Medium-Term Nutritional and Metabolic Outcome of Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-S).

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.

Long-term Outcomes of Transoral Outlet Reduction (TORe) for Dumping Syndrome and Weight Regain After Roux-en-Y Gastric Bypass.

BACKGROUND: Both weight regain and dumping syndrome (DS) after Roux-en-Y gastric bypass (RYGB) have been related to the dilation of gastro-jejunal anastomosis. The aim of this study is to assess the safety and long-term efficacy of endoscopic transoral outlet reduction (TORe) for DS and/or weight regain after RYBG. MATERIALS AND METHODS: A retrospective analysis was performed on a prospective database. Sigstad's score, early and late Arts Dumping Score (ADS) questionnaires, absolute weight loss (AWL), percentage of total body weight loss (%TBWL), and percentage of excess weight loss (%EWL) were assessed at baseline and at 6, 12, and 24 months after TORe. RESULTS: Eighty-seven patients (median age 46 years, 79% female) underwent TORe. The median baseline BMI was 36.2 kg/m2. Out of 87 patients, 58 were classified as "dumpers" due to Sigstad's score ≥ 7. The resolution rate of DS (Sigstad's score < 7) was 68.9%, 66.7%, and 57.2% at 6, 12, and 24 months after TORe, respectively. A significant decrease in Sigstad's score as well as in early and late ADS questionnaires was observed (p < 0.001). The median Sigstad's score dropped from 15 (11-8.5) pre-operatively to 2 (0-12) at 24 months. The %TBWL was 10.5%, 9.9%, and 8.1% at 6, 12, and 24 months, respectively. Further, "dumpers" with resolution of DS showed better weight loss results compared with those with persistent DS (p < 0.001). The only adverse event observed was a perigastric fluid collection successfully managed conservatively. CONCLUSION: TORe is a minimally invasive treatment for DS and/or weight regain after RYGB, with evidence of long-term efficacy.

Dietary supplements for obesity.

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: ß-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean.

Modern vision of the Mediterranean diet.

The Mediterranean diet is the most well-known and researched dietary pattern worldwide. It is characterized by the consumption of a wide variety of foods, such as extra-virgin olive oil (EVOO), legumes, cereals, nuts, fruits, vegetables, dairy products, fish, and wine. Many of these foods provide several phytonutrients, among which polyphenols and vitamins play an important role. Data from several studies have strongly established that nutrition is a key factor in promoting a healthy lifestyle and preventing many chronic diseases. In particular, a large number of studies have established the protective effects of the Mediterranean diet against several chronic diseases, among which are diabetes, cardiovascular diseases, cancer, aging disorders, and against overall mortality. Animal and human translational studies have revealed the biological mechanisms regulating the beneficial effects of the traditional Mediterranean diet. Indeed, several studies demonstrated that this nutritional pattern has lipid-lowering, anticancer, antimicrobial, and anti-oxidative effects. Moreover, the Mediterranean diet is considered environmentally sustainable. In this review, we describe the composition of the Mediterranean diet, assess its beneficial effects, and analyze their epigenomic, genomic, metagenomic, and transcriptomic aspects. In the future it will be important to continue exploring the molecular mechanisms through which the Mediterranean diet exerts its protective effects and to standardize its components and serving sizes to understand more precisely its effects on human health.

Metabolomics application for the design of an optimal diet.

Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual's response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases. Metabolomics is vital to nearly every aspect of precision nutrition. It can be targeted or untargeted, and it has many applications. Indeed, it can be used to comprehensively characterize the thousands of chemicals in foods, identify food by-products in human biofluids or tissues, characterize nutrient deficiencies or excesses, monitor biochemical responses to dietary interventions, track long- or short-term dietary habits, and guide the development of nutritional therapies. Indeed, metabolomics can be coupled with genomics and proteomics to study and advance the field of precision nutrition. Integrating omics with epidemiological and clinical data will begin to define the beneficial effects of human food metabolites. In this review, we present the metabolome and its relationship to precision nutrition. Moreover, we describe the different techniques used in metabolomics and present how metabolomics has been applied to advance the field of precision nutrition by providing notable examples and cases.

