102,640 research outputs found
Impact of different bariatric surgical procedures on insulin action and beta-cell function in type 2 diabetes.
No full textMechanisms of early improvement/resolution of type 2 diabetes after bariatric surgery
No full textBariatric surgery represents the main option for obtaining substantial and long-term weight loss in morbidly obese subjects. In addition, malabsorptive (biliopancreatic diversion, BPD) and restrictive (roux-en-Y gastric bypass, RYGB) surgery, originally devised to treat obesity, has also been shown to help diabetes. Indeed, type 2 diabetes is improved or even reversed soon after these operations and well before significant weight loss occurs. Two hypotheses have been proposed to explain the early effects of bariatric surgery on diabetes--namely, the hindgut hypothesis and the foregut hypothesis. The former states that diabetes control results from the more rapid delivery of nutrients to the distal small intestine, thereby enhancing the release of hormones such as glucagon-like peptide-1 (GLP-1). The latter theory contends that exclusion of the proximal small intestine reduces or suppresses the secretion of anti-incretin hormones, leading to improvement of blood glucose control as a consequence. In fact, increased GLP-1 plasma levels stimulate insulin secretion and suppress glucagon secretion, thereby improving glucose metabolism. Recent studies have shown that improved intestinal gluconeogenesis may also be involved in the amelioration of glucose homoeostasis following RYGB. Although no large trials have specifically addressed the effects of bariatric surgery on the remission or reversal of type 2 diabetes independent of weight loss and/or caloric restriction, there are sufficient data in the literature to support the idea that this type of surgery--specifically, RYGB and BPD--can lead to early improvement of glucose control independent of weight loss
Obesity Surgery and Cancer: What Are the Unanswered Questions?
No full textObesity has become a global epidemic with a soaring economic encumbrance due to its related morbidity and mortality. Amongst obesity-related conditions, cancer is indeed the most redoubtable. Bariatric surgery has been proven to be the most effective treatment for obesity and its associated metabolic and cardiovascular disorders. However, the understanding of whether and how bariatric surgery determines a reduction in cancer risk is limited. Obesity-related malignancies primarily include colorectal and hormone-sensitive (endometrium, breast, prostate) cancers. Additionally, esophago-gastric tumors are growing to be recognized as a new category mainly associated with post-bariatric surgery outcomes. In fact, certain types of surgical procedures have been described to induce the development and subsequent progression of pre-cancerous esophageal and gastric lesions. This emerging category is of great concern and further research is required to possibly prevent such risks. Published data has generated conflicting results. In fact, while overall cancer risk reduction was reported particularly in women, some authors showed no improvement or even increased cancer incidence. Although various studies have reported beneficial effects of surgery on risk of specific cancer development, fundamental insights into the pathogenesis of obesity-related cancer are indispensable to fully elucidate its mechanisms
Insulin sensitivity and secretion modifications after bariatric surgery
No full textType 2 diabetes mellitus is increasing over time as result of the obesity epidemics. In fact, the prevalence of Type 2 diabetes across Europe in 2010 was estimated to be 8.2% of the population and its projection for 2030 sees figures of 10.1%. This increase in the number of diabetic individuals has also dramatically raised the health expense, with spending on diabetes in Europe in 2010 accounting for 10% of the total healthcare cost. A meta-analysis of the literature evidenced that the clinical and laboratory manifestations of Type 2 diabetes are resolved in 78.1%, and are improved in 86.6% of obese patients (body mass index >35 kg/m2) after bariatric surgery. However, a gradation of effects of different surgical techniques in improving glucose control does exist, with the largest and durable effects observed in prevalently malabsorptive procedures. The outcome of bariatric surgery on insulin sensitivity and secretion is different in relation to the type of operation performed. In fact, while Roux-en-Y Gastric Bypass enhances insulin secretion after a meal thus improving glucose metabolism, Bilio-Pancreatic Diversion acts through the amelioration of insulin sensitivity allowing a subsequent reduction of insulin hypersecretion, which is a typical feature of the insulin resistance state. Gastric banding action is mediated uniquely through the weight loss, and the effect of sleeve gastrectomy is still to be elucidated. Incretin secretion is dramatically increased under nutrient stimulation after gastric bypass leading, probably, to an overstimulation of pancreatic β-cells resulting in the increase of insulin secretio
Early effects of gastric banding (LGB) and of biliopancreatic diversion (BPD) on insulin sensitivity and on glucose and insulin response after OGTT
No full textBariatric surgery improves glucose metabolism
Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test
No full textThe rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense
Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update
No full textDicarboxylic acids (DA) are formed from the omega-oxidation of monocarboxylic acids when the beta-oxidation of free fatty acids is impaired. Medium-chain DA have the peculiar characteristic of being water soluble due to the presence of two carboxylic terminal groups in the molecule. Contrary to both long- and medium-chain triglycerides which are administered as emulsions, they can be given by a peripheral vein as inorganic salts. DA are beta-oxidized at level of both peroxisomes and mitochondria via carnitine-independent pathway. The products of beta-oxidation of odd-chain DA are acetyl-CoA and malonyl-CoA, which cannot be oxidized further, are used in lipogenesis. Moreover even-chain DA produce acetyl-CoA and succinyl-CoA, which is a gluconeogenetic precursor. Azelaic acid (C9), does not show acute or chronic toxicity effects in animals but much of it is lost in urine (more than 50% of the given dose). Sebacic acid (C10) is lost in urine to a smaller extent (about 12% of the administered dose) and its energy density (6.64 kcal/g) is greater than that of C9 (4.97 kcal/g). Dodecanedioic acid (C12) seems to be the best candidate for parenteral nutrition, because it is eliminated in the urine only in minimal amounts (3.90% of the given dose), it is rapidly utilized by tissues, and it has a high energy density (7.20 kcal/g)
Pharmacokinetics of sebacic acid in rats
No full textThe pharmacokinetics of disodium sebacate (Sb) was studied in Wistar rats of both sexes. Sebacate was administered either as intra-peritoneal (i.p.) bolus (six doses ranging from 10 mg to 320 mg) or as oral bolus (two doses: 80 and 160 mg). Plasma and urinary concentrations of Sb and urinary concentrations of Sb and its products of beta-oxidation (suberic and adipic acids) were measured by an improved method using gas-liquid chromatography/mass-spectrometry. A single compartment with two linear elimination routes was selected after no increase in significance was shown by an additional compartment and after a saturable mechanism was found to be unsuitable. Both renal and non-renal elimination parameters were obtained by Marquardt non linear fitting of plasma concentrations together with urinary elimination. The data reported are calculated from the analysis on the whole population of rats and referred to an average body weight (bw) of 100 g. The Sb half-time was 31.5 min. The tissue elimination rate was 0.0122 min-1. The overall volume of distribution was found to be 26.817 ml/100 g bw. The renal clearance was 0.291 ml/min/100 g of bw, which is much less than the value of GFR reported in literature (about 1 ml/min/100 g bw), suggesting the presence of Sb reabsorption from the ultrafiltrate. The value of Sb renal clearance was found to be a concentration-independent function, suggesting the presence of a passive back-diffusion. The relative bioavailability of the oral form compared to the i.p. form was 69.09%, showing a good absorption of the drug
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