Chang Ye

Effect of maternal weight, adipokines, glucose intolerance and lipids on infant birth weight among women without gestational diabetes mellitus

Background: The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight. Methods: We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery. Results: The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05–1.27, per 1 kg/m2 increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05–1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30–0.82, per 1 standard deviation change). Interpretation: Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels.

Cardiometabolic Implications of Postpartum Weight Changes in the First Year After Delivery

OBJECTIVE The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her ultimate risk of diabetes and vascular disease. However, there is little direct evidence supporting this hypothesis. In this context, we sought to evaluate the cardiometabolic implications of patterns of postpartum weight change and the time course thereof in the first year after pregnancy. RESEARCH DESIGN AND METHODS Three hundred five women underwent cardiometabolic characterization at recruitment in pregnancy and at 3 and 12 months postpartum. Based on their respective weight changes between prepregnancy and 3 months postpartum (loss or gain) and between 3 and 12 months postpartum (loss or gain), participants were stratified into four groups: loss/loss, gain/loss, loss/gain, and gain/gain. RESULTS Most women (81.0%) had higher weight at 3 months postpartum compared with prepregnancy. Between 3 and 12 months, most women (74.4%) lost weight. At 3 months, there were modest differences between the four groups in mean adjusted LDL cholesterol (P = 0.01) and apolipoprotein-B (apoB; P = 0.02) but no significant differences in adjusted blood pressure, fasting and 2-h glucose, HDL, triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and C-reactive protein. By 12 months postpartum, however, clear gradients emerged, with mean adjusted diastolic blood pressure (P = 0.02), HOMA-IR (P = 0.0003), LDL (P = 0.001), and apoB (P < 0.0001) all progressively increasing from the loss/loss group to gain/loss to loss/gain to gain/gain. Similarly, at 12 months, mean adjusted adiponectin showed a stepwise decrease from loss/loss to gain/loss to loss/gain to gain/gain (P = 0.003). CONCLUSIONS An adverse cardiometabolic profile emerges as early as 1 year postpartum in women who do not lose weight between 3 and 12 months after delivery.

Maternal Pregravid Weight Is the Primary Determinant of Serum Leptin and Its Metabolic Associations in Pregnancy, Irrespective of Gestational Glucose Tolerance Status

CONTEXT Several previous studies have investigated circulating levels of the adipokine leptin in relation to gestational diabetes mellitus (GDM). However, these studies have yielded markedly conflicting results, including increased, decreased, and unchanged leptin levels in women with GDM as compared with their peers. OBJECTIVE We sought to evaluate the metabolic determinants of serum leptin in a well-characterized cohort reflecting the full spectrum of glucose intolerance in pregnancy. DESIGN, SETTING, AND PARTICIPANTS Metabolic characterization, including oral glucose tolerance test (OGTT) and measurement of serum leptin, insulin, lipids, adiponectin, and C-reactive protein, was performed in 817 pregnant women. The OGTT identified 198 women with GDM, 142 with gestational impaired glucose tolerance, and 477 with normal glucose tolerance. RESULTS Median leptin (ng/ml) did not differ between the normal glucose tolerance (33.7), gestational impaired glucose tolerance (36.3), and GDM (36.4) groups (P = 0.085). On univariate correlation analysis, leptin was most strongly associated with prepregnancy body mass index (BMI) (r = 0.54, P < 0.0001), fasting insulin (r = 0.60, P < 0.0001), and C-reactive protein (r = 0.38, P < 0.0001) but only weakly associated with area under the glucose curve (AUC(glucose)) on the OGTT (r = 0.10, P = 0.0066). On multiple linear regression analysis, the strongest independent determinant of leptin was prepregnancy BMI (t = 11.55, P < 0.0001), whereas AUC(glucose) was not a significant predictor (t = -0.95, P = 0.34). Furthermore, although its respective associations with fasting insulin, triglycerides, and adiponectin varied across tertiles of prepregnancy BMI, leptin was not significantly associated with AUC(glucose) in any BMI tertile. CONCLUSIONS Pregravid BMI, rather than gestational glucose tolerance, is the primary determinant of serum leptin concentration in pregnancy.

