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

AIMS/HYPOTHESIS: Adiponectin 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 METHODS: Lean women (BMI <25 kg/m(2)) 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. RESULTS: Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9+/-1.4 vs 13.5+/-1.8 microg/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/INTERPRETATION: These 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.

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 3,356 +/- 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 infant's 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.

Factors associated with fetal growth and body composition as measured by ultrasound.

OBJECTIVE: This study seeks to determine which parental demographic and metabolic factors best correlate with fetal growth and body composition as estimated by ultrasound. STUDY DESIGN: Thirty-one gravid patients had ultrasound estimates of fetal anthropometry in mid-third trimester. These measurements included estimated fetal weight, abdominal subcutaneous fat, and/or thigh subcutaneous fat thickness. Independent variables included diagnosis of gestational diabetes, parental demographic factors, neonatal sex, and late gestation estimates of carbohydrate metabolism. RESULTS: In the multivariate stepwise model the strongest predictor of ultrasound estimated fetal weight was basal hepatic glucose production, followed by late gestation insulin sensitivity (total R (2) = 0.27). The strongest predictors of abdominal subcutaneous fat thickness were weight gain and presence of gestational diabetes (total R (2) = 0.25). CONCLUSION: Measures of maternal carbohydrate metabolism, rather than fat mass, explain sonographic measurements of fetal weight. We speculate that factors other than maternal carbohydrate metabolism further explain the variances of fetal adiposity.

Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus.

OBJECTIVE: We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (IS(OGTT)) or fasting glucose/insulin levels (IS(QUICKI) and IS(HOMA)) can be used to predict insulin sensitivity in women before and during pregnancy. RESEARCH DESIGN AND METHODS: A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU. m(-2). min(-1) insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12-14 weeks) and late (34-36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (IS(CLAMP)) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6(-2)H(2)]glucose. RESULTS: Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between IS(CLAMP) and IS(OGTT) (r(2) = 0.74, P < 0.0001), IS(QUICKI) (r(2) = 0.64, P < 0.0001), and IS(HOMA) (r(2) = 0.53, P < 0.0001). The IS(OGTT) provided a significantly better correlation (P < 0.0001) than either IS(QUICKI) or IS(HOMA.) Multivariate analysis showed a significant group effect (P < 0.0003) on the prediction model, and separate equations were developed for the NGT (r(2) = 0.64, P < 0.0001) and GDM (r(2) = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the correlation between IS(CLAMP) and IS(OGTT) pregravid was r(2) = 0.63 (P = 0.0002), during early pregnancy was r(2) = 0.80 (P < 0.0001), and during late pregnancy was r(2) = 0.64 (P = 0.0002). CONCLUSIONS: Estimates of insulin sensitivity from the IS(OGTT) during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM.

Anthropometric estimation of maternal body composition in late gestation.

OBJECTIVE: To construct a model to estimate maternal body composition in late gestation using anthropometric measurements. METHODS: Twenty healthy pregnant women at 30 weeks' gestation had estimates of body composition using hydrodensitometry, with corrections for residual lung volume, and total body water using H(2)(18)O (development group). Total body water was estimated from (18)O abundances measured by gas-isotope-ratio mass spectrometry. Maternal age, height, weight, and seven skinfold sites were correlated with fat mass using stepwise regression analysis. The anthropometric model to estimate fat mass was then tested prospectively in a second group of 20 subjects and correlated with underwater weighing and total body water measurements (validation group). Statistical analysis used chi(2), paired t and Wilcoxon sign-rank tests. RESULTS: There were no statistically significant differences in maternal demographics between groups. The fat mass of development group subjects using underwater weighing and total body water was 22.7 +/- 7.6 kg. Using the development group, a model was derived that explained 91% of the variance in fat mass by underwater weighing and total body water using maternal weight and triceps, subscapular, and suprailiac skinfolds (r(2) = 0.91, P <.001). When tested prospectively in the validation group, the correlation remained statistically significant (r(2) = 0.89, P <.001). There was no statistically significant (P =.88) difference between the anthropometric estimates of fat mass and underwater weighing and total body water measurements (95% confidence interval -2.476, 2.748 kg of fat mass). CONCLUSION: This anthropometric model can be used to predict maternal fat mass in late gestation.