Preanalytical, analytical, and computational factors affect homeostasis model assessment estimates

OBJECTIVE - We investigated how beta-cell function and insulin sensitivity or resistance are affected by the type of blood sample collected or choice of insulin assay and homeostatis model assessment (HOMA) calculator (http://www.dtu.ox.ac.uk). RESEARCH DESIGN AND METHODS - Insulin was measured Using 11 different assays in serum and 1 assay in heparinized plasma. Fasting subjects with normoglycemia (n = 12), pre-diabetes, i.e., impaired fasting glucose or impaired glucose tolerance (n = 18), or type 2 diabetes (n = 67) were recruited. Patients treated with insulin or those who were insulin antibody-positive were excluded. HOMA estimates were calculated using specific insulin (SI) or radioimmunoassay (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% were > 300 pmol/l. beta-Cell function derived from different insulin assays ranged from 67 to 122% (median) for those with normoglycemia (P = 0.026), from 89 to 138% for those With pre-diabetes (P = 0.990), and from 50 to 81% for those with type 2 diabetes (P < 0.0001). Furthermore, insulin resistance ranged from 0.8 to 2.0 (P = 0.0007), from 1.9 to 3.2 (P = 0.842), and from 1.5 to 2.9 (P < 0.0001), respectively. This twofold 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 with serum, which is now more commonly used. beta-Cell function differed by 11% and insulin resistance by 15% when estimates derived from specific insulin were calculated using the RIA rather than the SI calculator. CONCLUSIONS - To enable comparison of HOMA estimates among individuals and different research studies, preanalytical factors and calculator selection should be standardized with insulin assays traceable to an insulin reference method procedure.