Ileal effect on blood glucose, HbA1c, and GLP-1 in Goto-Kakizaki rats.

BACKGROUND: There have been enumerable studies on the effects of glucagon-like peptide-1 (GLP-1) on satiety and pancreatic islet function, stimulating the advocacy of surgical transposition of the ileum (rich in GLP-1-generating L-cells) higher in the gastrointestinal tract for earlier stimulation. In the Goto-Kakizaki rat with naturally occurring type 2 diabetes, we studied the influence of ileal exclusion (IE) and ileal resection (IR) on blood glucose, hemoglobin A1c (HbA1c), and GLP-1. METHODS: In six control (Ctrl), 10 IE, and 10 IR rats, over 12 weeks of follow-up, we determined blood glucose, HbA1c, and GLP-1. RESULTS: Two animals in the IE and IR groups did not survive to week 13. Both operated groups weighed more than the Ctrl group at baseline and at 13 weeks; thus, IE and IR did not retard weight gain (p < 0.05). All three groups were equally hyperglycemic at week 13: 255 ± 10.2 Ctrl, 262 ± 11.0 IE, 292 ± 17.8 IR (mg/dl ± SEM). The three groups had statistically identical markedly elevated HbA1c percentages at week 13: 14.7 ± 28 Ctrl, 11.7 ± 3.4 IE, 13.8 ± 3.5 IR (% ± SEM). The end-study GLP-1 values (pM ± SEM) were 5 ± 0.9 Ctrl, 33 ± 8.9 IE, and 25 ± 6.7 IR. P values for intergroup differences were IE vs. Ctrl 0.02, IR vs. Ctrl 0.02, and IE vs. IR 0.59. CONCLUSIONS: Neither IE nor IR resulted in a decrease in the mean GLP-1 level. On the contrary, the exclusion or resection of the L-cell rich ileum raised GLP-1 levels 5- to 6-fold. This increase in the GLP-1 was not associated with the mitigation of hyperglycemia or elevated HbA1c levels.

Effects on GLP-1, PYY, and leptin by direct stimulation of terminal ileum and cecum in humans: implications for ileal transposition.

BACKGROUND: We do not have a unified, scientifically tested theory of causation for obesity and its co-morbidities, nor do we have explanations for the mechanics of the metabolic/bariatric surgery procedures. Integral to proffered hypotheses are the actions of the hormones glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin. The objective of this study was to obtain blood levels of GLP-1, PYY, and leptin after stimulation of the terminal ileum and cecum by a static infusion of a food hydrolysate in morbidly obese patients undergoing a duodenal switch procedure. SETTING: University Hospital. METHODS: Plasma levels of GLP-1, PYY, and leptin were obtained at 0, 30, 60, 90, and 120 minutes after instillation of 240 mL of a food hydrolysate into the ileum or cecum. RESULTS: The mean±SD GLP-1 values by cecal stimulation for 0, 30, 60, 90, and 120 minutes were: 41.3±23.2; 39.6±21.8; 38.9±19.1; 47.4±22.3; 51.7±27.3 pM, and by ileal stimulation: 55.0±32.8; 83.4±16.1; 78.7±23.8; 84.7±23.5; 76.4±25.6. The mean±SD PYY values by cecal stimulation were: 62.1±24.8; 91.1±32.8; 102.1±39.6; 119.6±37.5; 130.3±36.7, and by ileal stimulation: 73.8±41.6; 138.1±17.7; 149.5±23.3; 165.7±24.3; 155.5±29.1. Percent change in PYY levels increased ~150%, GLP-1 increased ~50%, and leptin decreased ~20%. CONCLUSION: Direct stimulation of the human terminal ileum and cecum by a food hydrolysate elicits significant plasma GLP-1 and PYY elevations and leptin decreases, peaking at 90-120 minutes. The ileal GLP-1 and PYY responses exceed those of the cecum, and the PYY effect is about 3-fold that of GLP-1. The results of this study question the satiety premise for ileal transposition.

Gastric plication: preclinical study of durability of serosa-to-serosa apposition.

