Efficacy of High-dose Liraglutide 3.0 mg in Patients with Poor Response to Bariatric Surgery: Real-world Experience and Updated Meta-analysis.

PURPOSE: Poor response to bariatric surgery, characterized by insufficient weight loss (IWL) or weight regain (WR), poses a significant challenge in obesity treatment. This study aims to assess the effectiveness of liraglutide in addressing this issue. MATERIALS AND METHODS: A retrospective, multicenter cohort study investigated the impact of liraglutide 3 mg on weight loss in adults with suboptimal responses or weight regain after bariatric surgery (BS). Additionally, a systematic review and meta-analysis were conducted for a comprehensive evaluation. RESULTS: A total of 119 patients (mean age 41.03 ± 11.2 years, 71.4% female) who experienced IWL or WR after BS received pharmacologic therapy with liraglutide 3 mg. Mean percent weight loss in the entire cohort was 5.6 ± 2.6% at 12 weeks and 9.3 ± 3.6% at 24 weeks with a significant reduction in waist circumference (p < 0.0001). No serious side effects were reported. A meta-analysis, utilizing the fixed effect model with the metafor package in R, included 6 and 5 papers for the change in body weight and BMI after liraglutide treatment, respectively. The analysis demonstrated a considerable reduction in body weight (7.9; CI - 10.4; - 5.4, p < 0.0001) and BMI (3.09; CI 3.89; - 2.28, p < 0.0001). CONCLUSION: Liraglutide 3 mg emerges as a viable option for significant weight loss in patients experiencing IWL or WR after BS. Its inclusion in a multimodal, sequential obesity treatment approach proves promising.

Excessive generalized and visceral adiposity is associated with a higher prevalence of diabetic retinopathy in Caucasian patients with type 2 diabetes.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus (T2D) has heterogeneous clinical phenotypes related to different risk of developing diabetes complications. We investigated the correlation between generalized and abdominal adiposity and the prevalence of both micro- and macrovascular complications in Caucasian patients with T2D. METHODS AND RESULTS: We evaluated 769 individuals with T2D consecutively referred to our diabetes center. Body mass index (BMI), waist circumference (WC), waist to hip (W/H) ratio, glycated hemoglobin (HbA1c), systolic and diastolic blood pressure, lipid profile, smoking habit, diabetes therapy, and micro- and macrovascular complications were recorded. Patients were divided into three groups based on BMI and WC: non-obese with normal WC (nWC, n = 220), non-obese with excess of abdominal fat (AF, n = 260) and obese (Ob, n = 289). We found that nWC, compared with AF and Ob individuals, were predominantly males (p<0.01), had lower HbA1c (p<0.01), diastolic blood pressure (p<0.01), triglycerides (p<0.01), and showed a significantly lower prevalence of diabetic retinopathy (DR) (p = 0.01). The rate of proliferative DR was significantly higher in Ob (13.2 %) compared to the other groups (p = 0.03). Multivariate analyses showed a significantly decreased prevalence of DR in nWC compared to both AF (OR 0.58, 95 CI 0.34-0.96; p = 0.03) and Ob (OR 0.57, 95 CI 0.33-0.98; p = 0.04) individuals. Conversely, DR was associated, mainly in women, to higher WC and W/H ratio. The prevalence of the other diabetes-related complications was similar among the studied groups. CONCLUSIONS: In our population, nWC subjects showed a lower prevalence of DR. An increased generalized and abdominal adiposity was associated to a higher prevalence of DR, especially among females.

High-dose liraglutide improves metabolic syndrome in poor responders to bariatric surgery.

