title: A novel hierarchal-based approach to measure insulin sensitivity and secretion in at-risk populations.
abstract: The pathogenesis of type 2 diabetes is characterized by insulin resistance and insulin secretory dysfunction. Few existing metabolic tests measure both characteristics, and no such tests are inexpensive enough to enable widespread use. A hierarchical approach uses 2 down-sampled tests in the dynamic insulin sensitivity and secretion test (DISST) family to first determine insulin sensitivity (SI) using 4 glucose measurements. Second the insulin secretion is determined for only participants with reduced SI using 3 C-peptide measurements from the original test. The hierarchical approach is assessed via its ability to classify 214 individual test responses of 71 females with an elevated risk of type 2 diabetes into 5 bins with equivalence to the fully sampled DISST. Using an arbitrary SI cut-off, 102 test responses were reassayed for C-peptide and unique insulin secretion characteristics estimated. The hierarchical approach correctly classified 84.5% of the test responses and 94.4% of the responses of individuals with increased fasting glucose. The hierarchical approach is a low-cost methodology for measuring key characteristics of type 2 diabetes. Thus the approach could provide an economical approach to studying the pathogenesis of type 2 diabetes, or in early risk screening. As the higher cost test uses the same clinical protocol as the low-cost test, the cost of the additional information is limited to the assay cost of C-peptide, and no additional procedures or callbacks are required.
authors.affiliation: University of Canterbury, New Zealand paul.docherty@canterbury.ac.nz.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Docherty
authors.affiliation: University of Canterbury, New Zealand.
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Chase
authors.affiliation: University of Canterbury, New Zealand.
authors.forename: Lisa
authors.initials: L
authors.lastname: Te Morenga
authors.affiliation: University of Canterbury, New Zealand.
authors.forename: Liam M
authors.initials: LM
authors.lastname: Fisk
mesh_terms: D000465:Algorithms; D002096:C-Peptide / Q000032:analysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D012016:Reference Values; D015203:Reproducibility of Results; D018570:Risk Assessment
chemical_list: D002096:C-Peptide; D007328:Insulin
keywords: a posteriori identification; hierarchical testing; insulin secretion; insulin sensitivity; type 2 diabetes