Renal Consequences of Gestational Diabetes Mellitus in Term Neonates: A Multidisciplinary Approach to the DOHaD Perspective in the Prevention and Early Recognition of Neonates of GDM Mothers at Risk of Hypertension and Chronic Renal Diseases in Later Life

Maria Cristina Aisa,Antonella Barbati,Benito Cappuccini,Elisabetta Torlone,Graziano Clerici,Gian Carlo Di Renzo,Sandro Gerli

doi:10.3390/jcm8040429

Abstract

Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30–40-day old newborns of GDM mothers (n = 139) who needed insulin therapy during pregnancy. We found that neonates of mothers who maintained strict control over normoglycemia (n = 65) during pregnancy and fulfilled the other criteria of the GDM management program showed no differences compared to control (n = 55). Conversely, those (n = 74), whose mothers did not maintain glycemic control and were not compliant to the management program, exhibited significantly lower levels of renal volumes and higher activity of N-acetyl-β-d-glucosaminidase and cathepsin B. Differences due to maternal pre-gestational and gestational body mass index (BMI) as well as to maternal weight gain were demonstrated. Our findings indicate that a multidisciplinary approach, which involves an appropriate management of GDM, prevents the negative effects of GDM on the kidneys at 30–40 days of postnatal age, indicating the fundamental role of glycemic control, as well as of an adequate range of maternal weight gain. Total renal volume, cortical volume, and urinary activity of N-acetyl-β-d-glucosaminidase and cathepsin B may be suggested as indicators for the early recognition of GDM neonates at long-term risk of hypertension and kidney disease.

Highlights

It is well established that conditions during fetal or early postnatal development influence the individual’s risk of developing non-communicable diseases in later life (Developmental Origins OfHealth and Disease (DOHaD) paradigm) [1,2]
Maternal Weight Gain in Classes 1–3 of Both Subgroups of gestational diabetes mellitus (GDM) Neonates As we found that obesity did not influence renal mass parameters and N-acetyl-β-d-glucosaminadase and Cathepsin B activity in the classes of Compliant GDM mother neonates, and, mostly, in Class 2 compared to Classes 1 and 3 of the Noncompliant GDM mother neonate subgroup, we investigated if these trends were related to maternal weight gain, as this parameter influences fetal health [44,45,46,47]
Glucosaminadase and Cathepsin B activity in the classes of Compliant GDM mother neonates, and, mostly, in Class 2 compared to Class 1 and 3 of the Noncompliant GDM mother neonate subgroup, we investigated if these trends were related to maternal weight gain, as this parameter influences fetal health [44,45,46,47]

Summary

Introduction

It is well established that conditions during fetal or early postnatal development influence the individual’s risk of developing non-communicable diseases in later life (Developmental Origins OfHealth and Disease (DOHaD) paradigm) [1,2]. Gestational diabetes is sometimes associated with high birth weight in infants, which is a known risk factor for subsequent hypertension, type 2 diabetes, renal disease, and cardiovascular disease, the effect on nephron number is unknown [15]. A direct correlation between reduced nephrogenesis, proteinuria, and gestational diabetes mellitus (GDM) in 3-year-olds has been recognized as a cause of kidney injury in offspring [16], and remarkably, a significant association between GDM and the rate of cardiovascular hospitalizations, including hypertensive disorders, in the offspring has recently been demonstrated in a population-based cohort study with up to 18 years of follow up [17]

Results

Discussion

Conclusion