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Introduction: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S), like other hypoabsorptive procedures, could be burdened by long-term nutritional deficiencies such as malnutrition, anemia, hypocalcemia, and hyperparathyroidism. Objectives: We aimed to report our experience in terms of mid-term (2 years) bariatric, nutritional, and metabolic results in patients who underwent SADI-S both as a primary or revisional procedure. Methods: One hundred twenty-one patients were scheduled for SADI-S as a primary or revisional procedure from July 2016 to February 2020 and completed at least 2 years of follow-up. Demographic features, bariatric, nutritional, and metabolic results were analyzed during a stepped follow-up at 3 months, 6 months, 1 year and 2 years. Results: Sixty-six patients (47 female and 19 male) were included. The median preoperative BMI was 53 (48–58) kg/m2. Comorbidities were reported in 48 (72.7%) patients. At 2 years, patients had a median BMI of 27 (27–31) kg/m2 (p < 0.001) with a median %EWL of 85.3% (72.1–96.1), a TWL of 75 (49–100) kg, and a %TWL of 50.9% (40.7–56.9). The complete remission rate was 87.5% for type 2 diabetes mellitus, 83.3% for obstructive sleep apnea syndrome and 64.5% for hypertension. The main nutritional deficiencies post SADI-S were vitamin D (31.82%) and folic acid deficiencies (9.09%). Conclusion: SADI-S could be considered as an efficient and safe procedure with regard to nutritional status, at least in mid-term (2 years) results. It represents a promising bariatric procedure because of the excellent metabolic and bariatric outcomes with acceptable nutritional deficiency rates. Nevertheless, larger studies with longer follow-ups are necessary to draw definitive conclusions.

BACKGROUND/OBJECTIVES: Several scoring systems have been specifically developed for risk stratification in COVID-19 patients. DESIGN: We compared, in a cohort of confirmed COVID-19 older patients, three specifically developed scores with a previously established early warning score. Main endpoint was all causes in-hospital death. SETTING: This is a single-center, retrospective observational study, conducted in the Emergency Department (ED) of an urban teaching hospital, referral center for COVID-19. PARTICIPANTS: We reviewed the clinical records of the confirmed COVID-19 patients aged 60 years or more consecutively admitted to our ED over a 6-week period (March 1st to April 15th, 2020). A total of 210 patients, aged between 60 and 98 years were included in the study cohort. MEASUREMENTS: International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol-Coronavirus Clinical Characterization Consortium (ISARIC-4C) score, COVID-GRAM Critical Illness Risk Score (COVID-GRAM), quick COVID-19 Severity Index (qCSI), National Early Warning Score (NEWS). RESULTS: Median age was 74 (67-82) and 133 (63.3%) were males. Globally, 42 patients (20.0%) deceased. All the score evaluated showed a fairly good predictive value with respect to in-hospital death. The ISARIC-4C score had the highest area under ROC curve (AUROC) 0.799 (0.738-0.851), followed by the COVID-GRAM 0.785 (0.723-0.838), NEWS 0.764 (0.700-0.819), and qCSI 0.749 (0.685-0.806). However, these differences were not statistical significant. CONCLUSION: Among the evaluated scores, the ISARIC-4C and the COVID-GRAM, calculated at ED admission, had the best performance, although the qCSI had similar efficacy by evaluating only three items. However, the NEWS, already widely validated in clinical practice, had a similar performance and could be appropriate for older patients with COVID-19.

Aims: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. Materials and Methods: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5–10.0% (58–86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). Results: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. Conclusions: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

To investigate the prevalence of biopsy-proven non-alcoholic steatohepatitis (NASH) in a cohort of patients with morbid obesity and with or without type 2 diabetes (T2D) and to find non-invasive predictors of NASH severity.We evaluated a cohort of 412 subjects (age 19-67 years, body mass index-BMI: 44.98 kg/mThe prevalence of biopsy-proven NASH was 63% and 78% in subjects with obesity and without or with T2D, respectively. T2D doubled the risk of NASH [OR 2.079 (95% IC=1.31-3.29)]. The prevalence of NAFL increased with the increase of BMI, while there was an inverse correlation between BMI and NASH (r=-0.145 p=0.003). Only mild liver fibrosis was observed. HOMA-IR was positively associated with hepatocyte ballooning (r=0.208, p0.0001) and fibrosis (r=0.159, p=0.008). The NNA highlighted a specificity of 77.3% using HDL-cholesterol, BMI, and HOMA-IR as main determinants of NASH.Our data show a higher prevalence of NASH in patients with morbid obesity than reported in the literature and the pivotal role of T2D among the risk factors for NASH development. However, the inverse correlation observed between BMI and biopsy-proven NASH suggests that over a certain threshold adiposity can be somewhat protective against liver damage. Our model predicts NASH presence with high specificity, thus helping identifying subjects who should promptly undergo liver biopsy.

