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New insulin sensitivity adjusted beta cell indices: validation according to a genetic study
Ken C Chiu1, Dorothy S Martinez, Nancy P Lee
1Division of Endocrinology, Diabetes, and Hypertension, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA. kchiu@mednet.ucla.edu
Pancreas
|July 29, 2003
Summary
The I27L polymorphism independently impacts beta cell function, as shown by new beta cell indices. These indices help identify glucose-tolerant individuals with a diminished beta cell reserve, aiding in diabetes research.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Research
Background:
- Hepatocyte nuclear factor-1alpha (HNF1alpha) is crucial for maturity-onset diabetes of the young 3 (MODY3).
- A common I27L polymorphism, unrelated to MODY3, affects beta cell function.
- Identifying individuals with low beta cell reserve is clinically significant.
Purpose of the Study:
- To develop novel beta cell indices for assessing beta cell reserve.
- To validate these indices against genetic data, specifically the I27L polymorphism.
- To investigate the independent impact of the I27L polymorphism on beta cell function.
Main Methods:
- Sixty glucose-tolerant subjects underwent hyperglycemic clamps to assess insulin sensitivity index (ISI), 1st phase insulin response (1stIR), and 2nd phase insulin response (2ndIR).
- Delta1stIR and delta2ndIR were calculated as the difference between actual and ISI-adjusted insulin responses.
- Genotyping was performed on genomic DNA to determine I27L polymorphism status.
Main Results:
- Significant differences in delta1stIR (P=0.0130) and delta2ndIR (P=0.0482) were observed across the three I27L genotype groups.
- Multivariate analysis confirmed the independent effect of the I27L polymorphism on delta1stIR (P=0.0130) and delta2ndIR (P=0.0369).
- Individuals with the LL genotype showed a higher prevalence (75% for delta1stIR, 63% for delta2ndIR) in the lowest quartile, indicating reduced beta cell function.
Conclusions:
- Novel beta cell indices effectively demonstrate the independent influence of the I27L polymorphism on beta cell function.
- These newly developed indices provide a valuable tool for identifying glucose-tolerant individuals with a reduced beta cell reserve.
- The findings contribute to a better understanding of genetic influences on beta cell function and diabetes risk.