], percentage of excess BMI loss [%EBL]) at 6 and 24 months from baseline and comorbidities at baseline and after 24 months. Results are expressed as mean+/-standard deviation. Statistical analysis was done by Student's t-test and chi (2)-test or Fisher's exact test. p < .05 was considered significant., Results: At the time of BIB removal (6 months), significantly better results in terms of weight loss in kilograms (16.7 +/- 4.7 vs. 6.6 +/- 2.6; p < 0.01), BMI (35.4 +/- 11.2 vs. 38.9 +/- 12.1; p < 0.01), %EBL (38.5 +/- 16.1 Vs 18.6 +/- 14.3; p < 0.01), and %EWL (33.9 +/- 18 vs. 24.3 +/- 17.0; p < 0.01) were observed in patients treated by intragastric balloon as compared to diet-treated patients. At 24 months from baseline, patient dropout was 1/130 (0.7%) and 25/130 (19.2%) in the BIB and diet groups, respectively (p < 0.001). At this time, patients treated with intragastric balloon have tended to regain weight, whereas diet-treated patients have already regained most of lost weight., Conclusions: Although the strength of this study may be limited by its retrospective design, the results indicate that, in the short-to-medium term, BIB is significantly superior to diet in terms of weight loss.

Background: Although obesity is an important cardiovascular risk factor, growing evidence shows that a substantial portion of obese subjects can be considered metabolically healthy but obese (MHO). However the extent to which obese subjects manifest small, dense low-density lipoprotein (LDL) particles without other characteristics of the metabolic syndrome (MS) remains unknown., Objective: The purpose of this study was to determine the difference between MHO (only meeting the obesity criteria) and obese subjects meeting all the criteria for the MS with regard to LDL size and high-sensitivity C-reactive protein (hs-CRP), as a biomarker of inflammation., Methods: Two hundred obese subjects (168 women, mean age 36.5 ± 5 years [range, 20-60]; mean body mass index [BMI; calculated as kg/m(2)] 39 ± 5 [range, 30-80.4]) were studied for LDL particles size and hs-CRP levels., Results: Of 200 enrolled obese subjects, 55 were defined MHO subjects meeting only obesity criteria. The other 145 met all five criteria and were defined as having MS. Although MHO and MS subjects had similar BMI, MHO subjects had a lower percentage of small LDL particles (8% vs 29%, P < 0.001), higher average LDL diameter (274 ± 5 vs 270 ± 7 Å, P < 0.001), and lower hs-CRP levels (P < 0.05) than MS patients., Conclusion: The major finding of this study is that MHO subjects compared to equally obese subjects meeting the criteria of the MS have statistically significant differences in size of LDL and concentration of hs-CRP. However, the absolute differences are very small and of uncertain clinical significance.

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.

Obesity is associated with increased cardiovascular morbidity and amortality. Endothelial dysfunction, involved in the pathogenesis of cardiovascular events, has been demonstrated in obese patients with invasive techniques requiring artery catheterization. The aim of our investigation was to evaluate, with a non-invasive method readily employable on clinical grounds, impaired vasodilatation and its relationship with insulin resistance in uncomplicated obesity. 15 uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI = 22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion pletysmography after increasing times of ischemia, and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/- 0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P < 0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs. 14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High correlation was found between M index and FBFr at all ischemia times. HOMA-IR and ISI were not related with FBFr. The non-invasive evaluation of endothelial dysfunction by a simple and reliable method based on venous occlusive plethysmography shows high correlation between impaired endothelium-dependent vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive test of endothelial function may be routinely performed in the assessment of cardiovascular risk 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.

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.

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.

Objective: Adrenomedullin (AM) is a potent hypotensive peptide which may be implicated in the insulin regulatory system. Acute hyperinsulinemia exerts no influence on plasma AM in normal subjects while no data on obese subjects has been reported., Purpose: The aim of the study was to investigate the effect of acute hyperinsulinemia on the plasma AM concentration in patients with uncomplicated obesity., Research Methods: We measured the plasma AM levels in 23 obese subjects (BMI 41.9 +/- 9.8 kg/m2), 21 females and 2 males (mean age 31 +/- 7.2 years), before and during a euglycemic hyperinsulinemic clamp. The control group consisted of 43 healthy subjects (HS) (22 males and 21 females; mean age 38 +/- 12 years; BMI 23.3 +/- 3.2 kg/m2)., Results: Baseline plasma AM was found to be higher in obese subjects (20.4 +/- 8.4 pg/ml) than in normal subjects (11.3 +/- 0.8 pg/ml) (p < 0.001). A significant increase in the plasma AM levels was observed in obese subjects during acute hyperinsulinemia (from 20.4 +/- 8.4 pg/ml at 0 min to 26 +/- 8.9 pg/ml at 120 min, p < 0.02). Plasma AM concentrations were significantly correlated with insulin levels at 30 min (r = 0.44; p = 0.04) and 120 min (r = 0.40, p = 0.05) during the clamp., Discussion: In conclusion, acute hyperinsulinemia induced a significant increase in the plasma levels of AM in uncomplicated obese subjects. Hyperinsulinemia may, at least in part, regulate levels of AM in obesity, explaining the high levels of the peptide in these subjects.

