Plasma Adiponectin and Pregnancy-Induced Insulin Resistance

Lindsay et al. (1) recently published an article in Diabetes Care that claims adiponectin is present in the cord blood of the offspring of diabetic and nondiabetic pregnant mothers and that its level does not correlate with their birth weight and skinfold thickness. Our data, obtained from a case-control study of nondiabetic women and women with gestational diabetes mellitus (GDM), further support the role of adiponectin in insulin resistance.

We observed significantly decreased plasma adiponectin levels (7.55 ± 2.04 μg/ml [means ± SD]) using radioimmunoassay (Linco Research, St. Charles, MO) (intra-assay precision coefficient of variation [CV] 3.86%, interassay CV 8.47%) in 30 women with GDM, all of whom were treated with insulin (aged 28.12 ± 2.71 years, gestational age 27.35 ± 6.15 weeks), compared with 40 nondiabetic pregnant women tested with oral glucose tolerance test (OGTT) (total group 9.91 ± 3.32, P < 0.01, Mann-Whitney, aged 26.91 ± 2.65 years, gestational age 23.17 ± 10.91 weeks, 15 in the first, 12 in the second, and 13 in the third trimester) and 30 age-matched nonpregnant nondiabetic women (12.54 ± 3.76, P < 0.01, aged 28.42 ± 3.48 years). GDM was diagnosed with a 75-g OGTT according to the World Health Organization recommendations. In the nondiabetic pregnant group, plasma adiponectin levels were significantly lower in the second (9.30 ± 2.78) and third (8.06 ± 2.44) trimesters compared with women in the first trimester (12.30 ± 3.20, P < 0.01). After correction for gestational age and BMI, the differences still remained significant. No difference was found in plasma adiponectin levels before and after insulin treatment in the GDM patients.

In the GDM group, plasma adiponectin levels were in a significant negative linear correlation with serum tumor necrosis factor-α (TNF-α) (r = −0.65, P < 0.0001, Spearman’s rank correlation test), leptin (r = −0.75, P = 0.0004), fasting C-peptide concentrations (r = −0.83, P < 0.0001), BMI (r = −0.67, P < 0.0001), and, as an indirect parameter of insulin resistance, fasting C-peptide/blood glucose ratio (r = −046, P = 0.0109). The same was found in the total group of nondiabetic pregnant women (TNF-α: r = −0.56, P = 0.0002; leptin: r = −0.45, P = 0.003; fasting C-peptide: r = −0.70, P < 0.0001; BMI: r = −0.51, P = 0.0007; C-peptide-to-blood glucose ratio: r = −0.43, P = 0.0046). In the nonpregnant nondiabetic control subjects, negative correlations with serum leptin (r = −0.44, P = 0.0134), fasting C-peptide concentrations (r = −0.46, P = 0.01), and BMIs (r = −0.57, P = 0.0008) were found.

Maternal plasma adiponectin levels correlated positively with the body weight of the neonates, in both the GDM (newborns, n = 30, 13 boys and 17 girls, maternal gestational age at delivery 38.22 ± 0.51 weeks, 14 Cesarean sections, body weight 3,151 ± 672 g, centile 55.87 ± 30.29%, r = 0.4345 Spearman’s rank correlation test, P = 0.0164) and the nondiabetic pregnant group (n = 20, 9 boys and 11 girls, gestational age at delivery 38.92 ± 0.32 weeks, 6 Cesarean sections, body weight 3,562 ± 359 g, centile 63.46 ± 15.80%, r = 0.6124, P = 0.0041) after the correction for gestational age.

There is an association between adiponectin concentrations and insulin sensitivity. The protein is exclusively produced in adipocytes. Its inverse relationship with the increasing BMI, fasting C-peptide concentrations, and C-peptide-to-blood glucose ratio of nondiabetic pregnant women and patients with GDM underlines the importance of adipose tissue and its secreted products, such as adiponectin, in pregnancy-induced insulin resistance. The negative correlation between TNF-α, leptin, and adiponectin may suggest a negative regulatory role of these cytokines in the expression and secretion of adiponectin. The peroxisome proliferator-activated receptor system in adipocytes is a known regulator of fat cell differentiation and the production of TNF-α, leptin, and adiponectin (2). On the other hand, TNF-α may inhibit peroxisome proliferator-activated receptor function in adipocytes. Through this mechanism, the TNF system may have a suppressive effect on adiponectin production during the course of pregnancy (3).

Maternal insulin resistance and adipocytokines may influence different anthropometric parameters (body weight, body length, and head circumference) of the neonates. TNF-α and leptin were in a negative correlation with these parameters in neonates of mothers with GDM (4). However, analyzing the relationship between these parameters and maternal plasma adiponectin levels, the significant positive linear correlation between adiponectin, and the neonatal body weight, both in GDM and nondiabetic pregnant women, suggests a regulatory role of the protein in neonatal development.