Foods of the Mediterranean diet: lacto-fermented food, the food pyramid and food combinations.

The Mediterranean diet proved to be one of the healthiest diets in the word. It has several beneficial effects and it prevents many non-communicable diseases, such as cancer, cardiovascular diseases, and obesity. Before being a culinary regime, the Mediterranean diet is characterized by specific cultural heritages and traditions, also influencing the lifestyle of the populations. The Mediterranean diet follows the so-called food pyramid, comprising several food combinations. Indeed, it is mainly composed by vegetables, fish and dairy products, while red meat and sweets are poorly consumed. Processed foods are mainly avoided, apart from lacto-fermented ones, the first processed foods consumed by humans. Food fermentation by microorganisms not only improves the functionality of bioactive metabolites, but also increases the shelf life and organoleptic properties of the food. Lactic acid bacteria play a vital role in transforming the food constituents, thereby enhancing their nutritional and functional properties. In addition, these foods introduce beneficial bacteria into gut microbiota, thus maintaining a healthy gut microbiome and corresponding gut-brain axis, thus providing an overall improvement in health and a reduced risk of non-communicable diseases and metabolic disorders. This review will focus on the Mediterranean diet, on its characterising food pyramid and food combinations, and on lacto-fermented foods, one of the components of the Mediterranean diet with the most beneficial effects.

Foods of the Mediterranean diet: citrus, cucumber and grape.

Fruit and vegetables are excellent sources of health-promoting bioactive compounds and nutraceuticals. Regular consumption of fruit and vegetables helps prevent the onset and progression of many non-communicable diseases. The Mediterranean diet envisages consumption of healthy vegetables and fruit on a daily basis for maximum health benefits. Traditional use envisages vegetable-based and fruit-based diets, and many studies scientifically proved the beneficial effects of Mediterranean vegetables and fruits. Rich in bioactive phytochemicals, citrus, cucumbers and grapes have antioxidant, anti-inflammatory, antimicrobial, cardioprotective, anti-ageing and anti-cancer properties. Studies indicate that intake of citrus, cucumbers and grapes reduces hypertension, hyperlipidemia, skin problems and infections and improves the health of the cardiovascular and nervous systems. These beneficial effects are mediated by several bioactive molecules present in Mediterranean diet vegetables and fruits, such as citrus, cucumbers and grapes. Indeed, they contains flavones, isoflavones, tannins, polyphenols and many beneficial natural molecules. This review focuses on the bioactive ingredients in citrus fruit, cucumbers and grapes, all components of the Mediterranean diet, and their health effects. A deep understanding of Mediterranean diet's components, as well as clinical trials to test natural molecules beneficial effects, will permit to further explore the therapeutic potential of the Mediterranean diet in several pathological conditions.

Main nutritional deficiencies.

Nutrition is the source of energy that is required to carry out all the processes of human body. A balanced diet is a combination of both macro- and micronutrients. "Nutritional inadequacy" involves an intake of nutrients that is lower than the estimated average requirement, whereas "nutritional deficiency" consists of severely reduced levels of one or more nutrients, making the body unable to normally perform its functions and thus leading to an increased risk of several diseases like cancer, diabetes, and heart disease. Malnutrition could be caused by environmental factors, like food scarcity, as well as disease conditions, like anorexia nervosa, fasting, swallowing inability, persistent vomiting, impaired digestion, intestinal malabsorption, or other chronic diseases. Nutritional biomarkers - like serum or plasma levels of nutrients such as folate, vitamin C, B vitamins, vitamin D, selenium, copper, zinc - could be used for the evaluation of nutrient intake and dietary exposure. Macronutrients deficiencies could cause kwashiorkor, marasmus, ketosis, growth retardation, wound healing, and increased infection susceptibility, whereas micronutrient - like iron, folate, zinc, iodine, and vitamin A - deficiencies lead to intellectual impairment, poor growth, perinatal complications, degenerative diseases associated with aging and higher morbidity and mortality. Preventing macro- and micronutrient deficiency is crucial and this could be achieved through supplementation and food-based approaches.