Circadian variation in the response to the glucose challenge test in pregnancy: implications for screening for gestational diabetes mellitus.

OBJECTIVE A common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a 1-h, 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (≥7.8 mmol/L). More important, the GCT is performed at any time of day, but there has been limited study of the effect of time of day on test performance. Thus, using their subsequent OGTT (performed in the morning), we sought to characterize the metabolic function of women with positive GCTs in relation to the timing of their test. RESEARCH DESIGN AND METHODS A total of 927 women with positive GCTs underwent a 3-h 100-g OGTT. They were stratified into four groups by time of day (hours) of their GCT: <0900 (n = 171), 0900–1059 (n = 288), 1100–1259 (n = 189), and ≥1300 (n = 279). RESULTS On the OGTT, the prevalence of GDM progressively decreased across the GCT groups from <0900 h (26.9%) to 0900–1059 h (25.0%) to 1100–1259 h (21.7%) to ≥1300 h (21.5%; P = 0.0022). After adjustment for GDM risk factors, mean adjusted glucose area under the curve (AUCgluc) similarly decreased across the groups, while insulin sensitivity (Matsuda index) and β-cell function (Insulin Secretion-Sensitivity Index-2) progressively increased (all P < 0.0001). In particular, compared with the <0900- and 0900–1059-h groups, women whose positive GCT occurred after 1300 h had superior metabolic function, as evidenced by lower AUCgluc, higher insulin sensitivity, and better β-cell function (all P ≤ 0.0097). CONCLUSIONS Among women with a positive GCT, those tested in the afternoon have better metabolic function and a lower risk of GDM on subsequent OGTT.

Hepatic Insulin Resistance Is an Early Determinant of Declining β-Cell Function in the First Year Postpartum After Glucose Intolerance in Pregnancy

OBJECTIVE The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their β-cell function, which occurs as early as the first year postpartum. We thus sought to identify early determinants of their declining β-cell function. RESEARCH DESIGN AND METHODS Women with recent gestational glucose intolerance (166) underwent oral glucose tolerance test at 3 and 12 months postpartum. They were stratified into those in whom β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) declined over this time (decliners; n = 92) and those in whom it did not (nondecliners; n = 74). RESULTS Between 3 and 12 months, hepatic insulin sensitivity (1/homeostasis model assessment of insulin resistance [HOMA-IR]) decreased in decliners but not in nondecliners. Over this time, the change in 1/HOMA-IR emerged as an independent predictor of the change in ISSI-2 (t = 5.5; P < 0.0001). Increased hepatic insulin sensitivity independently predicted a lower likelihood of declining β-cell function (odds ratio = 0.13 [95% CI 0.06–0.29]; P < 0.0001). CONCLUSIONS Hepatic insulin resistance is an early determinant of declining β-cell function after gestational dysglycemia.

Maternal Serum Prolactin and Prediction of Postpartum β-Cell Function and Risk of Prediabetes/Diabetes

OBJECTIVE The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic β-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of β-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of β-cell function in pregnancy. Given their respective roles in the β-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman’s underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODS Three hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTS The postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (β = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35–0.72, P = 0.0002). CONCLUSIONS Serum prolactin in pregnancy predicts postpartum β-cell function and risk of prediabetes/diabetes.

Determinants of Insulin Resistance in Infants at Age 1 Year: Impact of gestational diabetes mellitus

OBJECTIVE The offspring of women with gestational diabetes mellitus (GDM) display a propensity for the early accrual of cardiometabolic risk factors, including insulin resistance, in childhood and adolescence. Thus, we sought to identify early life determinants of insulin resistance in infants of women with and without GDM. RESEARCH DESIGN AND METHODS In total, 104 full-term, singleton infants born to women with (n = 36) and without (n = 68) GDM were evaluated at age 1 year, with insulin resistance assessed by homeostasis model (HOMA-IR). RESULTS HOMA-IR at 1 year did not differ between infants born to mothers with and without GDM (P = 0.74). The sole independent predictor of infant HOMA-IR in the non-GDM group was birth weight (t = 3.33, P = 0.002). In contrast, weight gain in the 1st year was the only independent predictor of HOMA-IR in infants of women with GDM (t = 2.19, P = 0.039). CONCLUSIONS In the 1st year of life, weight gain in infants born to women with GDM is associated with insulin resistance, unlike in their peers.

