Decreased maternal lipolysis in intrauterine growth restriction in the third trimester

OBJECTIVE: Intrauterine growth restriction (IUGR) is a common complication of pregnancy. There are many possible aetiologic factors of maternal, placental and/or fetal origin. Often there is no known explanation. The aim of this study was to investigate whether a reduction in maternal energy substrate production could be one of the factors involved in IUGR. DESIGN: Measurement of maternal energy substrate production and glucoregulatory hormones in women with growth-restricted fetuses. SETTINGS: University Hospital, Uppsala, Sweden. POPULATION: Ten healthy pregnant women with IUGR were compared with eight recently reported healthy women with normal pregnancies. The women were studied at 35.4+/-1.6 weeks of gestation after an overnight fast. METHODS: Rates of glycerol and glucose production were analysed by gas chromatography/mass spectrometry following constant-rate infusion of [1,1,2,3,3-(2)H5]glycerol and [6,6-(2)H2]glucose. MAIN OUTCOME MEASURE: Third trimester glycerol and glucose production. RESULTS: Glycerol production, reflecting lipolysis, was lower in the women with IUGR than in those with normal pregnancies, 2.36+/-0.58 versus 3.06+/-0.66 micromol kg-1 minute-1 (P=0.033), whereas there was no difference in rate of glucose production (glucose production rate [GPR]), 12.1+/-1.5 versus 13.2+/-1.5 micromol kg-1 minute-1 (P=0.23). Plasma glycerol levels were increased in the women with IUGR (P=0.008). CONCLUSIONS: Lipolysis is lower in pregnancies complicated by IUGR as compared with normal pregnancies. Increased lipolysis during pregnancy provides substrate for maternal energy metabolism, which spares glucose for the fetus. A reduced maternal production of energy substrate could be one of several factors underlying IUGR. A lack of relationship between insulin levels and either lipolysis or GPR suggests defective regulation of energy substrate production in this group of pregnant women.     

Fuel metabolism during pregnancy.

This article reviews carbohydrate and fat metabolism in both healthy pregnant women and women with gestational diabetes. Emphasis is placed on more recent investigations that have utilized stable, nonradioactive isotopes with insulin clamps to study gestational fuel metabolism. In early pregnancy, glucose-stimulated insulin secretion is increased, insulin sensitivity is unchanged or enhanced, and glucose tolerance is normal or slightly improved. Late gestation is characterized by accelerated fetal growth, rising concentrations of several diabetogenic hormones, and increased insulin resistance. The increased resistance reduces maternal glucose utilization, sparing carbohydrates for the rapidly growing fetus. The inhibitory effect of insulin on the rate of lipolysis is also significantly reduced during the third trimester of pregnancy. An earlier than normal switch from carbohydrate to fat utilization serves to promote the use of lipids as a maternal energy source. Women with gestational diabetes have been reported to have either comparable or increased insulin resistance during late gestation with several studies also demonstrating reduced insulin secretory capacity.     

妊娠期妇女糖耐量胰岛素 胰岛素抵抗变化规律的观察

目的：观察不同孕期孕妇的糖耐量、胰岛素释放、胰岛素抵抗，以了解妊娠期糖代谢变化的规律。方法：对早、中、晚孕期三组共１２４例正常孕妇及２３例健康非孕妇女作为对照组进行７５ｇ口服糖耐量试验（ＯＧＴＴ）。其中１３例自早孕期开始纵向跟踪。以胰岛素曲线下面积与血糖曲线下面积的比值反映胰岛素抵抗（ＩＳＲ）。结果：各个孕期的空腹血糖无明显差异，但均显著低于非孕期（Ｐ＜００５），服糖后血糖、胰岛素释放、胰岛素抵抗均随孕期延长逐渐上升。于中孕期开始出现显著性改变，至晚孕期进一步加重均显著高于孕早期（Ｐ＜００５）。结论：中孕期是妊娠期糖代谢开始出现根本性变化的时期，于此期对孕妇进行血糖监测，有助于妊娠期糖尿病（ＧＤＭ）的早期诊断。晚孕期是ＧＤＭ最容易发生的时期     

