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Background and aim Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage. Methods and results We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m2) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC0-30] x insulin [AUC0-30]) during OGTT, insulin response as (insulin [dAUC0-120]/glucose [dAUC0-120] or Insulinogenic Index (IGI = (I30–I0)/(G30-G0)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p Conclusions In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.

A number of meta-analyses have demonstrated the effectiveness of bariatric surgery in improving morbid obesity and its associated co-morbidities. The aim of the study was to evaluate at long term a cohort of obese patients with type 2 diabetes (T2DM) submitted to laparoscopic sleeve gastrectomy (LSG) analyzing the incidence of weight regain (WR) and the impact of the WR on T2DM evolution. Seventy-eight morbid obese patients (54 females) with T2DM, aged 49.6 ± 8.7 years, weight 121.1 ± 24.4 kg, BMI 44.1 ± 7.2 kg/m2, underwent primary LSG. The trend over time of T2DM after LSG was analyzed in the different groups, subdivided on the basis of the absence or presence of WR and of its different degrees: no regain (NR), mild regain (MR), and severe regain (SR) groups. In the NR group, 54% show complete remission, 46% persistence, and no case of diabetes relapse; in the MR group, 59% show complete remission, 36% persistence, and 5% relapse; in the SR group, 61% show complete remission, 22% persistence, and 17% relapse. A statistically significant difference concerns the preoperative values of fasting glucose, glycosylated hemoglobin, and duration of diabetes, major in the group with diabetes relapse (respectively, p = 0.002, p = 0.001, and p

In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population. Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS). In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02). In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the long-term follow-up. One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively. LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-up.

Background. Laparoscopic gastric sleeve (LGS) has been recently introduced as a stand-alone, restrictive bariatric surgery. Theoretically, LGS attenuates micronutrients deficiencies and associated complications that were typically observed following malabsorptive procedures. The aim of this study was to assess some micronutrients and mineral deficiencies in patients undergoing LGS. Methods. In the period between July 2008 and April 2010, 138 obese patients (110 females and 28 males) with mean BMI 44.4 kg/m2 ± 6.5, mean age 4 3 . 9 ± 1 0 . 9 years were enrolled and underwent LGS. Patients were followed up with routine laboratory tests and anthropometric measurements and assessed for nutritional status, as regards vitamin B12, folic acid, iron, hemoglobin, calcium, and vitamin D, every three months throughout 12 months. Results. 12 months after sleeve, patients did not show iron deficiency and/or anemia; plasma calcium levels were in the normal range without supplementation from the sixth month after the operation. Vitamin B12 and folic acid were adequately supplemented for all the follow-up period. Vitamin D was in suboptimal levels, despite daily multivitamin supplementation. Conclusion. In this study, we showed that LGS is an effective surgery for the management of morbid obesity. An adequate supplementation is important to avoid micronutrients deficiencies and greater weight loss does not require higher dosage of multivitamins.

Le ipoglicemie funzionali possono costituire un primo passo verso la malattia diabetica oppure essere una conseguenza di un intervento chirurgico sul tratto gastrointestinale superiore. Nell’ambito di quest’ultima categoria, accanto agli interventi di gastrectomia che in passato venivano fatti, spesso in urgenza, per la presenza di una patologia ulcerosa, si sta delineando una forma di ipoglicemia associata ad alcuni interventi di chirurgia bariatrica, effettuati per favorire la perdita di peso in pazienti obesi. Al di la di queste condizioni rimangono le forme cosiddette “reattive idiopatiche” che costituiscono un’alterazione del ricambio glucidico controversa. Alcuni studiosi, infatti, arrivano addirittura a negarne l’esistenza, quando e noto che nella comune pratica clinica spesso i pazienti ci riferiscono una sintomatologia suggestiva per la presenza di ipoglicemia in particolare a meta mattina, piu o meno a distanza di 3–4 ore dalla prima colazione. Tuttavia, l’ipoglicemia e spesso un’autodiagnosi, intendendo con questo che spesso il paziente si reca dal medico accusando una mancanza di zuccheri e di sentirsi immediatamente meglio assumendo qualcosa di dolce. Addirittura si possono trovare articoli sulle riviste non mediche che confortano le persone e aiutano a fortificare la convinzione di andare spesso in ipoglicemia. Va da se che il rimedio a questa autodiagnosi e normalmente molto ben accetto dalle persone che si sentono “costrette” ad assumere quando stanno male bibite zuccherate se non proprio caramelle, cioccolatini e altri dolci. Questo atteggiamento contrasta totalmente con le prescrizioni del medico che, laddove ravvisi veramente la presenza di una sindrome ipoglicemica funzionale, dovra prescrivere proprio l’abolizione di carboidrati raffinati nella dieta e in questo articolo cercheremo di capirne il perche.

Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants.We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits.Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits.Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Fifty patients (body mass index 53.5 ± 8.4 kg/m2) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4–7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (

Objective To compare the effect of sleeve gastrectomy vs medical therapy on type 2 diabetes mellitus and other obesity-related comorbidities (obstructive sleep apnea syndrome, hypertension, and dyslipidemia) in prospectively enrolled and matched obese patients with type 2 diabetes. Design A prospective cohort study. Morbidly obese patients with type 2 diabetes who either underwent sleeve gastrectomy or conventional therapy were followed up and assessed for their diabetic state and other comorbidities every 3 months for 18 months. Setting Centre for the Surgical-Medical Treatment of Morbid Obesity, Policlinico “Umberto I,” University of Rome “Sapienza,” Italy. Patients A total of 30 morbidly obese patients with type 2 diabetes who underwent sleeve gastrectomy (group A) and a total of 30 morbidly obese patients with type 2 diabetes who underwent conventional therapy (group B). Results In group A, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A 1c level were 41.3 (6.0), 166.6 (68.1) mg/dL, and 7.9% (2.1%), respectively, and, at 18 months, these values were 28.3 (5.4), 96.2 (29.4) mg/dL, and 6.0% (1.5%), respectively. For 80% of patients, diabetes was resolved. With regard to other comorbidities, the prevalence of obstructive sleep apnea syndrome dropped from 50% to 10%, and patients reduced significantly their use of medication for hypertension and dyslipidemia. In group B, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A 1c level were 39.0 (5.5), 183.7 (63.5) mg/dL, and 8.1% (1.7%), respectively, and, at 18 months, these values were 39.8 (5.0), 150 (48) mg/dL, and 7.1% (1.3%), respectively. All patients remained diabetic and continued or increased their level of hypoglycemic therapy. With regard to other comorbidities, we observed an increase in the use of medication for hypertension and dyslipidemia, and the prevalence of obstructive sleep apnea syndrome did not change. Conclusions This study confirms the efficacy of sleeve gastrectomy in the treatment of morbidly obese type 2 diabetic patients when compared with conventional medical treatment.

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available onFTOin the Italian population. Aims of our study are to investigate: (1) the association ofFTOgene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n=752) of Italian obese subjects; (2) the association between the twoFTOSNPs and age of onset of obesity. Our results demonstrate a strong association betweenFTOSNPs rs9939609 (P<0.043) and rs9930506 (P<0.029) with BMI in the Italian population.FTOrs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2per G allele). We also observed that the association with BMI of the twoFTOvariants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability inFTOon BMI in a large Italian population.

Background Type 2 diabetes mellitus (T2DM) and obesity are diseases of epidemic proportions. Long-term realistic weight loss by nonsurgical methods has a variable effect on glycemic control, and only a proportion of patients with T2DM have a worthwhile response. Laparoscopic sleeve gastrectomy (LSG) has been proposed as an advantageous bariatric procedure for patients with a lower body mass index (BMI). Our objective was to compare the effects of LSG and medical therapy on patients with T2DM and a BMI of 2 . Methods A total of 18 nonmorbidly obese patients with T2DM, diagnosed according to the American Diabetes Association guidelines, were consecutively enrolled. Of these patients, 9 underwent LSG (group A) and 9 underwent conventional medical therapy (group B). The 2 groups were matched for BMI, glycated hemoglobin (HbA1c) and C-peptide levels, pretrial therapy type, and number of patients with a T2DM duration of >10 years. Results In group A, T2DM resolution was achieved in 8 (88.8%) of the 9 patients (T2DM duration 5.2 yr). Hypertension was controlled in all 8 of 9 patients. Dyslipidemia was corrected. In 1 patient, obstructive sleep apnea syndrome improved. In group B, all 9 patients continued to have T2DM and required hypertensive and hypolipemic therapies throughout the observation period. At baseline, 3 patients were affected by obstructive sleep apnea syndrome and remained affected 1 year later. Conclusion The results of the present study have confirmed the efficacy of LSG in the treatment of nonmorbidly obese T2DM patients, with a remission rate of 88.8% without undesirable excessive weight loss. The results in this group of patients add to those obtained by us in patients with a BMI >35 kg/m 2 .

Background Apolipoprotein C3 (APOC3) is a component of triglyceride-rich lipoproteins, and APOC3 rs2854116 and rs2854117 polymorphisms have been associated with non-alcoholic fatty liver disease, hypertriglyceridaemia, and insulin-resistance. Objective To determine if the APOC3 variants alter the susceptibility of obese subjects to develop liver damage, hypertrigliceridaemia, and insulin-resistance. Methods The study was carried out on 585 unrelated obese Italians (median body mass index BMI = 41 kg/m2) who were genotyped for the rs2854116 and rs2854117 variants. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose, insulin, lipid parameters. Indices of insulin-resistance (HOMA and ISI) were calculated. Alanine transaminase (ALT) and aspartate transaminase (AST) were used as markers of liver injury. Results The study subjects were divided into two groups: those homozygous for the wild-type alleles at both SNPs (-482C and -455T alleles) and those who were carriers of at least one variant allele or both (-482T, -455C or both). Also each SNP was analysed independently. No significant differences were found in ALT and AST levels and in the lipid profile between the two groups. Insulin concentrations, glucose tolerance and insulin sensitivity were similar in the two groups. Conclusion We did not identify any significant association between APOC3 polymorphisms and fatty liver disease, lipids, and insulin-resistance in obese subjects, thus not confirming the suggested role of these APOC3 gene sequence variants.

occur at a higher frequency in ileal segments of refed guinea pigs (p=0.028). Ca2+-imaging in longitudinal muscle myenteric plexus preparations (N=3-4) revealed elevated responses to orexigenic ghrelin in fasted animals (p=0.013), but the percentage of responders to anorexigenic CCK-8 was higher in refed animals (p