Exposure to maternal diabetes is associated with altered fetal growth patterns: A hypothesis regarding metabolic allocation to growth under hyperglycemic‐hypoxemic conditions

Abstract

The prevalence of diabetes is rising worldwide, including women who grew poorly in early life, presenting intergenerational health problems for their offspring. It is well documented that fetuses exposed to maternal diabetes during pregnancy experience both macrosomia and poor growth outcomes in birth size. Less is known about the in utero growth patterns that precede these risk factor expressions. Fetal growth patterns and the effects of clinical class and glycemic control were investigated in 37 diabetic pregnant women and their fetuses and compared to 29 nondiabetic, nonsmoking maternal/fetal pairs who were participants in a biweekly longitudinal ultrasound study with measurements of the head, limb, and trunk dimensions. White clinical class of the diabetic women was recorded (A2-FR) and glycosylated hemoglobin levels taken at the time of measurement assessed glycemic control (median 6.9%, interquartile range 5.6-9.2%). No significant difference in fetal weight was found by exposure. The exposed sample had greater abdominal circumferences from 21 weeks (P < or = 0.05) and shorter legs, but greater upper arm and thigh circumferences accompanied increasing glycemia in the second trimester. In the third trimester, exposed fetuses had a smaller slope for the occipital frontal diameter (P = 0.00) and were brachycephalic. They experienced a proximal/distal growth gradient in limb proportionality with higher humerus / femur ratios (P = 0.04) and arms relatively long by comparison with legs (P = 0.02). HbA1c levels above 7.5% accompanied shorter femur length for thigh circumference after 30 gestational weeks of age. Significant effects of diabetic clinical class and glycemic control were identified in growth rate timing. These growth patterns suggest that hypoxemic and hyperglycemic signals cross-talk with their target receptors in a developmentally regulated, hierarchical sequence. The increase in fetal fat often documented with diabetic pregnancy may reflect altered growth at the level of cell differentiation and proximate mechanisms controlling body composition. These data suggest that the maternal-fetal interchange circuit, designed to share and capture resources on the fetal side, may not have had a long evolutionary history of overabundance as a selective force, and modern health problems drive postnatal sequelae that become exacerbated by increasing longevity.

Associação entre perfil glicêmico materno e o índice de líquido amniótico em gestações complicadas pelo Diabetes mellituspré-gestacional

“…Quando o Diabetes mellitus está presente desde o início da gravidez, estados hiperglicêmicos no primeiro e no segundo trimestre promovem alterações na programação da placenta com alterações no perfil das proteínas transportadoras de glicose (GLUTs), que passam a se expressar de forma diversa nessas placentas. 23,24 Dessa forma, qualquer elevação nos níveis glicêmicos dessas gestantes, no terceiro trimestre, favorece maior transporte da glicose para a circulação fetal. Isso pode facilitar a manutenção do estado de maior produção do líquido amniótico e promover maior crescimento fetal.…”

“…25,26,27 Com isso não se constata redução significativa do volume de líquido, mesmo que se obtenha estrito controle no perfil glicêmico. Torna-se importante monitorar o aumento excessivo do volume de líquido, uma vez que a mudança do status quo é que poderá acrescentar risco significativo de descontrole da homeostase materna e/ou fetal 24 . O estudo da placenta de gestantes portadoras de diabetes demonstra que, no termo, a morfologia vilosa é diferente.…”

Influences of olive leaf extract in the kidney of diabetic pregnant mice and their offspring

“…However, gestational diabetes cause greater insulin resistance (Setji, Brown, & Feinglos, 2005), which leads to increase levels of glucose transported across the placenta to the fetus and cause fetal hyperglycemia (Lampl & Jeanty, 2004). The reduced body weight fetuses in STZinduced diabetic group may be due to fetal hypoinsulinemia which causes the growth restriction in fetuses (Aerts & Van Assche, 2006).…”

Relationships between Neonatal Weight, Limb Lengths, Skinfold Thicknesses, Body Breadths and Circumferences in an Australian Cohort

“…Lampl et al [32] reported a relatively shorter tibia compared to the thigh, and lower limb relative to upper limb length, among maternal smoke-exposed mid-gestation foetuses, while Lindsay et al [33] reported that tibia and forearm lengths, and especially thigh length, showed greater differences between control and maternal smoke-exposed neonates than total crown-rump length. In relation to diabetes, Lampl et al [34] found stronger effects in the lower limb than the upper limb and in the tibia than the femur, while Catalano et al [12] reported that upper arm, lower arm and lower leg lengths, but not crown-rump or thigh lengths, were significantly smaller in diabetes-exposed neonates, though differences were modest. However, broader trends in these characteristics relative to birth weight are unknown.…”

“…[16]–[23]) and postnatal limb proportions may be particularly sensitive to environmental stressors [24]–[31]. Studies investigating the effects of specific stressors on neonatal development (maternal smoking [32]–[33] or diabetes [12], [34]) suggest that neonatal trunk, limb and limb segment lengths and proportions are indeed differentially affected. Lampl et al [32] reported a relatively shorter tibia compared to the thigh, and lower limb relative to upper limb length, among maternal smoke-exposed mid-gestation foetuses, while Lindsay et al [33] reported that tibia and forearm lengths, and especially thigh length, showed greater differences between control and maternal smoke-exposed neonates than total crown-rump length.…”