Description of the condition
Introduction and definition
Gestational diabetes mellitus (GDM) is a complication of pregnancy that is defined as carbohydrate intolerance resulting in hyperglycaemia (abnormally high blood sugar) of variable severity with onset or first recognition during pregnancy (WHO 1999). GDM defined in this way includes women with undiagnosed pre-existing diabetes, as well as those for whom the first onset is during pregnancy (especially during the third trimester of pregnancy).
Pathophysiology and symptoms
In normal pregnancy, relative maternal insulin resistance develops, beginning in the second trimester, with a progressive decline in insulin sensitivity until term. This physiological change facilitates the transport of glucose across the placenta to stimulate normal fetal growth and development. For women with GDM, a greater degree of maternal insulin resistance may lead to maternal hyperglycaemia, increased glucose transport across the placenta, fetal hyperinsulinaemia and accelerated growth in the fetus (Setji 2005). Usually, pregnancy-induced maternal insulin resistance resolves promptly after the baby is born.
While many women are asymptomatic, symptoms and signs associated with hyperglycaemia, such as polyuria (increased urinary frequency), polydipsia (increased thirst), blurred vision and fatigue, may be seen where GDM is undetected or poorly controlled (Kjos 1999).
Risk factors for GDM
Observational studies have helped to identify a multitude of risk factors for GDM; these include maternal body mass index (BMI) of at least 30 kg/m², physical inactivity (Chasan-Taber 2008), advancing maternal age (Morisset 2010), increasing parity, and ethnicity. Diets low in fibre, with a high glycaemic load have been shown to increase the risk of GDM (Zhang 2006). Women are also at an increased risk of GDM who have had a previous macrocosmic baby (birthweight 4000 grams or more), have had previous GDM (Petry 2010), have a family history or first-degree relative with diabetes, or have polycystic ovarian syndrome (Reece 2010). Weight gain during pregnancy for women who are overweight or obese has also been shown to correlate with GDM risk (Hedderson 2010; Morisset 2010).
The prevalence of GDM appears to be increasing worldwide in parallel with increasing rates of type 2 diabetes mellitus and maternal obesity (Bottalico 2007; Dabelea 2005). Depending on the population sampled and diagnostic criteria used, reported prevalences range from 1% to 14% (ADA 2004; Mulla 2010). Diagnostic methods vary and there are currently no uniformly accepted international diagnostic criteria. The World Health Organization (WHO) recommends a 75 gram oral glucose tolerance test (OGTT) at 24 to 28 weeks' gestation. The woman is fasted prior to being given a 75 gram glucose load, with measurement of the blood glucose concentration two hours later (WHO 1999). The diagnosis of GDM is made if the blood glucose concentration at two hours is greater than or equal to 7.8 mmol/L. In some parts of the world a 100 gram three-hour OGTT is used. Universal screening is encouraged due to an absence of pre-identifiable risk factors in up to 50% of cases (Carr 1998). However, in some parts of the world, screening is only performed in 'high-risk' women, following an assessment of risk factors. Due to the lack of consistent screening procedures and diagnostic criteria between and within countries, different populations of women are diagnosed with GDM in different parts of the world.
The Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study addresses the absence of internationally agreed diagnostic criteria for GDM, and was designed to clarify risks of adverse outcomes associated with degrees of maternal glucose intolerance (Coustan 2010). Following this study, a task force of the International Association of Diabetes in Pregnancy Study Group (IADPSG) recommended new criteria for the diagnosis of GDM, which diagnoses GDM if any of the following three 75 gram, two-hour OGTT thresholds are met or exceeded: fasting plasma glucose: 5.1 mmol/L (92 mg/dL), one-hour plasma glucose: 10.0 mmol/L (180 mg/dL) or two-hour plasma glucose: 8.5 mmol/L (153 mg/dL) (IADPSG Consensus Panel 2010). Global adoption of these recommendations would likely have widespread implications, including for some regions/countries, a substantial change in practice, and in most cases, a substantial increase in the diagnosis of GDM, and accordingly significant challenges for healthcare systems. A number of studies have already revealed higher GDM prevalence when using the IADPSG, compared with other (including WHO) criteria (Edwards 2011; Moses 2011; O'Sullivan 2011), yet have also confirmed the increase in adverse pregnancy outcomes for the diagnosed women (O'Sullivan 2011); thus revealing a potential important opportunity the proposed criteria may provide for reducing maternal and infant morbidity. Debate surrounding the potential risks, costs and benefits of global use of these diagnostic criteria is ongoing (Langer 2013).
Health consequences of GDM
GDM is associated with an increased occurrence of a number of complications during pregnancy including pre-eclampsia (Dodd 2007) and the requirement for induction of labour or caesarean section (Dodd 2007; Reece 2010). Fetal consequences may include macrosomia (large baby), which in turn may be associated with adverse maternal outcomes such as uterine rupture, and perineal lacerations (Reece 2010). Women who develop GDM have a significantly increased risk of developing type 2 diabetes later in life (Bellamy 2009); they also are at an increased risk of developing GDM in future pregnancies (Bottalico 2007).
