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The adipose tissue is a complex organ that regulates food intake and energy expenditure as well as induces low-grade inflammation. This review deals with changes in the composition and activity of the adipose organ after bariatric surgery, focusing on epicardial and ectopic fat and on relationships between white and brown adipose tissues. Postoperative improvements of ectopic fat and epicardial fat size and composition account for the metabolic recovery and the decreased cardiovascular risk. Following Roux-en-Y gastric bypass or biliopancreatic diversion, a proportional increase in the size and activity of the metabolically active brown adipose tissue was observed, most likely related to the postoperative rearrangement of the entero-hormonal pattern with an increase of GLP-1 production: this aspect would promote the postoperative weight loss and maintenance of post-surgery benefits.

Background: In severely obese patients with type 2 diabetes (T2DM), the metabolic benefits after biliopancreatic diversion (BPD) are due to mechanisms independent of weight loss. Therefore, the anti-diabetic effect of BPD in overweight or mildly obese T2DM patients was investigated., Methods: Ninety T2DM patients with BMI 25-35 underwent BPD and were evaluated 1 and 5 years after the operation (follow-up rate 100 and 83%, respectively)., Results: T2DM control (Hb1Ac < 7%) and remission (Hb1Ac < 6 without antidiabetics) was observed in 86.6 and 65% of cases at 1 year and 64.0% and 26.5% at 5 years, respectively. The long-term T2DM remission was predicted by baseline BMI value. Both before BPD and throughout the follow-up period, HOMA values were similar in the metabolically successful and unsuccessful subjects, while C-peptide normalized for FBG value as a marker of beta cell mass and insulin secretion increased progressively only in the former from 1.06 ± 0.64 to 1.44 ± 1.08 mcg/l ml/dl -1  * 100 (p < 0.002)., Conclusions: In T2DM patients with BMI of 25-35, a positive metabolic outcome is less frequent than in their counterparts with morbid obesity. In T2DM overweight patients, in spite of a short-term normalization of FBG and HbA1c levels and a well-sustained increase of insulin sensitivity, a long-term T2DM relapse occurs in the majority of the cases. While the surgically obtained decrease in insulin resistance leads to T2DM control in half of the patients, the increase in insulin secretion is mandatory for T2DM stable remission.

Importance: In obese patients with type 2 diabetes (T2DM), the marked weight loss following bariatric surgery is accompanied in a consistent number of cases by T2DM resolution or control. The clinical need of preoperative parameters reliable in predicting a positive metabolic outcome at long term following the operation has then emerged., Observation: A cohort of 135 consecutive T2DM patients with a wide range of body mass index (BMI) at more than 5 years following biliopancreatic diversion (BPD) was considered. The 5-year-T2DM resolution, defined as glycosylated hemoglobin (HbA1 C ) lower than 6.5% without antidiabetic therapy, was related to demographic, anthropometric, and biochemical findings prior to the operation. The long-term metabolic outcome was positively related to baseline BMI values and negatively with the preoperative use of insulin., Conclusion: BMI and insulin therapy at the time of surgery are associated with the probability of T2DM long lasting remission and could be used as solid predictors before surgery. In the overweight and non morbidly obese diabetic patients, bariatric surgery is less efficient in determining long term T2DM resolution than in their morbid obese counterparts.

Background: A deranged adipokine system is implicated in obesity and in type 2 diabetes mellitus (T2DM), and the lack of remission of T2DM after bariatric surgery could be also accounted for by the postoperative persistence of this condition., Methods: Thirty T2DM patients undergoing biliopancreatic diversion (BPD) with a wide range of baseline body mass index (BMI) were evaluated prior to and at 1 and 5 years following BPD. Besides the usual clinical evaluations, acute insulin response (AIR) to intravenous glucose load as a parameter of insulin secretion and the serum leptin and adiponectin concentration were measured throughout the follow-up period in all patients., Results: A long-term T2DM remission was observed in 21 patients (70 %). Serum leptin level reduced at the first year and remained substantially unchanged at a long term in both the remitter and non-remitter patients, while following the operation, a progressive significant increase of serum adiponectin level was observed only in remitter patients (from 9.2 to 12.3 μg/mL at 1 year and to 15.18 μg/mL at 5 years in the remitters and from 8.8 to 8.75 μg/mL at 1 year and to 11.8 μg/mL at 5 years in the non-remitters). Serum leptin mean values were positively associated with the BMI ones both prior to and following BPD (p < 0.005), while serum adiponectin values were positively related (p < 0.04) to the postoperative AIR data., Conclusions: The improvement of the pattern of cytokine production, as evidenced by postoperative rise in serum adiponectin concentration, might play a role in T2DM remission after bariatric surgery.

