February 2020 | Feabhra 2020

Improving Reliability of GDM Diagnosis

Fri, 14 February 20 11:54

UCD Research to Improve Reliability of Glucose Measurements Commended

A body of research by UCD researchers into improving the reliability of gestational diabetes diagnosis has been commended in a recently published Clinical Chemistry editorial.  The three papers were key outputs of PhD research by Dr Niamh Daly (UCD Medicine 2004, PhD 2018) and Dr Eimer O’Malley, current PhD student under the supervision of Prof Michael Turner at the UCD Centre for Human Reproduction, Coombe Women & Infants Hospital.

The diagnosis of gestational diabetes mellitus (GDM), a glucose intolerance that emerges during pregnancy, is highly dependent on reliable measurement of plasma glucose levels.  Correct diagnosis and management is important as maternal hyperglycaemia is associated with increased birth weight, increased risk of Caesarean delivery and pregnancy-related complications.

The UCD Centre for Human Reproduction at the Coombe Women & Infants Hospital have undertaken extensive research into ensuring the analytical reliability of plasma glucose measurement in the context of diagnosing GDM.  In routine diabetes care, plasma levels are typically measured at specified intervals before and after a glucose challenge.  However while non-obstetric diabetes diagnosis involves extensive characterisation and monitoring, gestational diabetes often relies on a single point measurement.

A major source of error in glucose measurement is the loss of glucose from blood specimens through red and white blood cell-mediated glycolysis.  This analytical error risks the under-diagnosis or misdiagnosis of GDM and has been the subject of much investigation by Prof Michael Turner’s group at the Coombe Hospital in recent years.

The Association of the American College of Endocrinology and the American Diabetes Association have developed guidelines on laboratory testing in diabetes.  The Turner group’s research has highlighted the critical importance of these analytical procedures in ensuring reliable glucose measurement and it is recognised that the recommendations are not always followed in GDM testing especially in resource-limited facilities.

PhD research at the UCD Centre for Human Reproduction has focused on examining and eliminating the sources of variability in plasma glucose measurement for the diagnosis of GDM.  They noted that strict observance of the recommended analytical chemistry protocol resulted in a 2.7-fold increase in the rate of diagnosis of GDM.

A prospective observation study evaluated the use of point of care measurements, which are routinely only recommended for monitoring GDM.  They concluded that in high-resource settings where measures to inhibit glycolysis are implemented, the use of POC measurements are not justified for reliable diagnosis.  In low- and medium-resource settings where strict compliance with analytical protocols cannot be assured, regression analysis using POC measurements may be acceptable compared with plasma samples which are subject to glycolysis.

The UCD group have also examined the use of alternative blood tubes which contain citrate as well as fluoride and EDTA (CFE tubes) compared with conventional NaF tubes.  They demonstrated a doubling of diagnostic sensitivity of oral glucose tolerance tests using the CFE tubes and recommended that their widespread adoption would minimise or eliminate variability in diagnostic sensitivity attributable to variable delays in sample processing.  There remain issues with the commercial availability of CFT tubes that limit their widespread adoption, however.

An editorial by Bruns, Metzger and Sacks in Clinical Chemistry highlighted the work of the UCD group and endorsed their conclusion of limited support for the use of glucose meters in GDM diagnosis.

We congratulate O’Malley and colleagues on their multiple, well-performed studies to define the best practices for diagnosis of GDM. They have highlighted the critical need to address preanalytical factors in measurements of glucose and provided valuable insights into ways to improve outcomes for women and newborns.

The editorial’s authors where co-investigators in a landmark 2008 multinational clinical study called the ‘Hyperglycaemia and Adverse Pregnancy Outcomes Study (HAPO)’ which examined the relationships between glucose intolerance and clinical outcomes in over 23,000 pregnancies.

References

Selected Publications by UCD Centre for Human Reproduction

Impact of Implementing Preanalytical Laboratory Standards on the Diagnosis of Gestational Diabetes Mellitus: A Prospective Observational Study.

Daly NFlynn ICarroll CFarren MMcKeating ATurner MJ.

Clin Chem. 2016 Feb;62(2):387-91. doi: 10.1373/clinchem.2015.247478. Epub 2015 Dec 4. PMID: 26637478

Comparison of Citrate-Fluoride-EDTA with Fluoride-EDTA Additives to Stabilize Plasma Glucose Measurements in Women Being Screened during Pregnancy with an Oral Glucose Tolerance Test: A Prospective Observational Study.

Daly NFlynn I, Carroll C, Stapleton M, O'Kelly R, Turner MJ.  Clin Chem. 2016 Jun;62(6):886-7. doi: 10.1373/clinchem.2016.254466. Epub 2016 Apr 21. PMID:27103574

A Prospective Evaluation of Point-of-Care Measurements of Maternal Glucose for the Diagnosis of Gestational Diabetes Mellitus.

O'Malley EG, Reynolds CME, O'Kelly R, Killalea A, Sheehan SR, Turner MJ. Clin Chem. 2020 Feb 1;66(2):316-323. doi: 10.1093/clinchem/hvz005. PMID:32040574

Editorial

Diagnosis of Gestational Diabetes Mellitus Will Be Flawed until We Can Measure Glucose.

Bruns DE, Metzger BE, Sacks DB. Clin Chem. 2020 Feb 1;66(2):265-267. doi: 10.1093/clinchem/hvz027. PMID: 32040567

2008 HAPO Study

Hyperglycemia and adverse pregnancy outcomes

HAPO Study Cooperative Research Group1, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA.  N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.