Year : 2017 | Volume
: 4 | Issue : 3 | Page : 161--165
Gestational diabetes mellitus: A diagnostic dilemma
Rakesh Agarwal1, Rashmi Baid2,
1 Department of Cardiology, IPGME&R, Kolkata, West Bengal, India
2 Department of Obstetrics and Gynaecology, IPGME&R, Kolkata, West Bengal, India
IPGMER and SSKM Hospital, AJC Bose Road, P.S-Bhowanipur, Kolkata - 700 020, West Bengal
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Despite decades of research and debate, confusion regarding screening and diagnostic criteria for GDM has been persistent. Despite initially been touted as the diagnostic criteria of choice, the Diabetes in Pregnancy Study Group India criteria themselves have been fraught with controversy. We review the disease and its history in brief with a timeline of different criteria proposed for its diagnosis which have only but added to dilemma in its diagnosis.
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Agarwal R, Baid R. Gestational diabetes mellitus: A diagnostic dilemma.CHRISMED J Health Res 2017;4:161-165
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Agarwal R, Baid R. Gestational diabetes mellitus: A diagnostic dilemma. CHRISMED J Health Res [serial online] 2017 [cited 2021 Sep 22 ];4:161-165
Available from: https://www.cjhr.org/text.asp?2017/4/3/161/210488
Pregnancy has been described as a transient excursion into the metabolic syndrome and as a window to women's health., Metabolic adaptations are necessary during pregnancy for the growth and development of the fetus and also to meet the altered demands of the mother. Glucose seems to be the major substrate for the human fetus throughout pregnancy. Hence, glucose metabolism has been the most extensively studied, yet little explored, subject of metabolism in pregnancy.
Diabetes mellitus is one of the oldest diseases known to humanity, being described in ancient texts more than 2000 years back. However, definitive medical literature on diabetic pregnancy has been scanty. In the preinsulin era, diabetes was thought to be incompatible with successful pregnancy. Blott, writing in Paris, in 1856, concluded that “true diabetes was inconsistent with conception.” Even in those who managed to conceive, death from uncontrolled diabetes was exceedingly common.
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies irrespective of whether insulin- or dietary-only treatment is utilized and whether the condition persists after pregnancy. It does not exclude the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy.
The data regarding prevalence of GDM and the number of women affected are important to allow for rational planning and allocation of resources and the preventive strategies that may be undertaken in future.
Confusion regarding screening and diagnostic criteria for GDM has been persistent. Timeline for major criteria and trials involving GDM includes the World Health Organization (WHO) criteria for diagnosing GDM in 1999, followed by the Australian Carbohydrate Intolerance Study in Pregnant Women trial underlining the benefits of treating GDM., The Diabetes in Pregnancy Study Group in India (DIPSI) guidelines were published in 2006, the Hyperglycemia and Adverse Pregnancy Outcome study in 2008, and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) revision of diagnostic criteria in 2010.,, In 2012, the American Dental Association (ADA) endorsed the IADPSG criteria. In 2013, the WHO adopted the IADPSG guidelines. The latest edition of ADA criteria was published in 2015.
Recent consensus has shifted toward accepting ADA criteria as the most useful for diagnosing GDM.
The ADA recommends two-step procedures for GDM diagnosis. However, in the community health centers, pregnant women are reluctant to undergo ADA procedures for two reasons:
The number of blood samples drawn are manyThey have to visit the antenatal clinic on two occasions for screening and again for diagnostic procedure.
Seldom, a pregnant woman visiting the antenatal clinic for the first time comes in the fasting state. If she is asked to come on another day in the fasting state, she may not return. Hence, it is important to have a test that detects the glucose intolerance without the woman necessarily undergoing a test in the fasting state, and it is preferable to perform the diagnostic test in the first visit itself.
The DIPSI criteria, on the other hand, recommend a single-step screening test to both diagnose and screen diabetes in pregnancy eliminating the problems associated with the ADA criteria. However, the DIPSI criteria have not been validated till date and not accepted by international authorities on the subject so far.
The first reference to diabetes in pregnancy is available since 1823, in the MD thesis of HG Bennewitz, University of Berlin, who described a single case in whom diabetes developed following conception, only to disappear after delivery. The baby weighed 12 pounds at birth and was said to be “robust and healthy.”
In 1882, Duncan focused the serious problems of diabetic pregnancy to the world through his observation of 22 pregnancies. Priscilla White introduced the world famous classification of diabetes in pregnancy in 1949. This was later followed by O'Sullivan and Mahan criteria for diagnosing GDM in 1964.
In India, the first “foetoplacental maternal unit” was started at the Institute of Obstetrics and Gynecology, Government Maternity and Children's Hospital, Egmore, by Prof. Sam GP Moses, Prof. Philips, and Prof. V Seshiah. In 1985, they organized the First International Colloquium on Diabetes in Pregnancy in Chennai followed by formation of the DIPSI in 2004.
