Interview with Professor Wing Hung Tam - Management of Gestational Diabetes Mellitus: Challenges in Hong Kong

Professor Wing Hung Tam
Department of Obstetrics and Gynaecology
The Chinese University of Hong Kong
Hong Kong  

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• What causes gestational diabetes mellitus (GDM), and why is it a cause for concern?
• How is GDM diagnosed, and what are the associated diagnostic challenges?
• What is the prevalence of GDM in Hong Kong?
• What are the risk factors for GDM that you have observed among Hong Kong mothers and what are the implications for GDM screening?
• How should GDM be managed?
• What is the role of vitamin D in GDM management?
• What advice would you give to women who are planning to have a baby?
• Summary

 

WHT: Professor Wing Hung Tam
R: Reporter
 

R: What causes gestational diabetes mellitus (GDM), and why is it a cause for concern?

WHT: Pregnancy is characterized by a physiological state of insulin resistance that results from anti-insulin effect of hormones produced from the placenta, and from maternal fat deposits. Beta cells in the pancreas normally increase insulin secretion to compensate for rising insulin resistance so that most women maintain normal glucose levels throughout their pregnancy. When insulin secretion becomes inadequate to meet tissue insulin demands, hyperglycaemia will result in GDM.¹

GDM increases mothers’ risk of pre-eclampsia, cesarean delivery and birth-related injuries.^2-4 Children born to mothers with GDM are at risk of neonatal jaundice, large-for-gestational age, and birth trauma, as well as developing obesity and diabetes mellitus (DM) later in life.^3-5
 

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R: How is GDM diagnosed, and what are the associated diagnostic challenges?

WHT: GDM is diagnosed based on glucose levels following a glucose load, usually an oral glucose tolerance test (OGTT), during the late second trimester.  In the past, there was no consensus on the diagnostic criteria for GDM.  

The Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study aimed to investigate if pregnancy outcomes were adversely affected at elevated glucose levels, which is below that of an overt DM. Results showed a linear association between elevated maternal glucose levels and adverse pregnancy outcomes, such as large-for-gestational age, cesarean section and neonatal hypoglycaemia.⁴

With the HAPO study findings, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel in 2010 proposed a new diagnostic approach towards GDM (Table 1) and overt diabetes in pregnancy (Table 2).⁶

 

 

Table 1. IADPSG threshold values for the diagnosis of GDM⁶

Glucose measure	Glucose concentration threshold
Fasting plasma glucose	5.1 mmol/L
1-hour plasma glucose	10.0 mmol/L
2-hour plasma glucose	8.5 mmol/L

 

Table 2. IADPSG threshold values for the diagnosis of overt diabetes in pregnancy⁶

Measure of glycaemia	Consensus threshold
Fasting plasma glucose	≥7.0 mmol/L
HbA1c	≥6.5%
Random plasma glucose	≥11.1 mmol/L + confirmation

 

These new criteria have generated debate. The American College of Obstetricians and Gynecologists decided to adhere to criteria established by the National Diabetes Data Group to maintain consistency of diagnoses within US populations.⁷ In its consensus statement on diagnosing GDM, the US National Institutes of Health (NIH) remarked that the IADPSG approach, which lowers the glucose threshold and promotes universal screening, would increase GDM rates by two-to three-fold.⁸ As a result, the NIH suggested that public health costs would rise and more women would undergo interventions without conclusive evidence of disease risk or treatment benefit.⁸

Despite the debate, the World Health Organization and the Australian Diabetes in Pregnancy Society updated their guidelines to reflect the IADPSG criteria (Table 3).^9-10

In Hong Kong, different hospitals adopt varying screening strategies and diagnostic approaches;¹¹ most public hospitals still maintain the WHO 1998 recommendations. The Hospital Authority Coordinating Committee (COC) in Obstetrics and Gynaecology has appointed a working group to standardise practice in all Hong Kong public hospitals.

 

Table 3. WHO 2013 and ADIPS 2014 diagnostic criteria for GDM¹⁰

Hyperglycaemia first detected at any time during pregnancy should be classified as either
Diabetes mellitus in pregnancy or;
Gestational diabetes mellitus
Diabetes mellitus in pregnancy should be diagnosed with the 2006 WHO criteria for diabetes if one or more of the following criteria are met:
Fasting,plasma glucose	≥7.0,mmol/L
2-hour,plasma glucose	≥11.1,mmol/L following a 75 g oral glucose load
Random,plasma glucose	≥11.1 mmol/L in the presence of diabetes symptoms.
The diagnosis of GDM at any time during pregnancy should be based on any one of the following values:
Fasting,plasma glucose	5.1–6.9,mmol/L
1-hour,post 75 g oral glucose load	≥10.0,mmol/L*
2-hour,post 75 g oral glucose load	8.5–11.0,mmol/L
*there are no established criteria for the diagnosis of diabetes,based on the 1-hour post-load value

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R: What is the prevalence of GDM in Hong Kong?

WHT: There are two studies that provide insight into Hong Kong’s prevalence of GDM if a universal OGTT screening programme was introduced.  The most recent figure is about 15%, based on the HAPO study dataset of 1,654 subjects recruited from the Prince of Wales Hospital between 2000 and 2006.¹²

An earlier study from the same unit reported a prevalence of 14.2% in a cohort of 942 Hong Kong women between 1990 and 1994.¹³ Unlike the HAPO study which established the WHO 2013 recommendations, mothers in this study were assessed according to the WHO 1998 criteria.

If the WHO 1998 criteria were applied to the HAPO cohort, it appears that the prevalence of GDM in Hong Kong rose 22% over a 10-year period. (unpublished personal data) A large epidemiological study also reported a marked increase in GDM prevalence in an urban city on mainland China.¹⁴
 

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R: What are the risk factors for GDM that you have observed among Hong Kong mothers and what are the implications for GDM screening?

