Long-Term effects of physical activity on weight loss, metabolic parameters and blood pressure in subjects undergoing bariatric surgery: A 5-year follow-up study.

BACKGROUND: bariatric surgery stands as an effective intervention for weight loss and improved metabolic control in obesity, although over time there is a proportion of weight regain and type-2-diabetes (T2D) relapse. AIMS: to explore the role of physical activity (PA) after surgery and its impact on metabolic parameters during a 5-year follow-up. METHODS: 148 individuals who underwent bariatric surgery completed scheduled examinations over 5-years. Physical assessments and laboratory tests were conducted pre-surgery and annually thereafter. PA levels were evaluated using the International Physical Activity Questionnaire. RESULTS: participants were split into the PA group, who engaged in regular physical activity, and No-PA group, who remained sedentary throughout. In T2D individuals before surgery, PA group showed significant reductions in blood pressure and a lower T2D recurrence (6.7 â€‹% vs 36 â€‹%) compared to No-PA group. In normoglycemic individuals, the PA group led to sustained BMI reduction and improved blood pressure control (p â€‹< â€‹0.001) compared to No-PA group, for the entire duration of follow-up. CONCLUSIONS: regular PA demonstrated cardio-metabolic benefits post-bariatric surgery. Integrating PA into post-bariatric care could enhance long-term outcomes.

Non-albumin proteinuria marks tubular involvement and is associated with arterial stiffness in subjects affected by severe obesity.

INTRODUCTION: Obesity is a well-established risk factor for kidney disease, and tubular damage can play a pivotal role in the development of obesity-related kidney damage. This study aimed to investigate the pathophysiological pathways involved in the development of non-albumin proteinuria (NAP), a marker of tubular involvement, in a cohort of subjects with severe obesity and preserved kidney function. METHODS: A total of 106 subjects with BMI ≥ 35 kg/m2 in waiting list for bariatric surgery underwent blood chemistry analysis including metabolic and lipid profile, vascular tests for cardiovascular risk stratification and a comprehensive assessment of kidney function, including renal resistive index (RRI) and NAP measurement. RESULTS: Nineteen patients with ACR ≥ 30 mg/g regardless of NAP values (ALB+), nineteen with NAP≥ 150 mg/g and albuminuria < 30 mg/g (iNAP) and sixty-eight without proteinuria (No-P) were found. Both ALB+ and iNAP groups exhibited a higher prevalence of hypertension and anti-hypertensive treatment compared to No-P, while the prevalence of diabetes was similar between groups. Concerning lipid profile, no differences in total, HDL and LDL cholesterol were found, while ALB+ patients had higher serum triglyceride levels than the other two groups. RRI and carotid-femoral pulse wave velocity (cf-PWV) was significantly higher in ALB+ and iNAP groups compared to No-P. Remarkably, cf-PWV remained still significant after adjustment for age, sex and MBP (p = 0.0004). In overall population, a multiple regression analysis showed that cf-PWV was an independent determinant of NAP in a model including age, sex, glycated hemoglobin, systolic and mean blood pressure (R2 =0.17, p = 0.031). CONCLUSION: iNAP subjects showed increased arterial stiffness comparable to that observed in ALB+ group, suggesting that they may represent a subgroup at higher cardiovascular risk, often unrecognized in clinical practice.

The renal resistive index is associated with microvascular remodeling in patients with severe obesity.

BACKGROUND: Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. METHODS: We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with N G -nitro arginine methyl ester (L-NAME), were measured. RESULTS: Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT ( P = 0.042). Multivariable analysis showed a relationship between M/L and RRI ( P  = 0.016, St. ß 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation ( P   =  0.036, St. ß = -0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. CONCLUSIONS: The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption.

Decreased Weight Loss Following Bariatric Surgery in Patients with Type 2 Diabetes.

