Micronutrients in Pregnancy as a Risk Factor for Diabetes and Effects on Mother and Baby: PRiDE Study
试验速览
- 阶段
- 不适用
- 入组人数
- 4,500
- 试验地点
- 1
- 主要终点
- Differences in B12 levels between GDM and Controls
研究概览
简要总结
There is a rapidly escalating epidemic of obesity and type 2 diabetes across the world, with the fastest rise occurring in low- and middle-income countries. India not only has one of the highest rates in the world, but the disease starts at a younger age and lower levels of body weight than in UK white caucasians. Among city-dwelling Indians, approximately 8% of people aged 30-40 years already have diabetes. This is creating a heavy burden of disease and disability, and an intolerable economic burden through medical costs and lost earnings. Until now, efforts to prevent diabetes have mainly focussed on modifying the diet, lifestyle and activity of at-risk adults (for example those who are overweight, have a family history of diabetes or already have high blood sugar). However, recent research has indicated that factors acting in early life (during development in the womb) place an individual at risk of later diabetes. These include maternal malnutrition and low birthweight, and diabetes in the mother during pregnancy. Our research has shown that Indian mothers often have low vitamin B12 levels, which in turn causes high blood levels of a harmful metabolite (homocysteine). We have shown that these mothers get more diabetes in pregnancy. Their children are more likely to born with a low birth weight, and develop more body fat and higher plasma insulin levels during childhood, which are signs of higher diabetes risk in later life. The risk is increased further if the mother has normal or high status for another B vitamin, folate. Thus, we have shown, for the first time a link between a specific nutritional deficiency in the mother and diabetes risk in the next generation. One possible mechanism for the effect of maternal nutrition on risk of diabetes in her children is through epigenetic effects, whereby the nutritional environment during early development affects the switches that control gene expression. Since these switches are passed on via either parent, we think it is possible that paternal vitamin B12 status could also be important.
详细描述
Background:
Risk of GDM and offspring's metabolic risk:
There is an escalating epidemic of type 2 diabetes (T2D) across the world in all ethnic groups, in particular, people of South Asian origin. 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. Some of the risk of developing metabolic diseases such as T2D and cardiovascular disorders (CVD) are evident even at birth. Indeed, recent research suggests that factors acting during early development, including foetal growth restriction and exposure to gestational diabetes (GDM) in the mother increases diabetes and obesity risk in later life. The investigators recent work has shown that maternal vitamin B12 insufficiency and hyper-homocysteinaemia, in combination with normal/high maternal folate status, is associated with an increased risk of GDM in the mothers, growth restriction in the foetus, and adiposity and insulin resistance in the children.
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. The current estimate is around 4% of all pregnancy though this could increase to as much as 17% if the new IADPSG guidelines are implemented. Women who develop GDM are at 7-8 times higher risk of T2D13 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. Though the exact etiological processes of such increased risk not clear, some of these effects could act through epigenetic mechanisms (intra-uterine programming).
The study by Krishnaveni et al raises an intriguing possibility for a simple measure for preventing GDM and future T2D. It is believed that the high prevalence of B12 insufficiency in India was attributed to vegetarianism. As the majority of the UK population is non-vegetarian, it is conceivable that B12 deficiency is unlikely during pregnancy. However, the investigators have recently shown: a) B12 deficiency is not uncommon in women of childbearing age (14%) and pregnant women (20% at 16-18 weeks of pregnancy) and b) B12 deficiency in GDM is associated with higher BMI and higher birth weight in a clinic population.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant women <16 years of age
- •High risk for GDM (at least 1 of the risk factors) - BMI >30
- •Previous GDM
- •First degree relatives with GDM
- •Previous unexplained still birth
- •Previous baby >4.5kg
- •Ethnic minority groups
- •Age >35years
排除标准
- •Pregestational Type 1 or Type 2 Diabetes
- •Diagnosis of B12 or folate deficiency in the current pregnancy
- •Previous pregnancies with NTDs
- •Diagnosis of severe aneamia (<10g/dL)
- •Vitamin B12 injections in the previous 6 months
结局指标
主要结局
Differences in B12 levels between GDM and Controls
时间窗: 5 Years
次要结局
- Differences in B12 levels in South Asians and White Caucasians(5 years)
- Differences between offspring birth weight between GDM and controls(5 years)
- Differences between offspring adiposity between GDM and controls(5 years)
- Differences between offspring birth weight between South Asians and White Caucasians(5 years)
- Differences between offspring adiposity between South Asians and White Caucasians(5 years)
- Clinical and Biochemical predictors of GDM in the first trimester(5 years)
- Predictors of abnormal post-natal OGTT in the first trimester(5.5 years)
研究者
Dr P Saravanan
Associate Clinical Professor
University of Warwick