Background: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. Methods: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. Results: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p, SCOPUS: ar.j, info:eu-repo/semantics/published

Background and aims The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P

Background: No data from randomised controlled trials of metabolic surgery for diabetes are available beyond 5 years of follow-up. We aimed to assess 10-year follow-up after surgery compared with medical therapy for the treatment of type 2 diabetes. Methods: We did a 10-year follow-up study of an open-label, single-centre (tertiary hospital in Rome, Italy), randomised controlled trial, in which patients with type 2 diabetes (baseline duration >5 years; glycated haemoglobin [HbA] >7·0%, and body-mass index >=35 kg/m) were randomly assigned (1:1:1) to medical therapy, Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD) by a computerised system. The primary endpoint of the study was diabetes remission at 2 years (HbA

Background/Objectives As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs sleeve gastrectomy (SG) on BMI after 1 year. Subjects/Methods In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813 kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12 kcal/kg body weight of high protein and high fat for 11 months plus 30 min of brisk walking daily and at least 3 h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. Results A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P < 0.001 vs medical arm), while ILM + liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P < 0.001). More women allocated themselves to the ILM + liraglutide group. Weight loss was 43 kg with SG, 26 kg with ILM + liraglutide and 15 kg with ILM alone. Lean body mass reductions were − 11.6 kg with SG, − 6.3 kg with ILM and − 8.3 kg with ILM + liraglutide. Prevalence of prediabetes was significantly lower with ILM + liraglutide, and insulin resistance was reduced by about 70% by both ILM + liraglutide and SG vs 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. Discussion At least in the short-term, liraglutide 3.0 mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomized, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

No data have been reported regarding the risk of hyperinsulinemic response and reactive hypoglycemia after single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S). Furthermore, comparative studies with other bariatric procedures are lacking.To compare response to oral glucose tolerance test (OGTT) in patients who underwent SADI-S, Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and biliopancreatic diversion (BPD).Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome.Consenting, nondiabetic patients matched for age, sex, and preoperative body mass index, who underwent SADI-S, RYGB, SG, and BPD, were recruited. A 75 g OGTT was performed pre and postoperatively. Plasma insulin and glucose (pGlu-mg/dL) were measured at baseline, and at +30, +60, +90, +120, +150, and +180 minutes. Severe hypoglycemia was defined as pGlu concentration55 mg/dL.Thirty-five patients were recruited: 9 SADI-S, 11 RYGB, 7 SG, and 8 BPD. Comparing preoperative and postoperative responses to OGTT, all procedures improved the glycemic control with better early results after SADI-S and BPD compared with RYGB and SG. No patients showed severe hypoglycemia. Significantly more patients who underwent RYGB and SG showed asymptomatic pGlu70 mg/dL during OGTT compared with SADI-S and BPD (63.6% and 57.1% vs 22.2% and 12.5%, respectively, P.05).Similar to BPD, SADI-S seems to be associated to insulin sensitivity and glucose homeostasis improvement, together with a reduced risk of hyperinsulinemia and, consequently, to hypoglycemia, often associated with RYGB and SG.

Summary Background Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients. Methods We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30–60 years with a body-mass index of 35 kg/m 2 or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux-en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A 1c (HbA 1c ) concentration of 6·5% or less (≤47·5 mmol/mol) and a fasting glucose concentration of 5·6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836. Findings Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0·0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA 1c concentration of 6·5% or less (≤47·5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0·0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion. Interpretation Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia. Funding Catholic University of Rome.

Both inflammation and immunity are involved in the development and progression of atherosclerosis. Obesity is considered a major modifiable cardiovascular risk factor, however, the correlation between increasing degrees of obesity and cardiovascular risk is not clear yet. Aim of our study was to investigate how different degrees of obesity are associated with inflammation and immune system responses.One-hundred healthy individuals were divided into 3 groups according to body mass index (BMI): 22 overweight (OW), 26 obese (O) and 52 morbidly obese (MO). High-sensitivity C-Reactive Protein (hs-CRP, immunonephelometry), leptin (radio-immunoassay) and CD4+CD28nullT-lymphocytes (flow-cytometry), a particular subset of T-lymphocytes with pro-atherogenic and plaque-destabilizing properties, were assessed.hs-CRP levels were significantly higher in O vs OW (p=0.036), in MO vs OW (p0.001) and in MO vs O (p=0.012). Similarly, leptin levels were higher in O vs OW (p=0.02), in MO vs OW (p0.001) and in MO vs O (p0.001). CD4+CD28nullT-lymphocytes were higher in O vs OW (p0.001), in O vs MO (p=0.03) and in MO vs OW (p=0.01). hs-CRP and leptin levels significantly correlated each other (r=0.39; p0.001) and with waist circumference (r=0.52; p0.001; r=0.64; p0.001) and BMI (r=0.60; p0.001; r=0.74; p0.001).Our study demonstrates that, notwithstanding higher levels of inflammation, MO are characterized by less detrimental immune activation, as shown by the reduced CD4+CD28nullT-cells expansion as compared to OW and O, which might translate in less immune vascular injury. These findings suggest that MO might represent a particular population, in which different pathophysiological mechanisms take part if compared with "classic" obesity.

