Vagal Nerve Stimulation and Glucose Metabolism
Condition: Type 2 Diabetes; Obesity; Gastric Emptying
MeSH terms: Obesity
Study type: Interventional

Summary: 
      The overall aim of this application is to determine the mechanism(s) by which common
      bariatric surgical procedures alter carbohydrate metabolism. The study proposed will examine
      the effect of vagal nerve stimulation on insulin secretion and action.
    

Detailed description: 
      The overall aim of this application is to determine the mechanism(s) by which common
      bariatric surgical procedures alter carbohydrate metabolism. Very often, resolution of
      diabetes occurs in the early post-operative period prior to the development of significant
      weight loss. It has been suggested that bariatric surgery alters insulin action but few
      studies have examined insulin secretion or postprandial glucose fluxes in such patients. At
      the present time, little is known about how the various bariatric surgical procedures alter
      glucose homeostasis. It is essential that the effect of bariatric surgery and meal size on
      these parameters be understood and accurately measured. Enteroendocrine secretion is affected
      by the rate of intestinal delivery of calories and may also be modulated by the enteric
      nervous system and the rate of direct delivery of nutrients to enteroendocrine cells. Direct
      measurement of intestinal transit is also an important part of understanding how bariatric
      surgery alters intestinal secretion of hormones that may alter glucose metabolism. The Oral
      and C-peptide Minimal Models when applied to C-peptide, glucose and insulin concentrations
      after ingestion of a standard labeled mixed meal can accurately measure insulin secretion and
      action. Subsequently, the disposition index provides a measurement of the appropriateness of
      insulin secretion for the prevailing insulin action. When coupled with established
      triple-tracer methodology, a mixed meal can be used to measure fasting and postprandial
      glucose fluxes. Though the vagal trunks are preserved during bariatric surgery, gastric
      transection during the formation of a gastric pouch for Roux-en-Y gastric bypass (RYGB), or
      during the sleeve gastrectomy for the duodenal switch procedure, may denervate post-gastric
      organs including the pancreas and intestine. Reversible vagal block results in weight loss,
      decreased caloric intake, earlier satiation and reduced hunger. The effect of this form of
      vagal denervation on glycemic control is unclear. There is evidence that hepatic
      parasympathetic input regulates insulin action in rodents. Vagal afferents are also important
      in hepatoportal glucose sensing.

      Subjects enrolled into the study would be on stable Vagal Nerve Stimulation Blocker (VNB)
      intervention in excess of 12 months, having taken part in prior observational study examining
      the long-term effects of vagal inhibition. All subjects will be studied three times after
      using a mixed meal. Participants will be admitted to the Mayo Clinic Clinical Research Unit
      at 17.00 hours the evening before the study. Following ingestion of a standardized low
      calorie mixed meal (400 Kcal: 55% carbohydrate, 30% fat, and 15% protein) subjects will fast
      overnight. During the experiment subjects will undergo a mixed meal study as outlined below
      (Lead-in Mixed Meal 1). On the day after study, subjects will be randomized to one of 2
      interventions: either discontinue use of the VNB or continue its use. Subjects will then be
      restudied (Mixed Meal 2) the day after admission to the Clinical Research Unit at 17.00 hours
      on the 13th day after randomization. To determine the metabolic effects, if any, of starting
      VNB therapy, on the day after study, VNB use will be resumed or discontinued depending on
      prior activation or inactivation. Subjects will then be restudied (Mixed Meal 3) the day
      after admission to the Clinical Research Unit at 17.00 hours on the 13th day after completion
      of Mixed Meal 2. Following completion of the study, VNB use will be resumed in all subjects.
    

Intervention name(s): VNB on; VNB off
Intervention type(s): Device; Device
Intervention description(s): The implanted Vagal Nerve Blocker will be on at the time of study.; The implanted Vagal Nerve Blocker will be off at the time of study.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Vagus; Diabetes; Obesity