Background: Bariatric surgery (BS) represents the most effective therapy for obesity class III, or class II with at least one weight-related comorbidity. However, some patients have insufficient weight loss or clinically relevant weight regain after a successful primary procedure. This study aimed to assess the efficacy of liraglutide treatment on weight loss, body composition and improvement of metabolic syndrome (MS) in patients defined as poor responders after BS. Methods: The study involved 59 non-diabetic adults with obesity (M/F: 17/42, age: 38.6 ± 11.8 years, BMI 38.3 ± 5.5 kg/m2) who had been treated with BS and experienced a poor response, categorized as either IWL (insufficient weight loss) or WR (weight regain). All patients were prescribed pharmacological therapy with liraglutide and attended nutritional counseling. Anthropometric and clinical measurements, body composition and the presence of MS defined according to the ATP-III classification were evaluated before starting liraglutide and after 24 weeks of treatment. Results: After 24 weeks of treatment with liraglutide, the mean weight loss was 8.4% ± 3.6% with no difference between gender, bariatric procedure, or type of poor response (IWL or WR). A significant decrease in fat mass, free-fat mass and total body water was documented. After 24 weeks, patients presented significantly lowered fasting glucose, total cholesterol, triglycerides, AST and ALT. The prevalence of MS was reduced from 35% at baseline to 1.6% after 24 weeks. No patients discontinued the treatment during the study. Conclusion: In patients who experience poor response after BS, liraglutide is well tolerated and promotes significant weight loss, ameliorates cardiometabolic comorbidities, and reduces the prevalence of MS.

New paradigm for the management of cardio-nephro-metabolic syndrome: multidisciplinary approach and role of telemedicine.

Heart failure (HF), type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are some of the most important health problems of this century, and these three conditions often coexist, one worsening the prognosis of the other two. No disease is more important than the others in the composition of risk, which is significantly increased by their overlap. Thus, it would be more appropriate to refer to this cluster as cardio-nephro-metabolic syndrome. The aim of this review is to promote the development of an integrated multidisciplinary approach to the treatment of HF, T2DM and CKD in a perspective of paradigm shift from an individual management among different specialists to a shared one. Nowadays, this is achievable thanks to telemedicine and optimized therapy consisting in the new drugs with pleiotropic effect available today. The need is to have technological solutions, which also include telemedicine, for the management of patients affected by all three diseases to consider their fragility, sometimes due to a wrong, partial, or incomplete treatment. Multicentric, multidisciplinary trials on cardio-nephro-metabolic syndrome and new telemedicine/telemonitoring technologies could help place the chronic and fragile patient at the center of such multidimensionally integrated care.

Identification of the Inappropriate Clinical Actions (DON'T) to Improve the Management of Patients with Type 2 Diabetes Failing Basal Insulin Supported Oral Treatment: Results of Survey for a Panel of Diabetes Specialists in Italy.

INTRODUCTION: Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT). METHODS: A panel of diabetes specialists was assembled to identify a list of ten corrective actions, "things not to do," for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration. RESULTS: A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues-do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient's adherence; (5) do not stop listening to the patient and verify learning. CONCLUSION: A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients' needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care.

Pharmacological treatment of nonresponders following bariatric surgery: a narrative review of the current evidence.

INTRODUCTION: Obesity is a complex chronic disease and requires a long-term multidisciplinary management. Even patients undergoing bariatric surgery, one the most effective treatments for obesity, can have insufficient weight loss (IWL) than expected (primary non responder) or weight regain (WR) after a successful primary procedure (secondary non responder). A poor response represents a challenge of bariatric surgery that can induce persistence or recurrence of obesity-related comorbidities, prejudicing benefits of surgery. Increasing evidence suggests that weight loss medications represent a useful strategy in obesity care also after bariatric surgery procedures. EVIDENCE ACQUISITION: This narrative review summarizes the evidence concerning anti-obesity therapy in the management of no-responders to primary bariatric surgery. Available data on liraglutide (one randomized double-blind placebo-controlled trial, three prospective and three retrospective studies), naltrexone/bupropion (three retrospective studies), orlistat (one case control prospective and one retrospective studies) and topiramate and phentermine (5 retrospective studies) have been considered. EVIDENCE SYNTHESIS: Available data suggest that weight loss medications could offer a significant adjunctive benefit to lifestyle and behavioral modifications in the life-long management of obesity. CONCLUSIONS: Newer treatment modalities including the use of anti-obesity drugs provide patients and healthcare providers with more options in the management of poor response after bariatric surgery.

Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity.

Obesity represents a major risk factor for metabolic disorders, but some individuals, "metabolically healthy" (MHO), show less clinical evidence of these complications, in contrast to "metabolically unhealthy" (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment-insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

The novel loss of function Ile354Val mutation in PPARG causes familial partial lipodystrophy.

AIMS: Familial partial lipodystrophy (FPLD) is a rare autosomal dominant disorder, mostly due to mutations in lamin A (LMNA) or in peroxisome proliferator-activated receptor gamma (PPARG) genes. In the present study, we aimed to identify and functionally characterize the genetic defect underlying FPLD in an Italian family presenting with several affected individuals in three consecutive generations. METHODS: Mutational screening by direct Sanger sequencing has been carried out on both LMNA and PPARG genes. In silico analyses and functional in vitro studies on transfected cell lines have been also performed to evaluate the biological impact of the identified mutation. RESULTS: We identified a novel PPARG missense mutation (i.e., PPARγ2 Ile354Val) segregating with FPLD in the study family. In silico analyses and in vitro experiments showed that probably altering the PPARγ2 ligand binding domain conformation, the Ile354Val aminoacid change leads to a significant reduction (i.e., ~ 30-35%) of transcriptional activity in the mutant receptor, with no evidences of a dominant negative effect on the wild-type receptor. CONCLUSIONS: Our present data extend the spectrum of PPARG mutations responsible for FPLD3 and reinforce the notion that even loss of function mutations affecting transcriptional activity to an extent lower than that observed in the case of haploinsufficiency are able to cause a severe FPLD3 phenotype.

Impact of unhealthy childhood and unfavorable parents' characteristics on adiposity in schoolchildren.

BACKGROUND: Childhood obesity is encouraged by low physical activity (PA), time spent using screens (screen time, ST), and by sugar-sweetened beverage consumption (SSBc). It is also influenced by unfavorable parents' characteristics, such as a high body mass index (BMI) and low education level (EL). Our aim was to evaluate the overall and specific influence of these factors on childhood adiposity. MATERIAL AND METHODS: Anthropometric parameters including BMI z-score, waist circumference (WC), waist to height ratio (WtHR), and fat mass were measured in a cohort of 1702 schoolchildren (6.0-14.5 years, mean 10.7 ± 1.8) and questionnaires concerning children's PA, ST, and SSBc, and parent's BMI and EL were administered to parents. RESULTS: Overweight/obesity prevalence was higher (P < .0001) in males (57%) than in females (43%). Less physically active children (28.9%) had a higher prevalence of overweight/obesity and higher BMI z-score, WC, WtHR, and fat mass relative to more physically active children (P < .05). PA was negatively associated with the BMI z-score (r = 0.18, P < .0001) and fat mass percentage (r = 0.18, P < .0001). Children with more ST had higher WC and WtHR than non-ST viewers (P < .05) but not BMI. Moreover, SSBc did not influence the anthropometric parameters. At multivariate analysis, male gender, less PA, and parental risk factors (parent's overweight/obesity and low/medium EL) were independently associated with overweight and obesity among childhood with a progressively increasing odds ratio (1.65, 1.40, and 1.80, respectively). CONCLUSIONS: Male gender, behavioral risk factors (particularly low PA), and parent's characteristics are important correlates of obesity in children.

Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk.

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.

Strong evidence of sexual dimorphic effect of adiposity excess on insulin sensitivity.

