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Scientific background

Impact of GDM mothers and their babies

There is an escalating epidemic of type 2 diabetes (T2D) across the world in all ethnic groups, in particular, people of South Asian origin [1]. Current strategies for preventing T2D rely mainly on altering risk factors such as obesity, sedentary lifestyle and healthy eating. Though this is important, it is unlikely to make a big impact on this escalating epidemic, which consumes significant proportion of health care budgets, world-wide [2]. Some of the risk of developing metabolic diseases such as T2D and cardiovascular disorders (CVD) are evident even at birth [3-5]. Indeed, recent research suggests that factors acting during early development, including fetal growth restriction and exposure to gestational diabetes mellitus (GDM) in the mother increase diabetes and obesity risk in later life [6-8].

GDM is described as glucose intolerance first recognised in pregnancy. Similar to T2D, GDM is also increasing at an alarming rate, attributed partly to increasing maternal age and body weight [9-10]. The current estimate is around 4% of all pregnancies [11] though this could increase to as much as 17% if the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG) guidelines are implemented [12]. Women who develop GDM are at 7-8 times higher risk of T2D [13] and the children born to them are at higher risk of developing T2D, abdominal obesity and metabolic syndrome later in life thus increasing their risk of CVD in adulthood [6-7, 14-15]. Though the exact mechanisms of such increased risk are not clear, some of these effects could act through intra-uterine programming (programming of the baby by certain maternal factors) [16-17].

Vitamin B12/folate imbalance in pregnancy

There is no published data on the rate of B12 deficiency in GDM women in the UK and limited data exists in non-GDM women in Caucasians. However, small preliminary studies by our group have shown that: a) B12 deficiency is not uncommon in women of childbearing age (14%) and pregnant women (20% at 16-18 weeks of pregnancy) [18] and b) B12 deficiency in GDM is associated with higher BMI and higher birth weight in a clinic population [19].

The implications of having low vitamin B12 levels in pregnancy are not insignificant. Studies have shown that maternal vitamin B12 insufficiency and high homocysteine levels (which occur in presence of B12 or folate deficiency), in combination with normal/high maternal folate status, is associated with growth restriction in the foetus, and adiposity and insulin resistance in the children [5, 8]. This may be due to an interaction between environmental/nutritional factors and the genetic makeup of the developing embryo (known as ‘intrauterine programming’). Such programming may result in functional changes without any structural changes in the genes (called epigenetic programming).

There remains plenty to be discovered about which factors are involved in such programming and how exactly they do so. However, since vitamin B12 and folic acid are known to crucially contribute to the synthesis and repair of DNA, it is conceivable that imbalances in their levels may be causally related to some of the abovementioned observations.

Association between B12/folate imbalance and GDM

An interesting study done by Krishnaveni et al showed that mothers with vitamin B12 insufficiency had 2 times the risk of developing GDM at 30 weeks gestation compared to mothers who had did not have B12 insufficiency (8.7% vs 4.6%) [8]. This group of mothers also had higher body mass index and on follow-up at 5 years after the index pregnancy, had higher rates of insulin resistance and type 2 diabetes [8]. However, this study was conducted in India, where a high prevalence of B12 insufficiency may be attributed to vegetarianism [5]. It will be interesting to see if the same relation can be replicated in a UK population by the PRiDE study.