BACKGROUND: Vertical gastric plication is a novel surgical approach for reducing the stomach capacity. Anterior surface plication and greater curvature plication are variations of vertical gastric plication that reduce the gastric capacity through infolding of the anterior surface or greater curvature of the stomach, respectively. These approaches have been tested, with positive results in a small number of preclinical and clinical trials. A key step toward greater investigation of vertical gastric plication as a viable bariatric procedure would be confirmation that the apposed serosal tissues can be securely and durably bonded. We compared the short-term durability of gastric plications and serosal bonds using a variety of fastening devices and techniques in a university hospital and private company setting. METHODS: A total of 30 anterior surface plication and 8 greater curvature plication procedures were performed using an open or a laparoscopic surgical technique in 38 hound dogs. The fastening devices used were T-tags, buttressed T-tags, 2 types of suture, and 4 types of staple-based fasteners. The density of the fastening devices was varied among the dogs. With 3 exceptions (2 in keeping with the study design and 1 due to complications), the dogs were followed up for 8 weeks. Histologic examinations and tensile testing were performed postmortem. RESULTS: All fastening devices created durable plication folds, except for 1 technique. The only technique that did not produce durable serosa-to-serosa adhesions was a staple/suture combination. Intentional abrasion of the apposed sites had no demonstrable effect on the bonds between the tissues in any group. Increasing the fastener density and number of rows increased the adhesions within the folds. CONCLUSION: Our findings have confirmed the short-term durability and development of dense fibrous appositions of the serosal folds for fastening approaches that create fixed serosal apposition. Additional studies are needed to identify the optimal fastening modality for anterior surface plication, greater curvature plication, and, ultimately, clinical applications of this procedure.

Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias.

OBJECTIVE: To present the longest follow-up report of any lipid-atherosclerosis intervention trial. SUMMARY OF BACKGROUND DATA: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a secondary, clinical/arteriographic, randomized controlled trial, was the first lipid-atherosclerosis trial to demonstrate unequivocally that low density lipoprotein cholesterol reduction reduced the incidence of coronary heart disease death and myocardial infarction. METHODS: We report POSCH 25 years follow-up for overall mortality, specific cause of death, and certain subgroup analyses, as well as a prediction for increase in life expectancy derived from the POSCH database, supplemented by the 2006 National Death Index, 1989-2006. RESULTS: There were 838 patients randomized in POSCH (421 surgery, 417 control). At 25 years follow-up, the difference in the restricted mean survival and the logrank (Mantel-Haenszel) statistic was statistically significant, with survival probabilities of 0.57 (surgery) and 0.51 (controls). Cause of death data indicated a significant increase in cardiovascular deaths in the control group; cancer deaths were also greater in the control group but this was not significant. The most compelling subgroup analysis was a significant increase in survival, starting at 5 years after randomization, in the surgery group for patients with an ejection fraction > or = 50%, with relative probabilities of 0.61 (surgery) and 0.51 (control). The estimated incremental increase in life expectancy over more than 25 years of follow-up was 1.0 year overall and 1.7 years in the cohort with an ejection fraction > or = 50%. CONCLUSIONS: A 25-year mortality follow-up in POSCH shows statistically significant gains in overall survival, cardiovascular disease-free survival, and life expectancy in the surgery group compared with the control group.

Micro-orifice metabolic/bariatric surgery under IV sedation/local anesthesia: porcine feasibility study.

BACKGROUND: As the volume and scope of metabolic/bariatric surgery increases, there is a definite trend toward the development and utilization of simpler and safer procedures. The laparoscopic approach has certain disadvantages that can be avoided by a technique for abdominal access via a micro-orifice incision under intravenous (IV) sedation/local anesthesia, without general anesthesia, insufflation, and intubation. METHODS: In a porcine model, we used the implantation of the TANTALUS System as a prototype for the micro-orifice, IV sedation/local anesthesia approach. The study was conducted in five ex vivo stomachs, four cadavers, and six in vivo animals, the last four of which underwent surgery under IV sedation/local anesthesia. RESULTS: Accurate implantation of electrodes was achieved in all ex vivo, cadaver, and in vivo preparations with no mucosal penetration, confirmed by examination of the open porcine stomachs. Operative time in this learning setting was 1 h 43 min in the last three operated animals. Feasibility was established for using the single incision to tunnel and construct subcutaneous pockets for the pulse generator and the charge coil. No major operative or postoperative complications occurred. CONCLUSIONS: Using the TANTALUS System as a metabolic/bariatric surgery prototype model, this study successfully tested the feasibility of micro-orifice surgery, under IV sedation/local anesthesia. This study will be followed by human trials that may offer an alternative approach for the performance of metabolic/bariatric surgery.