Bilio-pancreatic diversion (BPD) induces permanent weight loss in previously severe obese patients through a malabsorptive mechanism. The aim of the study was to evaluate the modifications of circulating thyroid hormones after BPD, a surgical procedure which interferes with the entero-hepatic circulation of biliary metabolites. Forty-five patients were studied before and 2 years after BPD. Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid antibodies, iodine urinary excretion, lipid profile, insulin and glucose plasma levels were assessed. The insulin-resistance HOMA IR index was calculated, and colour Doppler ultrasonography of the neck was performed. The subjects (23%) had subclinical hypothyroidism prior to BPD (TSH levels above the normal range with normal fT3 and fT4 levels). After 2 years 40.42% of the population showed subclinical hypothyroidism, while 6.3% became frankly hypothyroid, all of them with no evidence of auto-immune thyroiditis. Most of the patients, who became sub-clinically hypothyroid only following BPD, had already thyroid alterations at the sonogram (multi-nodular euthyroid goiter and thyroidal cysts) prior to surgery. BPD increases the prevalence of subclinical or even frank hypothyroidism, without causing a defect in thyroid function itself, through several integrated mechanisms. (1) It induces iodine malabsorption, which is partially compensated by iodine excretion contraction. (2) The entero-hepatic open circulation determines fT3 loss, which induces subclinical or frank hypothyroidism in patients with pre-existing thyroid alterations, interfering also with the weight loss progress. Iodine supplementation should be recommended in those patients reporting thyroid alterations at the sonogram prior to BPD, LT4 therapy should be strictly monitored in patients suffering of subclinical hypopthiroidism and T3 therapy should eventually be considered for patients diagnosed with frank hypothyroidism prior to BPD.

OBJECTIVE—The purpose of this study was to elucidate the mechanisms of diabetes reversibility after malabsorptive bariatric surgery. RESEARCH DESIGN AND METHODS—Peripheral insulin sensitivity and β-cell function after either intravenous (IVGTT) or oral glucose tolerance (OGTT) tests and minimal model analysis were assessed in nine obese, type 2 diabetic subjects before and 1 month after biliopancreatic diversion and compared with those in six normal-weight control subjects. Insulin-dependent whole-body glucose disposal was measured by the euglycemic clamp, and glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were also measured. RESULTS—The first phase of insulin secretion after the IVGTT was fully normalized after the operation. The disposition index from OGTT data was increased about 10-fold and became similar to the values found in control subjects, and the disposition index from IVGTT data increased about 3.5-fold, similarly to what happened after the euglycemic clamp. The area under the curve (AUC) for GIP decreased about four times (from 3,000 ± 816 to 577 ± 155 pmol · l−1 · min, P < 0.05). On the contrary, the AUC for GLP1 almost tripled (from 150.4 ± 24.4 to 424.4 ± 64.3 pmol · l−1 · min, P < 0.001). No significant correlation was found between GIP or GLP1 percent changes and modification of the sensitivity indexes independently of the route of glucose administration. CONCLUSIONS—Restoration of the first-phase insulin secretion and normalization of insulin sensitivity in type 2 diabetic subjects after malabsorptive bariatric surgery seem to be related to the reduction of the effect of some intestinal factor(s) resulting from intestinal bypass.

Objective: To assess whether insulin sensitivity can explain the associations of leg-fat mass (LFM) and trunk-fat mass (TFM) with the cardiovascular disease (CVD) risk profile in healthy European men and women. Methods and Procedures: We studied 142 healthy men and women of a multicenter European study on insulin sensitivity, aged 30–60 years, from the centres in Hoorn, the Netherlands and Rome, Italy. Whole-body dual-energy X-ray absorptiometry (DXA) was used to determine fat and lean soft tissue mass in the trunk and legs. Fasting glucose, insulin, and lipid levels were measured. Insulin sensitivity (M/I-ratio) was measured during a euglycemic-hyperinsulinemic clamp. Associations between fat distribution and CVD risk factors were studied with linear regression analyses with adjustment for other body compartments, and subsequent adjustment for insulin sensitivity. Results: In men, larger LFM was significantly and independently associated with lower triglyceride levels (TGs) and higher high-density lipoprotein (HDL) cholesterol (P < 0.10) and tended to be associated also with lower low-density lipoprotein (LDL) cholesterol, and lower fasting insulin levels. In women, larger LFM was associated with favorable values of all CVD risk factors, although the associations were not statistically significant. In both sexes, larger TFM was independently and significantly associated with unfavorable values of most CVD risk factors, and most associations did not markedly change after adjustment for insulin sensitivity. Discussion: In a relatively young and healthy European population, larger LFM is associated with a lower and TFM with a higher cardiovascular and metabolic risk, which can not be explained by insulin sensitivity.

