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Free Leptin, Bound Leptin, and Soluble Leptin Receptor in Normal and Diabetic Pregnancies

Department of Biological Sciences, University of Warwick (K.L., C.J.O., G.F.M., P.O.), Coventry, United Kingdom CV4 7AL; the Department of Endocrinology, Medizinische Hochschule (R.H., G.B.), D-30623 Hannover, Germany; and Royal United Hospital (D.D.), Bath, United Kingdom

Address all correspondence and requests for reprints to: P. O’Hare, M.D., F.R.C.P., Department of Biological Sciences, University of Warwick, Coventry, United Kingdom CV4 7AL.

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.

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