Lower Plasma Ghrelin Levels are Found in Women with Diabetes-Complicated Pregnancies

Abstract

Objective:To evaluate the associations of glycemic control and gestational age with ghrelin and proinsulin levels in cord blood and mothers’ peripheral blood during pregnancy.Methods:This is a cross-sectional comparative study of twenty-four pregnant women with gestational diabetes (GD), 18 with type 2 diabetes mellitus (T2DM), and 36 without diabetes, as well as their neonates. Levels of proinsulin, ghrelin, and glycated hemoglobin A1c (HbA1c) were measured from maternal blood during the last week before caesarian delivery and in neonatal umbilical cord blood samples.Results:Mothers with GD and T2DM had significantly lower ghrelin levels compared to the healthy mothers (p<0.001). Maternal proinsulin was lower in women with GD than in women without diabetes (p<0.001). Proinsulin was significantly elevated in the neonates of women with GD and in women with HbA1c ≥6.5% (p<0.001). However, maternal ghrelin levels were higher (p=0.031) and neonate proinsulin levels lower in the pre-term offspring of mothers with GD (p=0.033). There was a negative correlation between HbA1c levels and birth weight (r=–0.407, p<0.001).Conclusion:Ghrelin levels were lower in pregnant women with diabetes, although pre-term birth appeared to reverse this trend in GD. Proinsulin levels were also low in pregnant women with diabetes and even lower in pre-term vs. at-term births. Both ghrelin and proinsulin levels were lower in pregnant women with diabetes and HbA1c of <6.5%. Thus, ghrelin participates in the adaptation to the caloric imbalance of diabetic pregnancy and may play a similar role in pregnancy-related complications, since high ghrelin concentrations may be necessary for normal fetal development.

Ghrelin in Serum and Urine of Post-Partum Women with Gestational Diabetes Mellitus

“…Diabetic pregnancy may involve a positive or negative caloric balance. Circulating ghrelin decreases during physiological pregnancy, which represents a natural insulin-resistant state [ 8 , 33 ]. However, gestational glucose-induced ghrelin suppression is preserved at a lower level, and is probably not related to the degree of insulin resistance [ 34 ].…”

“…Gómez-Díaz et al [ 8 ] observed that pregnant women with GDM and T2DM had significantly lower serum ghrelin levels compared with non-diabetic patients. This statistical difference can be connected to the fact that approximately half of the patients were receiving insulin in the study of Gómez-Díaz et al [ 8 ], who in fact admitted that this treatment heterogeneity might have been a confounding factor. Meanwhile, all of the women with GDM in our study were treated with insulin during pregnancy until delivery, yet the serum and urine samples were taken 48 h after delivery, which means at least 48 h without gestational treatment.…”

“…Moreover, our study was performed two days after delivery, which means two days after placenta delivery, whereas Gómez-Díaz et al [ 8 ] evaluated the serum ghrelin levels in each mother during the last week before cesarean delivery. The ghrelin concentrations during pregnancy are partially related to the placental factors.…”

“…In recent years, the importance of ghrelin as a significant risk factor for developing T2DM in patients with a history of GDM has been underlined [ 7 ]. Ghrelin is a 28 amino acid peptide that is mainly secreted in the stomach fundus cells, but is also produced, in smaller amounts, in other bodily organs, such as the hypothalamus, heart, pancreatic cells, lungs, adrenals, kidneys, and placenta [ 8 , 9 , 10 ]. Ghrelin is an orexigenic peptide that plays an important role in regulating disorders, such as insulin resistance, obesity, and diabetes [ 11 ].…”

The role of new adipokines in gestational diabetes mellitus pathogenesis

“…The concentrations were lower in pregnant women with diabetes and HbA1c of < 6.5%. It has been suggested that ghrelin is involved in the adaptation to the caloric imbalance in GDM patients and may play a similar role in pregnancy-related complications, since high ghrelin concentrations may be vital for normal fetal development [28]. Riedl et al have observed that whereas basal ghrelin concentrations are suppressed during pregnancy, the downregulation of ghrelin by glucose uptake is markedly reduced [29].…”