We measured serum levels of free
leptin, bound
leptin, and soluble
leptin receptor by specific RIA methods in 20 normal and
19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total
leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound
leptin levels, as there is no significant change in free
leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free
leptin levels (P < 0.001).
Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound
leptin levels between the normal and diabetic subjects at any stage [free
leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound
leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble
leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble
leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound
leptin levels between the normal and
insulin-dependent diabetic subjects either during pregnancy or postpartum, but female
insulin-dependent diabetic subjects have significantly higher soluble
leptin receptor levels. We speculate that high soluble
leptin receptor levels might be implicated in the development of the
leptin resistance in this group.