Clinical utility and approaches for estimating insulin sensitivity in pregnancy

Insulin sensitivity as estimated by using the hyperinsulinemic-euglycemic clamp during pregnancy has been related to maternal energy expenditure, fat accretion and fetal growth. To determine whether less time consuming and invasive methods could be employed, we examined whether selected indices 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. A 2-h euglycemic-hyperinsulinemic clamp (5 mol/L glucose, 40 mU x m(-2) x min (-1) insulin), and 120 min OGTT (75 g load pregravid, 100 g pregnant), was 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)H2]-glucose. Univariate analysis with combined groups and periods of pregnancy resulted in significant correlations between IS(CLAP) and IS(OGTT), (r2 = .74, P < .0001), IS(QUICKI) (r2 = .64, P < .0001), and IS(HOMA) (r2 = .53, P < .0001). The IS(OGTT) provided a significantly better correlation (P < .0001) than either IS(QUICKI') or IS(HOMA). Multivariate analysis revealed a significant group effect (P < .0003) on the prediction model, and separate equations were developed for the NGT (r2 = .64, P < .0001) and GDM (r2 = .85, P < .0001) groups. When subdivided by period of pregnancy the correlation between IS(CLAMP) and IS(OGTT) pregravid was r = .63, P = .0002, during early pregnancy; r2 = .80, P < .0001 and during late pregnancy; r2 = .64, P = .0002. The IS(OGTT) provides an excellent means of estimating maternal insulin sensitivity during pregnancy. The information obtained from the IS(OGTT) will be useful in making clinical decisions on maternal care and facilitating optimal pregnancy outcome.     

Adipokines and their relation to maternal energy substrate production,insulin resistance and fetal size

Objective

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

Study design

Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

Results

Median (range) rate of glucose production was 805 (653–1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110–576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (−0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5 mg/L and median level of leptin was 47.1 (9.9–58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5 mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r = −0.50, p < 0.035, r = −0.77, p < 0.001, r = −0.67, p < 0.002, and r = −0.51, p < 0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r = 0.76, p < 0.001 and r = 0.73, p < 0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

Conclusion

The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.     

Body mass index: a true indicator of body fat in obese gravidas

OBJECTIVE: To determine the relationship between body mass index (BMI) and percent body fat in overweight/obese pregnant women (BMI >25) before and during pregnancy. STUDY DESIGN: Thirteen overweight women were evaluated longitudinally (prospective cohort study design) before conception, in early gestation (12-22 weeks) and in late gestation (31-36 weeks). BMI was calculated as weight (kg)/height (m)2, and percent body fat was estimated using hydrodensitometry with correction for residual lung volume. RESULTS: The correlation between BMI and percent body fat before conception was r2 = 0.86 (p = 0.001). Furthermore, the correlation remained strong in early pregnancy, r2 = 0.84 (p = 0.001), but was less strong yet significant, r2 = 0.54 (p = 0.004), in late gestation. CONCLUSION: In overweight women, the correlation between BMI and percent body fat remained significant during pregnancy. However, the correlation weakened as the pregnancy advanced.     