Screening and Diagnosis of Gestational Diabetes Mellitus
For many years, controversy and debates have existed about GDM with regard to the following issues:
Its clinical significance and benefit of treatmentOptimal strategies for detection and diagnosisAppropriate treatment goals and methods.
Several randomized clinical trials have compared standard treatment of GDM to no intervention and established better outcomes with treatment. Yet, the opinion about the policy and detection of GDM has not been settled. The Fourth International Workshop-Conference on GDM for the first time suggested the strategy of blood glucose testing of all pregnant women than screening only the high-risk group.
For years together, it was a practice that “risk assessment” for GDM should be conducted as part of the initial prenatal evaluation. Those considered high risk should undergo initial blood glucose testing in early pregnancy. This strategy was also accepted in the “summary and recommendations” report of the International Workshop-Conferences on GDM. Based on the reports from the Toronto Tri-Hospital and other data confirming the low prevalence of GDM among younger women, the Fourth and Fifth International Workshop-Conferences and the ADA Expert Committee recommended a strategy for potential exclusion from blood glucose testing on the basis of below-average risk for GDM. Moses et al., however, found a prevalence up to 2.8%, compared to 6.3% overall in lean Caucasian women <25 years age. They suggested that the published guidelines for identifying pregnancies required further study.
There is no consensus among international bodies as to whether screening for GDM is essential and whether universal or selective screening is most appropriate. The best way would be to develop a definitive test which requires little preparation and takes little time to perform, without requiring prior interposition of a screening test and which could be applied to the entire obstetric population. In countries like India with a high prevalence of diabetes with and without pregnancy, a universal screening would appear appropriate.
Seshiah et al. documented the increased prevalence of GDM in Indian population and suggested the necessity of universal screening for glucose intolerance in pregnancy and the use of a 2 h plasma ≥140 mg/dL as a one-step procedure as it is simple and economical and can serve both as a screening and diagnostic criteria.
Despite several studies, no consensus has been reached regarding the diagnostic criteria for gestational diabetes yet.
As per the ADA guideline, “As the ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in women of childbearing age, the number of pregnant women with undiagnosed type 2 diabetes has increased. Because of this, it is reasonable to screen women with risk factors for diabetes at their initial prenatal visit using standard diagnostic criteria. Women with diabetes found at this visit should receive a diagnosis of overt, not gestational, diabetes.”
The recent NICE 2015 guidelines have recommended a fasting plasma glucose (FPG) value of 100 mg/dL in addition to the 2 h cut point of 140 mg/dL after a 75 g glucose challenge.
The WHO updated its 1999 criteria in 2013 for diagnosis of the same and came up with the following recommendations:
Hyperglycemia first detected at any time during pregnancy should be classified as either: (1) diabetes mellitus in pregnancy (2) GDMDiabetes in pregnancy should be diagnosed by the 2006 WHO criteria for diabetes if one or more of the following criteria are met:FPG ≥7.0 mmol/L (126 mg/dl)2 h PG ≥11.1 mmol/L (200 mg/dl) following a 75 g oral glucose loadRandom PG ≥11.1 mmol/L (200 mg/dl) in the presence of diabetes symptoms.
GDM should be diagnosed at any time in pregnancy if one or more of the following criteria are met:
FPG 5.1–6.9 mmol/L (92–125 mg/dl)1 h PG ≥10.0 mmol/L (180 mg/dl) following a 75 g oral glucose load2 h PG 8.5–11.0 mmol/L (153–199 mg/dl) following a 75 g oral glucose load.
The American College of Obstetricians and Gynecologists announced in 2011 that they continue to recommend the use of prior diagnostic criteria for GDM.
Disadvantages of these multiple criteria are:
Most of the time pregnant women do not come in the fasting state because of commutation and belief not to fast for long hours. The dropout rate is very high when a pregnant woman is asked to come again for the glucose tolerance testAttending the first prenatal visit in the fasting state is impractical in many settingsIn all GDM, FPG values do not reflect the 2 h postglucose with 75 g oral glucose (2 h PG), which is the hallmark of GDM. Ethnically, Asian Indians have high insulin resistance, and as a consequence, their 2 h PG is higher compared to Caucasians. The insulin resistance during pregnancy escalates further and hence FPG is not an appropriate option to diagnose GDM in Asian Indian women. In this population by following FPG >5.1 mmol/L as cutoff value, 76% of pregnant women would have missed the diagnosis of GDM made by the WHO 1999 criterion.