Background and Aim: Obesity is associated with a great variability to insulin sensitivity degree. Several formulae developed from measurements in the fasting state and during the oral glucose tolerance test (OGTT) have been proposed to assess insulin sensitivity., Aim: In this work we sought to compare the published insulin sensitivity indices with the metabolized glucose index obtained by hyperinsulinemic euglycemic clamp in uncomplicated obese subjects. Uncomplicated obesity provides a good model in order to study insulin sensitivity per se., Methods and Results: In this protocol, 65 obese women affected by uncomplicated obesity (without impaired glucose tolerance, diabetes, hypertension and dyslipidemia) underwent 2 h OGTT and euglycemic hyperinsulinemic clamp. Common formulae obtained in the fasting state and from a 2h OGTT were calculated. Simple linear regression analysis showed that ISI (r=0.592, p=0.01), 2 h OGIS (r=0.576, p=0.02), MCRest (r=0.507, p=0.02), 120 insulin (r=-0.494, p=0.03) and fasting insulin (r=-0.382, p =0.02) are significantly correlated to the M index obtained from the hyperinsulinemic euglycemic clamp. The Bland-Altman plot confirmed the good agreement between indices from OGTT and the clamp., Conclusion: OGTT-derived indices provide a good assessment of insulin sensitivity in obesity. OGTT could easily be applied in a large number of obese patients in order to obtain information on both glucose tolerance and insulin sensitivity.

Several genetic variants of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) have been identified, among which Pro12Ala, a missense mutation in exon 2, is highly prevalent in Caucasian populations. Up to now, conflicting results with regard to the association between this mutation and complex traits, such as obesity, insulin sensitivity and Type 2 diabetes, have been reported. We investigated the influence of the Pro12Ala polymorphism of PPAR-gamma2 on insulin sensitivity in a large Italian population sample, n=1215, in whom extensive clinical and biochemical analyses were performed. To estimate the insulin sensitivity status, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated; in the obese/overweight subjects an oral glucose tolerance test (OGTT) was also performed and the Matsuda insulin sensitivity index (ISI) calculated. The insulin secretion index (homeostasis model assessment of percent beta-cell function, HOMA-beta%) was utilized to evaluate beta-cell function. The effect of the Pro12Ala polymorphism on quantitative variables was tested using multiple linear regression analysis. X12Ala (either Pro12Ala or Ala12Ala) genotype was associated with significantly lower fasting insulin levels compared to Pro/Pro (P=0.01 after correction for multiple comparisons) in all subjects. Consistent with this finding, significantly lower HOMA-IR was observed in X12Ala carriers (P=0.013 after correction for multiple comparisons) in all cohort. Moreover, no significant interaction effect was observed between body mass index and X12Ala polymorphism and between gender and X12Ala polymorphism in modulating insulin sensitivity. Our observations substantially extend previous findings and demonstrated that X12Ala variant is significantly associated with greater insulin sensitivity.

Background: Plasma ghrelin levels have been shown to decrease after insulin infusion in lean subjects. Nevertheless, the mechanism of the suggested inhibitory effect of insulin on ghrelin is still unclear and no data about the effect of acute insulin infusion on plasma ghrelin concentration in obese subjects are available., Objective: We sight to evaluate plasma ghrelin concentration during an hyperinsulinemic euglycemic clamp in uncomplicated obese subjects., Methods: 35 uncomplicated obese subjects, body mass index (BMI) 43.3+/-10.1 kg/m(2), 33 women and 2 men, mean age 34.9+/-10, with a history of excess fat of at least 10 years underwent euglycemic hyperinsulinemic clamp. Blood samples for ghrelin were performed at baseline and steady state of euglycemic insulin clamp., Results: Ghrelin concentrations decreased over time to 10.6+/-15% (range 2-39%) of baseline, from a mean of 205.53+/-93.79 pg/ml to 179.03+/-70.43 pg/ml during the clamp (95% CI, 10.69 to 36.44, P<0.01). In a univariate linear regression analysis baseline plasma ghrelin levels were inversely correlated to BMI (r=-0.564, P=0.04). A linear positive trend between whole body glucose utilization (M(FFMkg) index) and ghrelin reduction during the clamp was found (chi(2) 3.05, p=0.05)., Conclusions: Our data seem to suggest that hyperinsulinemia during a euglycemic clamp is able to suppress plasma ghrelin concentrations in uncomplicated obesity. This effect appears to be positively related to insulin sensitivity.

