Low Prepregnancy Adiponectin Concentrations Are Associated With a Marked Increase in Risk for Development of Gestational Diabetes Mellitus

OBJECTIVE

To examine whether circulating total and high–molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984–1996) with a serum sample obtained and who had a subsequent pregnancy (1984–2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies.

RESULTS

Compared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7–2.9], 3.7 [1.9–7.2], and 5.2 [2.6–10.1]; P_trend <0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P_trend <0.001). The combined effects of having total adiponectin levels below the median (<10.29 mg/mL) and being overweight or obese (BMI ≥25.0 kg/m²) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6–12.5]).

CONCLUSIONS

Prepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention.Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first diagnosis during pregnancy, is a common complication of pregnancy. Women with a history of GDM have a sevenfold increased risk of developing type 2 diabetes after delivery (1), and the children of women with GDM are more likely to be obese and develop diabetes (2,3). The underlying etiology of GDM appears to be similar to the physiological abnormalities that characterize diabetes outside of pregnancy and is thought to be due to an inability of the pancreatic β-cells to compensate for the increased insulin resistance induced by pregnancy (4,5). The extent to which insulin resistance or reduced insulin sensitivity leading to GDM occurs even years before pregnancy has not been determined in population-based studies. There is increasing interest in identifying prepregnancy risk factors and biomarkers for GDM to inform future preconception prevention strategies, given the proven success of specific prevention strategies for type 2 diabetes in high-risk populations (6).Adiponectin is an abundant adipocyte-derived hormone demonstrated to have actions consistent with protection against insulin resistance, inflammation, and atherosclerosis (7). Total adiponectin circulates in the bloodstream as three discrete complexes: a lower–molecular weight trimer, a mid–molecular weight hexamer, and a high–molecular weight (HMW) complex (8). Some evidence suggests that HMW adiponectin is the isoform that mediates the insulin-sensitizing and antiatherogenic effects (9,10). Prospective studies examining adiponectin and incident type 2 diabetes reported that lower circulating total adiponectin concentrations were associated with a higher risk of type 2 diabetes in a dose-response relationship (11). Both total adiponectin (12) and HMW adiponectin (13) are known to decrease significantly in normal pregnancies in response to decreased insulin sensitivity; therefore, it is important to determine whether prepregnancy levels of adiponectin are related to subsequent risk of GDM in order to clarify the temporal sequence of the association. The aim of this study is to examine the association between prepregnancy total and HMW adiponectin concentrations and the risk of developing GDM and to determine whether these associations are independent of known metabolic risk factors for GDM.