BACKGROUND: Bariatric surgery represents the most effective treatment for achieving significant and sustained weight loss. We aimed to assess whether presence of type 2 diabetes (T2D) at baseline, and T2D remission following bariatric surgery affect the weight loss outcome. METHODS: Data of 312 consecutive morbidly obese subjects who underwent bariatric surgery were analysed. Patients underwent either RYGB (77%), or sleeve gastrectomy (23%), and their body weight was followed-up for 1, 2, 3, 4, and 5 years at regular ambulatory visits (N = 269, 312, 210, 151, 105, at each year, respectively). T2D remission was assessed according to the ADA criteria. RESULTS: In the whole dataset, 92 patients were affected by T2D. Patients with T2D were older than patients without T2D (52 ± 9 vs 45 ± 11 years, p < 0.0001), but there were no differences in baseline BMI, sex, and type of intervention received. We found that presence of T2D at baseline was associated with smaller weight loss at 1, 2, 3, 4, and 5 years following bariatric surgery (δ BMI at 2 years: - 13.7 [7.7] vs - 16.4 [7.3] kg/m2; at 5 years - 12.9 [8.8] vs - 16.3 [8.7] kg/m2 in patients with T2D vs patients without T2D respectively, all p < 0.05). When dividing the patients with T2D in remitters and non-remitters, non-remitters had significantly smaller weight loss compared to remitters (δ BMI at 2 years: - 11.8 [6.3] vs - 15.4 [7.8] kg/m2; at 5 years: - 8.0 [7.1] vs - 15.0 [7.2] kg/m2, non-remitters vs remitters respectively, all p < 0.05). CONCLUSIONS: T2D is independently associated to smaller weight loss following bariatric surgery, especially in subjects not achieving diabetes remission. • Patients with T2D achieve smaller weight loss following bariatric surgery • When dividing the T2D patients in remitters and non-remitters, non-remitters achieve significantly smaller weight loss compared to remitters.

The Beneficial Effects of Bariatric-Surgery-Induced Weight Loss on Renal Function.

Obesity represents an independent risk factor for the development of chronic kidney disease (CKD), leading to specific histopathological alterations, known as obesity-related glomerulopathy. Bariatric surgery is the most effective means of inducing and maintaining sustained weight loss. Furthermore, in the context of bariatric-surgery-induced weight loss, a reduction in the proinflammatory state and an improvement in the adipokine profile occur, which may also contribute to the improvement of renal function following bariatric surgery. However, the assessment of renal function in the context of obesity and following marked weight loss is difficult, since the formulas adopted to estimate glomerular function use biomarkers whose production is dependent on muscle mass (creatinine) or adipose tissue mass and inflammation (cystatin-c). Thus, following bariatric surgery, the extent to which reductions in plasma concentrations reflect the actual improvement in renal function is not clear. Despite this limitation, the available literature suggests that in patients with hyperfiltration at baseline, GFR is reduced following bariatric surgery, whereas GFR is increased in patients with decreased GFR at baseline. These findings are also confirmed in the few studies that have used measured rather than estimated GFR. Albuminuria is also decreased following bariatric surgery. Moreover, bariatric surgery seems superior in achieving the remission of albuminuria and early CKD than the best medical treatment. In this article, we discuss the pathophysiology of renal complications in obesity, review the mechanisms through which weight loss induces improvements in renal function, and provide an overview of the renal outcomes following bariatric surgery.

Progressive Additive Benefits of Prehabilitation and Subsequent Bariatric Surgery on Cardiac Autonomic Regulation as Assessed by Means of a Simple Unitary Composite Index: Preliminary Data from an Observational Study.

Obesity is associated with an increased risk of several chronic comorbidities, which may also be determined by dysfunctional autonomic nervous system (ANS). The influence of bariatric surgery (BS) on ANS balance was explored in previous studies, but with high heterogeneity in both the assessment timing and methods employed. In the present observational study, we applied a clinical protocol which considers two subsequent phases. Twenty-nine non-diabetic obese subjects were studied at baseline (T0), after one month of lifestyle modification (prehabilitation) (phase 1-T1), and after eight months following BS (phase 2-T2). ANS regulation was assessed across the three study epochs by means of ANSI, a single composite percent-ranked proxy of autonomic balance, being free of gender and age bias, economical and simple to apply in a clinical setting. The aim of the present study was to investigate the effects of the clinical protocol based on prehabilitation and subsequent BS on the ANS regulation by means of ANSI. Potential intertwined correlations with metabolic parameters were also investigated. Notably, we observed a progressive improvement in ANS control, even by employing ANSI. Moreover, the reduction in the markers of sympathetic overactivity was found to significantly correlate with the amelioration in some metabolic parameters (fasting glucose, insulin levels, and waist circumference), as well as in stress and tiredness perception. In conclusion, this study provides convincing evidence that a unitary proxy of cardiac autonomic regulation (CAR) may reflect the progressive improvement in autonomic regulation following behavioral and surgical interventions in obese patients. Intriguingly, this might contribute to reducing cardiovascular and metabolic risk.

Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels.

BACKGROUND: Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans. METHODS: Ninety-five subjects undergoing elective laparoscopic surgery were recruited and stratified based on their body mass index status (above or below 30 kg/m2) and age (above or below 40 years) in 4 groups: Young Nonobese, Young Obese, Old Nonobese, and Old Obese. We measured small resistance arteries' endothelial function by pressurized micromyography before and after incubation with a SIRT1 agonist (SRT1720) and a mitochondria reactive oxygen species (mtROS) scavenger (MitoTEMPO). We assessed vascular levels of mtROS and nitric oxide availability by confocal microscopy and vascular gene expression of SIRT1 and mitochondrial proteins by qPCR. Chromatin immunoprecipitation assay was employed to investigate SIRT1-dependent epigenetic regulation of mitochondrial proteins. RESULTS: Compared with Young Nonobese, obese and older patients showed lower vascular expression of SIRT1 and antioxidant proteins (FOXO3 [forkhead box protein O3] and SOD2) and higher expression of pro-oxidant and aging mitochondria proteins p66Shc and Arginase II. Old Obese, Young Obese and Old Nonobese groups endothelial dysfunction was rescued by SRT1720. The restoration was comparable to the one obtained with mitoTEMPO. These effects were explained by SIRT1-dependent chromatin changes leading to reduced p66Shc expression and upregulation of proteins involved in mitochondria respiratory chain. CONCLUSIONS: SIRT1 is a novel central modulator of the earliest microvascular damage induced by age and obesity. Through a complex epigenetic control mainly involving p66Shc and Arginase II, it influences mtROS levels, NO availability, and the expression of proteins of the mitochondria respiratory chain. Therapeutic modulation of SIRT1 restores obesity- and age-related endothelial dysfunction. Early targeting of SIRT1 might represent a crucial strategy to prevent age- and obesity-related microvascular dysfunction.

Glomerular hyperfiltration in morbid obesity: Role of the inflammasome signalling.

AIM: Obesity is associated with glomerular hyperfiltration which may precede the development of overt renal damage. Few studies evaluated the link between inflammasome signalling and hyperfiltration. The aim is to evaluate the relationship between IL1-ß/Caspase-1, insulin sensitivity and hyperfiltration in subjects with severe obesity, before and after weight loss. METHODS: Forty-six patients with BMI > 35 kg/m2 , without type-2-diabetes or hypertension, were evaluated at baseline and 6 months after bariatric surgery with oral glucose tollerance test, bioimpedance analysis and blood tests. The eGFR was calculated according to EPIcr-cys formula and insulin sensitivity by Oral Glucose Insulin Sensitivity. IL-1ß/Caspase-1 were measured with the ELISA-kit. HF was defined as eGFR ≥ 140 ml/min (non-indexed for BSA). RESULTS: Sixteen subjects at baseline had hyperfiltration, with a higher insulin resistance, BMI, lean mass and plasma levels of IL-1ß/Caspase-1. After surgery, there was a reduction in BMI and improvement in insulin resistance in all patients. However, in 8 of 16 patients hyperfiltration persisted and IL-1ß/Caspase-1 levels did not decrease (3.22 ± 0.79 vs. 3.13 ± 1.03 and 23.7 ± 12.1 vs. 20.6 ± 9.1, pre vs. post, pg/ml), while cytokines normalized in all the other patients in parallel with the eGFR. In a logistic regression model, correcting for the main covariates, lean mass and IL-1ß before surgery (p = .01 and p = .03, respectively), were the only predictors of hyperfiltration. CONCLUSION: Weight loss is effective in reducing hyperfiltration in most, but not all patients. Hyperfiltration remains unchanged in subjects who do not have a reduction in IL-1ß/Caspase-1, suggesting a pathogenetic role of the inflammasome signalling in the early stages of nephropathy.

