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Background: The effectiveness of restrictive procedures has been inferior to that of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric banding and sleeve gastrectomy, confirm the strive for more efficacious solutions with less complications. We investigated the balance between effectiveness and complications for a new restrictive procedure, a Transoral Endoscopic Vertical Gastroplasty (TOGa®) Methods: Seventy-nine morbidly obese patients were submitted to one out of three surgical procedures: TOGa® (29 patients), laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion (BPD; 30 patients). Mean BMI were 41.7 (35.4-46.6), 44.8 (36.4-54), and 47.5 (41-60.3), respectively. All the patients reached a 2-year follow-up. Results: In TOGa® group BMI, respectively at 12 and 24 months, was 34.5 and 35.5, with 44 and 48.3 % of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and 29.2 kg/m, with 80 and 85 % of patients with BMI < 35. In BPD group, BMI was 30 and 29.6 kg/m, with 100 and 93.3 % of patients with BMI < 35. In TOGa® group, 59 % of patients with an initial BMI < 45 reached a BMI < 35, in comparison to 48 % recorded in the whole group and to 14.3 % in patients with initial BMI ≥ 45. Conclusions: In selected patients, TOGa®, was associated with good results after two years in terms of weight loss, even in comparison with LRYGBP and BPD. Minimal trauma, absence of complications, and short hospital stay justify this procedure for patients with low BMI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The surgical option could represent a valid alternative to medical therapy in some diabetic patients. However, no data are available on long-term effects of metabolic surgery on diabetic complications. We aimed to determine whether patients with newly diagnosed type 2 diabetes who underwent bilio-pancreatic diversion (BPD) had less micro- and macrovascular complications than those who received conventional therapy.Research Design and Methods: This was an unblinded, case-controlled trial with 10-years' follow-up, conducted from July 1998 through October 2009 at the Day Hospital of Metabolic Diseases, Catholic University, Rome, Italy. A consecutive sample of 110 obese patients (BMI >35 kg/m(2)) with newly diagnosed type 2 diabetes was enrolled. The study was completed by 50 subjects. The main outcome measure was long-term effects (10 years) of BPD versus those associated with conventional therapy on microvascular outcome, micro- and macroalbuminuria, and glomerular filtration rate (GFR). Secondary measures included macrovascular outcomes, type 2 diabetes remission, glycated hemoglobin, and hyperlipidemia.Results: Ten-year GFR variation was -45.7 ± 18.8% in the medical arm and 13.6 ± 24.5% in the surgical arm (P < 0.001). Ten-year hypercreatininemia prevalence was 39.3% in control subjects and 9% in BPD subjects (P = 0.001). After 10 years, all BPD subjects recovered from microalbuminuria, whereas microalbuminuria appeared or progressed to macroalbuminuria in control subjects. Three myocardial infarctions, determined by electrocardiogram, and one stroke occurred in control subjects. After the 10-year follow-up, coronary heart disease (CHD) probability was 0.22 ± 0.10 and 0.05 ± 0.04 in the medical and surgical groups, respectively (P < 0.001). Remission from type 2 diabetes was observed in all patients within 1 year of surgery. Surgical and medical subjects had lost 34.60 ± 10.25 and 0.38 ± 6.10% of initial weight at the 10-year follow-up (P < 0.001).Conclusions: Renal and cardiovascular complications were dramatically reduced in the surgical arm, indicating long-term benefits of BPD on diabetic complications, at least in the case of morbid obesity with decompensated type 2 diabetes. [ABSTRACT FROM AUTHOR]

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.

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 ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m-2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = -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. [ABSTRACT FROM AUTHOR]

Medium-chain dicarboxylic acids are produced by higher plants and animals via fatty acid ω-oxidation or by β-oxidation of longer-chain dicarboxylic acids. In plants, dicarboxylic acids are components of the natural protective polymers cutin and suberin; in animals, dicarboxylic acids are mainly oxidized in mitochondria, where they are transported through four different pathways. Their energy density is intermediate between glucose and fatty acids. Dicarboxylic acid administration does not require insulin or stimulate insulin secretion, and the β-oxidation of dicarboxylic acids produces succinic acid, a gluconeogenic substrate. Therefore, dicarboxylic acids might be a suitable fuel substrate, particularly in clinical conditions in which marked insulin resistance and/or impairment of aerobic glycolysis occur. [ABSTRACT FROM AUTHOR]

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 µmol ⋅ kg fat-free mass-1 ⋅ min-1 at 1 week and to 64.73 ± 3.42 µmol ⋅ 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 m²; P < 0.01) and total insulin output (43.76 ± 4.07 to 25.48 ± 1.69 and 30.50 ± 4.71 nmol/m²; P < 0.05) dramatically decreased, while a significant improvement in β-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 β-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. Diabetes 55:2025-2031, 2006 [ABSTRACT FROM AUTHOR]

Background: Suppression of ghrelin production after Roux-en-Y gastric bypass that suggested its contribution to appetite reduction has been reported. Objective: Because biliopancreatic diversion (BPD) does not affect appetite, we compared ghrelin production and 24-h pulsatility between healthy control subjects and obese subjects before and after BPD. Design: A computerized algorithm identified peak heights, clearance rate, and peak frequency of ghrelin over 24 h. Twenty-four- hour energy expenditure was measured in the calorimetric chamber, and energy intakes were computed. Insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp. Results: Mean (±SD) 24-h plasma ghrelin concentrations were significantly (P < 0.0001) higher in control than in obese subjects (338.17 ± 22.09 and 164.47 ± 29.19 μg/L, respectively), but they increased to 204.64 ± 28.51 μg/L in the obese subjects after BPD (P < 0.01). The pulsatility index was 0.098 ± 0.016 and 0.041 ± 0.014 μg · L-1 · min-1 in control and obese subjects, respectively (P < 0.01), and decreased to 0.025 ± 0.007 μg · l-1 · min-1 after BPD (P < 0.05). Energy intakes before and after BFP did not differ significantly. Although metabolizable energy after BPD was 40% of the energy intake, that (per kg fat-free mass) after BPD did not different significantly from that before BPD. Conclusions: Weight loss induced by malabsorptive bariatric surgery is associated with greater ghrelin concentrations, which, however, remain consistently lower than those in control subjects, whereas ghrelin pulsatility is subverted. Higher ghrelin concentrationsmaycontribute to the high calorie intakes observed in post-BPD subjects. The lack of normal pulsatility may explain the new impulse of these subjects to eat very frequently. [ABSTRACT FROM AUTHOR]

The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)α or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFα or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFα and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes. Diabetes 54: 2685-2693, 2005 [ABSTRACT FROM AUTHOR]

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]

Aim of the present study was to assess, in a pair-matched analysis design, risk factors for post-transplant diabetes mellitus (PTDM) in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx in relation to their baseline immunosuppression. PTDM was defined according to the 2003 American Diabetes Association and World Health Organization experts committee definition. As risk factors for PTDM development were considered: age, family history of diabetes, body mass index (BMI), baseline immunosuppression, doses and blood levels of the immunosuppressive agents used. Baseline immunosuppression consisted of CSA, TAC and SRL + CNI. Thirty-two pair-matched controls were identified among the 538 KTx and included in the risk analysis. Significant risk factors for the development of PTDM were identified in the family history of diabetes ( P < 0.02) and BMI ( P < 0.05). Higher BMI and positive family history for diabetes mellitus were significant risk factors for the development of PTDM, regardless of the immunosuppressive agent used. [ABSTRACT FROM AUTHOR]