Setting: Obesity surgery has been proposed as a treatment option for diabetic patients with body mass index (BMI)<35 kg/m(2), but the efficacy of metabolic surgery has not been conclusively determined., Objectives: To evaluate the long-term metabolic outcome of non-morbidly obese (NMO) patients with type 2 diabetes (T2D) after biliopancreatic diversion (BPD)., Material and Methods: Two groups of T2D patients with different degree of obesity (NMO, 17 cases, BMI 25-35 kg/m(2); and morbidly obese [MO], 13 cases, BMI>35 kg/m(2)) were studied before and at 1 and 5 years after BPD in a university hospital setting. Insulin secretion was assessed by acute insulin response (AIR) to intravenous glucose and by insulinogenic index (IGI)., Results: In all MO patients, T2D was remitted or controlled (1 case) at 1 year and results were maintained at 5 years; AIR (μU/mL) and IGI (μU/mg) improved (P<.001) at 1 year (from .1±3.1 to 18.52±21.9, and from 6.0±8.5 to 9.1±22.8, respectively) with a further increase (to 24.8±25.5 and to 14.3±13.8, respectively) at 5 years. Within the NMO group, T2D was remitted in 1/17 and controlled in 14/17 patients at 1 year, and in 2/17 and in 4/17 patients at 5 years, respectively; AIR (μU/mL) and IGI (μU/mg) remained unchanged throughout the postoperative period (from .31±9.26 to 1.5±2.8 at 1 yr and to .4±3.29 at 5 yr for AIR, and from 2.2±4.9 to 1.3±9.0 at 1 yr and to 2.3±3.3 at 5 yr for IGI)., Conclusions: After BPD, restoration of β-cell secretion/production plays a pivotal role in determining postoperative T2D remission., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study aims to investigate if the benefits on glycemic control following Roux-en-Y gastric bypass (RYGB) in morbidly obese type 2 diabetes (T2DM) patients are maintained in the 30-35 kg/m(2) BMI (body mass index) range, comparing results with those in literature., Methods: The study participants were twenty T2DM patients aging 35-70 years, BMI 30.0-34.9 kg/m(2), minimum diabetes duration 3 years, glycosylated haemoglobin (HbA1c) ≥7.5% despite good clinical practice medical therapy, submitted to laparoscopic RYGB, and monitored during 36 months. Twenty-seven matched diabetic patients as controls., Results: Five females, mean age 57 (42-69) years, weight 96.0 (70-111) kg, BMI 32.9 (30.3-34.9) kg/m(2), waist circumference 112 (100-128) cm, diabetes duration 14 (3-28) years, HbA1c 9.5 (7.5-14.2) %, and C-peptide 3.2 (1,6-9.1) mcg/l. Ten patients were on insulin. There was no mortality, and there were two major late complications. BMI and waist decreased stabilizing around 25 kg/m(2) and 92 cm. Fasting serum glucose and HbA1c reached values around 150 mg/dl and 7%, which subsequently maintained. There was remission in 25% of cases, control 45%, and all the others improved. HOMA-IR and insulin sensitivity index normalized at 1 month, then maintained. AIR and insulinogenic index showed no postoperative changes. Diabetes remission correlated negatively with duration (p < 0.05; r (2) = 0.61), while control positively with C-peptide (p < 0.05; r (2) = 0.19). In the control group, FSG, HbA1c, serum triglyceride, and cholesterol significantly decreased with considerable progressive increase of antidiabetic/antihyperlipemic therapy. All patients had HbA1c >7% at 2-3 years., Conclusions: Glycemic control obtained by RYGB in this study was less good than that reported by others, apparently due to different patient selection criteria. Our results do not support RYGB weight loss-independent effect on beta-cell function in the T2DM patients with BMI 30-35 kg/m(2).

