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

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.

Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

“…Fasting and 2-h post-prandial plasma glucose targets for treated-GDM mothers differed between studies as follows; 5.0 mmol/L and 6.7 mmol/L [ 33 , 37 ], 5.3 mmol/L and 7.8 mmol/L [ 29 ], 5.3 mmol/L and 6.7 mmol/L [ 25 , 26 ], 5.5 mmol/L and 6.5 mmol/L [ 23 ], 5.5 mmol/L and 6.7 mmol/L [ 6 , 19 ], and 5.5 mmol/L and 7.0 mmol/L [ 11 , 12 , 20 , 24 ]. Two studies [ 10 , 32 ] used HbA1c between 3.5–5.3% as the mean blood glucose target.…”

“…Three studies [ 17 , 18 , 22 ] used ‘diet only’, and one study [ 23 ] used ‘insulin only’ to treat GDM while others used combinations of treatments such as ‘diet with insulin if required’ [ 10 , 11 , 19 , 20 , 21 , 26 , 27 , 28 , 29 , 31 , 33 , 37 ], ‘diet and exercise with insulin, if required’ [ 6 , 12 , 32 , 34 , 36 ]. Metformin, alone or in combination with insulin, was used in two studies [ 24 , 35 ], while glyburide alone or in combination with diet was used in another two studies [ 25 , 30 ].…”

“…Glycaemic control in GDM women using modified dietary interventions alone has resulted in lower birth weights and less macrosomia [ 16 ], despite the high heterogeneity in diet observed among different populations [ 17 ]. Similarly, using pharmaceutical interventions along with or without lifestyle changes has resulted in reduced risk of macrosomia [ 18 ] and has prevented GDM-associated adverse health conditions in neonates [ 19 ]. Nevertheless, the effect of GDM treatments on neonatal adiposity is understudied, and the evidence for whether good glycaemic control in GDM can normalise foetal adiposity is contradictory [ 20 , 21 , 22 ].…”

Programmed Adult Kidney Disease: Importance of Fetal Environment

“…Neonates of diabetic mothers, with inadequate glycemic control, had lower cortical and total renal volume, suggesting a lower nephron number. However, newborns of diabetic mothers, with strict glycemic control, had similar values as control newborns (Aisa et al, 2019). Thus, it is evident that variations in the maternal glycemic status can lead to different outcomes in the offspring's kidneys (Aisa et al, 2019).…”

Newborn Screening Samples for Diabetes Research: An Underused Resource

“…Precision medicine is rapidly becoming a reality, with risk prediction for certain disorders in the near future potentially modifying diseases. Biomarkers, obtained from other biological samples such as urine, have shown promise in risk stratification, the creation of risk scores combining different measures and disease modeling for type 1 diabetes, thyroid disorders in pregnancy and the effects of GDM on the developing urinary tract [ 50 , 51 , 52 ]. Perhaps, in the future, NBS results may play a role in disease models as a component of scoring systems involving different clinical and neonatal parameters.…”