OBJECTIVE—The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring. RESEARCH DESIGN AND METHODS—Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and β-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry. RESULTS—No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 ± 79.32 vs. 513.81 ± 70.70 ml−1 · min−1 · m−2 in women, P < 0.0001; 416.42 ± 76.17 vs. 484.242 ± 45.76 ml−1 · min−1 · m−2 in men, P < 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 ± 21.20 vs. 35.71 ± 10.02 nmol · m−2, P < 0.01) but did not differ significantly in women. β-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and β-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring. CONCLUSIONS—Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring.

A large body of literature indicates the rapidity with which Roux-en-Y gastric bypass (RYGB) improves glycemic control. However, the underlying physiologic mechanisms are still a matter of debate.Catholic University, School of Medicine, Rome, Italy.Ten morbidly obese patients, before and 4 weeks after RYGB, and 10 healthy controls were studied. We measured insulin sensitivity as the homeostasis model assessment-estimated insulin resistance (HOMA-IR) and by the euglycemic hyperinsulinemic clamp, and phosphorylation of protein kinase B (Akt) on Ser473 and Thr308 and of GSK3 α-β on Ser 9 and Ser21 in skeletal muscle biopsy specimens by Western blot analysis.Obese patients before RYGB displayed reduced insulin sensitivity (M value) and clearance and increased fasting Akt phosphorylation on Ser473 compared with controls. M significantly increased after surgery (from 2.6 ± 0.6 to 2.8 ± 0.7 mg/kg fat free mass/min, P = .026) but remained far below the values in controls (10.0 ± 3.8 mg/kg fat free mass/min, P.001). Insulin clearance increased from 453.5 ± 117.5 to 555.2 ± 61.6 (P = .00076), becoming similar to that of controls 582.2 ± 59.0 mU/m(2)/min. HOMA-IR decreased from 4.1 ± 0.07 to 2.3 ± 0.5 (P = .004), becoming comparable with controls (2.2 ± 0.9). The hyperphosphorylation of Akt on Ser473 observed at fasting before RYGB was significantly reduced thereafter, becoming similar to that of healthy controls; the other phosphorylation states remained unchanged.Following RYGB, we found a prompt improvement of hepatic insulin resistance with normalization of hepatic insulin clearance and a small amelioration of whole-body insulin sensitivity. The supranormal levels of Akt Ser473 observed at fast in the skeletal muscle tissue at baseline were normalized after RYGB, and their changes correlated with those of both hepatic and peripheral insulin resistance. Although other mechanisms of action, such as the effect of weight loss and reduced food intake, cannot be excluded, the reduction of muscle Akt hyperphosphorylation on the serine residue can play a role in the early improvement of insulin sensitivity.

Objective: The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone-releasing hormone (GHRH)/arginine test in severe obesity before and after surgically-induced weight loss. Research Methods and Procedures: Our study population included 11 severely obese women 39 ± 12 years of age, with a mean BMI of 48.6 ± 2.4 kg/m2, re-studied in a phase of stabilized body weight, with a BMI of 33.4 ± 1.2 kg/m2, 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test. Results: Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 ± 0.05 ng/mL to 1 ± 0.3 ng/mL (p < 0.05) and from 514.76 ± 98.7 ng/mL for 120 minutes to 1957.3 ± 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 ± 77.9 before BPD vs. 574.1 ± 32.7 after BPD), ghrelin AUC significantly increased from −3253.9 ± 2180.9 pg/mL for 120 minutes to 1142.3 ± 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin-like growth factor (IGF)-1 concentration did not change significantly (133.6 ± 9.9 ng/mL before vs. 153.3 ± 25.2 ng/mL after BPD). Discussion: Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.