Objective: The present study was planned to investigate, by means of quantitative FDG-PET, how bariatric surgery (BS) modifies the metabolic pattern of the whole body and different tissues in slightly obese patients with type 2 diabetes mellitus (T2DM)., Design and Methods: Before, 1 and 4 months after BS, 21 consecutive slightly obese T2DM patients underwent blood sampling to estimate plasma levels of glucose, insulin, glycosylated hemoglobin. At the same time points, these patients underwent a dynamic (18) F-FDG PET study of thorax and upper abdomen in fasting state and after washout of T2DM therapy. Gjedde-Patlak analysis was applied to estimate glucose uptake in the whole body and in different tissues (myocardium, skeletal back muscle, adipose tissue, and liver)., Results: Surgical intervention quickly lowered levels of both insulin and glucose documenting an amelioration of glucose tolerance. Similarly, skeletal muscle and myocardial glucose uptake significantly increased soon after surgery (P < 0.001 and P < 0.01 at 1 month versus baseline, respectively) and remained substantially stable thereafter. By contrast, glucose uptake slightly decreased from its baseline values in the liver (P < 0.01 at 4 months) while no response could be documented over time in the adipose tissue., Conclusions: These findings document that BS-induced modification of glucose homeostasis in slightly obese T2DM patients is mostly due to an increase in muscle glucose consumption. The surgically modified metabolic pattern of these patients might be of interest as a new model to investigate mechanism underlying insulin resistance., (Copyright © 2012 The Obesity Society.)

Objective: Biliopancreatic diversion (BPD) resolves type 2 diabetes in near totality of morbidly obeses [BMI (body mass index) ≥35 kg/m]. However, studies of BPD effect in BMI range 25.0 to 34.9 kg/m, including about 90% of diabetic patients, are lacking., Materials and Methods: If BPD effects are independent of weight changes, they should be maintained in patients who, being mildly obese or overweight, will lose little or no weight after operation. Thirty type 2 diabetic patients with BMI 25 to 34.9 were submitted to BPD and monitored 12 months. Thirty-eight diabetic patients selected from a large database, kept 1 year on medical therapy, served as controls., Results: Nineteen male and 11 female. Mean age 56.4 ± 7.4 years, weight 84.8 ± 11.1 kg, BMI 30.6 ± 2.9 kg/m, waist circumference 104 ± 9.4 cm, diabetes duration 11.2 ± 6.9 years, HbA1c 9.3±1.5. Twelve patients on insulin. Fifteen (2 F) with BMI < 30 (mean: 28.1). No mortality or major adverse events occurred. BMI progressively decreased, stabilizing around 25 since the fourth month, without excessive weight loss. One year after BPD, mean HbA1c was 6.3%±0.8, with 25 patients (83%) controlled (HbA1c≤7%) on free diet, without antidiabetics, and the remaining improved. Acute insulin response to intravenous glucose had increased from 1.2 ± 2.9 to 4.2 ± 4.4 μIU/mL. Diabetes resolution correlated positively with BMI. HbA1c decreased at 1 year in the control group, along with an overall increased amount of antidiabetic therapy., Conclusions: BPD improves or resolves diabetes in BMI 25 to 35 without causing excessive weight loss, its action being on insulin sensitivity and beta-cell function. The strikingly different response between morbidly obese and low BMI patients might depend on different beta-cell defect. ClinicalTrials.gov Identifier: NCT00996294.

