Diabetes in pregnancy

Gestational diabetes mellitus: Risks and management during and after pregnancy

This review article discusses current evidence for the importance of gestational diabetes mellitus, opportunities to reduce risk to mother and child and recommendations for clinical care.

Summary points

Gestational diabetes mellitus (GDM) is caused by reduced pancreatic β-cell function, which results from the full spectrum of causes of β-cell dysfunction in young women.
GDM is associated with a modest increase in adverse perinatal outcomes, an increased risk of obesity in offspring and a high risk of subsequent development of diabetes mellitus in mothers.
GDM is treated nutritionally; insulin or oral antidiabetic agents can be added if maternal glucose levels and/or fetal growth parameters indicate a sufficiently high risk of perinatal complications.
Long-term management of mothers includes assessment of the level and type of diabetes risk, and lifestyle and/or pharmacological approaches for women at risk of type 2 diabetes mellitus.
Long-term management of offspring should focus on detection and mitigation of the development of obesity and its complications.
A great need exists for high-quality clinical evidence to determine optimal approaches for the management of GDM during and after pregnancy.

Buchanan TA et al. Nat Rev Endocrinol 2012; 8: 639–649. doi: 10.1038/nrendo.2012.96

Genetics of gestational diabetes mellitus and maternal metabolism

New progress has been made in defining the genetic architecture of gestational diabetes mellitus and maternal metabolism during pregnancy. This review highlights recent developments in the area.

Summary points

Women with a history of gestational diabetes mellitus (GDM) are at long-term risk for developing type 2 diabetes (T2DM), raising the question to what extent GDM and T2DM share a common genetic architecture.
Meta-analysis of candidate gene studies and genome-wide association analysis (GWAS) have identified a number of genes which are reproducibly associated with GDM, including TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B, and IRS1, loci that are also associated with risk of T2DM.
The majority of these genes encode proteins important for beta cell function or development.
Candidate gene and GWAS have also identified genes associated with maternal metabolic traits, most of which are also associated with metabolic traits in the general population.
Two genes, BACE2 and HKDC1, are uniquely associated with maternal metabolic traits.
Taken as a whole, available data suggest that there are similarities and differences between the genetic architecture of GDM and T2DM and metabolic quantitative traits in pregnant and non-pregnant populations.

Lowe Jr WL et al. Curr Diab Rep 2016; 16: 15. doi: 10.1007/s11892-015-0709-z

β-cell adaptation in pregnancy

This article provides an overview of how glucose metabolism changes during pregnancy, how β-cells adapt to these changes, and what happens when adaptation fails and gestational diabetes ensues.

Summary points

During pregnancy, the proper growth and development of the fetus depends on appropriate nutrient flow from mother to fetus across the placenta.
In the later stages of pregnancy, the growing fetus diverts an increasing fraction of maternal glucose across the placenta, thus lowering glucose in the maternal circulation.
In counterbalance to the fetal glucose diversion, the placenta secretes hormones that increase maternal insulin resistance and hepatic glucose production.
The pancreas anticipates the increase in insulin resistance that occurs late in pregnancy by increasing β-cell numbers and function earlier in pregnancy.
In rodents, this β-cell expansion depends on secreted placental lactogens that signal through the prolactin receptor.
At the end of pregnancy, the β-cell population contracts back to its pre-pregnancy size.
Women with gestational diabetes may have a pregnancy-specific defect in the placental-β-cell axis.

Baeyens L et al. Diabetes Obes Metab 2016; 18(Suppl 1): 63–70. doi: 10.1111/dom.12716

Risk factors for gestational diabetes: Is prevention possible?

This review provides an overview of emerging diet, lifestyle, and other factors that may help to prevent gestational diabetes mellitus, and the challenges associated with prevention.

Summary points

Well-documented risk factors for gestational diabetes mellitus (GDM) include advanced maternal age, family history of diabetes, previous GDM, having a macrosomic baby, non-Caucasian race/ethnicity, being overweight or obese and cigarette smoking.
Genetic factors have also been implicated in the etiology of GDM; a number of candidate genes have been identified.
In addition to these, research in the past decade from observational studies has identified diet and lifestyle factors that are associated with GDM risk.
Data from at least seven observational epidemiological studies provided evidence that increased recreational physical activity before and/or during pregnancy were related to a lower GDM risk.
In addition to physical activity, dietary factors both during and before pregnancy are related to GDM risk.
Findings from intervention studies on the effect of diet and lifestyle on the prevention of GDM have been largely controversial and inconsistent.
Large-scale multiple-arm lifestyle intervention studies are needed.

Zhang C et al. Diabetologia 2016; 59: 1385–1390. doi: 10.1007/s00125-016-3979-3

Medicine Matters Diabetes

Diabetes in pregnancy

Pathophysiology and risk factors

Gestational diabetes mellitus: Risks and management during and after pregnancy

Genetics of gestational diabetes mellitus and maternal metabolism

β-cell adaptation in pregnancy

Risk factors for gestational diabetes: Is prevention possible?

Contents