Larraine Huston-Presley

Increased fetal adiposity: a very sensitive marker of abnormal in utero development.

OBJECTIVE Because offspring of women with gestational diabetes mellitus have an increased risk of obesity and diabetes mellitus as young adults, our purpose was to characterize body composition at birth in infants of women with gestational diabetes mellitus and normal glucose tolerance. STUDY DESIGN One hundred ninety-five infants of women with gestational diabetes mellitus and 220 infants of women with normal glucose tolerance had anthropometric measurements and total body electrical conductivity body composition evaluations at birth. Parental demographic, anthropometric, medical and family history data, and diagnostic glucose values were used to develop a stepwise regression model that related to fetal growth and body composition. RESULTS There was no significant difference in birth weight (gestational diabetes mellitus [3398+/-550 g] vs normal glucose tolerance [3337+/-549 g], P=.26) or fat-free mass (gestational diabetes mellitus [2962+/-405 g] vs normal glucose tolerance [2975+/-408 g], P=.74) between groups. However, infants of women with gestational diabetes mellitus had significantly greater skinfold measures (P=.0001) and fat mass (gestational diabetes mellitus [436+/-206 g] vs normal glucose tolerance [362+/-198 g], P=.0002) compared with infants of women with normal glucose tolerance. In the gestational diabetes mellitus group, although gestational age had the strongest correlation with birth weight and fat-free mass, fasting glucose level had the strongest correlation with neonatal adiposity. CONCLUSION Infants of women with gestational diabetes mellitus, even when they are average weight for gestational age, have increased body fat compared with infants of women with normal glucose tolerance. Maternal fasting glucose level was the strongest predictor of fat mass in infants of women with gestational diabetes mellitus. This increase in body fat may be a significant risk factor for obesity in early childhood and possibly in later life.

Perinatal risk factors for childhood obesity and metabolic dysregulation

BACKGROUND Childhood obesity has increased significantly in recent decades. OBJECTIVE The objective was to examine the perinatal risk factors related to childhood obesity. DESIGN In a prospective study, 89 women with normal glucose tolerance (NGT) or gestational diabetes mellitus (GDM) and their offspring were evaluated at birth and at 8.8 +/- 1.8 y. At birth, obstetrical data, parental anthropometric measures, and neonatal body composition were assessed; at follow-up, diet and activity were assessed and laboratory studies were conducted. Weight was classified by using weight for age and sex, and body composition was measured by using dual-energy X-ray absorptiometry. In childhood, data were analyzed as tertiles and prediction models were developed by using logistic and stepwise regression. RESULTS No significant differences in Centers for Disease Control and Prevention weight percentiles, body composition, and most metabolic measures were observed between children of mothers with NGT and GDM at follow-up. Children in the upper tertile for weight had greater energy intake (P = 0.02), skinfold thickness (P = 0.0001), and leptin concentrations (P < 0.0001) than did those in tertiles 1 and 2. Children in the upper tertile for percentage body fat had greater waist circumference (P = 0.0001), insulin resistance (P = 0.002), and triglyceride (P = 0.009) and leptin (P = 0.0001) concentrations than did children in tertiles 1 and 2. The correlation between body fat at birth and follow-up was r = 0.29 (P = 0.02). The strongest perinatal predictor for a child in the upper tertile for weight was maternal pregravid body mass index (BMI; kg/m(2)) >30 (odds ratio: 3.75; 95% CI: 1.39, 10.10; P = 0.009) and for percentage body fat was maternal pregravid BMI >30 (odds ratio: 5.45; 95% CI: 1.62, 18.41; P = 0.006). CONCLUSION Maternal pregravid BMI, independent of maternal glucose status or birth weight, was the strongest predictor of childhood obesity.

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

Aims/hypothesisAdiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy.Subjects, materials and methodsLean women (BMI <25 kg/m²) were evaluated longitudinally before conception, and in early (12–14 weeks) and late (34–36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point.ResultsAdiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9±1.4 vs 13.5±1.8 μg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7±2.9 vs 18.9±2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9±0.6 vs 6.2±0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production.Conclusions/interpretationThese data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.

The influence of obesity and gestational diabetes mellitus on accretion and the distribution of adipose tissue in pregnancy

OBJECTIVE The purpose of this study was to evaluate the effect of pregravid obesity and gestational diabetes mellitus (GDM) on the longitudinal accretion and distribution of adipose tissue in pregnancy. STUDY DESIGN Women with normal glucose tolerance and GDM were evaluated before conception, early (12-14 weeks) and late (33-36 weeks) in gestation. Fat mass, lean body mass, and percent body fat were assessed longitudinally with hydrodensitometry. Serial biceps, triceps, subscapular, iliac, costal, mid thigh, and lower thigh skinfold measurements quantified the changes in fat mass distribution. Pregravid obesity was defined as >25% body fat. RESULTS Subjects included 19 patients with GDM (5 lean women, 14 obese women), and 33 patients with normal glucose tolerance (controls; 12 lean women, 21 obese women). GDM and control subjects were similar in pregravid percent body fat (29.6% vs 27.9%, P=.47) and fat mass (20.8 kg vs 18.2 kg, P=.37). Values for subjects with GDM and controls were also similar in terms of percent body fat, fat mass, and weight gained (change in percent body fat, -0.7% vs 1.9% [P=.07]; change in fat mass, 3.8 kg vs 5.0 kg [P=.08]; change in weight, 12.0 kg vs 13.2 kg [P=.35]). Lean subjects gained more percent body fat compared with obese subjects (change in percent body fat, 3.3% vs 0.1% [P=.004]) but gained similar amounts of fat mass (change in fat mass, 4.7 kg vs 4.2 kg [P=.58]), lean body mass (7.6 kg vs 8.8 kg [P=.18]), and weight (change in weight, 12.3kg vs 13.0 kg [P=.61]) The distribution of adipose tissue that was accumulated as estimated with skinfold measurements was similar between patients with GDM and glucose tolerance (P>.05 for all changes in skinfolds), but significantly different between lean and obese patients (P<.05 for all changes in skinfolds). Lean women gained a predominance of adipose tissue peripherally over that in obese women. CONCLUSION Lean women accrue significantly more fat mass than obese women, regardless of glucose tolerance. Pregestational obesity rather than GDM influences the distribution of adipose accretion.

