The Effect of Glucose Analytical Error and Biological Variation on the Risk of Misclassification of Community Patients using American Diabetes Association Diagnostic Criteria

Background & Aims: Current American Diabetes Association (ADA) guidelines state a fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) is diagnostic of diabetes, 100-126 mg/dL (5.6-7.0 mmol/L) pre-diabetes and <100 mg/dL (5.6 mmol/L) as healthy. The objective was to evaluate the impact of analytic error of glucose measurement and biological variation on misclassification of healthy, pre-diabetic and diabetic patients. Methods: NHANES 2015 FPG dataset was used as a population sample (n=2972) for simulation studies: prevalence of 13.1% diabetics by FPG. FPG results were categorized using ADA criteria. FPG concentrations were then modified in a statistical model by addition of bias, imprecision and biological variation. The fraction of modified FPG results misclassified between ADA healthy, pre-diabetic and diabetic groups was assessed. Results: The fractions of FPG results misclassified as functions of bias and precision were determined. Representative results were: (A) Biologic variation of FPG alone misclassified: 15% of Healthy values as Pre-diabetics, 20% of Pre-diabetics as Healthy, 3 % of Pre-diabetics as Diabetic, and 4% of Diabetic as Pre-diabetics. (B) Addition of 2% precision and -5% bias misclassified: 44% of Pre-diabetics as Healthy and 11% of Diabetics as Pre-diabetics and 11% of Diabetics as Pre-diabetic. (C) Addition of 2% precision and +5% bias misclassified: 36% of Healthy patients as Pre-diabetics, 11% of Pre-diabetics as Diabetic and 11% of Pre-diabetics as Healthy. Conclusions: This simulation model demonstrated significant risk of misclassification errors of diabetics, pre-diabetics and healthy patients due to bias of FPG methods and demonstrated minor influence of precision.