Sex hormone-binding globulin in gestational diabetes

BACKGROUND: Insulin is an important regulator of serum sex hormone-binding globulin (SHBG) concentration which works by inhibiting its production in hepatocytes. Low SHBG level is associated with increased insulin resistance and hyperinsulinemia. Our purpose was to compare maternal serum SHBG level between normal and gestational diabetic pregnant women and to study the relationships between SHBG, SHBG/insulin and SHBG/glucose ratio and several endocrine, metabolic and clinical parameters. METHODS: Serum SHBG concentrations were measured in 34 women with gestational diabetes and in 32 matched controls. Glucose, insulin, C-peptide, fructosamine, beta-HCG, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A, apolipoprotein B, total and free T4, total and free estriol, T3 and IGF-1 were measured. Insulin sensitivity was estimated using the short insulin tolerance test. RESULTS: SHBG, SHBG/insulinemia ratio and SHBG/glucose ratio were significantly lower in the diabetic group (309.54 +/- 112.22 vs 460.54 +/- 144.54, p = 0.00001), (33.55 +/- 16.62 vs 72.56 +/- 66.50, p = 0.0006 using log-transformed values), (5.88 +/- 1.87 vs 3.39 +/- 1.23, p < 0.00001). SHBG was negatively correlated with insulinemia (r = -0.40, p = 0.001), C-peptide (r = -0.41, p = 0.001), glycemia (r = -0.27, p = 0.02), diastolic blood pressure (r = -0.41, p = 0.001) and beta-HCG (r = -0.41, p = 0.001) and positively correlated with LDL-c (r = 0.25, p = 0.04) and apolipoprotein B (r = 0.33, p = 0.007). CONCLUSIONS: SHBG concentrations are lower in gestational diabetic pregnant women and are related to insulin levels but not to peripheral insulin sensitivity. Since insulinemia was similar in normal and gestational diabetic pregnant women, we speculate that gestational diabetes is characterized by a higher peripheral insulin resistance, a fasting normal insulinemia and a higher hepatic insulin sensitivity, at least in other actions than on carbohydrate metabolism. The role of sex steroids, T4 and IGF-1 in regulating SHBG appears to be limited during pregnancy.     

妊娠期外阴阴道念珠菌病的发病分析

目的:了解妊娠期外阴阴道念珠菌病(VVC)的发病情况以及影响因素。方法:回顾性调查2005年1月1日至2005年6月20日在北京大学第一医院分娩的1119例孕妇孕前及孕期VVC的发病情况。结果:1119例孕妇中,孕前曾患VVC共212例(18·95%),孕前9个月内曾患VVC的孕妇较未感染者孕期VVC发生率明显升高(P<0·01)。1119例孕妇中孕期VVC感染102例(9·12%),明显高于孕前9个月内发生率(P<0.01),其中,妊娠早期22例,中期39例,晚期41例;血糖正常孕妇VVC发生率与血糖异常孕妇发生率比较,差异无显著性(P>0.05)。结论:妊娠中、晚期VVC发病率高于早期。妊娠前9个月内曾患有VVC是孕期VVC的高危因素,妊娠期糖代谢异常者孕期VVC的发生率未见明显增加。     

Perinatal complications in women with gestational diabetes mellitus

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.     

Maternal plasma leptin levels and their relationship to insulin and glucose in gestational-onset diabetes

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean +/- SD 16.52 +/- 5.07 ng/ml, range 10.84-27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 +/- 1.47 ng/ml, range 7.28-13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.     

Maternal obesity and familial history of diabetes have opposing effects on infant birth weight in women with mild glucose intolerance in pregnancy.

OBJECTIVE: Pregnant women with an abnormal screening glucose challenge test (GCT) but without gestational diabetes mellitus (GDM) on subsequent oral glucose tolerance test (OGTT) are at increased risk of delivering macrosomic and large for gestational age (LGA) neonates. We thus sought to evaluate the maternal constitutional and biochemical factors that determine infant birth weight in this patient population. METHODS: Women with an abnormal GCT were evaluated at the time of their OGTT in late pregnancy. This analysis was restricted to Caucasian women without GDM (N = 86). Maternal demographic and biochemical factors were evaluated in relation to infant birth weight and LGA. RESULTS: After adjustment for length of gestation, birth weight was positively associated with pre-pregnancy body mass index (BMI) (r = 0.31, p = 0.0063) and negatively correlated with maternal serum levels of the insulin-sensitizing protein adiponectin (r = -0.30, p = 0.0084). On multiple linear regression analysis, pre-pregnancy BMI and weight gain in pregnancy were positive independent determinants of infant birth weight, while family history of diabetes emerged as a negative independent correlate. Logistic regression analysis confirmed that pre-pregnancy BMI was a positive predictor of LGA (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.05-1.49), whereas family history of diabetes was again identified as a negative determinant (OR = 0.10, 95% CI 0.02-0.59). In contrast, neither measures of glycemia nor insulin resistance/sensitivity were independently associated with birth weight or LGA. CONCLUSION: In pregnant women with an abnormal GCT but without GDM, pre-gravid maternal obesity predicts increased infant birth weight, whereas family history of diabetes is independently associated with decreased infant size.     

