Showing papers by "Francesco Rubino published in 2014"

Bariatric, metabolic, and diabetes surgery: what's in a name?

Abstract: Objective:This study investigated the practical clinical consequences of offering surgery for metabolic disease and diabetes as opposed to weight loss.Background:The terms “metabolic” and “diabetes surgery” indicate a surgical approach whose primary intent is the control of metabolic alterations/hyp

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

Abstract: Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity (SI). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess SI. SI improved after DJB (SI = 1.14 ± 0.32 × 10(-4) min(-1) ⋅ pM(-1)) and jejunectomy (SI = 0.80 ± 0.14 × 10(-4) min(-1) ⋅ pM(-1)), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized SI in diabetic rats as shown by SI levels equivalent to those of Wistar rats (SI = 1.01 ± 0.06 × 10(-4) min(-1) ⋅ pM(-1); P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on SI, therefore contributing to the control of diabetes after gastric bypass surgery.

Incretins or anti-incretins? A new model for the "entero-pancreatic axis".

Abstract: The role of incretins in glucose homeostasis is well known. Yet, in recent years, the sustained weight loss and rapid glycemic control following bariatric surgery has challenged our understanding of the intestinal-pancreatic interaction. This in turn led to the introduction of metabolic surgery, an innovative medical discipline in which a surgical manipulation of the gastrointestinal tract (e. g., through a Roux-en-Y gastric bypass, RYGB, or Bilio-Pancreatic-Diversion, BPD) yields a sustained remission of diabetes mellitus. The pathophysiological background of this metabolic effect is, amongst other things, based on the anti-incretin theory. This theory postulates that in addition to the well-known incretin effect, nutrient passage through the GI-tract could also activate negative feedback mechanisms (anti-incretins) to balance the effects of incretins and other postprandial glucose-lowering mechanisms (i. e., suppression of ghrelin, glucagon, and hepatic glucose production via activation of nutrient sensing). This in turn prevents postprandial hyperinsulinemic hypoglycemia. The bypass of the duodenum, the entire jejunum and the first portion of the ileum by BPD induce normalization of peripheral insulin sensitivity, while the bypass of a shorter intestinal tract by RYGB mainly improves the hepatic insulin sensitivity. In addition, RYGB greatly increases insulin secretion. Therefore, metabolic surgery highlights the important role of the small intestine in glucose homeostasis, while until few years ago, it was only the pancreas and the liver that were thought to represent the regulatory organs for glucose disposal.

Surgical control of obesity and diabetes: the role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis.

Abstract: Objective To elucidate the specific role of gastric vs. intestinal manipulations in the regulation of body weight and glucose homeostasis. Design and Methods The effects of intestinal bypass alone (duodenal-jejunal bypass -DJB) and gastric resection alone (SG) in Zucker Diabetic Fatty (ZDF) rats were compared. Additional animals underwent a combination procedure (SG + DJB). Outcome measures included changes in weight, food intake (FI), oral glucose tolerance (GT) and gut hormones. Results DJB did not substantially affect weight and FI, whereas SG significantly reduced weight gain and food consumption. DJB rats showed weight-independent improvement in GT, which improved less after SG. Furthermore, SG significantly suppressed plasma ghrelin and increased insulin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide and peptide YY response to oral glucose whereas DJB had no effects on postprandial levels of these hormones. DJB restored postprandial glucagon suppression in diabetic rats whereas SG did not affect glucagon response. The combination procedure (SG + DJB) induced greater weight loss and better GT than SG alone without reducing food intake further. Conclusions These findings reveal a dominant role of the stomach in the regulation of body weight and incretin response to oral glucose whereas intestinal bypass primarily affects glucose homeostasis by a weight-, insulin- and incretin-independent mechanism

Is the gut the "sweet spot" for the treatment of diabetes?