Bariatric surgery and the COVID-19 pandemic: SICOB recommendations on how to perform surgery during the outbreak and when to resume the activities in phase 2 of lockdown.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related disease, coronavirus disease 2019 (COVID-19), has been rapidly spreading all over the world and is responsible for the current pandemic. The current pandemic has found the Italian national health system unprepared to provide an appropriate and prompt response, heavily affecting surgical activities. Based on the limited data available in the literature and personal experiences, the Società Italiana di Chirurgia dell'OBesità e Malattie Metaboliche (SICOB) provides recommendations regarding the triage of bariatric surgical procedures during the COVID-19 pandemic defining a dedicated path for surgery in morbidly obese patients with known or suspected COVID-19 who may require emergency operations. Finally, the current paper delineates a strategy to resume outpatient visits and elective bariatric surgery once the acute phase of the pandemic is over. Models developed during the COVID-19 crisis should be integrated into hospital practices for future use in similar scenarios. Surgeons are presented with a golden opportunity to embrace systemic change and to drive their professional future.

Weight Loss After Bariatric Surgery Significantly Improves Carotid and Cardiac Function in Apparently Healthy People with Morbid Obesity.

PURPOSE: Obesity clearly increases cardiovascular risk, often inducing high blood pressure (BP), impaired left ventricular (LV) function, and increased arterial stiffness. Intensive weight loss and bariatric surgery induce improvement in hypertension and diabetes for morbid obesity. Carotid artery haemodynamics is a powerful prognostic indicator for stroke and cognitive decline independent of BP. The aim of this study was to evaluate the impact of a 3-stage bariatric strategy of diet, bariatric surgery, and consequent weight loss on carotid haemodynamics and cardiac diastolic function. MATERIAL AND METHODS: This prospective study included 26 patients (45 ± 10 years, 4 men) with severe obesity undergoing bariatric surgery without comorbidities (hypertension, diabetes, etc.). Anthropometry, BP, Doppler echocardiography, and common carotid haemodynamics by ultrasound were measured at three times: (1) baseline, (2) after 1-month diet (post-diet), and (3) 8 months after surgery (post-surgery). The lnDU-loop method was used to estimate local carotid pulse wave velocity (ncPWV). RESULTS: Baseline BMI was 47.9 ± 7.1 kg/m2 and reduced by 5% and 30% post-diet and post-surgery, respectively. BP decreased only post-diet, without pulse pressure change. However, ncPWV, 6.27 ± 1.35 m/s at baseline, was significantly reduced by 10% and 23% post-diet and post-surgery, respectively, also adjusted for BP changes. The E/A ratio rose from 0.95 ± 0.20 to 1.27 ± 0.31 (p < 0.005), without change in LV geometry or mass, while heart rate and cardiac output fell substantially. CONCLUSION: Weight loss following diet and bariatric surgery is associated with reduced carotid arterial stiffness and improved LV diastolic function. Diet and bariatric surgery are effective treatments for morbid obesity with its concomitant adverse cardiovascular effects.

Impact of Postprandial Hypoglycemia on Weight Loss After Bariatric Surgery.

INTRODUCTION: Postprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS. AIMS: To assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D). METHODS: Data from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2 years were analyzed. At each follow-up visit, the patient's anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms. RESULTS: Before surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2 h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006). CONCLUSIONS: Mild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2 years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.

Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling.

OBJECTIVE: Interleukin (IL)-1ß is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1ß and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery. METHODS: A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1ß levels and caspase-1 were measured. RESULTS: Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1ß and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1ß levels normalized only in Ob-NGT. CONCLUSIONS: Plasma IL-1ß and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1ß normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.

Postprandial hypoglycaemia after Roux-en-Y gastric bypass in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery. PPHG was defined as a plasma glucose level of ≤3.3 mmol/l when not taking glucose-lowering agents. Insulin sensitivity was assessed by oral glucose insulin sensitivity index and beta-cell function by mathematical modelling of the plasma glucose, insulin and C-peptide concentrations. RESULTS: After surgery, PPHG occurred in 11 of 35 individuals who underwent RYGB. Before surgery, BMI was lower, glycaemic control less good and time of glucose peak earlier in the PPHG vs No PPHG group, and the duration of diabetes was shorter with PPHG (all p ≤ 0.05). In addition, insulin sensitivity was greater in the PPHG than No PPHG group (p = 0.03). After surgery, BMI and fasting glucose and insulin levels decreased similarly in the two groups; insulin secretion during the first hour of the OGTT increased more in the PPHG than No PPHG group (p = 0.04). Beta-cell glucose sensitivity increased more in individuals with PPHG than those without (p = 0.002). Over the same time interval, the glucagon-like peptide 1 (GLP-1) response was lower in individuals with PPHG before surgery (p = 0.05), and increased more after surgery. At 2 h after glucose ingestion in the OGTT, postsurgery plasma glucagon level was significantly lower in the PPHG than No PPHG group. CONCLUSIONS/INTERPRETATION: In morbidly obese individuals with type 2 diabetes, spontaneous PPHG may occur after bariatric surgery independently of a remission of diabetes. Before surgery, individuals had a shorter duration and were more insulin sensitive. Two years after surgery, these individuals developed greater beta-cell glucose sensitivity, and showed greater insulin and GLP-1 release early in the OGTT.