Visceral adiposity is a cardiovascular risk factor of growing interest. This study sought to evaluate the hypothesis of a relation between epicardial adipose tissue, the visceral adipose tissue deposited around the heart, and left ventricular morphology in healthy subjects with a wide range of adiposity. We found for the first time that an increase in epicardial fat is significantly related to an increase in left ventricular mass.

Objective: A massive amount of fat tissue, as that observed in obese subjects with BMI over 50 kg/m(2), could affect cardiac morphology and performance, but few data on this issue are available. We sought to evaluate cardiac structure and function in uncomplicated severely obese subjects., Research Methods and Procedures: We studied 55 uncomplicated severely obese patients, 40 women, 15 men, mean age 35.5 +/- 10.2 years, BMI 51.2 +/- 8.8 kg/m(2), range 43 to 81 kg/m(2), with a history of fat excess of at least 10 years, and 55 age-matched normal-weight subjects (40 women, 15 men, mean BMI 23.8 +/- 1.2 kg/m(2)) as a control group. Each subject underwent an echocardiogram to evaluate left ventricular (LV) mass and geometry and systolic and diastolic function., Results: Severely obese subjects showed greater LV mass and indexed LV mass than normal-weight subjects (p < 0.01 for all parameters). Nevertheless, LV mass was appropriate for sex, height(2.7), and stroke work in most (77%) uncomplicated severely obese subjects. In addition, no significant difference in LV mass indices and LV mass appropriateness between obese subjects with BMI > or = 50 kg/m(2) and those with BMI < or = 50 kg/m(2) was found. Obese subjects also showed higher ejection fraction and midwall shortening than normal-weight subjects (p = 0.05 and p < 0.01, respectively), suggesting a hyperdynamic systolic function. No significant difference in systolic performance between obese subjects with BMI > or = 50 kg/m(2) and those with BMI < or = 50 kg/m(2) was seen., Discussion: Our data show that uncomplicated severe obesity, despite the massive fat tissue amount, is associated largely with adapted and appropriate changes in cardiac structure and function.

Several association studies have indicated the insulin receptor substrate-1 (IRS-1) gene G972R variant as a genetic risk factor for insulin resistance, particularly in presence of obesity. A few studies have also suggested a possible effect of the G972R variant on insulin secretion. The aim of this study was to evaluate the role of the IRS-1 gene G972R variant in 61 subjects with "uncomplicated" obesity [i.e. without diabetes, hypertension, dyslipidemia, coronary artery disease (CAD)], studied by hyperinsulinemic-euglycemic clamp. The presence of the G972R variant, detected in real-time with LightCycler hybridisation probes, was related to the indexes of insulin sensitivity. Furthermore, the possible role of this variant on insulin secretion was studied by means of insulin release indexes derived from oral tolerance test (OGTT). Twenty-four point five percent (24.5%) (no.=15) of the obese subjects proved to be carriers of the G972R variant. M index (p<0.05), non-oxidative glucose (p<0.01), insulin clearance (p<0.03) and insulin sensitivity index (ISI) (p<0.005) were all significantly reduced in G972R carriers compared to non-carriers, indicating a significant reduction in insulin sensitivity in carriers of the variant. A logistic regression analysis confirmed the independent association between the G972R variant and reduced insulin sensitivity (p<0.03). The interaction between obesity and the G972R variant was also independently associated with a reduced insulin sensitivity (p<0.005), suggesting that obesity and G972R variant were more than additive in predicting insulin resistance. The analysis of insulin release indexes did not show any significant differences. Our results demonstrate the association of the G972R variant of the IRS-1 gene with reduced insulin sensitivity in obese subjects, and indicate a possible interaction between the IRS-1 variant and obesity in worsening of insulin sensitivity.

