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

Impaired Glucose Tolerance Clinical Trial

— Pilot OGTT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00841867
• Other study ID #: DK61539
• Secondary ID: R01DK061539
• Status: Completed
• Phase: N/A
• First received: February 10, 2009
• Last updated: November 16, 2016
• Start date: December 2008
• Est. completion date: October 2009

Study information

• Verified date: November 2016
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Glucose Intolerance
• Impaired Glucose Tolerance

Intervention

Procedure:
• All subjects will undergo a 120 minute Oral Glucose Tolerance Test at study visit 2.
All subjects will ingest a 75 g glucose solution (Glucola brand) and have blood drawn at 7 timepoints over 120 minutes.

Locations

Country	Name	City	State
United States	UCLA General Clinical Research Center (GCRC)	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No