Gestational diabetes mellitus (GDM) increases the risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Novel findings show that high serum levels of γ-glutamyltransferase (GGT) measured many years before pregnancy are a risk factor for development of GDM.
A team of researchers at Kaiser Permanente Northern California (Oakland, USA) set out to investigate whether women who develop GDM already have metabolic abnormalities in the years before they become pregnant. In this study, they specifically focused on liver enzymes, whose levels have been associated with insulin resistance and T2DM in other populations.
The investigators measured the levels of three liver enzymes—GGT, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)—in frozen serum samples previously collected from 256 women who were not pregnant at the time of serum collection but who developed GDM during a subsequent pregnancy. Insulin and glucose levels were also measured to assess the degree of insulin resistance, as defined by HOMA, in these women. The average time between serum collection and development of GDM in the studied patients was 7 years. For each of the case patients, the researchers selected two control individuals without GDM matched for year of serum collection, age at serum collection, age at delivery of the index pregnancy and number of intervening pregnancies.
“We found that being in the highest quartile of GGT levels was associated with a twofold increased risk of subsequent GDM,” recounts Sneha Sridhar, corresponding author of the article in which the findings are reported. This association was stronger among women in the highest tertile of insulin resistance as defined by HOMA, whereas no association between GGT and insulin resistance was found among women in the two lower tertiles of insulin resistance. The levels of AST and ALT were not associated with risk of GDM.
On the basis of these findings, Sridhar suggests that liver function tests could one day play a part in helping care providers monitor women for early signs of insulin resistance. “Our next analysis will examine the role that prepregnancy lipid levels have in determining risk of subsequent GDM,” Sridhar adds. “We hope to eventually develop a risk model to help identify women who would benefit from interventions during the preconception period.”
Sridhar, S. B. et al. Pregravid liver enzyme levels and risk of gestational diabetes during a subsequent pregnancy. Diabetes Care 10.2337/dc13-2229
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Osório, J. Prepregnancy GGT levels predict risk of gestational diabetes mellitus. Nat Rev Endocrinol 10, 378 (2014). https://doi.org/10.1038/nrendo.2014.79
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