Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications

The prevalence of GDM is rapidly increasing and is set continue climbing in the context of the global obesity epidemic. GDM has serious adverse implications for the health of current and future generations through genetic and environmental mechanisms which remain incompletely understood. In addition, the disease poses a significant economic burden for healthcare systems, with variability in clinical practice often determined by resource limitations. The optimal timing of screening and diagnostic thresholds for GDM remain uncertain. Emerging evidence suggests intrauterine exposure to metformin may have an adverse impact on the offspring of women with GDM. There is an ongoing need for long-term follow-up of children exposed to metformin to clarify these potential associations and provide a more robust evidence base to inform clinical practice. Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. The prevalence is rising and correlates with the increase in maternal obesity over recent decades. The etiology of GDM is complex, with genetic and environmental factors implicated in mechanistic and epidemiological studies. GDM begets important short- and long-term health risks for the mother, developing fetus, and offspring. This includes the high likelihood of subsequent maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes in the offspring. The most clinically and cost-effective methods of screening for GDM remain uncertain. Whilst treatments with lifestyle and pharmacological interventions have demonstrated short-term benefits, the long-term impact for the offspring of intrauterine exposure to antidiabetic medication remains unclear. Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. The prevalence is rising and correlates with the increase in maternal obesity over recent decades. The etiology of GDM is complex, with genetic and environmental factors implicated in mechanistic and epidemiological studies. GDM begets important short- and long-term health risks for the mother, developing fetus, and offspring. This includes the high likelihood of subsequent maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes in the offspring. The most clinically and cost-effective methods of screening for GDM remain uncertain. Whilst treatments with lifestyle and pharmacological interventions have demonstrated short-term benefits, the long-term impact for the offspring of intrauterine exposure to antidiabetic medication remains unclear. a gene variant which may occur at a given site on a chromosome. the set of chemical changes to the genome (an organism’s entire DNA sequence) that modify gene expression but do not change the DNA sequence itself. an observational study of all the genetic variants in a population to determine genetic variants which are associated with a specific phenotype. a preliminary screening test for GDM which involves administration of a 50-g oral glucose load followed by measurement of the plasma glucose level 1 hour later. Women with a glucose level above a predefined threshold will proceed to an OGTT as a diagnostic test for GDM. blood glucose levels which are higher than normal, but have not reached the diabetic range. Defined as a blood glucose level of between 7.8 mmol/l (140 mg/dl) and 11.0 mmol/l (196 mg/dl) 2 hours after a 75-g OGTT. birth weight greater than or equal to the 90th percentile for a given gestational age. the plural of locus; a fixed site on a chromosome at which an allele is located. excessive birth weight, usually defined as more than 4 kg. a cluster of common conditions including obesity, hypertension, dyslipidemia, insulin resistance, and T2DM, which are associated with an increased risk of cardiovascular events. a group of rare forms of diabetes caused by a mutation in a single gene. For example, maturity onset diabetes of the young is most commonly caused by a mutation in the HNF1A gene. a test used to diagnose GDM and also diabetes outside of pregnancy. Plasma glucose levels are measured fasting and once or more following the ingestion of an oral glucose load. Several variations of the test exist involving different glucose loads, intervals, and durations of sampling. an excessive amount of amniotic fluid surrounding the fetus in the amniotic sac, associated with an increased risk of pregnancy complications, including preterm birth. an umbrella term used to describe those who have blood glucose levels higher than normal but have not reached the diabetic range, and who have an increased risk of T2DM. It includes those with impaired glucose tolerance. an emergency complication of labor when, following delivery of the infant’s head, the anterior shoulder becomes stuck behind the mother’s pubic symphysis. Assistance is required to release the shoulder and allow delivery of the infant. the most common type of genetic variation; a change at a single nucleotide position in the genome, where each variant is present in at least 1% of the population.