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Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test
Ravi Retnakaran1, Sandy Shen, Anthony J Hanley
1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada. rretnakaran@mtsinai.on.ca
Obesity (Silver Spring, Md.)
|June 14, 2008
Summary
The study found that the product of the area under the insulin curve to the glucose curve (AUC(ins/gluc)) and the Matsuda index, derived from an oral glucose tolerance test (OGTT), demonstrates a hyperbolic relationship. This pairing serves as a potential measure of beta-cell function across various glucose tolerance levels.
Area of Science:
- Metabolic Physiology
- Endocrinology
- Biostatistics
Background:
- The disposition index, derived from intravenous glucose tolerance tests (IVGTT), is a validated measure of beta-cell compensatory capacity.
- A hyperbolic relationship between insulin secretion and sensitivity is fundamental to the disposition index's utility.
- Establishing an analogous measure using oral glucose tolerance tests (OGTT) requires validating this hyperbolic relationship with OGTT-derived parameters.
Purpose of the Study:
- To determine if a hyperbolic relationship exists between OGTT-derived measures of insulin secretion and insulin sensitivity.
- To identify specific OGTT-based indices that satisfy the criteria for a hyperbolic relationship.
- To evaluate the potential of a derived index as a measure of beta-cell function.
Main Methods:
- Tested five OGTT-derived insulin secretion measures against two insulin sensitivity measures (Matsuda index and 1/HOMA-IR).
- Utilized a log-linear regression model (log(secretion) = constant + beta * log(sensitivity)) to assess the hyperbolic relationship (beta ≈ -1).
- Analyzed data from women with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and a separate dataset including diabetes.
Main Results:
- The combination of total AUC(ins/gluc) and Matsuda index was the only pairing demonstrating a significant hyperbolic relationship (beta ≈ -1) in NGT and IGT groups.
- This hyperbolic relationship was confirmed across NGT, IGT, and diabetes groups in a separate dataset.
- The product of AUC(ins/gluc) and Matsuda index progressively decreased from NGT to IGT to diabetes, indicating declining beta-cell function.
Conclusions:
- A hyperbolic relationship can be established between OGTT-derived AUC(ins/gluc) and Matsuda index.
- The product of AUC(ins/gluc) and Matsuda index is a promising OGTT-based indicator of beta-cell function.
- This index offers a potential alternative to IVGTT-derived measures for assessing beta-cell compensation.
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