OBJECTIVE: Besides its presence in various tissues, ghrelin has recently been shown to be present in blood and breast milk. No previous studies, however, have evaluated the level of this hormone under the condition of pregestational and gestational diabetes mellitus (P-GDM and GDM, respectively). This study was undertaken to show whether a relation exists between serum and milk ghrelin levels in lactating mothers with and without diabetes. METHODS: Venous blood was obtained from four groups of women (age range 22-37 y): GDM lactating (n = 12), P-GM lactating (n = 3), healthy non-diabetic lactating (n = 14), and healthy non-lactating (n = 14). Colostrum and mature milk samples were collected just before suckling. The ghrelin level was determined by radioimmunoassay and high-performance liquid chromatography. RESULTS: Radioimmunoassay results showed that women with GDM and P-GDM had greater than two-fold lower colostrum and serum levels of ghrelin than did lactating women with no GDM at 2 d after parturition. The GDM and non-diabetic groups at 15 d after delivery, however, showed similar levels of ghrelin in mature milk and serum. High-performance liquid chromatographic results indicated that in serum the deacylated form of ghrelin was 18-fold higher than the acylated form. Furthermore, in milk the acylated form of ghrelin was 24-fold that of the active form. CONCLUSION: These results indicate that mothers with GDM have a substantial (greater than two-fold) decrease in their serum and colostral ghrelin levels. This is, however, a temporary effect lasting only up to early postparturition (2 d after delivery). This peptide hormone restores to completely normal levels at day 15 of parturition, but not P-GDM. The significance of these results in terms of the health of the mother and her newborn, however, has yet to be determined.