Globally, there is an alarming increase in the incidence of Type II diabetes mellitus (T2DM). It is well recognized that women who develop gestational diabetes (GDM) in their pregnancies are at increased risk of T2DM in later life. In addition, poor glycaemic control in pregnancy impacts adversely on the neonatal outcome, as well as the long term disease risks of that child. The risk of these outcomes increases continuously as maternal fasting plasma glucose levels increases. Several adverse outcomes have been associated with DM during pregnancy. These include pre-eclampsia, polyhydramnios, fetal macrosomia, fetal hepatomegaly and cardiomegaly, birth trauma, operative delivery, perinatal mortality and neonatal respiratory problems and metabolic complications such as hypoglycaemia, hyperbilirubinaemia, hypocalcaemia and polycythaemia. Despite five decades of research there is little consensus regarding the optimal approach to screening for GDM. Recently most international organisations have recommended that all women should be screened for GDM. South Africa is a diverse multi-racial society with an increasing burden of non-communicable diseases. The health system is already overburdened, and the optimal approach to screening for GDM remains unclear. A prospective cohort observational study was conducted at the Eyethu Yarona clinic (Lion Park Clinic), in Johannesburg, South Africa (SA). One thousand (1000) consecutive non-diabetic women who were less than 26 weeks pregnant were recruited. At recruitment the women completed a demographic questionnaire, and had a random glucose and glycated haemoglobin (HbA1c) drawn. A fasting blood glucose was assessed within 2 weeks, and a serum specimen was frozen at -40°C for further testing at a later stage. Patients had a 75 g 2-hour oral glucose tolerance test (OGTT) and HbA1c between 24 – 28 weeks gestation. All glucose measurements were done at the laboratory using standardized tests (venous blood) and on a Roche Accuchek Active® glucometer (Roche Diagnostics, Mannheim, Germany) (capillary blood). GDM was diagnosed according to the International Federation of Gynecology and Obstetrics (FIGO) criteria, i.e. any one abnormal reading was diagnostic of GDM: 0-hour ≥5.1 mmol/l, 1-hour ≥10 mmol/l, or 2-hour ≥8.5 mmol/l. Thereafter a nested cohort study of HIV negative patients was conducted to investigate the association between the concentrations of biomarkers associated with glucose homeostasis and GDM in a South African population. C-reactive protein (CRP), adiponectin, and fasting insulin were measured on the stored serum samples. The Insulin Sensitivity Index (HOMA-IR = fasting insulin (microU/L) x fasting glucose (mmol/L) / 22.5), and Quantitative Insulin Sensitivity Check Index (QUICKI = 1 / [log (I0) + log (G0)]) were calculated for further evaluation of markers of insulin sensitivity. The significance of this research was to assess the burden of disease of GDM in a South African population. The different diagnostic criteria were also compared, as well as the universal versus the traditional risk-factor based screening approach to GDM. Screening methods were compared so as to propose a simple, effective, cost efficient screening and diagnostic tool that may be implemented at primary health care level, which will in turn identify those pregnant women who warrant referral to a high care obstetric unit, thus improving both maternal and neonatal outcomes in our population. / Thesis (PhD) - University of Pretoria, 2017. / SEMDSA / SASA / Roche / Obstetrics and Gynaecology / PhD / Unrestricted