Foods of the Mediterranean diet: tomato, olives, chili pepper, wheat flour and wheat germ.

Mediterranean people, which follows a diet rich in minimally-processed plant-based foods, are believed to live longer and healthier lives than many other populations in the Western world. Epidemiological and clinical data suggest that the Mediterranean diet has beneficial effects for several chronic diseases, such as cardiovascular diseases, obesity, cancer and diabetes. Although the mechanisms of action of the Mediterranean diet are not completely clear, the synergistic effects of a number of its components and their bioactive phytochemicals exert antioxidant, anti-inflammatory, anti-microbial and anti-cancer effects. The Mediterranean diet includes daily consumption of whole cereals, fruit, vegetables and legumes in moderate proportions, weekly consumption of white meat in low to moderate proportions and occasionally sweets and chocolates in small amounts. Since olive oil is the main lipids source, it has special significance for health. Healthy fruit and vegetables, rich in phytochemicals, are a major proportion of this diet and contribute to the overall nutritional value and bioactivity of its components. Here we review the nutritional and health benefits of wheat germ, tomatoes, olives and chili pepper, items at the base of Mediterranean diet food pyramid that provides beneficial molecules, such as polyphenols, vitamins and flavonoids, and exert anti-inflammatory, anti-microbial and anti-oxidative actions.

Foods of the Mediterranean diet: garlic and Mediterranean legumes.

The Mediterranean diet is a dietary regime derived from the one followed by the ancient civilizations of the Mediterranean region. It is characterized by many healthy constituents, among which are cereals, legumes, fruits, vegetables, olives, and white meat. Many studies suggest that this dietary regime is the key to obtaining a healthy and long life, like that of the Mediterranean peoples. Despite its popularity among health professionals, this diet is still confined to a certain geographical area of the world. Due to globalization and the modern busy lifestyle, this cultural diet is losing ground even in its home region, with more and more people embracing the so-called Western diet. An awareness of health benefits of the individual components of the Mediterranean diet will therefore draw attention from all over the world to this healthy and affordable dietary pattern, which can not only improve the overall health, but also reduce the risk of developing chronic and infectious diseases. In this regard, garlic and Mediterranean legumes present a huge repertoire of phytochemicals having both nutritive and nutraceutical properties, which therefore should be included in our daily dietary routines in moderate proportions. This narrative review aims at summarizing the principal components and health benefits of the Mediterranean diet, in particular of garlic and legumes.

Next-Generation Sequencing of a Large Gene Panel for Outcome Prediction of Bariatric Surgery in Patients with Severe Obesity.

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet-Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery.

Prevalence and predictors of non-alcoholic steatohepatitis in subjects with morbid obesity and with or without type 2 diabetes.

AIM: 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. METHODS: We evaluated a cohort of 412 subjects (age 19-67 years, body mass index-BMI: 44.98 kg/m2), who underwent fine-needle liver biopsy during bariatric surgery. Thirty-six percent of the subjects were affected by T2D. Liver biopsies were classified according to the Kleiner's NAFLD Activity Score (NAS). NAFLD Fibrosis Score (NFS), AST/ALT ratio, AST to Platelet ratio (APRI), fibrosis-4 score (FIB4) were calculated. A neural network analysis (NNA) was run to predict NASH severity. RESULTS: The 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, p<0.0001) 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. CONCLUSIONS: 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.

Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial.

