Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels

doi:10.1016/j.ajog.2003.11.033

American Journal of Obstetrics and Gynecology

Volume 191, Issue 3, September 2004, Pages 804-808

https://doi.org/10.1016/j.ajog.2003.11.033 Get rights and content

Objective

The purpose of this study was to determine whether there is a difference in body composition and the factors that are associated with fat mass in the large-for-gestational-age infants of women with gestational diabetes mellitus compared with the large-for-gestational-age infants of women with normal glucose tolerance levels.

Study design

Large for gestational age was defined as weight >90th percentile for gestational age, race, and sex on the basis of our population's normative data. Anthropometric measurements and/or total body electrical conductivity estimated body composition that included fat mass, percent body fat, and lean body mass were obtained. Multiple stepwise regression was used to determine factors correlating with fat mass.

Results

Fifty cases of women with gestational diabetes mellitus and 52 cases of women with normal glucose tolerance levels were evaluated. Infants of mothers with gestational diabetes mellitus had increased fat mass (662 vs 563 g; P = .02) and percent body fat (16.2% vs 13.5%; P = .002) but decreased lean body mass (3400 vs 3557 g; P = .0009), as compared with infants of mothers with normal glucose tolerance levels, despite similar birth weights. Stepwise regression on all 102 women showed gestational age and a diagnosis of gestational diabetes mellitus correlated with fat mass (r² = 0.11; P = .001). For gestational diabetes mellitus alone, both gestational age and fasting value of the oral glucose tolerance test correlated with fat mass and percent body fat (r² = 0.33 [P = .0009] and r² = 0.26 [P = .005], respectively).

Conclusion

Large-for-gestational-age infants of mothers with gestational diabetes mellitus have increased fat mass and decreased lean body mass compared with infants of mothers with normal glucose tolerance levels. In gestational diabetes mellitus, gestational age and fasting value of the oral glucose tolerance test correlated best with fat mass.

Section snippets

Material and methods

A retrospective analysis of data that were gathered prospectively over a 10-year period at MetroHealth Medical Center/Case Western Reserve University General Clinical Research Center was performed. The protocol was approved by the hospital Institutional Review Board. Written informed consent was obtained from each study subject. Aspects of body composition of these infants have been reported in previous publications from our group.4., 8., 9., 10. However, the specific objectives and hypothesis

Results

A total of 102 infants were evaluated. The study population consisted of 50 GDM and 52 CTL infants. Of the 50 GDM infants, 24 infants were diet controlled (GDMA1), and 26 infants required insulin therapy (GDMA2). Maternal clinical characteristics of the study population are described in Table I. Women with GDM were older, weighed more at the beginning of pregnancy, and were more likely to be black and smokers than CTL women. Parity, maternal height, and weight gain were similar between groups.

Comment

Our findings are consistent with previous studies that showed an increase in fat mass in GDM infants,4., 5. and, more specifically, an increased fat mass and decreased LBM in macrosomic infants of women with GDM.4., 7. Although McFarland et al⁷ found an increased fat mass by anthropometric measurements in infants of diabetic women, the study was limited by a small sample size. Our study evaluated the body compositions of the largest number of LGA infants of women with GDM that has been reported