Metabolic syndrome is related to multiple cardiovascular risk factors. Visceral adipose tissue (VAT) plays a key role in metabolic syndrome. Easy detection of VAT could be an important tool to increase knowledge of metabolic syndrome. The objective of this study was to study the relationship of echocardiographic epicardial adipose tissue to anthropometric and clinical parameters of metabolic syndrome. We selected 72 consecutive subjects, 46.5 +/- 17.4 yr of age, with a body mass index between 22 and 47 kg/m(2). Each subject underwent transthoracic echocardiogram to measure epicardial fat thickness on right ventricle and magnetic resonance imaging to calculate visceral adipose tissue. Anthropometric, metabolic, and cardiac parameters were also evaluated. Echocardiographic epicardial adipose tissue showed a very good correlation with magnetic resonance imaging abdominal VAT and epicardial fat measurement (Bland-Altman plot and linear regression). Multiple regression analysis showed that waist circumference (r(2) = 0.428; P = 0.01), diastolic blood pressure (r(2) = 0. 387; P = 0.02), and fasting insulin (r(2) = 0.387; P = 0.03) were the strongest independent variables correlated with epicardial adipose tissue. Echocardiographic epicardial adipose tissue could be applied as an easy and reliable imaging indicator of VAT and cardiovascular risk.

Objective: Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism., Design: Prospective study., Patients: We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2)., Measurements: All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy., Results: Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005)., Conclusion: In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.

Gastric bypass has been reported to be associated with markedly suppressed plasma ghrelin levels, suggesting that it is one of the possible weight-reducing factors related to this procedure. The aim of this study was the evaluation of plasma ghrelin levels in patients who had undergone laparoscopic Roux-en-Y gastric bypass (LRYGBP) and laparoscopic adjustable silicone gastric banding (LASGB). Normoweight, obese subjects and patients who had undergone total gastrectomy were used as controls. In this cross-sectional study, we selected 10 subjects who underwent LASGB, 11 subjects with LRYGBP, 10 obese subjects, eight patients with total gastrectomy, and eight normoweight subjects. Plasma ghrelin, insulin, and glucose profiles were determined before and after breakfast and lunch. Obese subjects showed a ghrelin plasma level significantly lower than normoweight subjects (407.3 +/- 21.6 vs. 813 +/- 72.4 pg/ml, P < 0.01). Patients with LRYGBP showed baseline ghrelin levels lower than LASGB (213.5 +/- 73.9 vs. 314.2 +/- 84.3 pg/ml, P = 0.04). Both groups of patients who underwent bariatric surgical procedures also had ghrelin lower than normoweight and obese subjects (P < 0.01 and P < 0.05, respectively). Patients with total gastrectomy showed plasmatic ghrelin levels extremely lower than those in all other groups (32.6 +/- 18.7 pg/ml, P < 0.001 for all). The ghrelin profile in both groups of subjects who underwent LRYGBP and LASGB did not show any meal-related changes as observed in obese and normoweight control groups. Significant difference in plasma ghrelin levels between LRYGBP and LASGB was found, suggesting that both procedures could induce weight loss by different mechanisms in which ghrelin could be involved.

Objective: We studied uncomplicated obesity as a model to evaluate the influence of insulin sensitivity per se on left ventricular mass (LVM) and geometry., Research Methods and Procedures: We selected 50 obese subjects (BMI > 30 kg/m(2); 38 women and 12 men; mean age, 38.4 +/- 10 years; BMI, 36.4 +/- 10.5 kg/m(2)) with normal blood pressure, glucose tolerance, and plasmatic lipid levels. Thirty lean subjects formed the control group. Each subject underwent euglycemic insulin clamp (7 pmol/min per kg) to evaluate whole body glucose use (M index) and echocardiogram to calculate LVM and indexed LVM., Results: Insulin-resistant obese subjects had higher LVM, LVM/h(2.7), LVM/body surface area, and LVM/fat-free mass(kg) (p = 0.001; p = <0.001 p = 0.001, and p = 0.04, respectively) than obese subjects with normal insulin sensitivity. Multivariate regression analysis showed that M index was the strongest independent correlate of LVM (r(2) = 0.34; p = 0.03)., Discussion: Our findings showed that insulin resistance, in uncomplicated obesity, is associated with an increased LVM and precocious changes of left ventricular geometry, whereas preserved insulin sensitivity is not associated with increased LVM.