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 [HbA1c] >7·0%, and body-mass index ≥35 kg/m2) 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 (HbA1c <6·5% and fasting glycaemia <5·55 mmol/L without ongoing medication for at least 1 year). In the 10-year analysis, durability of diabetes remission was analysed by intention to treat (ITT). This study is registered with ClinicalTrials.gov, NCT00888836. FINDINGS: Between April 30, 2009, and Oct 31, 2011, of 72 patients assessed for eligibility, 60 were included. The 10-year follow-up rate was 95·0% (57 of 60). Of all patients who were surgically treated, 15 (37·5%) maintained diabetes remission throughout the 10-year period. Specifically, 10-year remission rates in the ITT population were 5·5% for medical therapy (95% CI 1·0-25·7; one participant went into remission after crossover to surgery), 50·0% for BPD (29·9-70·1), and 25·0% for RYGB (11·2-46·9; p=0·0082). 20 (58·8%) of 34 participants who were observed to be in remission at 2 years had a relapse of hyperglycaemia during the follow-up period (BPD 52·6% [95% CI 31·7-72·7]; RYGB 66·7% [41·7-84·8]). All individuals with relapse, however, maintained adequate glycaemic control at 10 years (mean HbA1c 6·7% [SD 0·2]). Participants in the RYGB and BPD groups had fewer diabetes-related complications than those in the medical therapy group (relative risk 0·07 [95% CI 0·01-0·48] for both comparisons). Serious adverse events occurred more frequently among participants in the BPD group (odds ratio [OR] for BPD vs medical therapy 2·7 [95% CI 1·3-5·6]; OR for RYGB vs medical therapy 0·7 [0·3-1·9]). INTERPRETATION: Metabolic surgery is more effective than conventional medical therapy in the long-term control of type 2 diabetes. Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes. FUNDING: Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Sarilumab use in severe SARS-CoV-2 pneumonia.

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

Identification of Proteins Associated with the Early Restoration of Insulin Sensitivity After Biliopancreatic Diversion.

CONTEXT: Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and nonalcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity. OBJECTIVE: To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD. DESIGN: Prospective single-center study including 20 insulin-resistant men with morbid obesity scheduled for BPD. Patient characteristics and blood samples were repeatedly collected from baseline up to 4 weeks postsurgery. IR was assessed by homeostatic model assessment for insulin resistance (HOMA-IR), Matsuda Index, and by studying metabolic profiles during meal tolerance tests. Unbiased proteomic analysis was performed to identify plasma proteins altered by BPD. Detailed plasma profiles were made on a selected set of proteins by targeted multiple reaction monitoring mass spectrometry (MRM/MS). Changes in plasma proteome were evaluated in relation to metabolic and inflammatory changes. RESULTS: BPD resulted in improved insulin sensitivity and reduced body weight. Proteomic analysis identified 29 proteins that changed following BPD. Changes in plasma levels of afamin, apolipoprotein A-IV (ApoA4), and apolipoprotein A-II (ApoA2) correlated significantly with changes in IR. CONCLUSION: Circulating levels of afamin, ApoA4, and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.

Postnatal Health in Children Born to Women After Bariatric Surgery.

INTRODUCTION: The aim of this study is to evaluate short- and long-term consequences in children born to women after different bariatric surgery (BS) procedures. METHODS: A questionnaire survey was given to the mothers referred from 1994 to 2019 to our center for pregnancy and delivery management after BS procedures: (a) malabsorptive surgery, (b) restrictive procedures, and (c) combined restrictive-malabsorptive procedures. RESULTS: Data from 74 children born after BS, aged 0 month to 12 years, were analyzed. The prevalence of children with underweight was 5.4%, normal weight 59.5%, overweight 16.2%, and obesity 18.9%. The prevalence of obesity was higher in children pre-school aged than that in school-aged ones. Neurodevelopmental disorders were more frequent if maternal BMI before bariatric surgery was ≥ 41 kg/m2 (p = 0.008), as well as if the pregnancy occurred less than 18 months after BS (p = 0.028). In school-aged children conceived within 18 months after BS, the highest risk of neurodevelopmental disorders (p = 0.028) and overweight (p = 0.018) was observed. The prevalence of neurodevelopmental disorders was much higher for small for gestational age babies (p = 0.048). Children born after biliopancreatic diversion (BPD) showed less maternal breastfeeding, shorter breastfeeding duration, more overweight, and more occurrence of atopic dermatitis in comparison with children born after other bariatric procedures. CONCLUSIONS: Postnatal health in children born to women after BS was impaired by long-term consequences and by other diseases later in life. Children born after BPD were particularly at higher risk for short and long term consequences when compared to children born after other BS procedures.