Abstract: Oskar Minkowski possessed a rare combination of talents: He was an internist with the intuition of a scientist and the dexterity of a surgeon. One day in 1889, he and his colleague Joseph von Mering at the University of Strasbourg performed a total pancreatectomy in a dog to investigate if pancreatic enzymes were necessary to break down fatty acids in the gut. The dog survived the operation but unexpectedly developed polyuria, thirst, hunger, and glycosuria. Minkowski joined the dots to realize the link between the pancreas and diabetes (1). This story is just one example of how surgical manipulations of anatomy can play a major role in advancing knowledge about physiology and disease. Many lessons about the functioning of the central nervous system, the pituitary gland, and the adrenals have been learned through the help of a scalpel (2), and Minkowski’s observation provided the fundamental clue that lead to the discovery of insulin by Banting and Best in 1921. More than a century later, surgery may again provide a unique opportunity to improve our understanding of glucose homeostasis, diabetes, and β-cell growth. Readers of Diabetes will know that a number of gastrointestinal (GI) operations used to cause weight loss (bariatric surgery) has also been shown to cause remission of type 2 diabetes (T2D) (3,4) as well as improvement of hypertension and dyslipidemia (5) and reduction of cardiovascular disease and death associated with diabetes and obesity (6). The mechanisms by which these operations control diabetes have become the subject of intense research in recent years, fueled by the experimental evidence that GI bypass surgeries can induce very rapid antidiabetes effects, independent of weight loss (7). The pathophysiology of T2D is complex but the disease is characterized by a combination of insulin resistance and defective insulin secretion that …

Lipidomic Profiling at the Interface of Metabolic Surgery and Cardiovascular Disease

Abstract: Bariatric surgery has helped patients attain not only significant and sustained weight loss but has also proved to be an effective means of mitigating or reversing various obesity-related comorbidities. The impressive rates of remission or resolution of type 2 diabetes mellitus (T2D) following bariatric surgery are well documented and have rightly received great attention. Less understood are the effects of bariatric surgery on cardiovascular disease (CVD) and its underlying risk factors. Thanks to the availability of increasingly sensitive laboratory tools, the emerging science of lipidomics and metagenomics is poised to offer significant contributions to our understanding of metabolically induced vascular diseases. They are set to identify novel mechanisms explaining how the varied approaches of bariatric surgery produce the remarkable improvements in multiple organs observed during patient follow-up. This article reviews recent and novel findings in patients through the lens of lipidomics with an emphasis on CVD.

Refractory hyperglycemia after gastric bypass surgery: a novel subtype of type 2 diabetes?

Abstract: Patients failing to respond to radically effective therapies can provide clues to identify distinct disease subtypes. For example, the recognition of insulin-sensitive and insulin-insensitive patients helped reveal diabetes variants now classified as type 1 and 2. After Roux-en-Y gastric bypass (RYGB), 40–80% of patients with type 2 diabetes (T2DM) experience diabetes remission, and nearly all enjoy improved glycemic control (1–3). Studying absolute nonresponders to RYGB may reveal disease subtypes with distinct pathophysiology. Published series of bariatric surgery, however, usually describe general rates of remitters and nonremitters but do not distinguish between partial responders versus absolute nonresponders. Long diabetes duration (>10 years), preoperative insulin use, and lesser postoperative weight loss are associated with lower diabetes remission rates after RYGB (4), suggesting that insufficient insulin reserve at late-stage T2DM and/or inadequate weight loss may reduce diabetes responsiveness to surgery. Precise clinical and laboratory characterization of nonremitters in traditional bariatric surgery series, …

Creating a “Transcampus” in Diabetes Research Between King’s College London and the Technische Universität Dresden: Update on Islet Biology and Transplantation

Abstract: Correspondence Prof. Dr. med. S. R. Bornstein Medizinische Klinik und Poliklinik III Technische Universität Dresden Universitätsklinikum Carl Gustav Carus Fetscherstraße 74 D-01307 Dresden Tel.: + 49/(0)351/458 5955 Fax: + 49/(0)351/458 6398 Stefan.Bornstein@uniklinikumdresden.de Creating a “Transcampus” in Diabetes Research Between King’s College London and the Technische Universität Dresden: Update on Islet Biology and Transplantation