Udgivelsesdato: 2007-Aug CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308 nondiabetic subjects [718 women and 590 men, age 30-60 yr, body mass index (BMI) 17-44 kg.m(-2)]. MAIN OUTCOME MEASURES: We measured IR (by a standardized euglycemic insulin clamp), waist girth, insulin response to an oral glucose tolerance test, and major CVRF, and analyzed their associations by multivariate models and factor analysis. RESULTS: BMI was positively related to all CVRFs. Waist circumference was related to higher blood pressure and serum triglycerides and lower high-density lipoprotein-cholesterol, IR to reduced glucose tolerance, higher free fatty acids, triglyceride and low-density lipoprotein-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P < or = 0.05 for all). By factor analysis, three main factors (related to IR, age, and fatness, respectively) appeared to underlie this pattern of associations. Each of BMI, waist girth, IR, and insulin response was independently associated with total CVRF load (all P < 0.001). CONCLUSIONS: When IR, fat mass and distribution, and insulin response are measured simultaneously in a large cohort, no one factor stands out as the sole driving force of the CVRF cluster, each being associated with one or more physiological pathways according to known cause-effect relationships

Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 ± 4.3 to 65.73 ± 3.22 μmol · kg fat-free mass−1 · min−1 at 1 week and to 64.73 ± 3.42 μmol · kg fat-free mass−1 · min−1 at 4 weeks; P < 0.0001) was fully normalized. Fasting insulin secretion rate (148.16 ± 20.07 to 70.0.2 ± 8.14 and 83.24 ± 8.28 pmol/min per m2; P < 0.01) and total insulin output (43.76 ± 4.07 to 25.48 ± 1.69 and 30.50 ± 4.71 nmol/m2; P < 0.05) dramatically decreased, while a significant improvement in β-cell glucose sensitivity was observed. Both fasting and glucose-stimulated gastrointestinal polypeptide (13.40 ± 1.99 to 6.58 ± 1.72 pmol/l at 1 week and 5.83 ± 0.80 pmol/l at 4 weeks) significantly (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased (1.75 ± 0.16 to 3.42 ± 0.41 pmol/l at 1 week and 3.62 ± 0.21 pmol/l at 4 weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by normalizing peripheral insulin sensitivity and enhancing β-cell sensitivity to glucose, these changes occurring very early after the operation. This operation may affect the enteroinsular axis function by diverting nutrients away from the proximal gastrointestinal tract and by delivering incompletely digested nutrients to the ileum.

Purpose: To assess the effects of bariatric surgery (BS) on cardiac mass, volumes and function as compared to persistent morbid obesity. Although beneficial effects of weight loss on cardiac function have been reported, systematic studies on the effect of BS as compared to persistent morbid obesity are lacking. Methods: One-hundred morbidly obese patients (body mass index -BMI- 47.7±7 kg/m2) referred for BS prospectively underwent an echocardiogram: 65 underwent BS and 35 did not. Fifty-one operated and 29 non-operated patients underwent repeat imaging after 2 years. Results: Operated patients showed a significant decrease in weight and BMI paralleled by a significant reduction of left ventricular (LV) mass (from 222.9±52.2 to 207.7±50g) and LV end-diastolic and end-systolic volumes (LVEDV from 124.6±29.3 to 119.4±28.7 and LVESV from 55.3±16.5 to 49.4±15ml) and by a significant increase of LV ejection fraction (from 55.9±4.8 to 59.2±4.4%). In contrast, in non-operated patients LV mass (from 226.5±71.4 to 241.4±94.7g), volumes [LVEDV from 52.8±5.1 to 54.2±6.6 and LVESV from 32.1±3.5 to 34.9±6ml] significantly increased and ejection fraction deteriorated (from 57.1±5.1 to 54.7±7.4%). At multivariate analysis, BS was the only significant predictor of change in LV end-systolic volume while weight change predicted change in LV mass. Conclusions: In extreme obesity the sustained weight loss achieved with BS is associated to an improvement of cardiac structure and function, while persistent severe obesity is associated to progressive deterioration. These favorable cardiac effects associated to previously described positive metabolic effects make BS an attractive therapeutic option in this setting of patients.

The rising prevalence of obesity is a major global health problem. In severe obesity, bariatric surgery (BS) allows to obtain a significant weight loss and comorbidities improvement, among them one of the factors is the thrombotic risk. In this observational study, we measured indices of leukocyte activation in severely obese patients as markers of increased thrombotic risk in relation with serum markers of inflammation before and after BS. Frequency of polymorphonuclear neutrophil-platelet (PLT) and monocyte (MONO)-PLT aggregates as well as of tissue factor (TF) expressing MONOs was measured in the peripheral blood of 58 consecutive obese patients and 30 healthy controls. In 31 of the 58 obese patients, data obtained at the enrollment were compared with those obtained at 3, 6, and 12 months after BS. Compared with healthy controls, obese patients showed a higher frequency of polymorphonuclear leukocyte (PMNL)-PLT aggregates (7.47 ± 2.45 [6.82–8.11]% vs 5.85 ± 1.89 [5.14–6.55]%, P = 0.001), MONO-PLT aggregates (12.31 ± 7.33 [10.38–14.24]% vs 8.14 ± 2.22 [7.31–8.97]%, P

Background Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management. Methods Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m2) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic–hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed. Results Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level. Conclusion Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevanceInsulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat.Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated.This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.