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Obesity in pregnancy accounts for the majority of large-for-gestational age infants with increased adiposity (ACOG, 2015; Dutton et al., 2018). It has been proposed that increased maternal availability of macronutrients and other signaling molecules to the fetal-placental unit, results in enhanced nutrient transfer, fetal overgrowth and changes in body composition (Durnwald et al., 2004), linking maternal metabolic perturbations to fetal programing (Dimasuay et al., 2016; Hernandez et al., 2020). Placental nutrient transport capacity is one key determinant of fetal growth.
Infants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity.
Placentas were collected from BMI-matched normoglycemic controls (NGT, n = 9) and T2DM (n = 9) women. Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated. Expression of glucose (GLUT1, -4), fatty acid (FATP2, -4, -6, FAT/CD36), amino acid (SNAT1, -2, -4, LAT1, -2) transporters, insulin signaling, and System A transporter activity was determined. Neonatal fat mass (%) was measured in a subset of neonates born to T2DM women.
GLUT1 protein expression was increased (p = 0.001) and GLUT4 decreased (p = 0.006) in BM from T2DM. MVM FATP6 expression was increased (p = 0.02) and correlated with birth weight in both T2DM and NGT groups (r = 0.65, p = 0.02). BM FATP6 expression was increased (p = 0.01) in T2DM. In MVM of T2DM placentas, SNAT1 expression was increased (p = 0.05) and correlated with birth weight (r = 0.84, p = 0.004); SNAT2 was increased (p = 0.01), however System A transporter activity was not different between groups. MVM LAT1 expression was increased (p = 0.01) in T2DM and correlated with birth weight (r = 0.59, p = 0.04) and neonatal fat mass (r = 0.76, p = 0.06).
In pregnancies complicated by T2DM placental protein expression of transporters for glucose, amino acids and fatty acids is increased, which may contribute to increased fetal growth and neonatal adiposity.
Adipose tissue development and lipid metabolism in the human fetus: The 2020 perspective focusing on maternal diabetes and obesity
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Neonatal fat depots have also received attention in recent years, because they are the most variable body compartment, subject to environmental influences and, hence, are a highly plastic trait. Newborns of pregnancies associated with maternal overnutrition such as pre-gestational diabetes mellitus, gestational diabetes mellitus (GDM) or maternal obesity are characterized by excessive fat accretion in utero [17–19]. The fat depots laid down in utero are associated with the proportion of fat in children [20] and, hence, represent a substantial risk factor for childhood obesity.
During development, the human fetus accrues the highest proportion of fat of all mammals. Precursors of fat lobules can be found at week 14 of pregnancy. Thereafter, they expand, filling with triacylglycerols during pregnancy. The resultant mature lipid-filled adipocytes emerge from a developmental programme of embryonic stem cells, which is regulated differently than adult adipogenesis.
Fetal triacylglycerol synthesis uses glycerol and fatty acids derived predominantly from glycolysis and lipogenesis in liver and adipocytes. The fatty acid composition of fetal adipose tissue at the end of pregnancy shows a preponderance of palmitic acid, and differs from the mother. Maternal diabetes mellitus does not influence this fatty acid profile. Glucose oxidation is the main source of energy for the fetus, but mitochondrial fatty acid oxidation also contributes. Indirect evidence suggests the presence of lipoprotein lipase in fetal adipose tissue. Its activity may be increased under hyperinsulinemic conditions as in maternal diabetes mellitus and obesity, thereby contributing to increased triacylglycerol deposition found in the newborns of such pregnancies. Fetal lipolysis is low. Changes in the expression of genes controlling metabolism in fetal adipose tissue appear to contribute actively to the increased neonatal fat mass found in diabetes and obesity. Many of these processes are under endocrine regulation, principally by insulin, and show sex-differences. Novel fatty acid derived signals such as oxylipins are present in cord blood with as yet undiscovered function. Despite many decades of research on fetal lipid deposition and metabolism, many key questions await answers.
Maternal obesity and developmental priming of risk of later disease
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The prevalence of obesity has increased markedly over recent decades. Maternal obesity is associated with increased risk of pregnancy complications, including gestational diabetes. In addition, maternal obesity is recognized to be associated with increased birth weight, neonatal adiposity, increased risk of childhood obesity, diabetes, and metabolic risk in the offspring, independent of the effects of gestational diabetes or maternal hyperglycemia. Furthermore, some of the effects of in utero overnutrition may have intergenerational effects. Many of the observations noted in epidemiological studies have also been seen in animal models of maternal obesity, which provide opportunities to investigate the underlying mechanisms. The mechanisms that mediate these effects are not entirely clear but may involve epigenetic changes, altered neurohormonal regulation, and dysregulated gut microbiota, to name but a few. Recent randomized clinical trials have highlighted the limited benefit of interventions during pregnancy, highlighting the need for a holistic approach, addressing different risk factors across the lifecourse, including in adolescents and the preconception period, in order to reduce the increasing public health burden of obesity and diabetes.
Maternal Diabetes
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  The incidence of diabetes in pregnancy is steadily rising, likely in parallel with the rising incidence of obesity among women of reproductive age.
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  Women with diabetes are at increased risk for fetal complications (such as congenital malformations, fetal growth abnormalities, and stillbirth) and perinatal/neonatal complications (such as prematurity, respiratory distress, and metabolic abnormalities including hypoglycemia and electrolyte derangements).
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  Good maternal glycemic control achieved preconception and maintained throughout pregnancy is key to optimizing fetal and neonatal outcomes.
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  Breastfeeding should be strongly encouraged and supported as it may reduce some of the possible adverse effects of intrauterine programming in the context of maternal diabetes.
Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes
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High maternal weight, dyslipidemia, and/or hyperglycemia place mother and child at risk, with the most common adverse outcome being high birth weight (macrosomia) [5–12]. Large for gestational age infants born to women with GDM have a higher percent body fat when compared to infants from uncomplicated pregnancies [13] and ∼70% of mothers [14] and offspring [15] will develop type 2 diabetes in later life. The influence of maternal disease on fetal outcomes is governed, to a large extent, by the placenta.
Maternal obesity is growing in prevalence and is associated with increased morbidity and mortality for both mother and child. Women who are obese during pregnancy have a greater risk of metabolic complications such as gestational diabetes mellitus (GDM) as well as type 2 diabetes after pregnancy. Children of obese and/or GDM mothers have an increased susceptibility to congenital abnormalities and a range of cardio-metabolic disorders. The placenta is at the interface of the maternal and fetal environments and, its function per se, plays a major role in dictating the impact of maternal health on fetal development. Here, we review the literature on how placental function is affected in pregnancies complicated by obesity, and pre-gestational and gestational diabetes. The focus is on the availability of three key substrates in these conditions: glucose, lipids, and amino acids, and their impact on placental metabolic activity. Maternal obesity and diabetes are not always associated with fetal compromise and the adaptation of the placenta may partially determine the outcome. Understanding the differences in metabolic adaptation may open avenues for therapeutic development.

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Supported by the National Institutes of Health, grants HD-22965 (P.C.) and P-50-HD 11089 (P.C.), and the General Clinical Research Center, grant MO1-RR-080.

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General Obstetrics and Gynecology: ObstetricsEvaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels

Objective

Study design

Results

Conclusion

Section snippets

Material and methods

Results

Comment

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Macrosomia in infants of diabetic mothers: characteristics, causes, prevention

Lean body mass as a reference standard

J Appl Physiol

Human intrauterine growth and accretion

Semin Perinatol

Examination of factors contributing to the risk of cesarean delivery in women with gestational diabetes

Obstet Gynecol

General Obstetrics and Gynecology: Obstetrics
Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels