Uncoupling protein (UCP)-2 is a member of the mitochondrial inner membrane carriers that uncouple proton entry in the mitochondrial matrix from ATP synthesis. The ؊866G/A polymorphism in the UCP2 gene, which enhances its transcriptional activity, was associated with enhanced risk for type 2 diabetes in obese subjects. We addressed the question of whether the ؊866G/A polymorphism contributes to variation in insulin sensitivity by genotyping 181 nondiabetic offspring of type 2 diabetic patients. Insulin sensitivity, assessed by the hyperinsulinemic-euglycemic clamp, was reduced in ؊866A/A carriers compared with ؊866A/G or ؊866G/G carriers (P ‫؍‬ 0.01). To directly investigate the correlation between UCP2 expression and insulin resistance, UCP2 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from 100 obese subjects who underwent laparoscopic adjustable gastric banding. UCP2 mRNA expression was significantly correlated with insulin resistance as assessed by the homeostasis model assessment index (r ‫؍‬ 0.27, P ‫؍‬ 0.007). We examined the association of the ؊866A/A genotype in a case-control study including 483 type 2 diabetic subjects and 565 control subjects. The ؊866A/A genotype was associated with diabetes in women (odds ratio 1.84, 95% CI 1.03-3.28; P ‫؍‬ 0.037), but not in men. These results indicate that the ؊866A/A genotype of the UCP2 gene may contribute to diabetes susceptibility by affecting insulin sensitivity.

Background and Objectives: Laparoscopy is gaining acceptance as a safe procedure for resection of liver neoplasms. The aim of this study is to evaluate surgical results and mid-term survival of minor hepatic resection performed for HCC. Methods: Data of 16 patients with HCC, undergoing laparoscopic hepatectomy from September 2005 to January 2009, were compared to a control group of 16 patients who underwent open resection (OR) during the same period. The two groups were matched in terms of type of resection, tumor size, and severity of cirrhosis. Results: One patient underwent conversion to an open approach. Laparoscopic approach resulted in shorter operating time (150 min, P:0.044) and lower blood loss (258 ml, P:0.008). There was no difference in perioperative morbidity and mortality rate; laparoscopic approach was associated with a shorter hospital stay (6.3 days, P:0.039). After a mean follow up of 32 months, disease free survival and overall survival were 40.2 and 23.3 months for laparoscopic group, and 47.7 and 31.4 months for OR group (P NS). Conclusion: Laparoscopic resection of HCC is feasible and safe in selected patients and can result in good surgical results, with similar outcomes in terms of overall and disease-free survival.

Context:Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure.Objective: The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart. Design: Left ventricular mass (LVM) was calculated through electrocardiogram reading in normotensive grade III obese patients (World Health Organization classification) undergoing bariatric surgery [laparoscopic adjustable gastric banding (LAGB)] at baseline and 1 yr later. The control group was composed of healthy lean normotensive subjects. Leptin receptors were detected by PCR and immunocytochemistry in human heart biopsies.Setting: This study was performed at university hospitals.Patients: Thirty-one grade 3 obese patients and 30 healthy nonobese normotensive, age-and sex-matched control subjects were studied.Intervention: Obese subjects underwent LAGB to induce weight loss and were evaluated at baseline and after 1 yr.Results: LVM, plasma leptin, glucose, insulin levels, and homeostasis model assessment index were higher in obese than in lean controls (P Ͻ 0.01); at univariate regression analysis, LVM correlated with body mass index, leptin, and homeostasis model assessment index; at multiple regression analysis, LVM only correlated with leptin levels (P ϭ 0.001). Obese subjects were reevaluated 1 yr after LAGB, when their body mass index changed from 46.2 Ϯ 1.24 to 36.6 Ϯ 1.05 kg/m 2 (P Ͻ 0.01); the decrease in LVM correlated only with the decrease in leptin levels (P Ͻ 0.01). We demonstrated that long and short isoforms of the leptin receptor and intracellular proteins mediating leptin signaling were expressed in human heart by RT-PCR, immunocytochemistry, or both methods. Conclusions

OBJECTIVE -Lifestyle modifications and pharmacological interventions can prevent type 2 diabetes in obese subjects with impaired glucose tolerance. The aim of this study was to compare laparoscopic adjustable gastric banding (LAGB) and conventional diet (No-LAGB) in the prevention (primary intervention study; 56 vs. 29 patients) and remission (secondary intervention study; 17 vs. 20 patients) of type 2 diabetes and hypertension in grade 3 obesity in a 4-year study.RESEARCH DESIGN AND METHODS -The subjects (n ϭ 122; age 48.5 Ϯ 1.05 years; BMI 45.7 Ϯ 0.67 kg/m 2 ) underwent a diagnostic workup, including psychological and psychiatric assessments, in preparation for the LAGB procedure. Of the 122 subjects, 73 had the surgery (LAGB group). The control group (No-LAGB group) consisted of the 49 subjects who refused the surgery but agreed to be followed up; 6 of these subjects dropped out by the 2nd year of the study, so that the final number of patients was 73 and 43 in the LAGB and No-LAGB groups, respectively. All patients had a yearly visit and oral glucose tolerance test.RESULTS -From baseline to the end of the 4-year follow-up, BMI decreased from 45.9 Ϯ 0.89 at baseline to 37.7 Ϯ 0.71 kg/m 2 in the LAGB group and remained steady in the No-LAGB group (from 45.2 Ϯ 1.04 to 46.5 Ϯ 1.37 kg/m 2 ), with no significant differences between the primary and secondary intervention groups. In the primary intervention study, five of the No-LAGB subjects (17.2%) and none of the LAGB subjects (0.0%; P ϭ 0.0001) progressed to type 2 diabetes; in the secondary intervention study, type 2 diabetes remitted in one No-LAGB patient (4.0%) and seven LAGB patients (45.0%; P ϭ 0.0052). Hypertension occurred in 11 No-LAGB patients (25.6%) and 1 LAGB patient (1.4%; P ϭ 0.0001) and remitted in 1 No-LAGB (2.3%) and 15 LAGB patients (20.5%; P ϭ 0.0001). A study of body mass composition revealed a significant reduction of fat mass and a transitory, but not significant, decrease of fat-free mass in LAGB patients.CONCLUSIONS -In morbid obesity, sustained and long-lasting weight loss obtained through LAGB prevents the occurrence of type 2 diabetes and hypertension and decreases the prevalence of these disorders. Diabetes Care 28:2703-2709, 2005O besity is a major risk factor for certain diseases, particularly cardiovascular disease. The risk is proportional to BMI and duration of obesity and increases with visceral obesity (1-6). Obesity, especially when associated with impaired glucose tolerance (IGT), is a leading cause of type 2 diabetes (7). Several large studies have demonstrated that it is possible to prevent the progression from IGT to type 2 diabetes by dietary intervention, lifestyle modifications (including physical activity), and drugs (8 -13). In some cases, these therapeutic approaches reduce cardiovascular morbidity and mortality in type 2 diabetes (14,15). Obesity and type 2 diabetes are often complicated by arterial hypertension, a link that is allegedly mediated by increased sympathetic tone (16); left ventricular hypertrophy is f...

Studies on thyroid function in obesity yielded inconsistent results; high thyroid‐stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)‐3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high‐density lipoprotein–cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high‐density lipoprotein–cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities.