Pre-analytical, analytical and computational factors affect HOMA estimates

Abstract

Objective We investigated how β-cell function and insulin sensitivity or resistance are affected by the type of blood sample collected or choice of insulin assay and HOMA-calculator (www.dtu.ox.ac.uk).

Research Design And Methods Insulin was measured using 11 different assays in serum and with one assay in heparinized plasma. Fasting subjects were recruited with normoglycemia (n=12), pre-diabetes IFG or IGT (n=18) or type 2 diabetes (n=67). Patients treated with insulin or insulin antibody positive were excluded. HOMA estimates were calculated using SI- or RIA-calculators (version 2.2).

Results All glucose values were within model (HOMA) limits but not all insulin results as 4.3% were <20 pmol/l and 1% >300 pmol/l. β-cell function derived from different insulin assays ranged from 67%-122% (median) for those with normoglycemia, p=0.026, 89%-138% for pre-diabetes, p=0.990, and 50%-81% for type 2 diabetes, p<0.0001. Furthermore, insulin resistance ranged from 0.8-2.0, p=0.0007, 1.9-3.2, p=0.842, and 1.5-2.9, p<0.0001, respectively. This 2-fold variation in HOMA estimates from the various insulin assays studied in serum may be significant metabolically. Insulin was 15% lower in heparinized plasma (used in the original HOMA study) compared to serum which is now more commonly used. β-cell function differed by 11% and insulin resistance 15% when estimates derived from specific insulin were calculated using the RIA- rather than SI-calculator.

Conclusions To enable comparison of HOMA estimates between individuals and different research studies, pre-analytical factors and calculator selection should be standardised with insulin assays traceable to an insulin reference method procedure.