Insulin-induced hypoglycaemia in diabetic women during late pregnancy and one year post partum

Insulin (0.1 IW/kg) later followed by glucose was injected intravenously in nine diabetic women in the supine position both during pregnancy and one year post partum. C-peptide was present in five subjects, indicating some residual beta-cell function. Their mean basal C-peptide level, before insulin, was twice as high in the pregnant as inthe non-pregnant state. C-peptide decreased progressively after insulin. The mean basal plasma glucose level was lower during pregnancy (4.8 mmol/l) than after it (9.6 mmol/l), but decreased to the same level (2.2 mmol/l) after insulin. The rate of fall in glucose was thus lower during pregnancy (kt = 2.54) than after (kt = 4.08), but was unrelated to the basal glucose levels. Basal levels of free fatty acids (FFA), 3-hydroxybutyrate (3-HB), cyclic AMP, and lactate were similar, while glycerol was lower during pregnancy. Insulin-induced changes in FFA, glycerol, 3-HB, cyclic AMP, and lactate were similar during and after pregnancy. Plasma amino acid concentrations were generally lower in pregnancy, significantly so only for arginine and glycine. Amino acid levels were unaffected by insulin in pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy, whereas leucine, isoleucine and tyrosine decreased significantly in the non-pregnancy state. We conclude that there are differences in metabolic responses to insulin in diabetic women during and after pregnancy, indicating a decreased sensitivity to insulin during pregnancy in some tissues.     

Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus

OBJECTIVE: This study prospectively evaluated the longitudinal changes in insulin sensitivity, insulin response, and endogenous (primarily hepatic) glucose production and suppression during insulin infusion in women with normal glucose tolerance (control) and gestational diabetes mellitus before and during a planned pregnancy. STUDY DESIGN: Eight control subjects and 7 subjects in whom gestational diabetes mellitus developed were evaluated with an oral glucose tolerance test, an intravenous glucose tolerance test, and hyperinsulinemic-euglycemic clamp with infusion of [6,6 (2)H2 ]glucose before conception and at 12 to 14 and 34 to 36 weeks' gestation. Insulin response was estimated as the area under the curve during the intravenous glucose tolerance test. Basal endogenous glucose production was estimated from isotope tracer dilution during steady state with [6,6 (2)H2 ]glucose and suppression during insulin infusion. Insulin sensitivity to glucose was defined as the glucose infusion rate required to maintain euglycemia during steady-state insulin infusion. Body composition was estimated with hydrodensitometry. Data were analyzed with 2-way analysis of variance with repeated measures for 2 groups. RESULTS: There were increases in first-phase (P =.006) and second-phase (P =. 0001) insulin responses in both groups with advancing gestation, but the increase in second-phase response was significantly greater (P =. 02) in the gestational diabetes mellitus group than in the control group. Basal glucose production increased significantly (P =.0001) with advancing gestation, and there was resistance to suppression during insulin infusion in both groups (P =.0001). There was less suppression of endogenous glucose production however, in the gestational diabetes mellitus group than in the control group (P =. 01). Insulin sensitivity decreased with advancing gestation in both groups (P =.0001), and there was lower insulin sensitivity in the gestational diabetes mellitus group than in the control group (P =. 04). Significant decreases in insulin sensitivity with time (P =. 0001) and between groups (P =.03) remained when the data were adjusted for differences in insulin concentration or residual hepatic glucose production. CONCLUSION: Obese women in whom gestational diabetes mellitus develops have a significant increase in insulin response but decreases in insulin sensitivity and suppression of hepatic glucose production during insulin infusion with advancing gestation with respect to a matched control group. These metabolic abnormalities in glucose metabolism are the hallmarks of type 2 diabetes, for which these women are at increased risk in later life.     