Maternal Interleukin-6: Marker of Fetal Growth and Adiposity

Fetal overgrowth and higher adiposity are hallmarks of pregnancy with maternal obesity and poor glucose tolerance, two conditions associated with decreased maternal insulin sensitivity. In non-pregnant individuals, adipokines, vasoactive peptides, and components of the immune system crosstalk with metabolic factors to generate signals triggering obesity and impaired insulin action. We have investigated circulating maternal and fetal cytokines and growth-factors as potential biochemical markers of fetal adiposity. Mothers and neonates were classified into three tertiles (T1-T3) using total neonatal fat mass as the outcome with 309 ± 25 g in T1, 478 ± 40 g in T2, and 529 ± 39 g in T3. Umbilical cord endothelin-1 (ET-1), C-peptide, and leptin were higher in T3 and T2 versus T1. Only cord leptin was strongly associated with fetal fat mass (P < .01), whereas neonatal lean body mass was negatively correlated with maternal insulin-like growth factor binding protein-I (IGFBP-I) (r = -0.53, P < .04). This study shows an association between increased fetal adiposity and maternal systemic interleukin-6 (IL-6). No such correlation was found with factors circulating in cord blood, suggesting that the stimuli favoring fetal fat accretion derive from maternal or placental sources rather than from the fetus.

Women’s reported weight: is there a discrepancy?

Objective: To compare self-reported pre-pregnancy weight & delivery weight with documented pre-pregnancy & delivery weight and determine whether there are differences compared with the Institute of Medicine’s (IOM) guidelines. Methods: This is a retrospective analysis of 234 women. Inclusion criteria included documented height, self-reported pre-pregnancy weight, self-reported delivery weight, documented pre-pregnancy weight ± 12 weeks from last menstrual period, and documented delivery weight ± 2 weeks from delivery. We determined the difference between self-reported pre-pregnancy weight vs. documented pre-pregnancy weight and self-reported delivery weight vs. documented delivery weight. Using documented pre-pregnancy weight and documented delivery weight, we calculated gestational weight gain (GWG) relative to IOM criteria. Results: Self-reported pre-pregnancy weight was 2.94 kg less than documented pre-pregnancy weight (p < 0.0001). Self-reported BMI was 1.11 mg/kg2 less than documented BMI (p < 0.0001). Self-reported GWG was 3.01 kg greater than documented GWG (p < 0.0001). Ninety-eight percent of normal weight correctly classified pregravid BMI in contrast to 86% of obese (p < 0.005) and 73% of overweight (p < 0.001). Conclusions: Overweight and obese women underestimated self-reported pre-pregnancy weight & overestimated GWG, thereby mistakenly categorizing IOM guidelines.

Relationship of neonatal body composition to maternal glucose control in women with gestational diabetes mellitus

Objective: To determine whether neonatal fat mass, which may be a better estimate of fetal overgrowth, is correlated with maternal fasting, preprandial and/or postprandial glucose values in women with gestational diabetes mellitus (GDM). Study Design: Women with GDM and no other medical or obstetric problems, and their infants, were the subjects of this study. Portable reflectance meters were used by all participants for self-monitoring of blood glucose levels. Average fasting, preprandial, 2-h postprandial and bedtime glucose values were determined for each subject. Neonatal body composition was obtained by total body electric conductivity and/or anthropometric measurements within 48 h after delivery. Results: Eighteen women with their infants participated in this study. The age (mean ± SD) of the mothers was 28.0 ± 5.7 years. Nine were treated with diet and nine with diet and insulin. An average of 40 fasting (84 ± 13 mg/dl), 50 preprandial (87 ± 14 mg/dl), 80 2-h postprandial (106 ± 19 mg/dl) and 17 bedtime (104 ± 19 mg/dl) glucose values were obtained from each subject. The average gestational age of the infants at birth was 38.3 ± 1.3 weeks with a mean weight of 3356 ± 526 g. Three infants were > 4 kg and seven infants were > 90th centile for gestational age. The strongest correlation with neonatal fat mass was maternal fasting glucose level (r = 0.71, p < 0.01). Neonatal fat mass was not found to be significantly correlated with any other mean glucose value. Additionally, the infants per cent body fat (r = 0.71, p < 0.01), sum of skinfold thicknesses (r = 0.70, p < 0.01), fat-free mass (r = 0.50, p < 0.05), and weight (r = 0.61, p < 0.01) were also found to be correlated with maternal fasting glucose level. No other maternal glucose measurements were correlated with either birth weight or estimates of fat free mass. Conclusion: Maternal fasting glucose levels correlated best with neonatal fat mass and other estimates of neonatal body composition.