The Role of Pulsatile Insulin Secretion (A Study Investigating the Effects of Partial Pacreatectomy on Glucose Metabolism)
Condition: Impaired Glucose Tolerance
MeSH terms: Glucose Intolerance
Study type: Observational

Summary: 
      The purpose of this study is to examine changes in sugar metabolism that may occur in
      subjects who have previously had part of their pancreas removed due to a benign lesion.
    

Detailed description: 
      Beta cells of the pancreas are the insulin producing cells. People with impaired fasting
      glucose have a beta cell mass ~50% of that of normal glucose tolerant subjects.

      A 2006 canine study by Dr. Peter Butler's group at UCLA demonstrated that glucose stimulated
      insulin secretion was deficient after 50% decrease in beta cell mass after distal
      pancreatectomy compared to those dogs who had sham surgery. The pancreatectomized dogs had
      impaired fasting glucose with impaired insulin secretion and insulin resistance. The
      decreased insulin secretion was a result of decreased insulin secretory pulses or bursts with
      no change seen in pulse frequency, the same pattern seen in humans with Type 2 diabetes.
      Conclusions derived from this study include the following:

        1. When beta cell mass declines to ~50% the capacity for the remaining beta cells to
           secrete insulin in appropriate secretory bursts is compromised, leading to a deficit in
           insulin secretion most obvious on glucose stimulation.

        2. The decreased insulin burst mass results in an additional component of insulin
           resistance, and this together with the compromised capacity for insulin secretion leads
           to decompensation of glucose regulation and diabetes onset.

      How does this translate in humans who have had partial pancreatectomy? In 1990, Kendall and
      colleagues published a study looking at the effects of hemipancreatectomy in healthy human
      subjects on insulin secretion and glucose tolerance. These subjects were donors for
      pancreatic transplantation. They showed that fasting insulin and c-peptide levels were lower
      one year after hemipancreatectomy. Seven of the 28 donors had abnormal glucose tolerance one
      year after hemipancreatectomy, but all 28 had normal fasting plasma glucose levels. This
      study and others like it confirm the development of impaired glucose tolerance after partial
      pancreatectomy, but pulsatile insulin secretion and hepatic insulin clearance were not
      measured.

      As stated above, the main objective of this pilot study is to establish and quantify the
      impact of a deficit in beta cell mass, due to partial pancreatectomy for benign tumors, on
      glucose tolerance. Results of this study may be used to develop a future metabolic study that
      uses glucose isotopes to establish the effects of partial pancreatectomy on glucose
      tolerance, basal and stimulated insulin secretion as well as hepatic and extrahepatic insulin
      sensitivity under conditions of usual physiology. This will enable us to further understand
      the relationship between loss of beta cells, decreased insulin secretion and increased
      insulin resistance in humans.
    

Intervention name(s): All subjects will undergo a 120 minute Oral Glucose Tolerance Test at study visit 2.
Intervention type(s): Procedure
Intervention description(s): All subjects will ingest a 75 g glucose solution (Glucola brand) and have blood drawn at 7 timepoints over 120 minutes.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects 18-80 years of age who have had partial pancreatectomy for benign lesions and
        healthy controls who have not had pancreas surgery.
      
Keywords: Impaired Glucose Tolerance; Diabetes