正常妊娠和妊娠高血压综合征妇女血清瘦素水平的动态检测

目的　动态检测正常妊娠、妊娠高血压综合征 (妊高征 )妇女血清瘦素水平的变化特点。方法　采用放射免疫法测定 40例正常非妊娠妇女 (对照组 )以及 5 0例正常妊娠和 14例妊高征妇女(观察组 )孕 16～ 2 0、2 4～ 2 8、3 2～ 3 6周及分娩前的血清瘦素水平及其新生儿的脐血瘦素水平 ,同时测量身高、体重、血压及胎盘重量。结果　 ( 1)随着孕周的增加 ,观察组妇女血清瘦素水平呈上升趋势 ,其中妊高征妇女血清瘦素水平为 ( 14 1± 2 2 )～ ( 2 5 4± 2 7) μg/L ,较正常妊娠妇女的 ( 13 4± 3 0 )～( 2 1 4± 3 7) μg/L明显上升 (P <0 0 1) ,并持续至妊娠结束 ,而正常妊娠妇女血清瘦素水平在孕 2 8～3 6周时上升明显 ,孕 2 8周前及孕 3 6周后上升缓慢。 ( 2 )体重、体重指数与血清瘦素水平的相关性分析结果显示 ,正常妊娠、对照组妇女均呈显著性正相关 (r =0 478～ 0 63 9,P <0 0 5或P <0 0 1) ,而妊高征妇女无显著相关性 (r=0 0 3 5～ 0 3 79,P >0 0 5 )。( 3 )收缩压、舒张压、平均动脉压与血清瘦素水平的相关性分析结果显示 ,正常妊娠、孕 2 0周前的妊高征及对照组妇女无显著相关性 (r=0 113～0 498,P >0 0 5 ) ,而妊高征妇女孕 2 0周后呈显著正相关 (r=0 63 9～ 0 85 2 ,P <0 0 5 )     

Glucose kinetics in nondiabetic and diabetic women during the third trimester of pregnancy

Glucose kinetics were measured with 78% enriched D-[U-13C] glucose by the prime constant infusion technique during the third trimester of pregnancy in nine nondiabetic women, nine insulin-dependent diabetic women, six gestational diabetic women, and five control women (nonpregnant, nondiabetic) after an overnight fast. The patients not dependent on insulin were diagnosed as diabetic by oral glucose tolerance tests with the use of O'Sullivan and Mahan's criteria as modified by Carpenter and Coustan during the third trimester. The turnover studies were repeated post partum (6 weeks to 5 months after delivery) in 14 of the 24 pregnant subjects. All pregnant groups had a progressive fall in plasma glucose concentration during the study, but there was a steady state of plasma glucose concentration during the turnover period. In comparison to the control subjects, both the pregnant nondiabetic and pregnant insulin-dependent diabetic women had significantly higher plasma insulin concentrations throughout the study (p less than 0.05). There were no differences in the glucose turnover rate between any of the pregnant groups (1.7 +/- 0.2 mg . kg-1 min-1 in pregnant nondiabetic women; 1.5 +/- 0.2 mg . kg-1 min-1 in pregnant insulin-dependent diabetic women; and 2.1 +/- 0.4 mg . kg-1 min-1 in gestational diabetic women) and the control group of women (1.8 +/- 0.2 mg . kg-1 min-1) (mean +/- SEM). When the pregnant patients were studied post partum, the glucose turnover rate was similar when referenced to body weight; however, because of a 9.6% to 14.5% fall in weight post partum, the absolute values were higher in the pregnant women. We conclude that, in the basal state after an overnight fast, (1) both nondiabetic and diabetic patients accelerated their glucose turnover rate during pregnancy to provide for increased maternal and fetoplacental metabolic requirements, and (2) in the diabetic subjects the nearly normal plasma glucose and insulin concentrations and other metabolic parameters, as well as the glucose turnover rate, suggested good metabolic control during pregnancy in most of the insulin-dependent and in all of the gestational diabetic patients.     

Patterns of free fatty acids, glycerol, D-beta-hydroxybutyrate and insulin in pregnant women and their newborn infants. Effects of a low and a high insulin response to glucose in the mothers.

