Retinol-binding protein 4 and insulin resistance in preeclampsia

Abstract

PreeclamPsia is a pregnancy-specific and multisystem disorder characterized by the onset of high blood pressure and proteinuria, which develop after 20 weeks of gestation in previously normotensive women or which are superimposed on preexisting hypertension. In severe cases, several other symptoms, such as renal and/or liver failure and eclampsia, complicate the clinical features. In addition, it can also complicate pregnancies with fetal growth restriction, with nonreassuring fetal status or even those with fetal death. It occurs in about 5% of all pregnancies and results in substantial maternal and neonatal morbidity and mortality [1,2].It is widely accepted that physiological insulin resistance persists in pregnant women, so glucose toler- abstract. Preeclampsia is characterized by the onset of high blood pressure and proteinuria during pregnancy, which results in substantial maternal and neonatal morbidity and mortality. Insulin resistance has been observed before the onset of preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, has been shown to be a potential regulator of insulin resistance originating from adipose tissue. Here we measured insulin resistance and RBP-4 levels in patients with preeclampsia and in women with normal pregnancies matched for gestational age and body mass index at Okayama University Hospital. Our aim was to examine the potential role of RBP4 in the pathophysiology of this disorder. There were no significant differences in RBP4 levels between all patients with preeclampsia and controls. However, the RBP4 level and homeostasis model assessment as an index of insulin resistance (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly higher than in overweight controls carrying normal pregnancies and in normal weight women with late-onset preeclampsia. In contrast, there were no significant differences between the overweight and normal weight groups among patients with early-onset preeclampsia and in healthy pregnant women. These data suggest that RBP4 might act in the pathophysiology of late-onset preeclampsia via increased insulin resistance in obese women.Key words: Preeclampsia, Insulin resistance, Retinol binding protein 4 ance might be lower than in the nonpregnant state. Maternal characteristics such as obesity, diabetes and insulin resistance increase the risk for preeclampsia [3][4][5]. Thus, insulin resistance has been observed before the onset of preeclampsia and has been implicated in its pathophysiology [6][7][8]. Adipocytokines such as tumor necrosis factor-α, leptin and adiponectin have been demonstrated to play a role in the regulation of glucose metabolism and insulin resistance in nonpregnant and pregnant women [9][10][11]. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, was shown to be correlated with insulin resistance [12]. Moreover, it was reported that circulating RBP4 was elevated in a mouse model for insulin resistance...

Potential interaction of brain natriuretic peptide with hyperadiponectinemia in preeclampsia

“…These findings suggest that there may be different levels of response to the elevated BNP level for adiponectin production between normal-weight and overweight preeclampsia patients. We also observed that HOMA-IR in overweight preeclampsia patients was significantly higher than that in normal-weight preeclampsia patients, consistent with ours and other previous reports (4,22). The poor response to BNP in adiponectin production in overweight preeclampsia patients might enhance insulin resistance, which results in endothelial dysfunction.…”

Circulating retinol-binding protein 4 levels in gestational diabetes mellitus: a meta-analysis of observational studies

“…While elevated maternal circulating RBP4 levels has been associated with increased rate of obstetrical complications such as preeclampsia and fetal growth restriction [34,35], one intriguing observation was regarding the occurrence of GDM. Previous reports on the association between circulating RBP4 levels and the risk of GDM have yielded inconsistent results.…”

Association of retinol binding protein 4 with risk of gestational diabetes

“…GDM is associated with adverse maternal (e.g., C-sections and increased risk of type 2 diabetes [T2DM]) and offspring (e.g., fetal hyperinsulinism, macrosomia, and birth injuries) outcomes [2,4,8,9]. Underlying pathophysiological disturbances commonly identified in GDM include reduced insulin secretion and abnormal insulin resistance [10,11,12,13,14,15]. …”