Veeshal H Patel, MD, MBA1, Dillon Kwiat, BS1, Elisabeth Leeflang, MD1, James Graham, BS2, Matthew Y Lin, MD1, Peter J Havel, DVM, PhD2, Michael R Harrison, MD1. 1University of California, San Francisco, 2University of California, Davis
Introduction: We hypothesize that a jejunoileal anastomosis and partial diversion using Magnamosis, a novel magnetic compression device, is technically feasible and will improve insulin resistance and metabolic syndrome similarly to patients who underwent bariatric surgery. Metabolic surgery has demonstrated improvements in various parameters including insulin resistance, triglyceride levels, and cholesterol. It may be technically feasible to perform a less-invasive operation through partial diversion, and thereby stimulate an increase in incretins from the L-cells of the ileum to glean these benefits.
Methods and Procedures: We performed a laparotomy and jejunoileal partial diversion using Magnamosis in five Rhesus macaques with induced insulin resistance through dietary modifications. After surgery, weight was monitored and a metabolic laboratory evaluation was performed weekly. Timed tests were performed at baseline and again at 3 and 6 weeks postoperatively for triglyceride levels, GLP-1, insulin, glucose, and bile acids. The primates were followed for 8 weeks prior to euthanasia. Results are represented as mean±SEM and all p-values were calculated using a two-sample Students’ t-test.
Results: All five monkeys successfully underwent surgery without technical or postoperative complications. Mean weight at 8 weeks decreased from baseline 17.9±1.2kg to 15.1±2.0kg (p=0.067), for a mean weight loss of 9.6%. At 6 weeks, there was a statistically significant decrease in mean triglyceride levels from 354.0±134mg/dL to 83.6±11.3mg/dL (p=9.8×10-15), mean fasting glucose from a baseline of 68.2±5.9mg/dL to 60.3±3.7mg/dL (p=0.0066), and fasting insulin from 96.4±21.3µU/mL to 35.2±8.2µU/mL (p=1.7×10-6). At 6 weeks, bile acid levels increased from 4.4±1.0µmol/L to 6.0±2.0µmol/L (p=5.93×10-7). Additionally, at 3 weeks, GLP-1 Active levels increased from the mean baseline value of 2.1±0.2ρg/mL to 7.0±1.6ρg/mL (p=4.5×10-7). At 6 weeks, mean total cholesterol decreased from 156.8±11.3mg/dL to 80.0±15.4mg/dL (p=0.023), LDL from 57.6±4.8mg/dL to 34.1±7.9mg/dL (p=0.062), and leptin from a baseline of 53±3.7ng/mL to 34.5±7.2ng/mL (p=0.032). Due to unanticipated effects of anesthesia during the timed mixed meal tolerance and oral glucose tolerance tests, we were unable to effectively demonstrate an improvement in insulin resistance.
Conclusions: The creation of a magnetic jejunoileal partial diversion in the rhesus monkey is technically feasible, safe, and reproducible. The translational similarities between the rhesus macaque metabolome and humans demonstrated expected improvements in specific metabolic parameters and GLP-1. More definitive tests of insulin resistance and additional markers of metabolic syndrome are necessary to elucidate the mechanism of action, improve future human translation, and further clarify the efficacy of this novel operation for metabolic surgery.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 84923
Program Number: P568
Presentation Session: iPoster Session (Non CME)
Presentation Type: Poster