Case Study: Pregnancy Gestational Diabetes

Case Study: Pregnancy Gestational Diabetes Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity, with onset or first recognised during pregnancy1. This definition includes women whose blood glucose goes back to normal after giving birth, those with undiagnosed type I or type II diabetes and also those with monogenic diabetic2. GDM is believed to complicate approximately 1% to 5% of all pregnancies and is associated with increased foetal and maternal morbidity and mortality1. The prevalence ranges from less than 1% to more than 10% due to the different populations or ethnic groups being studied and lack of uniformity on diagnostic test employed1. Women from Indian subcontinent have an increased prevalence rate of GDM by eleven fold whereas those from South East Asia have eight fold increased rate3. This is followed by women from Arab or Mediterranean with six fold and Afro-Carribbean women with three fold3. The pathophysiology of gestational diabetes mellitus includes increase in maternal insulin resistance, autoimmune ÃŽ ²-cell dysfunction and genetic abnormalities which causing impaired insulin secretion4. Progression of insulin resistance normally starts near the mid-pregnancy throughout the third trimester and progresses to resistance level seen in Type II diabetes4. There are two type of insulin resistance namely physiological insulin resistant and chronic insulin resistant with ÃŽ ²-cell dysfunction. It has been suggested that physiological insulin resistance is contributed by combination of increased maternal adiposity and effects of placental growth hormones4. A study revealed the defects of postreceptor in the insulin-signalling pathway of skeletal muscle and adipose tissue has caused the insulin sensitivity reduction in pregnancy5. The alterations in the pathway reduce the insulin-mediated glucose uptake in skeletal muscle which is a major tissue for glucose disposal5. The inc rease in physiological insulin resistance and alterations in glucose metabolism are believed been influenced by placental growth hormones. This is proven when resistance abates soon after labouring in women with normal glucose tolerance6. Chronic insulin resistance is a condition where patients have ÃŽ ²-cell dysfunction which is presented before pregnancy and exacerbated during pregnancy due to some physiological changes6. Chronic insulin resistance occurred mostly in women with GDM and this had been demonstrated in a study where normal women have higher insulin sensitivity than those with GDM after physiological insulin resistance abates4. It is also believed that obesity play a role in developing insulin resistance since GDM women tend to be obese6. Among the women diagnosed with GDM, a minority of less than 10% of them have presence of cytoplasmic islet cell antibodies and anti-GAD antibodies in their circulation6. These are the markers used to identify the individuals who develop autoimmune diabetes namely Type I diabetes. Patients with autoimmune destruction of pancreatic ÃŽ ²-cells will then have inadequate amount of insulin which leads to hyperglycaemia. This subtype of patients most probably will experience rapid metabolic deterioration after pregnancy due to the autoimmune destructive condition6. Besides autoimmune ÃŽ ²-cells destruction, genetic abnormalities caused by autosomal and mitochondrial DNA mutations also contributed to less than 10% of GDM6. The autosomal mutation, for instance maturity-onset diabetes of the young (MODY) has a dominant inheritance pattern whereas mitochondria DNA mutations has maternal inheritance pattern4, 6. Both of these monogenic forms of diabetic have a younger age onset than non-immune t ype of diabetes and the patients do not suffer from obesity and insulin resistance6. The genes involved in the monogenic diabetes appear to posses a crucial influence on ÃŽ ²-cells regulation which severe enough resulting hyperglycaemic if mutation occurs even with the absence of insulin resistance6. 