Objective: Biliopancreatic diversion (BPD) restores normal glucose tolerance in a few weeks in morbid obese subjects with type 2 diabetes, improving insulin sensitivity. However, there is less known about the effects of BPD on insulin secretion. We tested the early effects of BPD on insulin secretion in obese subjects with and without type 2 diabetes., Methods and Procedures: Twenty-one consecutive morbid obese subjects, 9 with type 2 diabetes (T2DM) and 12 with normal fasting glucose (NFG) were evaluated, just before and 1 month after BPD, by measuring body weight (BW), glucose, adipocitokines, homeostasis model assessment of insulin resistance (HOMA-IR), acute insulin response (AIR) to e.v. glucose and the insulinogenic index adjusted for insulin resistance ([DeltaI5/DeltaG5]/HOMA-IR)., Results: Preoperatively, those with T2DM differed from those with NFG in showing higher levels of fasting glucose, reduced AIR (57.9 +/- 29.5 vs. 644.9 +/- 143.1 pmol/l, P < 0.01) and reduced adjusted insulinogenic index (1.0 +/- 0.5 vs. 17.6 +/- 3.9 1/mmol(2), P < 0.001). One month following BPD, in both groups BW was reduced (by approximately 11%), but all subjects were still severely obese; HOMA-IR and leptin decreased significanlty, while high-molecular weight (HMW) adiponectin and adjusted insulinogenic index increased. In the T2DM group, fasting glucose returned to non-diabetic values. AIR did not change in the NFG group, while in the T2DM group it showed a significant increase (from 58.0 +/- 29.5 to 273.8 +/- 47.2 pmol/l, P < 0.01). In the T2DM group, the AIR percentage variation from baseline was significantly related to changes in fasting glucose (r = 0.70, P = 0.02), suggesting an important relationship exists between impaired AIR and hyperglycaemia., Discussion: BPD is able to restore AIR in T2DM even just 1 month after surgery. AIR restoration is associated with normalization of fasting glucose concentrations.

Objective: Ghrelin is a recently discovered hormone that is produced mainly by the stomach and that increases food intake in rodents and humans. It has been postulated that the weight loss after gastric bypass surgery for obesity might be related to changes in serum ghrelin concentration., Research Methods and Procedures: Serum leptin and ghrelin concentrations were measured in a group of obese patients before biliopancreatic diversion (BPD) and 2 and 12 months postoperatively. Insulin sensitivity was determined from serum glucose and insulin levels according to the homeostatic model of assessment for insulin resistance (HOMA IR)., Results: A sharp drop was observed in body weight, in BMI values, in HOMA IR data, and in serum leptin concentration at 2 and 12 months after BPD, whereas a significant increase of serum ghrelin level was observed at 12 months, when food intake had returned to preoperative levels. A negative correlation between the postoperative changes of serum ghrelin concentration and those of HOMA IR values was observed at 2 and 12 months after BPD., Discussion: No evidence upholding a relationship between serum ghrelin concentration and food intake after BPD was seen; the postoperative changes likely reflected the achievement of a new state of energy balance. The negative relationship observed between post-BPD changes in HOMA IR values and changes in serum ghrelin concentration supported the role of insulin in the modulation of ghrelin production.

Objective: To gain insight into the specific mechanisms by which biliopancreatic diversion (BPD) can improve insulin action., Materials and Methods: Nondiabetic severely obese patients (n=20) undergoing BPD were included. Waist-to-hip ratio and serum concentration of glucose, insulin, and leptin were determined before, at 4-day, and at 2 months after the operation. Insulin sensitivity was calculated according to the homeostatic model assessment (HOMA IR)., Results: A marked increase of insulin sensitivity was observed by the fourth day after the operation; at the second postoperative month, when body weight was still in the obese range and the food intake was substantially similar to the preoperative one, a further improvement of insulin action towards normality was found. Moreover, before BPD HOMA IR data were independently correlated both to BMI and waist-to-hip ratio values, whereas at 2 months after the operation data were in positive correlation only with the BMI., Discussion: In obese patients, BPD seems to achieve recovery of insulin sensitivity by specific mechanisms independent of weight loss: the main causes of this sharp improvement might be both the intramyocellular fat depletion and the interruption of enteroinsular axis.