To assess the effect of Roux-en-Y gastric bypass (RYGB) on high-density lipoprotein cholesterol (HDL-C) concentration and its apolipoprotein A4 (ApoA4) content at 1 year after bariatric surgery in comparison with a hypocaloric diet. Secondary aim was to measure total cholesterol and triglycerides levels and insulin sensitivity after interventions.Very few prospective uncontrolled studies have investigated the effects of RYGB on cardiovascular risk factors. No controlled studies had as primary goal the changes in HDL-C after gastric bypass.Forty subjects with a body mass index more than 40 or 35 kg/m or more in the presence of diabetes were enrolled. Twenty of them underwent RYGB, whereas 20 received lifestyle modification suggestions and medical therapy for obesity complications (diabetes, hypertension, and hyperlipidemia).A significant (P0.0001) increase in HDL-C concentrations was observed only in the surgical arm (from 41.95 ± 7.24 to 56.55 ± 9.01 mg/dL). Mean systolic and diastolic blood pressures were significantly reduced (P0.0001) in both groups with no between-group differences, probably in relation to the optimization of the antihypertensive treatment. Plasma concentration of ApoA4, a major HDL-C protein fraction, significantly increased 1 year after RYGB (from 496.61 ± 400.41 to 987.88 ± 637.41μg/L, P0.01). Circulating triglycerides concentration significantly decreased after surgery, whereas both peripheral and hepatic insulin resistance increased significantly.Our study shows that HDL-C and ApoA4 significantly increase after gastric bypass and that this increase is associated with a net improvement in hepatic insulin sensitivity. Furthermore, we speculate that ApoA4, which induces satiety in animals, can eventually play a role on the appetite reduction after RYGB because there is a strict and inverse relationship between weight and ApoA4 changes. (NCT01707771).

Transoral gastroplasty (TOGA) is a safe and less invasive procedure than traditional bariatric surgery. We studied the effects of TOGA on the risk of progression from prediabetes to overt type 2 diabetes mellitus (T2DM) or on regression from diabetes or prediabetes to a lower risk category.Prospective, observational study (October 2008 to October 2010) performed at Catholic University, Rome, Italy. Fifty consecutive subjects 18-60 years old, 35 ≥ body mass index55 kg/m², were enrolled. Glucose tolerance, insulin sensitivity, and secretion were studied at baseline and 1 week and 1, 6, and 12 months after TOGA. Plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and ghrelin levels were measured.Forty-three patients (86%) completed the 1-year postoperative follow-up. Patients lost 16.90% of baseline weight (P level × factor time0.001). Body mass index decreased from 42.24 ± 3.43 to 34.65 ± 4.58 kg/m² (P.001). Twenty-three patients (53.5%) were diagnosed as normal glucose tolerance (NGT) before treatment, 2 (4.6%) were impaired fasting glucose (IFG), 12 (27.9%) were impaired glucose tolerance (IGT), 1 (2.3%) had both IFG and IGT, and 5 (11.6%) had T2DM. At 1-year posttreatment, the percentages changed to 86.0% NGT, 2.3% IFG, 11.6% IGT, 0% IFG plus IGT, and 0% T2DM, respectively. Peripheral insulin resistance and homeostasis model of assessment-insulin resistance improved significantly. Fasting glucose-dependent insulinotropic peptide and ghrelin decreased from 316.9 ± 143.1 to 156.2 ± 68.2 pg/mL (P.001) and from 630.6 ± 52.1 to 456.7 ± 73.1 pg/mL (P.001), respectively, whereas GLP-1 increased from 16.2 ± 4.9 to 23.7 ± 9.5 pg/mL (P.001).TOGA induced glucose disposal improvement with regression of diabetes to NGT or IGT and regression of IGT and IFG to NGT in half of the cases. Regressors showed a much larger increase of GLP-1 levels than progressors.

The mechanisms of type 2 diabetes remission after bariatric surgery is still not fully elucidated. In the present study, we tried to simulate the Roux-en-Y gastric bypass with a canonical or longer biliary limb by infusing a liquid formula diet into different intestinal sections. Nutrients (Nutrison Energy) were infused into mid- or proximal jejunum and duodenum during three successive days in 10 diabetic and 10 normal glucose-tolerant subjects. Plasma glucose, insulin, C-peptide, glucagon, incretins, and nonesterified fatty acids (NEFA) were measured before and up to 360 min following. Glucose rate of appearance (Ra) and insulin sensitivity (SI), secretion rate (ISR), and clearance were assessed by mathematical models. SI increased when nutrients were delivered in mid-jejunum vs. duodenum (SI × 104 min−1·pM−1: 1.11 ± 0.44 vs. 0.62 ± 0.22, P < 0.015, in controls and 0.79 ± 0.34 vs. 0.40 ± 0.20, P < 0.05, in diabetic subjects), whereas glucose Ra was not affected. In controls, Sensitivity of NEFA production was doubled in mid-jejunum vs. duodenum (2.80 ± 1.36 vs. 1.13 ± 0.78 × 106, P < 0.005) and insulin clearance increased in mid-jejunum vs. duodenum (2.05 ± 1.05 vs. 1.09 ± 0.38 l/min, P < 0.03). Bypass of duodenum and proximal jejunum by nutrients enhances insulin sensitivity, inhibits lipolysis, and increases insulin clearance. These results may further our knowledge of the effects of bariatric surgery on both insulin resistance and diabetes.