For the infant, GDM is associated with a range of complications. Babies born to mothers with GDM are more likely to be macrosomic or large-for-gestational age (LGA) (Crowther 2005; Metzger 2008; Reece 2009; Reece 2010). LGA infants are at increased risk of birth injury, including perinatal asphyxia, and shoulder dystocia, bone fractures or nerve palsies (Henriksen 2008; Reece 2010). These infants are also at increased risk of developing type 2 diabetes, hypertension, obesity and metabolic syndrome later in life (ADA 2004; Reece 2010; Whincup 2008). In addition, babies born to mothers with GDM are at increased risk of neonatal hypoglycaemia (Dodd 2007), respiratory distress syndrome, polycythaemia (raised red blood cell count), hyperbilirubinaemia, and being born preterm (Metzger 2008; Reece 2009; Reece 2010). Such health consequences together contribute to a need for enhanced neonatal care (Svare 1999). If untreated, GDM may be associated with an increased risk of perinatal mortality.
Importantly, in a recent randomised controlled trial, the treatment of women with mild GDM (dietary intervention, self-monitoring of blood glucose and insulin therapy if needed) was shown to significantly reduce the risk of a number of such complications including fetal overgrowth, shoulder dystocia, caesarean delivery and hypertensive disorders (Landon 2009). The Cochrane review 'Treatments for gestational diabetes' similarly concluded that some specific treatments (including dietary advice and insulin) for mild GDM may reduce the risk of maternal and perinatal morbidity (Alwan 2009).
Maternal hyperglycaemia less severe than that associated with a diagnosis of GDM, may similarly result in clinically important complications for the both mother and her infant (Han 2012a; Metzger 2008). While the risk of adverse maternal and infant pregnancy outcomes appears to increase with increasing levels of glucose impairment (Dodd 2007), the concentration at which pregnancy hyperglycaemia becomes pathological has not been conclusively determined (Metzger 2008; Mulla 2010).
Description of the intervention
The aim of dietary advice or related interventions in pregnancy is to optimise glycaemic control, preventing maternal hyperglycaemia and reducing post-prandial glucose concentrations. Dietary advice may be aimed at ensuring women's diets provide sufficient energy and nutrients to allow normal fetal growth while avoiding accelerated fetal growth patterns, and minimising excessive weight gain (Dornhorst 2002). As glucose is the primary source of energy for fetal growth (Moses 2006), excessive fetal growth is most effectively limited by sustaining low post-prandial glucose concentrations (Dornhorst 2002).
The benefits of low glycaemic index (GI) diets have been shown for individuals being treated for type 2 diabetes (Brand-Miller 2003), and some evidence exists to suggest similar benefits may be conferred for women with GDM (Cheung 2009). GI quantitatively defines the effect of carbohydrate-based foods on blood glucose concentration (Jenkins 1981). The GI value for a food is determined by comparing the blood glucose response to that food to the response to an equivalent amount of standard glucose (Foster-Powell 2002). Foods with a 'low' GI (less than 55) induce a gradual increase in blood glucose due to slow digestion and absorption, whereas foods that produce a rapid rise in blood glucose concentration are referred to as 'high' GI (greater than 70). Examples of low GI foods are whole-grain bread and dairy foods. High GI foods include potatoes, highly processed carbohydrate foods such as white bread and some breakfast cereals (Atkinson 2008; Jenkins 1981).
Other suggested dietary recommendations for GDM prevention have included the consumption of a high fibre diet (Fraser 1983), and changing the proportion of each macronutrient that makes up the woman’s overall intake, for example increasing the proportion of fat in the diet to compensate for carbohydrate proportion changes (Dornhorst 2002). While high fat diets may have a low GI, they are generally contraindicated due to known associated cardiovascular health risks.
Benefits of exercise during pregnancy are now recognised, and thus women are encouraged to engage in 'light-to-moderate' exercise in the absence of any known pregnancy or medical complications (ACOG 2002; Davies 2003; Dempsey 2005). The Royal College of Obstetricians and Gynaecologists recommend that all women participate in aerobic and strength-conditioning exercise, with the goal to maintain a good fitness level, as part of a healthy lifestyle during their pregnancy (RCOG 2006). Women often reduce their levels of physical activity during pregnancy (Pereira 2007), many due to a perceived risk to maternal or fetal health (Clarke 2004) and the impact of early pregnancy symptoms such as nausea and fatigue (Pereira 2007).
