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Diabesity is a term often used to indicate the association of type-2 diabetes mellitus (T2DM) with obesity; the prevalence of both conditions is rapidly increasing worldwide and has reached epidemic proportions. Insulin resistance represents the major determinant of T2DM, which becomes manifest once relative β-cell failure ensues and insulin secretion is no longer sufficient to compensate for insulin resistance. In recent years, gastrointestinal surgery has emerged as the most effective option for the treatment of obesity and diabetes, with level-1 evidence of diabetes remission. Restrictive gastric operations such as gastric banding can improve insulin resistance in proportion to weight loss, while gastrointestinal bypass procedures, such as roux-en-y gastric-bypass (RYGB) and biliopancreatic diversion (BPD), can improve glucose homeostasis even before a significant weight loss is reached, suggesting weight-independent mechanisms of action. Studies comparing RYGB to BPD show that RYGB primarily enhances insulin secretion and reduces hepatic glucose output, whereas BPD rapidly improves glycemia primarily through the normalization of insulin sensitivity. Given the fact that BPD involves a significantly longer bypass of the proximal intestine than RYGB, these data suggest that the exclusion of a greater length of small bowel from the transit of food may cause broader and more profound influence on insulin sensitivity.

Objective: Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women., Research Design and Methods: Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method., Results: No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P < or = 0.01) as was the decrease in dehydroepiandrosterone (P < or = 0.05 and P < or = 0.01, respectively). CBG decreased from 51.50 +/- 12.76 to 34.33 +/- 7.24 mg/l (P < or = 0.01) following BPD. FCI increased from 11.15 +/- 2.85 to 18.16 +/- 6.82 (P < or = 0.05). Insulin secretion decreased (52.04 +/- 16.71 vs. 30.62 +/- 16.32 nmol/m(-2); P < or = 0.05), and insulin sensitivity increased by 163% (P < or = 0.0001). Serum CBG was related to BMI (r(0) = 0.708; P = 0.0001), body weight (r(0) = 0.643; P = 0.0001), body fat percent (r(0) = 0.462; P = 0.001), C-reactive protein (r(0) = 0.619; P = 0.004), and leptin (r(0) = 0.579; P = 0.007) and negatively to M value (r(0) = -0.603; P = 0.005)., Conclusions: After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.

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

The article presents a study which explained the modifications of circulating thyroid hormones and insulin sensitivity before and after Bilio-pancreatic diversion (BPD). It is stated that there are no pieces of evidence of auto-immune thyroiditis among the patients who became sub-clinically hypothyroid only following BPD. The result of colour doppler ultrasonography of the thyroid and respiratory exchange measurements is stated.

Background: Cardiovascular and metabolic comorbidities are dramatically increased in severe obesity, a condition highly resistant to nonsurgical therapy. Objective: The objective was to identify predictors of weight loss and reversal of comorbidity in obese patients undergoing malabsorptive bariatric surgery. Design: Morbidly obese men and women (n = 107) were studied before and 2 y after biliopancreatic diversion (BPD). Body composition, serum lipid profile, oral glucose tolerance, and blood pressure were measured. Insulin sensitivity was determined by use of a euglycemic clamp. The length of the small intestine was measured during surgery. Results: Intestinal length was 671 ± 99 cm, and the residual absorbing intestine after BPD ranged from 54% to 24% of initial length. Patients lost an average of 36% of their initial weight, with ≈50% of them reaching a body mass index (in kg/m2)<30. Serum cholesterol decreased (from 4.58 ± 1.11 to 3.34 ± 0.73 mmol/L; P < 0.0001), as did serum triacylglycerols (from 1.52 ± 0.59 to 0.88 ± 0.35 mmol/L; P < 0.0001), whereas insulin sensitivity rose 150% (from 26 ± 4 to 64 ± 11 μmol · min-1 · kg fat-free mass-1; P < 0.0001). Diabetes (in 23% of patients before surgery) and hypertension (in 83%) were reduced (by 88% and 96%, respectively) after surgery. In a multivariate model (including sex, age, intestinal length, presence of diabetes, insulin sensitivity, and initial fat mass), age and diabetes were independent, negative predictors of weight loss, whereas initial fat mass was a strong positive predictor (r2 = 0.51). Conclusions: Two years after BPD in morbidly obese patients, comorbidities are largely corrected and insulin resistance is fully reversed despite persistent obesity. Initial fat mass, but not residual intestinal length, is the strongest predictor of weight loss after BPD. [ABSTRACT FROM AUTHOR]

Presents a study on the effect of long-term low-fat intake on leptin levels in obese persons. Analysis of energy intake before and after bilio-pancreatic diversion; Increase in whole body glucose uptake; Maximum diurnal variation of leptin levels.

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. [ABSTRACT FROM AUTHOR]

Background: Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed. Methods: In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy). Results: At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group). Conclusions: In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; ClinicalTrials.gov number, NCT00888836.) [ABSTRACT FROM PUBLISHER]