OBJECTIVE To elucidate the mechanisms of improvement/reversal of type 2 diabetes after Roux-en-Y gastric bypass (RYGB). METHODS Fourteen morbidly obese subjects, 7 with normal glucose tolerance and 7 with type 2 diabetes, were studied before and 1 month after RYGB by euglycemic hyperinsulinemic clamp (EHC), by intravenous glucose tolerance test (IVGTT) and by oral glucose tolerance test (OGTT) in 3 different sessions. Intravenous glucose tolerance test IVGTT and OGTT insulin secretion rate (ISR) and sensitivity were obtained by the minimal model. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured. Six healthy volunteers were used as controls. RESULTS Total ISR largely increased in diabetic subjects only when glucose was administered orally (37.8 ± 14.9 vs 68.3 ± 22.8 nmol; P < 0.05, preoperatively vs postoperatively). The first-phase insulin secretion was restored in type 2 diabetic after the IVGTT (Φ1 × 10: 104 ± 54 vs 228 ± 88; P < 0.05, preoperatively vs postoperatively; 242 ± 99 in controls). Insulin sensitivity by EHC (M × 10) was slightly but significantly improved in both normotolerant and diabetic subjects (1.46 ± 0.22 vs 1.37 ± 0.55 mmol·min·kg; P < 0.05 and 1.53 ± 0.23 vs 1.28 ± 0.62 mmol·min·kg; P < 0.05, respectively). Quantitative insulin sensitivity check index was improved in all normotolerant (0.32 ± 0.02 vs 0.30 ± 0.02; P < 0.05) and diabetic subjects (0.33 ± 0.03 vs 0.31 ± 0.02; P < 0.05). GIP and GLP-1 levels increased both at fast and after OGTT mainly in type 2 diabetic subjects. CONCLUSIONS The large increase of ISR response to the OGTT together with the restoration of the first-phase insulin secretion in diabetic subjects might explain the reversal of type 2 diabetes after RYGB. The large incretin secretion after the oral glucose load might contribute to the increased ISR.

This was a cross-sectional and longitudinal study of factors contributing to the number of cardiometabolic risk factors, common carotid artery intima-media thickness (CCA-IMT) and R-R interval in clinically healthy subjects without diabetes.Anthropometric and cardiometabolic parameters were measured in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study cohort at baseline (n=1211) and 3years later (n=974). At baseline, insulin sensitivity was assessed by the euglycaemic clamp technique. The CCA-IMT was echographically measured and the R-R interval was electrocardiographically evaluated at baseline and at the 3-year follow-up.Higher baseline BMI, fasting insulin and tobacco use as well as greater changes in BMI and fasting insulin but lower adiponectin levels, were associated with a greater number of cardiometabolic risk factors at the 3-year follow-up independently of insulin sensitivity (all P0.02). The CCA-IMT increased with the number of cardiometabolic risk factors (P=0.008), but was not related to fasting insulin, whereas higher fasting insulinaemia and its 3-year changes were significantly associated with a smaller R-R interval (P=0.005 and P=0.002, respectively). These relationships were independent of baseline age, gender, BMI, adiponectin, insulin sensitivity, tobacco use and physical activity.In clinically healthy subjects, fasting insulinaemia, adiponectin and lifestyle parameters are related to the presence of one or two cardiometabolic risk factors before criteria for the metabolic syndrome are met. These results underline the importance of fasting insulinaemia as an independent cardiometabolic risk factor at an early stage of disease development in a healthy general population.

Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m(2)).Seventy-one healthy, insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance index2.5), divided into normal-weight (n = 13; BMI = 23.2 +/- 1.6), obese (n = 35; BMI=32.6+/-2.5), and severely obese (n=23; BMI=49.0+/-7.9) groups, were enrolled. Vascular function was evaluated by flow-mediated dilation and carotid intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin, vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known markers of vascular health/protection, also were measured.Flow-mediated dilation was higher in severely obese than in obese and normal-weight individuals (P=.019 and P=.011 respectively). Intima-media thickness was consistently lower in severely obese than in obese individuals (P=.040) and similar in severely obese and normal-weight individuals (P.99). Levels of high-sensitivity C-reactive protein and leptin were higher in severely obese than in obese and normal-weight individuals (high-sensitivity C-reactive protein: P=.018 and P=.05, respectively; leptin: P.001 for both comparisons). CD34+KDR+ endothelial progenitor cells were significantly higher in severely obese versus obese individuals (P=.039).Our study demonstrates that vascular function is paradoxically better in severely obese than in obese subjects and similar to that found in normal-weight subjects. Despite higher levels of high-sensitivity C-reactive protein and leptin, severely obese individuals may be partially protected from atherosclerosis, possibly by a greater mobilization of endothelial progenitor cells.