AIMS: Our aims were to investigate in several large samples, with a wide range of adiposity, whether: (1) the effect of BMI on insulin sensitivity is different between sexes; (2) also waist circumference plays a sex-specific role on insulin sensitivity; and (3) serum adiponectin and resistin are mediators of such sex-dimorphic effect. METHODS: Samples used were: Gargano study 1 (GS1), GS2 and Catania study (CS) comprising 3274 individuals. Adiponectin and resistin were measured by ELISA. Associations between variables were tested by linear models. RESULTS: In all samples, relationship between BMI and HOMAIR was steeper in males than in females (BMI-by-sex interaction p = 0.04-0.0007). No interaction was observed on serum adiponectin and resistin (p = 0.40-059), which are therefore unlikely to mediate the sex-dimorphic effect of BMI on insulin resistance. Relationship between waist circumference and HOMAIR was similar between sexes in GS1 and GS2 but not in CS (waist-by-sex interaction p = 0.01), comprising much heavier individuals. This suggests that a sex-dimorphic effect of abdominal adiposity on insulin resistance is observable only in the context of high BMI. CONCLUSIONS: Our findings represent a proof of concept that BMI and insulin sensitivity are associated in a sex-specific manner. This may explain why females are protected from diabetes and cardiovascular disease, compared to males of similar BMI.

Chronic lymphocytic thyroiditis: could it be influenced by a petrochemical complex? Data from a cytological study in South-Eastern Sicily.

INTRODUCTION: In genetically predisposed individuals, exogenous factors (including pollution) influence the development of Hashimoto's thyroiditis/chronic lymphocytic thyroiditis (CLT). CLT may also be a risk factor for associated thyroid cancer. Few data are available on the role of pollution from petrochemical complexes, one of which is located in the Siracusa province (South-Eastern Sicily), in the pathogenesis of CLT. AIMS: i) To study the frequency of CLT in fine-needle aspiration cytology (FNAC)-interrogated thyroid nodules from patients who were stably resident in their zones, comparing it in patients living in the petrochemical complex area (zone A) with that of patients from a control area (zone B). ii) To study the frequency of CLT in the FNAC categories of malignancy risk, comparing the two zones. PATIENTS AND METHODS: We retrospectively evaluated cytologically adequate slides of 1323 nodules in 1013 outpatients who underwent ultrasound-guided FNAC from 2006 to 2012. We stratified by area of residence, gender, and FNAC categories of malignancy risk. RESULTS: CLT was detected with significantly greater frequency in either patients or nodules from zone A compared with zone B (32.0% vs 23.1%, P=0.002 or 28.2% vs 18.8%, P=0.0001), with a female preponderance (F=35.2% vs M=21.1% or 30.4% vs 20.4%, zone A and F=26.5% vs 12.3% or 21.6% vs 9.5%, zone B). Regardless of zone, CLT was approximately twofold more frequent in the suspiciously malignant+malignant classes (TH4+THY5=47.6%, zone A and 32.4%, zone B) compared with the benign+intermediate classes (THY2+THY3=27.3%, zone A and 18.2%, zone B), but with a clear stepwise THY2 through THY5 increase only in zone A (THY2=25.3%, THY5=66.7%; THY2=18.6%, THY5=28.6% in zone B). CONCLUSIONS: The petrochemical complex-related pollution is an environmental factor involved in the development of CLT and, likely, in the CLT association with thyroid neoplasms.

Joint effect of insulin signaling genes on insulin secretion and glucose homeostasis.

CONTEXT: Reduced insulin signaling in insulin secreting ß-cells causes defective insulin secretion and hyperglycemia in mice. OBJECTIVE: We investigated whether functional polymorphisms affecting insulin signaling (ie, ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; and TRIB3 Q84R, rs2295490) exert a joint effect on insulin secretion and abnormal glucose homeostasis (AGH). DESIGN: Insulin secretion was evaluated by 1) the disposition index (DI) from an oral glucose tolerance test (OGTT) in 829 individuals; 2) insulin secretion stimulation index (SI) in islets from nondiabetic donors after glucose (n = 92) or glibenclamide (n = 89) stimulation. AGH (including impaired fasting glucose and/or impaired glucose tolerance or type 2 diabetes; T2D) was evaluated in case-control studies from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) Consortium (n = 6607). RESULTS: Genotype risk score, obtained by totaling individual weighted risk allele effects, was associated with the following: 1) DI (P = .005); 2) glucose and glibenclamide SI (P = .046 and P = .009); or 3) AGH (odds ratio 1.08, 95% confidence interval 1.03-1.13; P = .001). We observed an inverse relationship between genetic effect and age at AGH onset, as indicated by a linear correlation between AGH-genotype risk score odds ratios and age-at-diagnosis cutoffs (R(2) = 0.80, P < .001). CONCLUSIONS: Functional polymorphisms affecting insulin signaling exert a joint effect on both in vivo and in vitro insulin secretion as well as on early-onset AGH. Our data provide further evidence that abnormal insulin signaling reduces ß-cell function and impairs glucose homeostasis.