Postpartum Metabolic Function in Women Delivering a Macrosomic Infant in the Absence of Gestational Diabetes Mellitus

OBJECTIVE Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and β-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for-gestational-age (LGA) delivery is often considered presumptive evidence of GDM, whether or not it was diagnosed at the time. If this clinical assumption is correct, however, we would expect these women to exhibit postpartum metabolic dysfunction. Thus, to test this hypothesis, we assessed metabolic function during and after pregnancy in a cohort of women stratified according to the presence/absence of GDM and LGA delivery, respectively. RESEARCH DESIGN AND METHODS A total of 562 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in late pregnancy and at 3 months’ postpartum. The women were stratified into three groups: those with neither GDM nor LGA delivery (nonGDM, n = 364), those without GDM but with LGA delivery (nonGDM–LGA, n = 46), and those with GDM (n = 152). RESULTS On logistic regression, GDM predicted postpartum glucose intolerance (OR 4.1 [95% CI 2.5–6.8]; P < 0.0001), whereas nonGDM–LGA did not (P = 0.65). At 3 months’ postpartum, the mean adjusted levels of fasting glucose and area under the glucose curve on the OGTT were significantly higher in the GDM women compared with either nonGDM or nonGDM–LGA (all P < 0.05), with no differences between the latter two groups. In a similar manner, mean adjusted insulin sensitivity (Matsuda index) and β-cell function (Insulin Secretion-Sensitivity Index-2) were lower in GDM women compared with either nonGDM or nonGDM–LGA (all P < 0.05), again with no differences between the latter two groups. CONCLUSIONS Women with nonGDM–LGA do not exhibit postpartum metabolic dysfunction, arguing against the assumption of undiagnosed GDM in these patients.

The persistence of maternal vitamin D deficiency and insufficiency during pregnancy and lactation irrespective of season and supplementation.

Pregnancy and lactation comprise a critical window spanning all seasons during which maternal vitamin D status potentially may influence the long‐term health of the newborn. Women typically receive calcium/vitamin D supplementation through antenatal vitamins, but there has been limited serial evaluation of maternal vitamin D status across this critical window.

Maternal Blood Pressure Before Pregnancy and Sex of the Baby: A Prospective Preconception Cohort Study

BACKGROUND Population‐level sociologic studies have suggested that adverse societal conditions may affect fetal viability in a sex‐specific manner and thereby modify the ratio of male vs. female babies. This concept suggests that there may exist certain physiologic features in a woman that relate to her likelihood of delivering a boy or girl. We thus established a preconception cohort to prospectively evaluate the relationship between maternal pregravid health and sex of the baby. METHODS In this analysis nested within an observational cohort study, 1,411 newly married women in Liuyang, China, underwent pregravid cardiometabolic characterization (including anthropometry and measurement of blood pressure, cholesterol, triglycerides, and glucose) at median 26.3 weeks before a singleton pregnancy, delivering at 39.0 ± 1.3 weeks gestation. RESULTS Systolic blood pressure before pregnancy was higher in women who delivered a boy than in those who had a girl (112.5 ± 11.9 vs. 109.6 ± 12.0 mm Hg, P < 0.0001). The prevalence of a male baby progressively increased across quintiles of pregravid systolic blood pressure (P < 0.0001). After covariate adjustment, mean adjusted pregravid systolic blood pressure was higher in mothers of boys vs. girls (106.0 vs. 103.3 mm Hg, P = 0.0015). On logistic regression analysis, pregravid systolic blood pressure emerged as the only significant predictor of having a male baby (adjusted odds ratio = 1.017 per mm Hg, 95% confidence interval = 1.007‐1.028). The pregravid difference in blood pressure between mothers of boys and girls was not present during any trimester of pregnancy. CONCLUSION Maternal blood pressure before pregnancy is a previously unrecognized factor that may be associated with the likelihood of delivering a boy or girl.