Twenty-eight healthy women, 17 with high and 11 with low insulin response to glucose but with normal glucose tolerance, were followed throughout pregnancy. Plasma FFA, glycerol and D-beta-hydroxybutyrate as well as plasma insulin and glucose in blood were determined before and during a glucose infusion test (GIT) in each trimester and after pregnancy. In 13 infants of high insulin responders (IHR) and 10 infants of low responders (ILR) an intravenous glucose tolerance test (IVGTT) was performed, and the above lipid parameters were studied at birth and during the IVGTT. The low responder group was postulated to consist mainly of prediabetic individuals (8). Their infants have previously been shown to have an increased glucose assimilation rate at IVGTT (12, 13), as has been shown for infants of diabetic mothers. There was little difference between the two groups of mothers except for the insulin levels during the GIT in non-pregnant and early pregnant subjects, which were considerably lower in the low responders. They all had decreased fasting levels of FFA, glycerol, and D-beta-hydroxybutyrate in mid-pregnancy and normal values in late pregnancy. The ILR showed the same changes in FFA and glycerol as the IHR, but their D-beta-hydroxybutyrate levels were higher at birth than those of the IHR and lower after birth. Another difference found, was the correlation between birth weight and fasting insulin (and to some extent the insulin level at birth) in the ILR group, which was not found in the IHR. Apart from those differences the ILR and the IHR seemed to handle their fat metabolism in a similar way in the early neonatal perinatal period.     

Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes

We used the minimal model technique to obtain concurrent measurements of whole-body insulin sensitivity and pancreatic B-cell responsiveness to glucose during the third trimester of pregnancy. Insulin sensitivity in normal pregnant women (n = 8) was reduced to only one third that of a group of nonpregnant women (n = 7) of similar age and relative weight. This marked insulin resistance was compensated by reciprocal enhancement of the first and second-phase insulin responses to intravenous glucose, which were increased threefold as compared with the nonpregnant women. Women with gestational diabetes mellitus (n = 16) had mean insulin sensitivity that was similar to that of the normal pregnant group, which indicates that insulin action was appropriate for the late phase of pregnancy in the gestational diabetic group. By contrast, the mean first-phase insulin response was significantly reduced in women with gestational diabetes mellitus, as compared with that of normal pregnant women (p less than 0.001). However, approximately one fifth of the group with gestational diabetes mellitus had first-phase responses that did not fall below the 95% confidence interval for the mean in normal pregnant women. The mean second-phase response was also lower in the group with gestational diabetes, although the difference was of borderline statistical significance (p less than 0.09). Our findings reveal the quantitative nature of the reciprocal changes in insulin sensitivity and B-cell function that normally accompany late pregnancy. They further indicate that during the third trimester, mild gestational diabetes is characterized by an impairment of pancreatic B-cell function rather than an exaggeration of the normal insulin resistance of late pregnancy.     

Use of oral glucose tolerance test in early pregnancy to predict late-onset gestational diabetes mellitus in high-risk women

AIM: To evaluate if any single plasma glucose level from the four values of the normal 100-g oral glucose tolerance test (OGTT) in early pregnancy (< or =20 weeks of gestation) could predict gestational diabetes mellitus (GDM) diagnosed from a second OGTT in late pregnancy (28-32 weeks). METHODS: Glucose levels of pregnant women at high-risk for GDM, who had had a normal early OGTT, and who underwent the second test in late pregnancy, were studied. Each of the four plasma glucose values of the early OGTT was determined for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The receiver operating characteristic curves of these four OGTT values were then constructed to find the optimal value to predict late-onset GDM. RESULTS: Of 193 pregnant women who had had a normal early OGTT, 154 also had a normal OGTT in late pregnancy while 39 had an abnormal test and were diagnosed with GDM. Among the four glucose values of the early OGTT, the 1-h value yielded the best diagnostic performance to predict late-onset GDM. The sensitivity, specificity, PPV, NPV, and area under the curve achieved from its optimal cutoff level of > or =155 mg/dL (8.6 mmol/L) were 89.7%, 64.3%, 38.9%, 96.1%, and 0.77, respectively. CONCLUSIONS: A 1-h glucose value > or =155 mg/dL at the early OGTT yielded the best diagnostic performance. However, the low specificity and PPV rendered it suboptimal to predict late-onset GDM. Nevertheless, a considerable number of high-risk women could avoid the second OGTT in late pregnancy due to its high sensitivity and NPV.     

