Unreliable testing procedures for gestational diabetes mellitus (GDM) may be leading to substantial underdiagnosis of the condition, researchers from the Australian National University (ANU) warn.
Delays in centrifugation of oral glucose tolerance test (OGTT) blood samples from pregnant women are associated with an 11.6% rate of diagnosis compared to 20.6% when centrifugation is done early, within 10 minutes of collection, they have found.
The discrepancy is due to ongoing glycolysis by erythrocytes and leukocytes in samples prior to centrifugation, resulting in lower measured blood glucose levels, according to Professor Christopher Nolan, from the ANU Medical School.
Professor Nolan and co-researchers from ACT Pathology made the findings in a comparison of early and delayed processing of OGTT samples from more than 12,000 pregnant women.
Their study compared OGTT results of 7,509 women obtained prior to May 2017 when blood samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation), against results obtained from 4,808 women with new protocols that required OGTT samples to be centrifuged within 10 minutes.
The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all).
The increase in the fasting plasma glucose concentration by 0.24 mmol/L contributed most to this increase in GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887) the study investigators said.
The findings have implications not only for management of women with GDM but also for interpretation of studies of GDM prevalence, said Professor Nolan.
“This is a real problem leading to unreliable gestational diabetes test results in many countries around the world,” he said.
He noted that current international guidelines for testing of gestational diabetes recommend the blood sample is placed in an ice slurry and centrifuged within 30 minutes of collection. However, this guideline is difficult to implement, particularly if the blood collection site is distant to the laboratory, like it commonly is for rural women.
A possible simple solution would be to switch from sodium fluoride to citrate in blood collection tubes because citrate immediately stabilises the blood cells and stops glucose consumption, he suggested.
“However, this would likely require a correction factor, or adjustment in the cut-points for diagnosis, due to a positive bias in plasma glucose concentrations measured from these tubes. As there is marked heterogeneity in preanalytical OGTT blood sample handling among pathology practices in Australia, this is an issue of major importance for Australian maternity services,” he concluded.