Pyrrhic victory? Long-term results of biliopancreatic diversion on patients with type 2 diabetes and severe obesity.

BACKGROUND: The long-term results after biliopancreatic diversion (BPD) in patients with type 2 diabetes (T2D) and severe obesity is still being debated. OBJECTIVE: Retrospective evaluation of the long-term metabolic and clinical conditions of patients with T2D following BPD. SETTING: University hospital. METHODS: A total of 173 patients with T2D and severe obesity were investigated prior to and at 3-5 and 10-20 years after BPD. Anthropometric, biochemical, and clinical findings preoperatively and throughout follow-up were considered. The long-term data were compared with those of a cohort of 173 T2D patients with obesity treated with conventional therapy. RESULTS: T2D resolved within the first postoperative phases in most patients, and in the long and very long term, the fasting blood glucose level remained above the normal range in only 8% of patients. Likewise, a stable improvement of blood lipid pattern was observed (follow-up rate 63%). In contrast, in nonsurgical patients in the long term, the glucose and lipid metabolic parameters remained in the pathologic range in all cases. In the BPD group, a very high number of severe BPD-related complications was recorded, and 27% of the BPD patients died, whereas in the control group, 87% of patients were still alive at the end of the follow-up period (P < .02). CONCLUSION: Despite the high T2D stable resolution rate and the normalization of most metabolic data at 10-20 years following surgery, these results indicate that BPD should be indicated with caution in the surgical treatment of T2D in patients with severe obesity.

Diabetes Resolution at 10 Years After Biliopancreatic Diversion in Overweight and Class 1 Obese Patients with Type 2 Diabetes.

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.

Effects of the Postoepartive Dietetic/Behavioral Counseling on the Weight Loss After Bariatric Surgery.

OBJECTIVE: Weight outcomes after bariatric surgery are due to an adequate adjustment of eating behavior to the new gastrointestinal conditions created by operation. The efficacy of dietary/behavior counseling for promoting weight loss and maintenance in a growing number of bariatric patients was investigated. MATERIAL AND METHODS: One hundred seventy-six non-diabetic obese patients undergoing Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) were investigated. The first group (CO, 88 subjects, 16 male) attended a standard surgical follow-up, while in the second (DIET, 88 subjects, 15 male) the surgeon was supported by a dietitian, and patients received behavioral-dietary sessions on individual request. Data prior to the operation and at 2 years were considered, the weight outcome being regarded as successful when postoperative body mass index (BMI) value was lower than 30 kg/m2. RESULTS: Weight results were better (p < 0.01) in the RYGBP than in the SG patients. In comparison to CO, in the DIET group a greater adherence to the bariatric program was observed (76% vs. 41%, < 0.01), while body weight data and prevalence of successful cases at 2 years (87 ± 23 vs. 83 ± 16 kg and 27% vs.33%, respectively) were similar. CONCLUSIONS: After RYSG and SG, postoperative dietetic/behavioral sessions delivered on patient's request does not influence weight results. The dietetic intervention promotes the adherence to bariatric program and prevents postoperative follow-up loss. In a dietitian/behavioral strategy after RYGBP and SG, a cognitive reinforcement of the compliance to bariatric program and a strengthening of the motivation to changes could promote better weight results.

Disordered eating and weight loss after bariatric surgery.

PURPOSES: Aberrant eating patterns are frequently observed in bariatric patients. Since bariatric operations produce alterations in food transit and in appetite/satiety balance, postoperative eating behavior changes are not surprising. METHODS: 88 consecutive obese patients undergoing Roux-en-Y gastric bypass (RYGBP, 50 cases) and Sleeve Gastrectomy (SG, 38 cases) were retrospectively evaluated. Beside anthropometric data measurement, eating behavior was assessed by direct interview prior to the operation and at the first and second postoperative years: patients were considered as eating disordered (ED) when referred habitual occurrence of binge eating and nibbling/grazing. Weight loss was assessed by percent of BMI loss (% Δ BMI). Together with standard follow-up, patients received additional behavioral/dietetic support upon request. RESULTS: Postoperative ED patients showed lower % Δ BMI than the not ED ones at one (30.7% ± 8,5 vs. 26.8% ± 10, p < 0.02) and two (32% ± 10.3 vs. 27.4% ± 12.9, p < 0.05) years after operation, the follow-up rate being 82% and 76%, respectively, without differences between RYGBP and SG group. After RYGBP, an improvement of eating behavior was observed (ED patients from 75 to 28% at 1 year and to 27% at 2 years), while no changes were observed after SG. In SG patients, the number of additional behavioral/dietetic support sessions throughout the follow-up was positively associated with % Δ BMI. DISCUSSION: The postoperative normalization of eating pattern has a role in weight loss after bariatric surgery. Behavioral/dietetic support is indicated in all SG patient, while after RYGBP is useful only when weight loss is unsatisfactory. LEVEL OF EVIDENCE: III: retrospective cohort study.

Adipose Tissue Composition in Obesity and After Bariatric Surgery.

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.

Type 2 Diabetes Remission and Control in Overweight and in Mildly Obese Diabetic Patients at Long-Term Follow-Up After Biliopancreatic Diversion.

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.

Early reduction of matrix metalloproteinase-8 serum levels is associated with leptin drop and predicts diabetes remission after bariatric surgery.

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 (>0ng/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.

Prediction of Diabetes Remission at Long Term Following Biliopancreatic Diversion.

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 (HbA1C) 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.

Adipokine Pattern After Bariatric Surgery: Beyond the Weight Loss.