γ-Glutamyltransferase Fractions in Obese Subjects with Type 2 Diabetes: Relation to Insulin Sensitivity and Effects of Bariatric Surgery.

BACKGROUND/OBJECTIVES: Gamma-glutamyltranspeptidase (GGT) levels are an independent risk marker for the development of type 2 diabetes (T2DM). We investigated the relationship between the newly identified serum GGT fractions and glucose metabolism in obese subjects before and after bariatric surgery. SUBJECTS/METHODS: Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a 5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365). Insulin sensitivity was assessed by the OGIS index and ß-cell function by C-peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed by gel-filtration chromatography. RESULTS: At T15, total GGT activity decreased by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all patients showed a reduction in total GGT, in particular b-GGT (≥ 60%) and m-GGT (≥ 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-, and m-GGT fractions at T0 were significantly higher than in patients with low-grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was a significant fall in total GGT as well as in each fraction in both groups. In a multiple regression model, b-GGT was the only fraction related to insulin sensitivity (p = 0.016; ß coeff. = - 14.0) independently of BMI, fasting glucose, and triglycerides. CONCLUSIONS: While GGT activity is generally associated with impaired glucose metabolism, fractional GGT analysis showed that the b-GGT fraction specifically and independently tracks with insulin resistance.

Sleeve Gastrectomy: Correlation of Long-Term Results with Remnant Morphology and Eating Disorders.

BACKGROUND: Remnant dimension is considered one of the crucial elements determining the success of sleeve gastrectomy (SG), and dilation of the gastric fundus is often believed to be the main cause of failure. OBJECTIVES: The main outcome of this study is to find correlations between remnant morphology in the immediate post-operative stage, its dilation in years, and the long-term results. The second purpose aims to correlate preoperative eating disorders, taste alteration, hunger perception, and early satiety with post-SG results. MATERIALS AND METHODS: Remnant morphology was evaluated, in the immediate post-operative stage and over the years (≥2 years), through X-ray of the oesophagus-stomach-duodenum calculating the surface in anteroposterior (AP) and right anterior oblique projection (RAO). Presurgery diagnosis of eating disorders and their evaluation through "Eating Disorder Inventory-3" (EDI3) during follow-up were performed. Change in taste perception, sense of appetite, and early satiety were evaluated. Patients were divided into two groups: "failed SGs (EWL<50%) and "efficient SGs" (EWL >50%). RESULTS: There were a total of 50 patients (37 F, 13 M), with mean age 52 years, preoperative weight 131 ± 21.8 kg, and BMI 47.4 ± 6.8 kg/m2. Post-operative remnant mean dimensions overlapped between the two groups. On a long-term basis, an increase of 57.2 and 48.4% was documented in the AP and RAO areas respectively. In "failed" SGs, dilation was significantly superior to "efficient" SGs (AP area 70.2 vs 46.1%; RAO area 59.3 vs 39%; body width 102% vs 41.7%). Preoperative eating disorders were more present in efficient SGs than in failed SGs with the exception of sweet eating. There were no significant changes to taste perception during follow-up. Fifty-two percent of efficient SGs vs 26% of failed SGs reported a persistent lack of sense of hunger; similarly, 92.5 vs 78% declared the persistence of a sense of early satiety. The two groups did not statistically differ as far as all the variables of the EDI3 are concerned. CONCLUSION: On a long-term basis, the remnant mean dilation is around 50% compared to the immediate post-operative stage but failed SGs showed larger remnant dilation than efficient SGs and, in percentage, the more dilated portion is the body of the stomach. As far as all the EDI3 variables obtained are concerned, the two groups did not statistically differ. Of all eating disorders, sweet eating seems to be weakly connected to SG failure.

Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis.

