Pregravid gamma-glutamyl transferase linked to gestational diabetes risk

By Will Boggs MD

NEW YORK (Reuters Health) - Elevated levels of gamma-glutamyl transferase (GGT) before pregnancy are associated with an increased risk of developing gestational diabetes, according to results from a case-control study.

"Physicians should be aware that elevated GGT levels may be an early sign of insulin resistance, even in the absence of other clinical indications," Sneha B. Sridhar from Kaiser Permanente Northern California in Oakland told Reuters Health by email.

"Monitoring GGT levels before pregnancy may help to identify women who are at increased risk for developing gestational diabetes and who may benefit from interventions starting early in pregnancy or even prior to pregnancy, to help maintain stable blood sugar levels," she said.

Researchers know from past studies that liver enzyme levels may change in response to the increased insulin resistance induced by pregnancy, but it is unclear whether pre-pregnancy levels of liver enzymes are related to the risk of subsequent gestational diabetes (GDM).

Sridhar and colleagues used data from 4098 women who completed a Multiphasic Health Checkup and subsequently delivered an infant to investigate the possible association between pregravid levels of GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and the risk of developing GDM.

Two hundred fifty-six women went on to develop confirmed GDM, and the researchers compared them to 497 matched controls, according to the May 2 Diabetes Care online report.

There was a clear trend of increasing risk of GDM with increasing quartile of GGT level, but this association disappeared after adjustment for insulin sensitivity, fasting status, and rate of gestational weight gain.

The association between GGT level and GDM risk was strongest for women in the highest tertile of insulin resistance before pregnancy, the researchers note, but there were no associations in the two lower tertiles of insulin resistance.

In further analyses, there was an increasing risk of GDM with increasing tertile of GGT when stratified by pre-pregnancy BMI, and the greatest risk of GDM was seen in the highest tertile of GGT with a pre-pregnancy BMI below 25.

Neither ALT nor AST was associated with an increased risk of GDM.

"It is possible that the association between GGT and subsequent GDM may be partly due to GGT being a marker of exposure to environmental pollutants that act as endocrine disruptors," Sridhar said. "While we were initially surprised by the lack of association between ALT and subsequent GDM, past research has been inconclusive on the relationship between ALT and type 2 diabetes."

"This study appears to be the first to find that high levels of GGT, measured years before pregnancy, are associated with increased risk of gestational diabetes," Sridhar concluded. "While more research is needed to determine why this is the case, liver function tests are relatively inexpensive and may someday help to inform the identification of women to target for interventions designed to prevent gestational diabetes."

SOURCE: http://bit.ly/1kJCT5a

Diabetes Care 2014.