Very severely obese patients have a high prevalence of type 2 diabetes mellitus and cardiovascular disease.

The prevalence of very severe obesity has increased progressively and faster than other classes of obesity over the last years. It is unclear whether the prevalence of obesity-related complications and health risks increases progressively or reaches a plateau above a certain degree of obesity. The aim of our study was to investigate whether the severity of obesity was correlated with the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose, impaired glucose tolerance (IGT), metabolic syndrome (MS), and cardiovascular diseases (CVDs) in a large cohort of patients with different degrees of obesity. A cross-sectional study was conducted in 938 obese patients without a previous diagnosis of diabetes. Patients were assigned to different categories of obesity: mild-moderate obesity (BMI 30-39.9 kg/m(2)), morbid obesity (BMI 40-49.9 kg/m(2)), and super-obesity (SO, BMI ≥50 kg/m(2)). The prevalence of IGF, IGT, screen-detected T2DM, MS, and CVD was higher in SO patients than in the other groups. Interestingly, the association between SO and either MS or CVD was independent of glucose tolerance status, indicating that factors other than glucose metabolism also favor cardio-metabolic complications in obese patients. In patients without screen-detected T2DM (n = 807), insulin sensitivity and secretion OGTT-derived indexes indicated that SO patients had the worst glucose homeostasis relative to the other categories of obesity, which was indicated by the most reduced disposition index in these patients, a predictor of future T2DM. In conclusion, SO patients have an extremely high prevalence of glucose metabolism deterioration, and cardio-metabolic complications are more prevalent in these patients compared to less obese patients.

Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance.

OBJECTIVE: Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity. DESIGN AND SETTING: 1. We first studied, incident cardiovascular events (a composite endpoint comprising myocardial infarction-MI, stroke and cardiovascular death) in 733 patients (2186 person-years, 175 events). 2. In a replication attempt, age at MI was tested in 331 individuals. 3. OGTT-derived insulin sensitivity index (ISI) was assessed in 829 individuals with fasting glucose <126 mg/dl. 4. NOS activity was measured in 40 strains of human vein endothelial cells (HUVECs). RESULTS: 1. Risk variants jointly predicted cardiovascular events (HR = 1.181; p = 0.0009) and, when added to clinical risk factors, significantly improved survival C-statistics; they also allowed a significantly correct reclassification (by net reclassification index) in the whole sample (135/733 individuals) and, even more, in obese patients (116/204 individuals). 2. Risk variants were jointly associated with age at MI (p = 0.006). 3. A significant association was also observed with ISI (p = 0.02). 4. Finally, risk variants were jointly associated with insulin-stimulated NOS activity in HUVECs (p = 0.009). CONCLUSIONS: Insulin signaling genes variants jointly affect cardiovascular disease, very likely by promoting whole body and endothelium-specific insulin resistance. Further studies are needed to address whether their genotyping help identify very high-risk patients who need specific and/or more aggressive preventive strategies.

Secular trends in the prevalence of overweight and obesity in Sicilian schoolchildren aged 11-13 years during the last decade.

