Impact of Glucose Measuring Systems and Sample Type on Diagnosis Rates of Diabetes Mellitus

Abstract

Introduction: The use of glucose point-of-care testing (POCT) devices for the diagnosis of diabetes mellitus (DM) is an ongoing controversy. In patient management, glucose concentrations are determined by POCT and core laboratory glucose methods, and the values are commonly compared even though the samples collected are different, namely, capillary whole blood and venous plasma. In individual patients it is difficult to distinguish between factors that can influence the results, such as sample type and measuring procedure. In this study, glucose concentrations obtained using POCT and core laboratory instruments were assessed to duplicate typical scenarios experienced in healthcare. Corresponding diagnosis rates of impaired glucose tolerance (IGT) and DM based on fixed, method-independent cutoffs were compared.

Methods: Glucose concentration was measured by the 2-h oral glucose tolerance test (OGTT) in samples collected from an inpatient cohort and a cohort from the general population. Two POCT methods, namely, a handheld unit-use glucometer and a small bench-top analyzer with batch reagents, and two core laboratory procedures were used to measure glucose concentrations. The sample types were whole blood and plasma samples collected from venous and capillary blood. The glycated hemoglobin level in whole blood was also determined.

Results: A total of 231 subjects were included in the study. The 2-h OGTT glucose concentrations in the capillary whole blood samples showed a positive bias of 0.8 mmol/L compared to those obtained using core laboratory plasma glucose methods, leading to increased rates of diabetes diagnosis. This bias decreased to 0.2 mmol/L when venous blood was used in the tests. A change in the method used by the core laboratory introduced a negative bias of 0.5 mmol/L and, consequently, a lower diagnosis rates.

Discussion and conclusion: Venous blood samples measured at the point-of-care are the most suitable sample type for the measurement of the glucose concentration in the 2-h OGTT. The investigated unit-use POCT method is suitable for the diagnosis of IGT and DM when venous blood samples are collected. Importantly, changes in measurement procedures can introduce a bias and affect diagnosis rates, thereby emphasizing the need for further harmonization of glucose methods. A plain language summary is available for this article.

Keywords: Capillary blood glucose; Diabetes mellitus; Glucose concentration measurement; Impaired glucose tolerance; OGTT; Oral glucose tolerance test; POCT; Plasma-referenced blood glucose; Point-of-care-testing; Unit use.

Fig. 1

Flow chart of the study sample processing. Steps in blue boxes were carried out in both cohorts; steps in orange boxes were add-ons for the outpatient cohort. In the inpatient cohort, plasma glucose (P-glucose) measurements using the StatStrip glucometer in venous blood samples were performed with blood from the collection system since no venous lithium heparin samples were collected, as indicated by the superscript *1. At the time the outpatients samples were collected, the Dimension RxL device was no longer available in the core laboratory, as indicated by superscript *2. Processing steps inside the box were carried out immediately and in close proximity of the patient. EDTA Ethylenediaminetetraacetic acid, HbA1c glycated hemoglobin. See text for more details on the devices (StatStrip glucometer [StatStrip], YSI 2300 STAT plus [YSI], Dimension Vista [Vista], Tosoh G8 analyzer [Tosoh G8], model XN 9000 hematology meter [XN 9000])

Fig. 2

Box-plots of P-glucose and glycated hemoglobin (HbA1c) in whole blood (B-HbA1c) measured at 2 h after glucose loading by oral glucose tolerance testing (OGTT). a Inpatient cohort, b outpatient cohort. Horizontal lines represent the cutoff for diagnosis of impaired glucose tolerance (IGT) and diabetes mellitus (DM). X-axis: c capillary samples, v venous samples

Fig. 3

Scatterplots and absolute difference plots comparing P-glucose in venous samples (Vista device) and point-of-care testing (POCT) unit use (StatStrip device) using capillary (a) and venous (b) samples from both cohorts. CLSI Clinical and Laboratory Standards Institute, FDA Food and Drug Administration, Rili-BAEK German Medical Association on Quality Assurance in Medical Laboratory Examinations. Difference plots are constructed according to Freckmann et al., with modification

Fig. 4

Scatterplots and absolute difference plots comparing P-glucose in inpatient venous samples measured using the Vista and XN 9000 [RxL] core laboratory systems. Difference plots according to Freckmann et al. [13], with modification

Fig. 5

Comparison of outpatient venous duplicate measurements displayed as scatter plots and accompanied by difference plots according to Freckmann et al. and additionally modified