Important Considerations and Limitations
1. Biological and Analytical Variability of Glucose- and Insulin-Based Measures
Although this tool applies defined cutoffs for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), 1-hour post-load glucose, the insulinogenic index, and first-phase insulin release, both glucose- and insulin-based measures are subject to important sources of biological and analytical variability.
In the RISE study, 354 adults with impaired glucose tolerance or type 2 diabetes mellitus underwent repeat standardized OGTT testing after six weeks. Reproducibility was only moderate, with concordance rates of 75.4% for fasting glucose and 60.7% for 2-hour post-load glucose, demonstrating that glycemic classification itself may change on repeat testing.2
In parallel, insulin concentrations exhibit substantial assay-dependent variability across laboratories. Commercial insulin immunoassays show excellent within-assay precision but large between-assay differences, with deviations from LC-MS reference values ranging from −298 to +303 pmol/L (equivalent to −49.7 to +50.5 µU/mL).3
Together, these biological and analytical sources of variability underscore that glucose and insulin-derived indices should be interpreted as relative risk markers rather than absolute thresholds, and always in the context of the donor’s demographic and metabolic profile.
2. Variability of Metabolic Syndrome Components
Metabolic syndrome is an important component of the proposed risk assessment tool. However, many of its components demonstrate intraindividual biologic variability (CVb).
- One study reported average CVb values of 7.4% for HDL cholesterol and 22.6% for triglycerides.4
- For blood pressure, within-individual variability assessed by ambulatory monitoring showed coefficients of variation of 5.4% for daytime systolic blood pressure and 6.1% for daytime diastolic blood pressure, with higher variability during nighttime measurements (7.0% and 8.4%, respectively).5
- In normoglycemic individuals evaluated over several consecutive days (mean fasting plasma glucose 4.9 mmol/L [88 mg/dL]), within-subject coefficients of variation for fasting plasma glucose—used in ATP III metabolic syndrome classification—ranged from 4.8% to 6.1%.6