Sid John,a K S Josepha,b
a Department of Obstetrics and Gynaecology, University
of British Columbia, Vancouver, British Columbia, Canada.b School of Population and Public Health, University
of British Columbia, Vancouver, British Columbia, Canada.
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Disclosure of interests: None declared.
Tennant et al used an elegant non-experimental approach to assess the
effects of fasting plasma glucose (FPG) and gestational diabetes
mellitus (GDM) diagnosis on GDM complications. Their study, based on
data from 2 hospitals in the UK, highlights inconsistencies in current
GDM diagnosis and management by showing that GDM complications are more
common among women with a lower FPG who are not diagnosed with GDM
(compared with women with a higher FPG who are diagnosed with GDM).
Thus, a woman with an FPG of 5.5 mmol/L, who is not diagnosed with GDM,
had a 32% risk of delivering a large-for-gestational age (LGA) infant,
while a woman with an FPG of 5.6 mmol/L, who is diagnosed with GDM, has
an LGA risk of 15%.
Diagnosis and intervention based on dichotomizing a biological parameter
that shows a linear relationship with adverse events can be fraught with
problems, especially when the events cluster around the parameter mean.
Lowering the FPG diagnostic threshold to ≥5.1 mmol/L would potentially
benefit a fraction of women with LGA infants (105 additional cases in
Tennant et al’s study) but not the majority of LGA cases that would
occur among women with an FPG <5.1 mmol/L (852 cases; Tennant
et al. Table 1). Similarly, such lowering of the FPG threshold would
potentially benefit 11 cases of shoulder dystocia but not the 68 cases
among women with an FPG <5.1 mmol/L. Tennant et al’s study
also highlights the slippery slope presented by dichotomization: if the
diagnostic threshold for GDM is lowered to ≥5.1 mmol/L, women with an
FPG of 5.0 mmol/L who are not diagnosed with GDM, would have a 22% risk
of LGA, while women with an FPG of 5.1 mmol/L who are diagnosed with
GDM, would have a 9% risk of LGA (Tennant et al. Supplementary Table
3).
The linear relation between plasma glucose and GDM complications, and
the dichotomized approach to diagnosis and management, also raise some
ethical and legal questions. If there is little difference in the risk
of GDM complications between women marginally below and those at and
marginally above the diagnostic threshold, is it defensible to label and
manage such women differently?
Although Tennant et al argue for a reconsideration of international GDM
diagnosis guidelines, they also advocate a graded approach for dealing
with hyperglycemia: lower levels of plasma glucose warrant less concern
and a lower intensity of intervention than higher levels. Concerns and
intervention would need to be appropriately modified by maternal factors
and other clinical inputs (e.g., fetal biometry). Such a graded approach
(with disease severity viewed on a spectrum) has long been a part of
medical theory and practice. On the other hand, there also exists a
strong desire among both physicians and patients for a simpler
framework, which favours the dichotomization and labeling approach to
diagnosis and management.
Although hyperglycemia is an important causal factor for LGA, shoulder
dystocia, and perinatal death, each of these complications is a
heterogenous entity with a multi-factorial etiology. Appropriate
diagnosis and treatment of hyperglycemia will address a fraction of such
complications, while a comprehensive attempt to prevent these
complications will require a multi-faceted strategy of fetal
surveillance, diagnosis, treatment and obstetric intervention. Defining
gestational diabetes using a hyperglycemic threshold is a seductive
proposition that represents a false dichotomy, and hyperglycemia is
perhaps better addressed clinically using a graded approach.