Abstract
INTRODUCTION: The diagnosis of diabetes mellitus is based on suitable cut-off values of specific biomarkers, such as the concentration of glucose in plasma. The German Diabetes Association has very recently published a clinical practice guideline on the definition, classification and diagnosis of diabetes mellitus that recommends measurements of plasma glucose concentration have an imprecision defined as a minimal difference (MD) of at a fasting plasma glucose concentration of 7.0 mmol/L. To obtain reliable values for the MD, we investigated long-term and short-term measurement uncertainty. METHODS: The imprecision was determined by two approaches: (1) a long-term dataset with imprecision based on the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK), in a medical laboratory operating 24/7, using internal quality control (IQC) data for four concentrations during a 10-year period; and (2) a detailed short-term dataset with imprecision assessed by hourly measurements of control materials. These datasets were used to calculate the MD cut-off (MD(cut-off)) as: [Formula: see text] = 2 [Formula: see text], where SD is the standard deviation and k = 2 represents a confidence level of 95%. RESULTS: The MD(cut-off) of ≤ 0.7 mmol/L at a fasting plasma glucose concentration of 7.0 mmol/L (MD(cut-off 7.0)) for the long-term and the short-term approaches were 0.44 and 0.40 mmol/L, respectively. The MD(cut-off 7.0) from both approaches was therefore below the recommended value of 0.7 mmol/L. It was noted that the variability in performance within and between instruments can be covered by reporting the long-term MD(cut-off 7.0) across all connected instruments. In this study, stable results for the MD(cut-off 7.0) were obtained after 1 year. CONCLUSION: Imprecision as measured by IQC data is remarkably stable over many years of operation. Current imprecision assessment usually focuses on only single instruments, whereas clinicians perceive the measurement as the result of the combined analytical performance of all instruments used for a certain assay. In the clinical setting, the MD may be a more useful measure of imprecision, and we suggest deriving the MD(cut-off) combined from all instruments and control cycles that are used in the patient care setting for a given analyte.