Evaluation of Fasting State-Oral Glucose Tolerance Test-Derived Measures of Insulin Release for the Detection of Genetically Impaired β-Cell FunctionReport as inadecuate




Evaluation of Fasting State-Oral Glucose Tolerance Test-Derived Measures of Insulin Release for the Detection of Genetically Impaired β-Cell Function - Download this document for free, or read online. Document in PDF available to download.

Background

To date, fasting state- and different oral glucose tolerance test OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common or recently introduced fasting state-OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction.

Methodology-Principal Findings

A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures p≤0.05. The indices were ranked according to their associations- statistical power, and the ranks an index obtained for its associations with all the tested SNPs or a subset were summed up resulting in a final ranking. This approach revealed area under the curve AUCInsulin0-30-AUCGlucose0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUCInsulin0-30-AUCGlucose0-30, corrected insulin response CIR, AUCC-Peptide0-30-AUCGlucose0-30, AUCC-Peptide0-120-AUCGlucose0-120, two different formulas for the incremental insulin response from 0–30 min, i.e., the insulinogenic indices IGI2 and IGI1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function HOMA-B; p<0.05. AUCC-Peptide0-120-AUCGlucose0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last.

Conclusions-Significance

With AUCInsulin0-30-AUCGlucose0-30, CIR, AUCC-Peptide0-30-AUCGlucose0-30, AUCC-Peptide0-120-AUCGlucose0-120, IGI2, IGI1, and insulin 30 min, dynamic measures of insulin secretion based on early insulin and C-peptide responses to oral glucose represent measures which are more appropriate to assess genetically determined β-cell dysfunction than fasting measures, i.e., HOMA-B. Genes predominantly influencing the incretin axis may possibly be best detected by AUCC-Peptide0-120-AUCGlucose0-120.



Author: Silke A. Herzberg-Schäfer , Harald Staiger , Martin Heni, Caroline Ketterer, Martina Guthoff, Konstantinos Kantartzis, Fausto Ma

Source: http://plos.srce.hr/



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