Ethnic differences in gestational diabetes : impact on South Asians

Background: GDM is a state of glucose intolerance first diagnosed in pregnancy. It is a pre-diabetes state, predisposing both the mother and offspring to future risk of diabetes. GDM is associated with increased risk to macrosomia, adiposity, Caesarean Section (CS) delivery, shoulder dystocia, and neonatal hypoglycaemia. SA have a greater than two fold risk of both GDM and future diabetes risk compared to WC. However, despite having higher levels of hyperglycaemia in pregnancy, SA babies are amongst the smallest babies in the world. The mechanism behind this increased glycaemic risk in SA is complex, multifactorial and unclear. Disordered hypothalamic-pituitary-adrenal axis (HPA) has been linked to adult diabetes, obesity and metabolic syndrome in WC but has not been studied in SA. The current management of GDM is largely based on evidence from studies in WC and has been extrapolated to other ethnic groups such as SA. This includes: diagnostic criteria to define GDM, postnatal screening methods for postpartum glucose abnormalities, effect of GDM on offspring birth weight (BW) and fetal growth in GDM. Through this research we aim to explore the ethnic differences between SA and WC in the applicability of diagnostic criteria, post partum screening methods, effect of GDM on BW, fetal growth patterns in GDM and also examine ethnic differences in HPA activity as a potential mechanism underlying the increased glycaemic risk in SA in pregnancy. Methods: i. Retrospective analysis of a routinely collected multicentre data (n=14477) over a 3-year period was used to study the applicability of various GDM diagnostic criteria and post partum screening methods. A subgroup analysis of the above data set was used to compare fetal growth between SA and WC (177 WC and 160 SA). ii. A retrospective analysis of a large birth weight cohort (n=53,128) from Leicestershire between 1994 and 2006 was used to compare the effect of maternal diabetes and GDM on BW in SA and WC. iii. To examine fetal growth in SA, a retrospective case control analysis of serial fetal biometry was performed between GDM and control population from India. (178 controls and 153 GDM) iv. To explore underlying HPA dysfunction as a potential mechanism for increased glycemia in SA and ethnic differences in HPA behaviour a prospective cohort study comprising of high risk pregnant SA and WC women was performed. Diurnal salivary and urinary cortisol excretion was studied in relation to glycaemia in SA and WC (n=100, 50 SA, 50WC) Results: i. The newer IADPSG detects obese women with mild fasting hyperglycaemia. The benefits of treatment of hyperglycemia are not well established. The increase in detection rates of GDM with the new NICE and IADPSG criteria were uniform across ethnic groups in a selectively screened population. ii. Postnatal screening with oral glucose tolerance test (OGTT) is associated with poor uptake in all ethnic groups, which improves substantially with using HbA1c. SA were more likely to attend postnatal screening with HbA1c compared to WC. Screening for postnatal diabetes using FPG is more likely to miss women of non-WC ethnicity owing to the larger proportion of post-load glucose abnormalities. iii. The BW increase associated with maternal diabetes was lower in SA by 139g compared to WC. iv. Important ethnic differences in fetal growth were noted. SA fetuses had overall smaller measures of head and abdomen circumferences, but with disproportionately smaller abdominal circumference compared to WC, signifying early evidence of a head sparing growth restricted pattern. v. SA fetuses of GDM mothers showed early evidence of increased abdominal adiposity at 20 weeks with smaller measures of other fat free mass and skeletal growth compared to non-GDM controls vi. SA had higher cortisol awakening responses compared to WC. First trimester waking cortisol was an independent predictor of glycaemia in the third trimester. Despite significantly lower BMI, SA had similar glucocorticoid (GC) excretion to WC. Urinary GC excretion was independently predicted by maternal adiposity and not BMI in SA. Conclusion: This research addresses important gaps in the literature in gestational diabetes in SA. There are important ethnic differences in the impact of maternal diabetes and gestational diabetes on BW and fetal growth, and evidence of early increase in adiposity at the expense of lean body mass in SA. This research provides novel evidence to support the argument for ethnicity tailored management of GDM. Our research also provides novel evidence for disordered HPA activity as a possible mechanism for the increased glycemic risk in SA. Larger randomized prospective studies incorporating offspring outcomes in relation to HPA are needed.