Abstract

BackgroundGestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. Adipokine imbalance in the presence of metabolic dysfunction may be a key event in promoting CVD. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy.MethodsThis population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy X-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting adiponectin and leptin levels were measured four times during pregnancy and at follow-up.ResultsWe found the L/A ratio higher in GDM women both during pregnancy and follow-up compared to non-GDM women. A high L/A ratio during pregnancy was associated with CV risk based on lipid ratios at follow-up, especially the TG/HDL-C ratio. Further, interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy. Finally, low adiponectin levels independently predicted increased lipid ratios at follow-up.ConclusionsTaken together, our findings suggest that high L/A ratio in pregnancy and in particularly in those with GDM are associated with an unfavorable CVD risk profile during follow-up. Future studies should investigate if a dysregulated leptin and adiponectin profile during pregnancy is associated with atherosclerotic disease during long-term follow-up.

Highlights

  • Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear

  • The present study investigated the significance of leptin, adiponectin and their ratio in pregnancy and follow-up between GDM vs. non-GDM women and associations with CV risk as evaluated by unfavorable lipid ratios at 5 years follow-up

  • Ratio was higher in GDM women both during pregnancy and follow-up compared to non-GDM women (2) a high L/A ratio during pregnancy was associated with CV risk based on unfavorable lipid ratios at follow-up, especially the TG/high density lipoprotein cholesterol (HDL-C) ratio (3) interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy (4) low adiponectin levels independently predicted unfavorable lipid ratios at follow-up

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Summary

Introduction

Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy. Adiponectin and leptin are two adipocytokines or adipokines that have been studied extensively due to their association with insulin resistance, obesity and cardiovascular (CV) risk. In individuals without manifest CV disease (CVD), high circulating leptin and low adiponectin levels are associated with multiple CVD risk including lipid dysregulation [1]. GDM women have lower adiponectin and higher leptin levels compared to non-GDM women [16, 17] and the L/A ratio has been associated with insulin resistance (HOMA-IR) during pregnancy [18]

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