妊娠期糖尿病合并慢性高血压孕妇胰岛素抵抗水平及其对妊娠结局的影响

目的探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)合并慢性高血压(chronic hypertension,CHT)孕妇的胰岛素抵抗(insulin resistance,IR)水平及其对妊娠结局的影响。方法本研究为回顾性病例对照研究。纳入2014年1月1日至2016年12月31日在北京大学第一医院规律产前检查并参加GDM一日门诊的单胎妊娠GDM孕妇2457例。回顾临床资料,采用稳态模型评估IR水平(homeostasis model assessment insulin resistance,HOMA-IR)。根据GDM孕妇是否合并CHT分为GDM合并CHT组(n=47)和GDM未合并CHT组(n=2410),并进一步根据孕前体重指数(body mass index,BMI)分为孕前BMI正常组(n=1590)及孕前超重和肥胖组(n=863)进行分层分析。采用两独立样本t检验、χ2检验分析组间孕妇年龄、HOMA-IR、孕前BMI、孕期增重、血糖等临床特征的差异。采用logistic回归模型分析HOMR-IR水平对妊娠结局的影响。结果合并CHT的GDM孕妇HOMA-IR(3.5±1.8与2.6±1.5,t=-3.290)、空腹血浆葡萄糖[(5.4±0.5)与(5.2±0.5)mmol/L,t=-3.005]、孕前BMI[(26.7±4.7)与(23.3±3.4)kg/m2,t=-4.842]以及发生子痫前期的比例[14.9%(7/47)与2.5%(61/2410),χ2=21.790]高于未合并CHT的GDM孕妇,但孕期增重少于未合并CHT者[(9.6±5.8)与(12.2±4.7)kg,t=3.790](P值均<0.01)。根据孕前BMI分层后,超重和肥胖孕妇中,GDM合并CHT组子痫前期的比例高于GDM未合并CHT组[15.2%(5/33)与4.2%(35/830),χ2=6.290,P=0.012],但HOMA-IR差异无统计学意义(P>0.05);而对于孕前BMI正常的孕妇,GDM合并CHT组HOMA-IR(3.0±1.5与2.3±1.2,t=-2.217)、空腹血浆葡萄糖[(5.4±0.5)与(5.1±0.5)mmol/L,t=-2.299]和子痫前期的比例[2/14与1.6%(26/1576),χ2=6.545]均高于未合并CHT组(P值均<0.05)。对于GDM合并CHT孕妇,HOMA-IR水平不会增加剖宫产、早产、大于胎龄儿、小于胎龄儿和巨大儿的发生风险(P值均>0.05)。控制年龄、空腹血浆葡萄糖、孕前BMI、孕期增重后,对于未合并CHT的GDM孕妇,HOMA-IR水平的增加会使早产的发生风险增加(OR=1.223,95%CI:1.093~1.369,P<0.001)。结论GDM合并CHT孕妇胰岛素抵抗程度更重,子痫前期的发病率更高,但其他不良妊娠结局的发生风险未见增加。     

Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus.

The purpose of this study was to evaluate insulin sensitivity, beta-cell function and islet-cell-directed autoimmunity in pregnant women with normal glucose tolerance and gestational diabetes mellitus (GDM). A total of 21 women with normal glucose tolerance and 21 women with GDM were evaluated at 24-36 weeks' gestation. Insulin resistance and beta-cell function were evaluated using the continuous infusion of glucose with model assessment (CIGMA) method, which aims to give a near-physiological stimulus and to evaluate the endogenous insulin and glucose response. Islet-cell autoantibody was positive in one woman with GDM, and glutamic acid decarboxylase autoantibodies were negative in both groups. The calculated CIGMA insulin resistance (CIGMA IR) was 2.04 +/- 1.74 and 1.08 +/- 1.22 in patients with GDM and in control subjects, respectively (p < 0.05). CIGMA percentage beta-cell values were 64.04 +/- 44.55% and 87.07 +/- 52.77% in patients with GDM and control subjects, respectively (p > 0.05). Decreased insulin sensitivity in late pregnancy was more evident in lean GDM subjects with mild hyperglycemia who did not require insulin therapy, and beta-cell function was partially preserved in this group of patients.