Metabolic surgery improves insulin resistance through the reduction of gut-secreted heat shock proteins.

Metabolic surgery improves insulin resistance and is associated with the remission of type 2 diabetes, but the mechanisms involved remain unknown. We find that human jejunal mucosa secretes heat shock proteins (HSPs) in vitro, in particular HSP70 and GRP78. Circulating levels of HSP70 are higher in people resistant to insulin, compared to the healthy and normalize after duodenal-jejunal bypass. Insulin sensitivity negatively correlates with the plasma level of HSP70, while body mass index does not. A high-energy diet increases the circulating levels of HSP70 and insulin resistance. HSP70 stimulates the accumulation of lipid droplets and inhibits Ser473 phosphorylation of Akt and glucose uptake in immortalized liver cells and peripheral blood cells. Serum depleted of HSPs, as well as the serum from the insulin-resistant people subjected to a duodenal-jejunal bypass, reverse these features, identifying gut-secreted HSPs as possible causes of insulin resistance. Duodenal-jejunal bypass might reduce the secretion of HSPs either by shortening the food transit or by decreasing the fat stimulation of endocrine cells.

Short-term Effects of Laparoscopic Adjustable Gastric Banding Versus Roux-en-Y Gastric Bypass.

OBJECTIVE: Bariatric surgery has been shown to have important long-term metabolic effects resulting in enhanced insulin sensitivity and improved glucose tolerance in patients with type 2 diabetes. The contribution of reduced caloric intake to these beneficial effects of surgery remains unclear. The aim of this study was to compare the short-term effects (1 week) of bariatric surgical procedures with a very low caloric intake (VLCI) on insulin sensitivity (IS) and insulin secretion (ISR) in nondiabetic obese subjects. RESEARCH DESIGN AND METHODS: Twenty obese patients without diabetes (BMI 44.2 ± 0.7 kg/m2) were admitted to the clinic for 1 week. At baseline and 1 week after VLCI (600 kcal/day), subjects received a hyperinsulinemic-euglycemic clamp with tracer infusion to quantify endogenous glucose production (EGP), lipolysis (rate of appearance of glycerol [RaGlycerol]), peripheral insulin sensitivity (insulin-stimulated glucose disposal [M value] divided by the steady-state plasma insulin concentration [M/I]), hepatic insulin sensitivity (Hep-IS [= 1/(EGP ⋅ insulin)]), and adipose insulin sensitivity (Adipo-IS [= 1/(RaGlycerol ⋅ insulin)]). An intravenous glucose bolus was administered at the end of the insulin clamp to measure ISR and ß-cell function (disposition index [DI]). Approximately 3 months later, patients were admitted for laparoscopic adjustable gastric banding (LAGB) (n = 10) or Roux-en-Y gastric bypass (RYGB) (n = 10), and were restudied 1 week after surgery under the same caloric regimen (600 kcal/day). RESULTS: After 1 week of VLCI, patients lost 2.1 kg without significant changes in Hep-IS, Adipo-IS, M/I, or DI. RYGB and LAGB led to greater weight loss (5.5 and 5.2 kg, respectively) and to significant improvement in Hep-IS, EGP, and lipolysis. Only RYGB improved Adipo-IS and M/I. No change in ISR or DI was observed in either surgical group. CONCLUSIONS: Bariatric surgery improves IS within 1 week. These metabolic effects were independent of caloric intake and more pronounced after RYGB compared with LAGB.

Early effect of Roux-en-Y gastric bypass on insulin sensitivity and signaling.

BACKGROUND: 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. SETTING: Catholic University, School of Medicine, Rome, Italy. METHODS: 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-ß on Ser 9 and Ser21 in skeletal muscle biopsy specimens by Western blot analysis. RESULTS: 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. CONCLUSIONS: 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.

Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial.

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 A1c (HbA1c) 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 HbA1c 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.