The Role of Pulsatile Insulin Secretion (A Study Investigating the Effects of Partial Pacreatectomy on Glucose Metabolism)

Study Overview
=================
Brief 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: 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. 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.

Official Title
-----------------
A Pilot Study Investigating the Effects of Partial Pancreatectomy on Glucose Tolerance

Conditions
-----------------
Impaired Glucose Tolerance

Intervention / Treatment
-----------------
* Procedure: All subjects will undergo a 120 minute Oral Glucose Tolerance Test at study visit 2.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and Female subjects 18-80 years of age who have had partial pancreatectomy due to a benign lesion OR are healthy control subjects are willing to fast (nothing to eat or drink for 10 hours)prior to visits Exclusion Criteria: Pancreatic malignancy Chronic pancreatitis Pregnant On steroid medications such as prednisone

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Subjects 18-80 years of age who have previously undergone partial pancreatectomy due to a benign lesion | Procedure: All subjects will undergo a 120 minute Oral Glucose Tolerance Test at study visit 2.<br>* All subjects will ingest a 75 g glucose solution (Glucola brand) and have blood drawn at 7 timepoints over 120 minutes.<br>|
| 2<br>Healthy control subjects, 18-80 years of age, who have not had partial pancreatectomy. | Procedure: All subjects will undergo a 120 minute Oral Glucose Tolerance Test at study visit 2.<br>* All subjects will ingest a 75 g glucose solution (Glucola brand) and have blood drawn at 7 timepoints over 120 minutes.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine differences in glucose metabolism between subjects who have had partial pancreatectomy due to a benign lesion and those who have not had such a surgery. |  | Outcome will be determined after all data has been collected. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Impaired Glucose Tolerance, Diabetes