Adiponectin Levels May Signal Risk for Gestational Diabetes

September 13, 2013

Low levels of adiponectin before pregnancy were associated with a 5-fold increased risk of gestational diabetes. This risk was 7-fold in obese or overweight women.

Low levels of adiponectin before pregnancy were associated with a 5-fold increased risk of developing gestational diabetes, according to a new study examining the association. In addition, the risk of gestational diabetes was 7-fold in women who were both overweight or obese and had low levels of adiponectin.

“It is fascinating to discover that metabolic abnormalities appear to be present, even years before pregnancy, in a large proportion of women who develop gestational diabetes,” said study author Monique M. Hedderson, PhD, research scientist with the Kaiser Permanente division of research in Oakland, Calif. “The findings from this study emphasize the importance of the pre-pregnancy period in future pregnancy outcomes.”

In the past 2 decades, there has been an approximate 90% increase in the prevalence of gestational diabetes mellitus. Prior research has shown that lower levels of adiponectin, a hormone that protects against insulin resistance, inflammation, and heart disease, have been associated with an increased risk of type 2 diabetes mellitus. In addition, the levels of total adiponectin and high molecular weight adiponectin have been known to decrease significantly during pregnancy.

To better understand gestational diabetes and uncover ways to prevent it, Hedderson and colleagues used an electronic health records system to retrospectively identify 4000 women who gave blood samples from 1985 to 1996 during routine care and who subsequently gave birth. Of the women in the system, 256 developed gestational diabetes. To compare outcomes, each woman with gestational diabetes was matched to 2 control women.

The results indicated that women in whom gestational diabetes developed, compared with matched controls, had significantly lower pre-pregnancy levels of total adiponectin (7.7 vs 10.6, respectively; P<.001) and high molecular weight adiponectin (2.8 vs 4.0, respectively; P<.001). When the women were classified into 4 quartiles by adiponectin levels, the researchers found that the risk for gestational diabetes was 5 times higher for women in the lowest quartile compared with those in the quartile with the highest levels.

In addition, overweight or obese women with lower-than-average levels of adiponectin had a 7-fold increased risk of gestational diabetes developing compared with women who had average body mass index (OR=6.7; 95% CI, 3.6-12.5). Finally, the researchers found that women who were normal weight but had lower-than-average levels of adiponectin had a 3.5-fold increased risk of gestational diabetes. These levels of increased risk occurred even after adjustment for race/ethnicity, body mass index, parity, family history of diabetes, smoking status, insulin, glucose, and fasting status.

“This is important because we know obesity is one of the strongest risk factors for gestational diabetes; less is known about risk factors among normal-weight women who develop gestational diabetes,” said Hedderson. “It was surprising that the association between adiponectin and gestational diabetes risk was independent of other known risk factors for gestational diabetes, including measures of insulin resistance. This suggests that it may be acting through a unique mechanism.”

Hedderson said that future research should focus on using risk prediction models and analyzing different intervention strategies to determine the effectiveness of using adiponectin clinically to identify women at risk for gestational diabetes.

Pertinent Points:
- Metabolic abnormalities of women with gestational diabetes may be present years before pregnancy.
- There is a growing body of evidence to suggest that making healthful lifestyle changes before pregnancy would reduce a number of pregnancy complications, including gestational diabetes.


Hedderson M, Darbinian J, Havel PJ, et al. Low pre-pregnancy adiponectin concentrations are associated with a marked increase in risk for development of gestational diabetes mellitus. Diabetes Care. 2013;doi:10.2337/dc13-0389.