3.0 Implications 3.1 Maternal implications GDM may implicate either immediate or long term mortality on pregnant women. Studies have demonstrated that GDM has complicated pregnancy by increasing duration of maternal hospitalization, caesarean delivery and also preeclampsia in pregnant women7, 8, 9. Caesarean delivery incidence is increased in GDM pregnancies in order to avoid birth trauma7. Women with GDM are also at increased risk to develop type II diabetes with trials showed that 30% to 50% former GDM women developed diabetes at 3 to 5 years after their delivery10. Women who have GDM with higher BMI are more susceptible to diabetes development. This is demonstrated by a study where approximately 60% of obese women and 30% of lean women during pregnancy have 15 years of prevalence in Type II diabetes11. The study is supported by other studies where maternal obesity plays an important role in developing diabetes later in life12. A considerable number of women with prior GDM were found to share some characteristics of those suffered from metabolic syndrome like elevated triglyceride levels, glucose intolerance, obesity and HDL cholesterol reduction. Women who are diagnosed with impaired glucose tolerance at 6-12 weeks postpartum showed increased triglycerides level and decreased HDL cholesterol as well as systolic blood pressure >140mmHg compared to those with similar BMI and normal glucose tolerance13. Atherosclerosis which is known to be contributed by inflammatory responses also studied in women with GDM with findings showed that hsCRP and interleukin-6, both are inflammatory mediators, were respectively higher in GDM women after 3 months postpartum than in normal subjects14. Studies of women prior GDM on insulin resistance and factors in metabolic syndrome suggest that lipid abnormalities and inflammatory mediators significantly related to cardiovascular threat. 3.2 Foetal and neonatal implications Offspring of mother with GDM have an increased risk of perinatal mortality as well as morbidity which involved hyperbirubinemia, hypoglycaemia, macrosomia, birth trauma, childhood risk of obesity and subsequently type II diabetes and cardiovascular disease15. Improper management of GDM women during pregnancy has contributed to a four fold increasing in perinatal mortality rates11. Approximately 20% of GDM pregnancies are found to be complicated by macrosomia which defined as foetus weight lies above the 90th percentile of gestational age or more than 4000g15, 16. Maternal nutrition is a crucial factor in foetal growth. Excess foetal growth is caused by diabetic intrauterine environment since glucose passes through placenta but maternal insulin unable to cross the placenta17. Besides, increased glucose load in foetal also promotes the growth hormone under influence of developing foetal pancreas and further encourages foetal growth and adiposity17. As a result, shoulder dystocia, a con dition where one of the shoulders being stuck behind mothers pelvic bone, preventing the birth of babys body can occur if foetal weight is above 4000g18. The chance of developing shoulder dystocia is even increased by two to six folds if the growth of the trunk and shoulder is not proportionate18. A study indicated that offspring of GDM women have increased body fat when compared with same weight offspring of controlled healthy women19. Offspring of women with GDM are also found to be on 30% heavier than expected according to their height20. The study also evaluated that there is a strong relationship between pancreas cell activation in diabetic intrauterine environment and childhood obesity, which then predisposes to obesity20. Maternal insulin insensitivity is then believed to associate with foetal overgrowth, predispose to childhood obesity and glucose intolerance. Cardiovascular abnormalities can be another implication on offspring of women with GDM. Diabetes is a known risk factor for cardiovascular disease and this issue is evaluated and examined in offspring of diabetic pregnancies. The results significantly showed that offspring of the diabetic pregnancies has higher systolic and mean arterial blood pressure, endothelial dysfunction markers as well as cholesterol level compared to offspring of healthy mothers20. 4.0 Screening and diagnosis All pregnant women will undergo universal screening for GDM between 24-28 weeks of gestation and those with high risk of GDM development should perform the screening at first trimester21. Women with high risk of developing GDM refer to those who fulfil one or more risk factors. For instance, over 35 years old, previously diagnosed with GDM or with macrosomic, from high risk populations like American Indian, South-East Asian and Arab, obesity which BMI ≠¥ 30kg/m ², diagnosed with polycystic ovary syndrome and first degree relative to diabetes3, 21. The screening test is called oral glucose challenge test (OGCT) and carried out where the pregnant women were given a sugary beverage with 50g glucose load to drink21. After an hour, plasma glucose is measured and if the reading is ≠¥10.3 mmol/L, GDM is diagnosed21. If the plasma glucose reading is