Objective: To validate transthoracic echocardiography as an easy and reliable imaging method for visceral adipose tissue (VAT) prediction. VAT is recognized as an important indicator of high cardiovascular and metabolic risk. Several methods are applied to estimate VAT, with different results., Research Methods and Procedures: We selected 60 healthy subjects (29 women, 31 men, 49.5 +/- 16.2 years) with a wide range of body mass indexes. Each subject underwent transthoracic echocardiogram and magnetic resonance imaging (MRI) to measure epicardial fat thickness on the right ventricle. Measurements of epicardial adipose tissue thickness were obtained from the same echocardiographic and MRI views and points. MRI was also used to measure VAT cross-sectional areas at the level of L4 to L5. Anthropometric indexes were also measured., Results: Subjects with predominant visceral fat accumulation showed higher epicardial adipose tissue thickness than subjects with predominant peripheral fat distribution: 9.97 +/- 2.88 vs. 4.34 +/- 1.98 (p = 0.005) and 7.19 +/- 2.74 vs. 3.43 +/- 1.64 (p = 0.004) in men and women, respectively. Simple linear regression analysis showed an excellent correlation between epicardial adipose tissue and waist circumference (r = 0.895, p = 0.01) and MRI abdominal VAT (r = 0.864, p = 0.01). Multiple regression analysis showed that epicardial adipose tissue thickness (r(2) = 0.442, p = 0.02) was the strongest independent variable correlated to MRI VAT. Bland test confirmed the good agreement between the two methods., Discussion: Epicardial adipose tissue showed a strong correlation with anthropometric and imaging measurements of VAT. Hence, transthoracic echocardiography could be an easy and reliable imaging method for VAT prediction.

Objective: To evaluate whether or not "uncomplicated" obesity (without associated comorbidities) is really associated with cardiac abnormalities., Research Methods and Procedures: We evaluated cardiac parameters in obese subjects with long-term obesity, normal glucose tolerance, normal blood pressure, and regular plasma lipids. We selected 75 obese patients [body mass index (BMI) >30 kg/m(2)], who included 58 women and 17 men (mean age, 33.7 +/- 11.9 years; BMI, 37.8 +/- 5.5 kg/m(2)) with a > or =10-year history of excess fat, and 60 age-matched normal-weight controls, who included 47 women and 13 men (mean age, 32.7 +/- 10.4 years; BMI, 23.1 +/- 1.4 kg/m(2)). Each subject underwent an oral glucose tolerance test to exclude impaired glucose tolerance or diabetes mellitus, bioelectrical impedance analysis to calculate fat mass and fat-free mass, and echocardiography., Results: Obese patients presented diastolic function impairment, hyperkinetic systole, and greater aortic root and left atrium compared with normal subjects. No statistically significant differences between obese subjects and normal subjects were found in indexed left ventricular mass (LVM/body surface area, LVM/height(2.7), and LVM/fat-free mass(kg)), and no changes in left ventricular geometry were observed. No statistically significant differences in cardiac parameters between extreme (BMI > 40 kg/m(2)) and mild obesity (BMI < 35 kg/m(2)) were observed., Discussion: In conclusion, our data showed that obesity, in the absence of glucose intolerance, hypertension, and dyslipidemia, seems to be associated only with an impairment of diastolic function and hyperkinetic systole, and not with left ventricular hypertrophy.

Cirrhosis is often associated with insulin resistance and glucose intolerance. We evaluated if these alterations are restored by liver transplantation (LT). Glucose tolerance (oral glucose tolerance test [OGTT]), peripheral insulin sensitivity (euglycemic insulin clamp technique), glucose oxidation (indirect calorimetry), nonoxidative glucose disposal, and insulin secretion (hyperglycemic clamp technique) were measured in 6 patients (Group 1) before and 6 months after LT, in 12 patients (Group 2) who underwent LT 6 to 30 months previously, and in 6 healthy individuals (controls). In Group 1, glucose tolerance and insulin sensitivity (3.24 +/- 0.37 mg/kg/min) were normalized after LT (8.6 +/- 0.77 mg/kg/min; P <.0001; P = not significant vs. controls). The improved insulin-mediated glucose uptake was the result of a normalization of nonoxidative glucose disposal. Fasting insulin and C-peptide decreased from 24.6 +/- 3.3 microU/mL and 4.37 +/- 0.46 ng/dL, respectively, to 12.7 +/- 1.9 microU/mL and 2.46 +/- 0.5 ng/dL (controls: 10.0 +/- 3 microU/mL and 1.45 +/- 0.34 ng/dL). The glucose-induced increase of insulin concentration, which was higher before LT, showed a significant reduction, although the first phase of beta-cell secretion remained significantly higher compared with that of controls. All these findings were also confirmed in Group 2. The present data indicate that LT normalizes glucose tolerance and insulin sensitivity in cirrhotic patients through an improvement of both hepatic glucose clearance and the peripheral glucose disposal. The latter effect may be the result of the correction of chronic hyperinsulinemia. An increased first-phase beta-cell insulin secretion in response to high glucose levels persists, suggesting that a memory of previous insulin resistance is maintained.