The present study evaluates trends in the prevalence of overweight and obesity in relation to gender and area of residence between two cohorts of students aged 11-13 years in Sicily. The analysis was performed on 1,839 schoolchildren, with 924 and 915 children being studied in 1999-2001 and 2009-2010, respectively. The children who were enrolled during 2009-2010 had significantly higher body mass indexes (BMI), BMI z-scores, and waist circumferences than the children who were studied during 1999-2001 (p<0.0001 for all); these differences was also observed when the cohort was subdivided according to gender or residence area The prevalence of obesity increased significantly from 7.9% in 1999-2001 to 13.7% in 2009-2010 (p<0.0001), whereas thinness decreased significantly from 10.1% to 2.3% (p<0.0001) in the same periods. The increase of trends in the prevalence of obesity was significantly higher in males (9.7% vs. 17.6%, p = 0.0006) than in females (6.3% vs. 9.8%, p = 0.04) and was slightly higher in urban areas (8.8% vs. 14.3%, p = 0.002) than in rural areas (7.8% vs. 13.0%, p = 0.012). The male gender was associated with a higher risk of being overweight or obese (odds ratio: 1.63; 95% confidence intervals: 1.24-2.15; p = 0.0005) in 2009-2010 than in 1999-2001, after adjusting for age and the residence area. In conclusion, this study showed an increasing trend in the prevalence of overweight and obesity in Sicilian schoolchildren during the last decade and that this trend was related to gender, age and the area of residence. More specifically, our data indicated that the prevalence of obesity increased by 5.8%, the prevalence of thinness decreased by 7.8% and the prevalence of normal-weight children did not change over the course of a decade. These results suggest a shift in the body weights of Sicilian children toward the upper percentiles.

Factors that influence basal insulin requirement in type 2 diabetes.

In clinical practice, basal insulin dosage (BID) for the treatment for type 2 diabetes given as slow-acting analogues or NPH insulin varies widely when adjusted for body weight (UI/kg). In this study, we investigated the interrelationship between BID and anthropometric, laboratory and clinical parameters. A total of 681 type 2 diabetic patients, treated with bedtime insulin in association with other antidiabetic drugs (preprandial insulin and/or oral agents), were studied. Anthropometric, clinical and biochemical parameters, as well as micro- and macrovascular complications, were evaluated. Non-alcoholic fatty liver disease (NAFLD) was assessed by liver ultrasound. BID was titrated to achieve a fasting blood glucose target of ≤6.7 mmol/L (120 mg/dL). In the multivariate analysis, BID was significantly associated with waist circumference (p = 0.04) and the insulin treatment duration (p = 0.004) as the type of insulin treatment ("basal-bolus" regimen vs. basal insulin only, p < 0.0001), the use of lipid-lowering drugs (p = 0.0003) and insulin sensitizers (p = 0.005). Several glycometabolic parameters were strongly associated with BID (HbA1c p = 0.01, FPG p < 0.0001, HDL p = 0.02, triglycerides p = 0.03). Moreover, the presence of severe NAFLD resulted in a higher BID (p = 0.03). We concluded that when starting and titrating the basal insulin in type 2 diabetes, certain anthropometric, laboratory and clinical factors can be useful to find optimal BID more quickly and appropriately.

Intragastric balloon in association with lifestyle and/or pharmacotherapy in the long-term management of obesity.

BACKGROUND: Intragastric balloon (BioEnterics Intragastric Balloon, BIB®) or pharmacotherapy are possible options for the treatment of obese patients when traditional approaches have failed. The aim of our study was to compare in obese patients the effect on weight loss and metabolic changes of lifestyle modifications associated with either BIB or pharmacotherapy or the two treatments in sequence as a maintenance strategy for weight loss. METHODS: Fifty obese patients were recruited and randomly assigned to lifestyle modifications combined with either BIB for 6 months (n = 30) or sibutramine (pharmacotherapy group) for 1 year (n = 20). After BIB removal, patients were randomly assigned to either correct lifestyle (BIB/lifestyle) or lifestyle plus pharmacotherapy (BIB/pharmacotherapy). RESULTS: At 6 months, patients treated with BIB lost significantly (P < 0.05) more weight (percent of initial weight lost, %IWL = 14.5 ± 1.2; percent of excess BMI lost, %EBL = 37.7 ± 3.2) than patients who received pharmacological treatment (%IWL = 9.1 ± 1.5, %EBL = 25.3 ± 4.1). At 1 year, the weight lost was significantly (P < 0.05) greater in patients treated with either BIB/pharmacotherapy (%IWL = 15.8 ± 2.3%, %EBL = 41.3 ± 6.7%) or BIB/lifestyle (%IWL = 14.3 ± 2.7, %EBL = 34.9 ± 6.5%) in respect to pharmacotherapy group (%IWL = 8.0 ± 1.4%, %EBL = 22.1 ± 3.9%). Moreover, patients treated sequentially with BIB/lifestyle or BIB/pharmacotherapy showed a significant (P < 0.05) improvement in insulin sensitivity and triglycerides levels. CONCLUSIONS: BIB represents an efficacious long-term obesity treatment when supplemental strategies, as lifestyle modifications or pharmacotherapy, are established for weight maintenance after its removal.