While hyperthyroidism and hypothyroidism cause dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) followed up for 3 yr, we measured insulin sensitivity (by the insulin clamp technique) and 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) most features of IR emerged [i.e., male sex, greater body mass index (BMI), waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides; reduced insulin-mediated glucose disposal; and ß-cell glucose sensitivity). In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity and, in a subset of 303 subjects, directly related to endogenous glucose production. In multiple regression models adjusting for sex, age, BMI, and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, ß-cell glucose sensitivity, and baseline glycemia. Serum tyrosine levels were higher with IR and were directly associated with fT3; higher α-hydroxybutyrate levels signaled enhanced oxidative stress, thereby impairing tyrosine degradation. In 25 patients with morbid obesity, surgery-induced weight loss improved IR and consensually lowered fT3 levels. High-normal fT3 levels are associated with IR both cross-sectionally and longitudinally, and predict deterioration of glucose tolerance. This association is supported by a metabolite pattern that points at increased oxidative stress as part of the IR syndrome.

Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery.

CONTEXT: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. OBJECTIVE: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and ß-cell function by mathematical modeling of the C-peptide response to glucose. RESULTS: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min-1 · m-2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min-1 · m-2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, ß-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min-1 · m2 · mM-1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. CONCLUSIONS: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better ß-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.

Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity.

CONTEXT: Alterations in bile acid (BA) synthesis and transport have the potential to affect multiple metabolic pathways in the pathophysiology of obesity. OBJECTIVE: The objective of the study was to investigate the effects of obesity on serum fluctuations of BAs and markers of BA synthesis. DESIGN: We measured BA fluctuations in 11 nonobese and 32 obese subjects and BA transporter expression in liver specimens from 42 individuals and specimens of duodenum, jejunum, ileum, colon, and pancreas from nine individuals. MAIN OUTCOME MEASURES: We analyzed serum BAs and markers of BA synthesis after overnight fasting, during a hyperinsulinemic-euglycemic clamp, or a mixed-meal tolerance test and the association of BA transporter expression with body mass index. RESULTS: BA synthesis markers were 2-fold higher (P < .01) and preferentially 12α-hydroxylated (P < .05) in obese subjects, and both measures were correlated with clamp-derived insulin sensitivity (r = -0.62, P < .0001, and r = -0.39, P = .01, respectively). Insulin infusion acutely reduced serum BAs in nonobese subjects, but this effect was blunted in obese subjects (δBAs -44.2% vs -4.2%, P < .05). The rise in serum BAs postprandially was also relatively blunted in obese subjects (δBAs +402% vs +133%, P < .01). Liver expression of the Na+-taurocholate cotransporting polypeptide and the bile salt export pump were negatively correlated with body mass index (r = -0.37, P = .02, and r = -0.48, P = .001, respectively). CONCLUSIONS: Obesity is associated with increased BA synthesis, preferential 12α-hydroxylation, and impaired serum BA fluctuations. The findings reveal new pathophysiological aspects of BA action in obesity that may lend themselves to therapeutic targeting in metabolic disease.

Increased Bile Acid Synthesis and Deconjugation After Biliopancreatic Diversion.

Biliopancreatic diversion (BPD) improves insulin sensitivity and decreases serum cholesterol out of proportion with weight loss. Mechanisms of these effects are unknown. One set of proposed contributors to metabolic improvements after bariatric surgeries is bile acids (BAs). We investigated the early and late effects of BPD on plasma BA levels, composition, and markers of BA synthesis in 15 patients with type 2 diabetes (T2D). We compared these to the early and late effects of Roux-en-Y gastric bypass (RYGB) in 22 patients with T2D and 16 with normal glucose tolerance. Seven weeks after BPD, insulin sensitivity had doubled and serum cholesterol had halved. At this time, BA synthesis markers and total plasma BAs, particularly unconjugated BAs, had markedly risen; this effect could not be entirely explained by low FGF19. In contrast, after RYGB, insulin sensitivity improved gradually with weight loss and cholesterol levels declined marginally; BA synthesis markers were decreased at an early time point (2 weeks) after surgery and returned to the normal range 1 year later. These findings indicate that BA synthesis contributes to the decreased serum cholesterol after BPD. Moreover, they suggest a potential role for altered enterohepatic circulation of BAs in improving insulin sensitivity and cholesterol metabolism after BPD.