WHT: The most common and important risk factors are advanced maternal age, obesity, excessive gestational weight gain in pregnancy, multiple pregnancies and family history of DM. As the pathophysiology of GDM and that of DM are very similar, a diagnosis of GDM in pregnancy actually unmasks the mother’s propensity for developing DM later in her life.

Most obstetric units currently adopt a risk factor-based screening approach and administer OGTT at 24–28 weeks of gestation to mothers with any risk factor of GDM. Some units provide random glucose tests to screen for GDM. 

Mothers, who had GDM during a previous pregnancy, have a history of polycystic ovarian syndrome or are on long-term corticosteroids, are at particular risk and warrant an OGTT in early pregnancy to exclude early onset GDM or DM in pregnancy.⁹ Furthermore, the Chinese ethnicity in itself is a risk factor for DM and GDM.

If a risk factor-based screening programme had been used in the Hong Kong HAPO study cohort, only two-thirds of women with GDM would have been identified. (unpublished personal data) Universal OGTT would identify all GDM cases, but the cost-effectiveness of this approach is still debatable
 

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R: How should GDM be managed?

WHT: In general, GDM is managed through dietary therapy and lifestyle modifications. The majority of mothers with GDM should respond to these measures without the need of pharmacological interventions, namely oral hypoglycemic drugs and insulin.  A small proportion of these mothers do need insulin if their glucose levels cannot be controlled with dietary therapy. All patients are also advised to carry out capillary glucose monitoring.

Two large randomized controlled trials (RCTs) clearly demonstrated the benefits of intervention for both mother and foetus, although the diagnostic criteria used in these studies differed from that of the WHO 2013 recommendations.³

However, there is inadequate information in the literature to conclude which types of dietary advice are best suited for women with GDM.¹⁵ Therefore, individual units should determine on their own dietary therapies for GDM mothers, based on their experience.
 

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R: What is the role of vitamin D in GDM management?

WHT: 1,25-dihydroxyvitamin D [1,25(OH)₂D] is an active metabolite of vitamin D that is known to stimulate insulin production and improve insulin sensitivity. Vitamin D deficiency therefore, was suggested to be part of the pathogenesis of GDM.  Over the last few years, several observational and cross-sectional studies have investigated the association between serum 25-hydroxyvitamin D [25(OH)D] levels and the risks of GDM. 

The results were mixed. Some studies reported increased odds of GDM in vitamin D deficient subjects (25(OH)D levels <50 nmol/L),^16-20 while others failed to establish an association.^21-23  Such discrepancies may be attributed to the diversity in the study designs, varying ethnicities of study groups with variable prevalence of vitamin D deficiency, and presence of confounders for GDM such as pre-pregnancy body mass index (BMI).

While three systematic review and meta-analysis concluded that rate of GDM is increased by about 50% for mothers with vitamin D deficiency,^24-26 a Cochrane systematic review suggested that there were no evidence to suggest that vitamin D deficiency was significantly associated with adverse pregnancy outcomes.²⁷

Using the new WHO 2013 criteria, Lacroix et al. (2014) demonstrated that lower vitamin D levels at the first trimester is associated with higher risk of GDM, after adjustment for confounding factors, and resulted in greater insulin resistance.²⁸ A study from Sydney also suggested that lower 25(OH)D levels are independently associated with poorer glycaemic control in GDM.²⁹ Although these studies suggest that low vitamin D levels are associated with an increased risk of GDM, evidence from RCTs is required to clarify whether vitamin D deficiency is a modifiable risk and to understand its magnitude of effect.

So far only two small RCTs from Iran have been published on the effect of vitamin D supplementation on maternal hyperglycaemia. Soheilykhah et al. (2013) demonstrated that vitamin D 50,000 IU every 2 weeks significantly improved insulin resistance compared with two other lower dose vitamin D regimens.³⁰ 

The other RCT involving 54 women with GDM found that with two courses of vitamin D 4,000 IU improved insulin resistance; the study however, was undermined by the fact that the treatment group had higher fasting plasma glucose levels and greater insulin resistance at baseline.³¹ An ongoing multicentre, European RCT will examine the potentially preventative roles of vitamin D and lifestyle interventions in obese women at high risk of developing GDM.³²

Recently, a study from northern England reported that mean vitamin D levels are lower in South Asians than in Europeans.³³ An observational study of 125 healthy women from Beijing also revealed that the rates of vitamin D deficiency and of severe vitamin D deficiency were 96.8% and 44.8% respectively.³⁴

As vitamin D supplementation is uncommon in Hong Kong’s routine antenatal care, it would be an important research study to look into the rate of vitamin D deficiency and its association with the high rate of GDM in this locality.
 

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R: What advice would you give to women who are planning to have a baby?

WHT: I would advise them to maintain a balanced diet and a healthy lifestyle that includes regular exercise, while taking folic acid supplement.  It is important for chronic smokers to quit smoking. Those who are obese with a BMI ≥ 25 kg/m² should seek medical advice on pre-conception counselling and will benefit from lifestyle modifications and weight reduction prior to conception.

The same advice applies to women with a history of GDM who are planning another pregnancy. Women who have risk factors of GDM should attend early antenatal visits for the screening and diagnosis of GDM.
 

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Summary Given that the WHO recently standardized classification and diagnosis of hyperglycemia first detected in pregnancy, it is the right time for Hong Kong practitioners to achieve a consensus on the diagnosis and management of the most common medical condition during pregnancy.

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WYE-EM-332-OCT-14

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