Background: Long-term anti-diabetic effects of BPD in overweight or class 1 obese T2DM patients were investigated reporting the results at 10 years after BPD performed in severely non-obese T2DM patients. Material and Methods: Thirty T2DM patients with BMI lower than 35 kg/m2 were investigated at 1, 5, and 10 years after BPD, and the results are compared with those of 30 T2DM patients followed for 10 years on pharmacological and/or behavioral conventional therapy. Results: Mean levels of fasting blood glucose (FBG) and serum glycated hemoglobin (HbA1C) showed a marked reduction 1 year after BPD, values remaining slightly above the diabetic range throughout the entire follow-up. T2DM remission was observed in about 50% of the cases at 5 and 10 years after the operation. In 16 patients (53%), severe BPD-related complications developed, in ten cases requiring a surgical revision of the operation. In the BPD group, one patient died for malignant lymphoma and two patients after surgical revision. Within the control group, during the 10-year follow-up, no changes in the diabetic status were observed, being the FBG and HbA1C mean values higher than those recorded in the BPD patients at any follow-up time. All T2DM subjects of the control group were alive at the end of the 10-year follow-up. Conclusion: Despite satisfactory long-term metabolic outcomes, these data indicate that BPD should be used with caution as a metabolic procedure in the treatment of T2DM in overweight or class 1obese patients. [ABSTRACT FROM AUTHOR]

Background: Beneficial effects of BPD on T2DM in BMI >35 kg/m patients are far better than those in patients with BMI 25-35. This study was aimed at investigating if a similar difference exists between patients with mild obesity (OB, BMI 30-35) or simple overweight (OW, BMI 25-30). Methods: Fifteen OB (six M) and 15 OW (13 M), diabetic for ≥3 years, with HbA1c ≥7.5% despite medical therapy, underwent BPD. OB/OW: age 55.1 ± 8.0/57.8 ± 6.7 years, BMI 33.1 ± 1.5/28.0 ± 1.3 kg/m, diabetes duration 11.6 ± 8.0/11.1 ± 6.1 years, insulin therapy 4/8 p. FSG and HbA1c were determined preoperatively and up to 2 years. Insulin resistance and beta-cell function were explored by means of HOMA-IR and IVGTT (AIR). Thirty-eight diabetic patients on medical therapy served as controls. Results: Mean BMI stabilized around 27 since the 4th month in OB, and 24 since 1st month in OW. FSG in OB/OW preop, 1, 12, 24 months: 234 ± 76/206 ± 62 mg/dL, 154 ± 49/176 ± 75, 131 ± 32/167 ± 48, 134 ± 41/154 ± 41 (cross-sectional n.s. at all times); HbA1c: 9.5 ± 1.6/9.1 ± 1.3, 7.3 ± 1.1/7.3 ± 1.2, 5.9 ± 0.6/7.1 ± 1.1 ( p < 0.01), 5.9 ± 0.9/6.9 ± 1.1 ( p < 0.01). HOMA-IR, preoperatively 10.7 ± 5.8/7.5 ± 5.4, went below 3.0 at 1 month and remained such until 2 years in both groups. AIR, preoperatively 1.11 ± 3.17/1.27 ± 2.68 μIU/mL, in OB significantly increased at 4 months to 7.63 ± 5.79, maintained up to 2 years with 6.95 ± 3.19, whereas in OW, statistical significance was reached only at 2 years with 5.02 ± 4.87. Conclusions: Significantly different BPD effect, thus biological severity of T2DM, also exists between mildly obese and simply overweight patients. The rise of AIR allows hoping that an increase of beta-cell mass may occur in the long run. ClinicalTrials.gov Identifier: NCT00996294 [ABSTRACT FROM AUTHOR]