Aims/hypothesis We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. Methods Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Withinday variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp. Results Basal GLP1 relative amplitude (amplitude/ mesor×100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775±94 to 846±161 pmol l-1 min in NGT, whereas GIP AUC decreased significantly from 1,373±565 to 513±186 pmol l-1 min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p=0.010) and GLP1 AUCs (p=0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD×diabetes, p=0.003). Insulin sensitivity was markedly improved (p

Aims The ADIPOQ gene encodes the protein adiponectin, and decreased circulating adiponectin levels have been observed in cardiovascular disease. We investigated the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G-11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid artery intima media thickness (IMT) in a cohort of healthy subjects participating in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study. Methods and results Anthropometric and metabolic assessment and B-mode ultrasound of the carotid IMT were measured in 1306 subjects [589 men; 717 women, mean ± SD age 43.8 ± 8.3 years, BMI 25.5 ± 4.0 kg/m2] recruited from 19 centres in 14 European countries. Carriers of the −11426G allele and homozygous carriers of the −11391G allele had significantly lower plasma adiponectin levels. These relationships remained significant after adjusting for age, sex, recruitment centre, and BMI. Carriers of SNP −11377G allele had significantly greater IMT values compared with C allele homozygotes [geometric mean (interquartile range) 601 (543–665) vs. 590 (537–647) μm, P = 0.021]. This relationship became stronger after correcting for key covariates, including plasma adiponectin levels ( P = 0.011). Conclusion Variation within the ADIPOQ gene promoter is directly associated with carotid IMT in healthy subjects and is independent of circulating adiponectin levels.

Aims/hypothesis The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing biliopancreatic diversion (BPD). Subjects and methods We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52± 7 kg/m2, mean±SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery. Results BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre- BPD 341±79 ml min-1 m-2, post-BPD 511±57 ml min-1 m-2, lean 478±49 ml min-1 m-2). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min-1 m-2 l mmol-1, median [interquartile range]) compared with lean subjects (82 [98]; p

Background. The HAIR-AN syndrome is a rare multisystem disorder in women, that consists of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The IR is likely due to a primary defect of the insulin receptor. Methods: We report the case of a 42-year-old Caucasian woman with HAIR-AN syndrome, impaired glucose tolerance (IGT), mild hyperlipemia, and hypertension, who underwent biliopancreatic diversion (BPD). Results: Within 24 months follow-up after BPD, impaired glucose tolerance, mild hyperlipemia, and hypertension completely reversed. Although insulin sensitivity, estimated by the euglycemic hyperinsulinemic clamp, did not improve, signs and symptoms of hyperandrogenism and acanthosis nigricans resolved fully. Conclusion: In HAIR-AN syndrome, malabsorptive bariatric surgery is effective in improving hyperandrogenism and acanthosis nigricans, with noteworthy esthetic consequences. BPD was followed by disappearance of co-morbidities of the syndrome, such as IGT, hypertension and hyperlipemia.

Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed. Methods In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of

De Roux-en-Y gastric bypass en de biliopancreatische deviatie kunnen bij morbide obese patienten de ziekteverschijnselen van diabetes aanzienlijk verbeteren en leiden vaak zelfs tot remissie van de ziekte. Er is behoefte aan prospectief, gerandomiseerd klinisch onderzoek waarin deze procedures worden vergeleken met niet-invasieve medische behandeling van diabetes.

Introduction Roux-en-Y gastric bypass (RYGB) is the most performed bariatric operation. Reactive hypoglycaemia is a frequent late complication occurring in about 72% of RYGB patients, which can present with various intensities up to the serious form of neuroglycopaenia. However, it seems to occur also after sleeve gastrectomy (SG) although much more rarely. Methods and analysis A single centre, open, 1-year randomised trial to compare the incidence of hypoglycaemia after RYGB or SG. A secondary objective is the assessment of the comparative ability of the two surgical procedures in determining the improvement or normalisation of insulin sensitivity, given the established relevance of insulin resistance in the cardiometabolic syndrome of obesity. Ethics and dissemination The study will be published and presented to international meetings and, due to the safety issue, it will represent a relevant information for national healthcare systems. The protocol was approved by the Catholic University Ethical Committee (A1534/CE/2012). Clinicaltrials.gov Registration n. NCT01581801.