The effect of adipokines in HIV associated pre-eclampsia : (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon like peptide-1, glucagon, insulin plasminogen activator inhibitor-1 and visfatin).

Abstract

Introduction: South Africa has a maternal ratio of 300 deaths/100,000 live births. Non-pregnancy related infections (mainly deaths in HIV infected pregnant women complicated by tuberculosis and pneumonia) accounts for 34.7% of maternal deaths followed by obstetric haemorrhage and hypertension accounts (15.8% and 14.8% respectively). Moreover, 61% of women South Africa is overweight or obese (almost double the global rate of 30%). In pregnancy, endocrine and metabolic maternal adaptations include increase in body weight, however, the impact of adipokines in HIV associated pre-eclampsia remains unknown. The aim of the study was to examine the levels of adipokines viz., C-peptide, ghrelin, gastric inhibitory polypeptide (GIP), glucagon like peptide 1 (GLP), plasminogen activator inhibitory (PAI) 1, visfatin, glucagon and insulin in HIV associated pre-eclampsia. Materials and Methods: Following institutional and regulatory approval, participants (n=301) were recruited from RK Khan Hospital and divided into groups non-pregnant (n=90), normotensive (n=121), early (n=32; EOPE) and late onset (n=58; LOPE) pre-eclampsia. The pregnant cohort was stratified according to their HIV status. Maternal clinical demographics, indications and mode of delivery were recorded. Serum was used to quantify the adipokines levels using the multiplex ELISA technique. Absorbance was read spectrophotometrically at 450 nm. Graph Pad Prism (version 6) was used to analyse all data. Result: C-peptide did not differ according to HIV status. With regards pregnancy type, there was a significant difference in c-peptide between the non-pregnant versus normotensive pregnant (p<0.01) and the normotensive versus LOPE groups (p<0.01) being elevated both the pre-eclamptic groups (EOPE +LOPE). Ghrelin did not differ across study groups (p>0.05), by HIV status (p>0.05). When considering HIV status, GIP varied between positive and negative groups (p<0.001). Additionally, there was a significant difference in GIP between the non-pregnant versus normotensive pregnant (p<0.01); normotensive pregnant versus EOPE (p<0.05) and the normotensive pregnant versus the LOPE group (p<0.01). GIP was elevated in the HIV positive EOPE group. Moreover, a significant difference in GLP-1 was noted across the study groups

(p<0.05) and between non-pregnant versus normotensive groups (p<0.01). When considering HIV status, HIV positive groups differed from negative study groups (p<0.05). Additionally, the Mann Whitney U test showed a significant difference between the non-pregnant and the normotensive group (p<0.01). Glucagon-like peptide-1 was significant different across the study groups, with its levels elevated in the pre-eclamptic groups compared to the normotensive pregnant group (p<0.05), additionally, there was a difference between non-pregnant versus normotensive pregnant groups (p<0.01). Glucagon did not differ across the study groups (p>0.05), however, was significantly different between the non-pregnant and normotensive group (p<0.05). HIV status did not affect glucagon levels (p>0.05). A significant difference between HIV positive non-pregnant and HIV negative non-pregnant was noted (p<0.05). Insulin was not significantly different across the study groups (p>0.05) and by HIV status (p>0.05). However, a significant difference between the non-pregnant versus normotensive group (p<0.05) was noted. PAI-1 did not differ across the study groups (p>0.05) and between the groups (p>0.05). PAI-1 did not differ according to HIV status (p>0.05). A significant difference in visfatin across the study groups (p<0.05) and between the non-pregnant versus normotensive pregnant group (p<0.05) and the late onset pre-eclamptic versus the non-pregnant group (p<0.01) was observed. There was no effect of HIV status on the level of visfatin across the study groups (p<0.05). There was a significant difference between the HIV positive versus negative non-pregnant groups (p<0.05), furthermore, we have observed low levels of visfatin in the HIV positive pre-eclamptic groups.

Discussion and conclusion: This study demonstrates elevated c-peptide, GIP, GLP-1, Insulin, PAI-1 and Visfatin in the pre-eclamptic groups compared to normotensive pregnant groups. These adipokines play a role in glucose homeostasis and have been reported to play a role in development of insulin resistance which is a high risk factor for developing pre-eclampsia. Several studies have reported that adipose tissue derived hormones, play a crucial role in the pathogenesis or as risk factors of pre-eclampsia development. Additionally, it is reported that adipokines are elevated in people with higher BMI (obese and overweight) which in turn predisposes one for developing pre-eclampsia. In terms of HIV status, we have observed that many of the adipokines were elevated in the HIV positive compared to the HIV negative group. This correlates with studies which reported that HIV plays a role in dysregulation of adipokines. In conclusion, our study is the first to examine adipokine dysregulation in the triad of HIV infection, pre-eclampsia and obesity. Furthermore, we have established that adipokines: C-peptide, GIP, GLP-1, PAI-1 and visfatin were significantly dysregulated hence they may have predictor test value in diagnosing pre-eclampsia development.