Laparoscopic sleeve gastrectomy for morbid obesity. Our initial experience.

AIM OF THE STUDY: The outcomes and initial results of laparoscopic sleeve gastrectomy (LSG) were evaluated at our Institution. METHODS: A retrospective analysis of the initial 6 patients who underwent laparoscopic sleeve gastrectomy (LSG), between November 2006 and May 2008, was performed. The aim of this study was to assess the safety and short-term efficacy of LSG as a treatment option for weight reduction. Data collected included operative time, postoperative complications, length of hospital stay and degree of weight reduction. RESULTS: Our 6 morbidly obese patients, who underwent LSG had an average preoperative BMI 58.2 kg/m2. There were 2 women and 4 men, with mean age 45 (range 41 to 55 years). Indication for LSG was related to BMI, high perioperative risk, and body habitus for five patients. One patient underwent LSG as an alternative to laparoscopic adjustable gastric banding (LAGB). Mean operative time was 2 hours (range 1.5-2.5). We had no conversion to open procedure. There were neither postoperative complications nor mortality. Median hospital stay was 2 days. For our first 4 patients Average %EWL and BMI were 24% and 44.5 kg/m2 at 6 months and % 31.2 and 41.2 kg/m2 at 1 year respectively. No patients have subsequently undergone a second-stage procedure. CONCLUSIONS: In our initial experience, LSG is a safe and effective treatment option for the high-risk and super super-obese patient. Follow-up will be necessary to evaluate long-term results when performed as single stage operation for morbid obesity.

ENPP1 Q121 variant, increased pulse pressure and reduced insulin signaling, and nitric oxide synthase activity in endothelial cells.

OBJECTIVE: Insulin resistance induces increased pulse pressure (PP), endothelial dysfunction (ED), and reduced bioavailability of endothelium-derived nitric oxide (NO). The genetic background of these 3 cardiovascular risk factors might be partly common. The ENPP1 K121Q polymorphism is associated with insulin resistance and cardiovascular risk. METHODS AND RESULTS: We investigated whether the K121Q polymorphism is associated with increased PP in white Caucasians and with ED in vitro. In 985 individuals, (390 unrelated and 595 from 248 families), the K121Q polymorphism was associated with PP (P=8.0 x 10(-4)). In the families, the Q121 variant accounted for 0.08 of PP heritability (P=9.4 x 10(-4)). This association was formally replicated in a second sample of 475 individuals (P=2.6 x 10(-2)) but not in 2 smaller samples of 289 and 236 individuals (P=0.49 and 0.21, respectively). In the individual patients' data meta-analysis, comprising 1985 individuals, PP was associated with the Q121 variant (P=1.2 x 10(-3)). Human endothelial cells carrying the KQ genotype showed, as compared to KK cells, reduced insulin-mediated insulin receptor autophosphorylation (P=0.03), Ser(473)-Akt phosphorylation (P=0.03), and NO synthase activity (P=0.003). CONCLUSIONS: Our data suggest that the ENPP1 Q121 variant is associated with increased PP in vivo and reduced insulin signaling and ED in vitro, thus indicating a possible pathogenic mechanism for the increased cardiovascular risk observed in ENPP1 Q121 carriers.