The DIPSI recommends that as a pregnant woman walks into the antenatal clinic in the fasting state, she has to be given a 75 g oral glucose load, and at 2 h, a venous blood sample is collected for estimating PG. This one-step procedure of challenging women with 75 g glucose and diagnosing GDM is simple, economical, and feasible. Screening is recommended between 24 and 28 weeks of gestation, and the diagnostic criteria of ADA are applicable. The reason for this is that “when a glucose tolerance test is administered to nonpregnant individuals, it is standard to use the 75 g, 2 h oral glucose tolerance test (OGTT). Using a different glucose challenge in pregnant versus nonpregnant patients leads to confusion in the laboratory and may result in errors in applying the proper diagnostic criteria.”
In the DIPSI study, a total of 862 consecutive pregnant women were subjected to 75 g oral glucose test irrespective of time of the last meal. Venous samples were collected at 2 h after oral glucose administration. They were advised to follow a diet containing at least 150 g carbohydrate daily and usual activity for at least 3 days and come to the prenatal clinic after an overnight fasting of 10–12 h. At the second visit, 800 of them responded and underwent 2 h 75 g oral glucose test in the fasting state recommended by the WHO. The observation in this study was all women diagnosed as GDM (n = 87) by 75 g glucose test irrespective of the last meal timings also satisfied the diagnostic criteria of 75 g oral glucose test performed in the fasting state recommended by the WHO. It was also found that there was no statistically significant difference (P > 0.05) between the PG levels of the 75 g glucose test in fasting and nonfasting state, irrespective of last meal timing, performed in the GDM and in normal glucose tolerant (NGT) pregnant women. The rationale behind this study outcome is that a NGT woman would be able to maintain euglycemia despite glucose challenge due to adequate insulin response, whereas in a woman with GDM who has impaired insulin secretion, her glycemic level increases with a meal and with glucose challenge and the glycemic excursion is expected to exaggerate. This cascading effect is advantageous as this would not result in false-positive diagnosis of GDM. Performing this test procedure in the nonfasting state, irrespective of last meal timing is prudent as glucose concentrations during the glucose tolerance are affected little by the time since the last meal.
Because there are difficulties in getting women to visit in a fasting state for the OGTT, Anjalakshi et al. conducted a study comparing the GTT done in the fasting and the nonfasting states. They found that the nonfasting OGTT had 100% specificity and sensitivity when compared to the fasting test taken as a “gold standard.” Based on this study, the DIPSI adopted the nonfasting OGTT as a single-step screening and diagnostic test for GDM in India.
Mohan et al. conducted a study recently in 1031 pregnant women attending antenatal clinics in urban and rural Tamil Nadu, India. Of the 83 women identified to have GDM by the WHO 1999 criteria, only 23 were diagnosed by the DIPSI criteria. Of the 106 women diagnosed to have GDM by the IADPSG criteria, only 24 were diagnosed by the DIPSI. The DIPSI nonfasting OGTT 2 h venous PG cut point of 140 mg/dl (7.8 mmol/l) had a very low sensitivity when compared to the WHO 1999 criteria (sensitivity 27.7%, specificity 97.7%) and IADPSG criteria (sensitivity 22.6%, specificity 97.8%). The “Women in India with GDM Strategy” study, however, showed that 78.5% of women did report for the second OGTT done in the fasting state even though no incentives were provided to the women.
A study from Delhi similarly reported that the nonfasting DIPSI criteria result in low sensitivity. Thus, two independent studies from different geographic locations showed that the DIPSI nonfasting OGTT is not suitable as a diagnostic test as it can miss a considerable number of women with GDM. One of the compelling arguments for a nonfasting test has been that most pregnant women will not come back for an OGTT in the fasting state. Diagnosis of GDM by the DIPSI criteria leaves 22.36% undiagnosed which may easily be detected through IADPSG, as per a recent study by Vij et al. A recent Sri Lankan study showed that the nonfasting test will miss as many as 60% of true GDMs. Worse, it will misdiagnose 33% of normal women as GDM who will be undergoing unnecessary monitoring through the rest of the pregnancy.
Despite decades of research and debate, controversy regarding the optimal strategy for screening and diagnosis of GDM has persisted. Despite initially been touted as the diagnostic criteria of choice, the DIPSI criteria themselves have not been fraught with controversy. A school of thought has emerged which questions the validity and sensitivity of the criteria considering that they would miss the many cases that present only with fasting hyperglycemia.
Obviously, the convenience of performing a DIPSI test is its chief advantage. Women need not be fasting, especially ones travelling long distances, and they could be diagnosed with a single blood test. Even if the test were repeated each trimester, the cost would be 66% less than the cost of performing other diagnostic procedures.
So, where do we stand? The enthusiasm associated with DIPSI criteria notwithstanding, the IADPSG criteria are the only outcome-based criteria and close to international consensus and cannot be discarded at the cost of implementing the DIPSI criteria, at least as long as more definite data regarding the DIPSI criteria are unavailable. This approach, as envisaged by Mohan et al., appears appropriate at the present time.
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Conflicts of interest
There are no conflicts of interest.
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