Besides the role in energy storing and body health isolating, adipose tissue produces proteins, the so-called adipokines, with pro-inflammatory or anti-inflammatory actions that contribute to metabolic control and to appetite and energy expenditure regulation. The marked adipose tissue loss following bariatric surgery corresponds to a rearrangement of serum adipokine pattern, with increase of anti-inflammatory and decrease of pro-inflammatory agents. This might play a relevant role in the postoperative improvement of metabolic conditions. However, after surgically induced weight loss, other investigations failed to evidence significant modifications of serum concentration of some adipokines. This review speculates that the composition of adipose tissue lost could influence postoperative changes in some adipokine concentration and that an adequate adipokine pattern plays a pivotal role for the long-term metabolic outcome.

Serum Leptin and Adiponectin Concentration in Type 2 Diabetes Patients in the Short and Long Term Following Biliopancreatic Diversion.

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.

Long-term clinical and functional impact of biliopancreatic diversion on type 2 diabetes in morbidly and non-morbidly obese patients.

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 ß-cell secretion/production plays a pivotal role in determining postoperative T2D remission.

From bariatric to metabolic surgery: Looking for a "disease modifier" surgery for type 2 diabetes.

In this review the recent evolution of the comprehension of clinical and metabolic consequences of bariatric surgery is depicted. At the beginning bariatric surgery aim was a significant and durable weight loss. Later on, it became evident that bariatric surgery was associated with metabolic changes, activated by unknown pathways, partially or totally independent of weight loss. Paradigm of this "metabolic" surgery is its effects on type 2 diabetes mellitus (T2DM). In morbid obese subjects it was observed a dramatic metabolic response leading to decrease blood glucose, till diabetes remission, before the achievement of clinically significant weight loss, opening the avenue to search for putative anti-diabetic "intestinal" factors. Both proximal duodenal (still unknown) and distal (GLP1) signals have been suggested as hormonal effectors of surgery on blood glucose decrease. Despite these findings T2DM remission was never considered a primary indication for bariatric surgery but only a secondary one. Recently T2DM remission in obese subjects with body mass index (BMI) greater than 35 has become a primary aim for surgery. This change supports the idea that "metabolic surgery" definition could more appropriate than bariatric, allowing to explore the possibility that metabolic surgery could represent a "disease modifier" for T2DM. Therefore, several patients have undergone surgery with a primary aim of a definitive cure of T2DM and today this surgery can be proposed as an alternative therapy. How much surgery can be considered truly metabolic is still unknown. To be truly "metabolic" it should be demonstrated that surgery could cause T2DM remission not only in subjects with BMI > 35 but also with BMI < 35 or even < 30. Available evidence on this topic is discussed in this mini-review.

The long-term impact of biliopancreatic diversion on glycemic control in the severely obese with type 2 diabetes mellitus in relation to preoperative duration of diabetes.

BACKGROUND: Bariatric surgery has been shown to be effective in severely obese patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: Evaluate the long-term efficacy of biliopancreatic diversion (BPD) for the treatment of T2DM depending on the preoperative duration of T2DM. SETTING: University Hospital. METHODS: Retrospective analysis investigating 2 subsets of severely obese patients who had undergone BPD from 1984 to 1995. The first included 52 patients with a preoperative T2DM duration of ~1 year (SD group - 49 on oral agents and 3 on insulin), and the second included 68 patients who had been diabetic for>5 years before BPD (LD group - 52 on oral agents and 16 on insulin). Postoperatively, T2DM was regarded as in remission when fasting serum glucose (FSG) was lower than 100 mg/dL on regular diet and without antidiabetic therapy. RESULTS: In the SD patients, the number of individuals without T2DM remission were lower both at 5-10 (0/31, 0% of patients, versus 8/54, 15% of patients, p<.04) and at>15 years (1/28, 3% of patients, versus 10/41, 24% of patients, p<.0012). Furthermore, after BPD, the number of patients with dyslipidemia strongly reduced (p<.001) in both groups, values at 5-10 years remaining very similar to those observed at>15 years. CONCLUSION: These results indicate that severely obese patients with longer T2DM duration have a worse metabolic outcome maintained at long and very long term following BPD.

Physical activity after surgically obtained weight loss: study with a SenseWear armband in subjects undergoing biliopancreatic diversion.

BACKGROUND: This study aimed to understand the role of the extra load of body mass in limiting physical activity and in preventing an active lifestyle in severely obese patients. MATERIALS AND METHODS: The study was carried out in a University Hospital setting, and investigates severely obese patients, having undergone biliopancreatic diversion (BPD) for obesity and control subjects with a body weight closely similar to that of the BPD subjects; energy intake was evaluated by alimentary interview and energy expenditure was assessed with the Body Media SenseWear® Pro armband (SWA). RESULTS: SWA metabolic efficiency (MET) was negatively associated with body mass index values (ρ = -0.464, p < 0.01), and the SWA overall energy expenditure was very similar to the energy alimentary intake in the obese patients and in the control subjects. Among the controls, the MET mean value was higher (p < 0.05) than that observed both in obese and in BPD subjects (1.392 ± 0.211 vs. 1.149 ± 0.181 and 1.252 ± 0.284, respectively); furthermore, in comparison with the obese and the BPD groups, among the control individuals a greater number of active persons (27% vs. 0 and 7%, respectively) and a lower number of sedentary persons (27% vs. 70 and 43%, respectively) was found (p < 0.01). CONCLUSIONS: These preliminary results suggest the reliability of SWA data in assessing energy expenditure and tend to rule out the hypothesis that in severely obese patients the extra load of body mass by itself is a main factor limiting physical activity and leading to a sedentary lifestyle.

Tissue specificity in fasting glucose utilization in slightly obese diabetic patients submitted to bariatric surgery.

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.