In subjects with obesity and type 2 diabetes mellitus (T2DM), biliopancreatic diversion (BPD) improves glucose stimulated insulin secretion, whereas the effects on other secretion mechanisms are still unknown. Our objective was to evaluate the early effects of BPD on nonglucose-stimulated insulin secretion. In 16 morbid obese subjects (9 with T2DM and 7 with normal fasting glucose (NFG)), we measured insulin secretion after glucose-dependent arginine stimulation test and after intravenous glucose tolerance test (IVGTT) before and 1 month after BPD. After surgery the mean weight lost was 13% in both groups. The acute insulin response during IVGTT was improved in T2DM after BDP (from 55 ± 10 to 277 ± 91 pmol/l, P = 0.03). A reduction of insulin response to arginine was observed in NFG, whereas opposite was found in T2DM. In particular, acute insulin response to arginine at basal glucose concentrations (AIRbasal) was reduced but insulin response at 14 mmol/l of plasma glucose (AIR14) was increased. Therefore, after BPD any statistical difference in AIR14 between NFG and T2DM disappeared (1,032 ± 123 for NFG and 665 ± 236 pmol/l for T2DM, P = ns). The same was observed for SlopeAIR, a measure of glucose potentiation, reduced in T2DM before BPD but increased after surgery, when no statistically significant difference resulted compared with NFG (SlopeAIR after BPD: 78 ± 11 in NFG and 56 ± 18 pmol/l in T2DM, P = ns). In conclusion, in obese T2DM subjects 1 month after BPD we observed a great improvement of both glucose- and nonglucose-stimulated insulin secretions. The mechanisms by which BDP improve insulin secretion are still unknown. [ABSTRACT FROM AUTHOR]

The associations between the degree of obesity, food intake, eating attitudes and behaviors and physical activity were evaluated in 500 men employees by the Public Transport Company (AMT) of Genova, Italy. The degree of obesity was evaluated by self reported body weight and stature values, eating habits and pattern by a questionnaire designed for subjects with Mediterranean eating style. Considering all behaviors, body mass index values were positively associated with usually eating sauces and well dressed food, and negatively connected with the behaviors being careful about what and how much is eaten and spending the weekly leisure time in physical activities. This study failed to evidence any specific eating pattern for overweight persons and suggests the main role of cognitive factors in determining body weight. [Copyright &y& Elsevier]

The article discusses a study on the effects of biliopancreatic diversion (BPD) on acute insulin response in type 2 diabetes mellitus with morbid obesity. It was found that acute insulin response (AIR) was significantly related to the change in fasting glucose, suggesting important relationships between impaired AIR and hyperglycemia. Results suggest that BPD affects beta cell function before and partially independently by clinically substantial weight loss.

Background We aimed at investigating whether the acute abrogation of leptin after bariatric surgery is able to reduce neutrophil activation and potentially affect type 2 diabetes mellitus (T2DM) remission. Methods Metabolic and inflammatory parameters ( i.e. leptin, IL-6 and neutrophil products) were compared at baseline (before bariatric surgery), one month, one and three years after surgery in morbid obese (MOB) T2DM patients ( n = 12) and non-MOB controls ( n = 32). In vitro , the effects of leptin on Il-6-induced human neutrophil degranulation and integrin upregulation were assessed. Results At baseline, MOB T2DM patients had a similar demographic, lipid and glycemic profiles than non-MOB T2DM controls, but higher levels of inflammatory mediators, such as CRP, fibrinogen, neutrophil-to-lymphocyte ratio (NLR), matrix metalloproteinase (MMP)-8 and leptin. One month after surgery, CRP, fibrinogen and MMP-8 were reduced only in MOB T2DM patients, while serum leptin was reduced in both groups. In the overall cohort, leptin and MMP-8 drops from baseline to one month post-surgery were positively correlated (Δleptin vs. ΔMMP8: r = 0.391, p = 0.025). Moreover, ΔMMP8 inversely correlated with fasting glucose levels at one-year follow-up and with glycated hemoglobin at both one- and three-year. At the cut-off point identified by ROC curve analysis (> 0 ng/mL), ΔMMP8 predicted complete T2DM remission at 3-year follow-up. In vitro , leptin increased IL-6-induced MMP-8 release and abrogated CD18 up-regulation. Conclusion Bariatric surgery is associated to an acute abrogation of leptin that could affect MMP-8 levels, particularly in MOB T2DM patients. This beneficial event is associated with T2DM remission at 3-year follow-up. [ABSTRACT FROM AUTHOR]