Regular aerobic exercise may lead to lower fasting and postprandial blood glucose concentrations in previously sedentary individuals. Exercise may decrease circulating glucose and insulin during, and for a period of time after, an exercise session (Clapp 1991; Clapp 1998). It has been shown outside of pregnancy that exercise may reduce the risk and delay the onset of the development of type 2 diabetes mellitus (Jeon 2007). Exercise has been shown to reduce insulin resistance in non-pregnant women and men, leading to effective prevention and management of type 2 diabetes (Clapp 2006; Knowler 2002; Redden 2011).
Suggested benefits of exercise during pregnancy include a reduction in lower back pain, fluid retention and cardiovascular stress (Schlüssel 2008). Exercise is believed to play a role in reducing the risk of complications such as preterm birth and pre-eclampsia (Dempsey 2005; Schlüssel 2008), and may help prevent excess pregnancy weight gain and post-partum weight retention (Schlüssel 2008). There is increasing evidence from observational studies indicating that pre-pregnancy exercise and exercise in early pregnancy is associated with a reduction in insulin resistance (Reece 2009), and consequently a reduced risk of developing GDM (Jeon 2007; Redden 2011).
How the intervention might work
Combined diet and exercise interventions
Whille dietary advice and exercise interventions alone for the prevention of type 2 diabetes and GDM have been widely assessed, more recently a shift towards combining such interventions in what may be regarded as 'lifestyle' interventions has been observed.
Several randomised controlled trials have established that the progression to type 2 diabetes can be prevented or postponed with lifestyle interventions in individuals with impaired glucose tolerance ('high-risk' individuals) (Knowler 2002; Li 2008; Ratner 2008; Tuomilehto 2001). Such studies have focused strongly on combining increased physical activity and dietary modification, along with weight reduction for overweight participants. Long-term follow-up studies of such lifestyle interventions (that lasted for a limited time), have shown sustained beneficial effects on risk factors and diabetes incidence (Tuomilehto 2011). It has been suggested that a key factor in the success of such interventions has been the comprehensive approach, addressing and working to correct several lifestyle-related risk factors simultaneously (Tuomilehto 2011).
As it is accepted that a multitude of risk factors may increase the risk of type 2 diabetes, these randomised trials focused on a number of lifestyle-related factors concurrently. In the Finnish Diabetes Prevention Study five lifestyle targets were predefined, including: weight loss greater than 5%, intake of fat lower than 30% energy, intake of saturated fats lower than 10% energy, intake of dietary fibre greater than 15 g/1000 kcal, and an increase of physical activity to at least four hours per week (Tuomilehto 2001). These targets were perceived as relatively modest, and it was believed that such lifestyle changes would be feasible to maintain in the long term (Tuomilehto 2011). No 'high-risk' individual with impaired glucose tolerance developed diabetes during the trial if they achieved at least four of the five lifestyle targets (Tuomilehto 2001). This trial was the first of a number to show that type 2 diabetes may be prevented with lifestyle interventions, and highlighted the importance of addressing multiple lifestyle-related risk factors for optimal benefit (Knowler 2002; Li 2008; Tuomilehto 2001).
Whilst such trials included 'high-risk' individuals, were not focused on pregnant women, and considered type 2 diabetes, they certainly offer some support for the use of lifestyle interventions in pregnant women for the prevention of GDM. Furthermore, the Cochrane reviews assessing dietary or exercise interventions alone (not lifestyle interventions) for the prevention of GDM have revealed inconclusive findings. The review 'Dietary advice in pregnancy for preventing gestational diabetes mellitus' (Tieu 2008) included three small trials, and concluded that while a low GI diet was beneficial for some outcomes for the mother (lower maternal fasting glucose concentration) and child (reduction in LGA infants, lower ponderal indexes) (Clapp 2006; Moses 2006), the evidence is limited (Tieu 2008). Similarly, the review 'Exercise for pregnant women for preventing gestational diabetes mellitus' (Han 2012b) concluded that there is limited evidence to currently support exercise during pregnancy for the prevention of glucose intolerance or GDM. This review included five trials and revealed no improvement in GDM incidence, nor any improvements for the reported infant outcomes (Han 2012b).
As it is widely acknowledged that a multitude of risk factors are associated with GDM, it is considered plausible that lifestyle interventions for women during pregnancy, aimed at correcting multiple lifestyle-related risk factors, may be effective in reducing the incidence of GDM. Such lifestyle interventions may combine, for example, dietary advice or modifications with exercise interventions.
Why it is important to do this review
There is an increased risk of perinatal complications associated with GDM (Han 2012a). Effective strategies are required to reduce the incidence of GDM and the associated health consequences for both the mother and her infant. This review will complement the existing reviews titled 'Dietary advice in pregnancy for preventing gestational diabetes mellitus' (Tieu 2008) and 'Exercise for pregnant women for preventing gestational diabetes mellitus' (Han 2012b), to assess combined diet and exercise interventions for preventing GDM.