Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes

OBJECTIVE: This article tests the hypothesis that women with impaired glucose tolerance (IGT) have the same pregnancy outcomes as those of their counterparts with normal glucose tolerance. RESEARCH DESIGN AND METHODS: From December 1998 to December 1999, 84 of 90 antenatal care base units (ACBUs) under the Tianjin Antenatal Care Network in China participated in the first screening program for gestational diabetes mellitus (GDM). A total of 9,471 pregnant women under the care of participating ACBUs were screened. Of the women screened, 154 were positive for IGT. Of the 154 women, 102 opted for conventional obstetric care. The comparison group was 302 women of normal glucose tolerance (NGT). The initial screening consisted of a 50-g 1-h glucose test, and was carried out at 26-30 gestational weeks. Women with a serum glucose > or =7.8 mmol/l were followed up with a 75-g 2-h oral glucose tolerance test. The World Health Organization's diagnostic criteria for GDM were used. RESULTS: Women with IGT were at increased risk for premature rupture of membranes (P-ROM) (odds ratio [OR] 10.07; 95% CI 2.90-34.93); preterm birth (6.42; 1.46-28.34); breech presentation (3.47; 1.11-10.84); and high birth weight (90th percentile or 4,000 g) (2.42; 1.07-5.46); adjusting for maternal age, pregravid BMI, hospital levels, and other confounding factors. CONCLUSIONS: The presence of IGT in pregnancy is predictive of poor pregnancy outcomes.     

Impaired glucose tolerance of pregnancy is a heterogeneous metabolic disorder as defined by the glycemic response to the oral glucose tolerance test

OBJECTIVE: Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a single abnormal value on an OGTT), however, are not well established. We sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia. RESEARCH DESIGN AND METHODS: A cross-sectional study was performed in pregnant women undergoing a 3-h, 100-g OGTT. The OGTT stratified participants into four groups: 1) GDM (n = 48), 2) 1-h IGT (single elevated value at 1 h) (n = 15), 3) 2-h/3-h IGT (single elevated value at either 2 or 3 h) (n = 23), and 4) normal glucose tolerance (NGT) (n = 93). Insulin sensitivity was measured by the validated insulin sensitivity index (IS(OGTT)) of Matsuda and DeFronzo. RESULTS: Measures of severity of glycemia (fasting glucose, area under the glucose curve from the OGTT, and glucose challenge test result) were highest in the GDM group, followed by the 1-h IGT, 2-h/3-h IGT, and NGT groups, respectively (each trend P < 0.0001). Consistent with this finding, IS(OGTT) was highest in the NGT group (5.1), followed by the 2-h/3-h IGT (4.6), 1-h IGT (3.8), and GDM (3.2) groups (trend P < 0.0001). Furthermore, on multiple linear regression analysis of IS(OGTT), both GDM and 1-h IGT were independently associated with reduced insulin sensitivity (whereas 2-h/3-h IGT was not). Mean adjusted adiponectin was highest in the NGT group (15.7 microg/ml), followed by the 2-h/3-h IGT (15.6 microg/ml), 1-h IGT (13.7 microg/ml), and GDM (12.0 microg/ml) groups (trend P = 0.0024). CONCLUSIONS: The metabolic implications of IGT in pregnancy vary in relation to the timing of the abnormal glucose value from the diagnostic OGTT. The metabolic phenotype associated with 1-h IGT resembles that of GDM, whereas the phenotype associated with 2-h/3-h IGT exhibits similarity to that of NGT.     

The association between impaired glucose tolerance and birth weight among black and white women in central North Carolina

OBJECTIVE: This study examines the relationship of glucose intolerance during pregnancy to birth weight among black and white participants of the Pregnancy, Infection, and Nutrition Study. RESEARCH DESIGN AND METHODS: This prospective cohort study recruited women from prenatal clinics in central North Carolina at 24-29 weeks' gestation. A 1-h 50-g glucose challenge test (GCT) and 100-g oral glucose tolerance test (OGTT) were conducted. Impaired glucose tolerance (IGT) was defined as one high value on the OGTT, gestational diabetes mellitus (GDM) as two or more high values, and normal glucose tolerance (NGT) was defined as a low or high value on the GCT screen but no high values on the OGTT. Women with known glucose status and birth outcome information were included in this analysis (n = 2055). RESULTS: Black women with IGT had higher rates of both macrosomia (38.5%) and large for gestational age (LGA) (53.9%) compared with white women (10.0% and 13.2%). Black infants' birth weights (3800 g) and prevalence of macrosomia and LGA were significantly higher among mothers with IGT compared with NGT women (birth weight, 3184 g; macrosomia, 7.0%; LGA, 11.6%). In contrast, among white infants, there was no significant increase in birth weight, macrosomia, or LGA associated with the mother's glucose tolerance status. In addition, there was no effect of GDM on birth weight in either group. CONCLUSIONS: This study suggests that, independent of maternal prepregnant weight, there may be significant increased risk of macrosomia among black IGT women but not among white IGT women. Further investigations into factors that may contribute to the observed results are needed.     

Prevalence of diabetes and impaired glucose tolerance in 64-year-old Swedish women: experiences of using repeated oral glucose tolerance tests

OBJECTIVE: The purpose of this study was to describe the prevalence of diabetes and impaired glucose tolerance (IGT) in middle-aged women and to examine the variability and practical use of the oral glucose tolerance test (OGTT) in the screening for IGT and diabetes. RESEARCH DESIGN AND METHODS: All 64-year-old women living in G?teborg, Sweden, were invited to take part in a screening examination (n = 4,856). Of these, 82% (n = 3,998) responded and 53% (n = 2,595) participated and underwent anthropometric measurements and a 75-g standardized OGTT that was repeated within 2 weeks in those not showing normal glucose tolerance (NGT). RESULTS: The prevalences of known and new diabetes, IGT at both OGTTs, and impaired fasting glucose were 4.7, 4.8, 14.4, and 6.4%, respectively. Half of the women with diabetes were previously undiagnosed, and 37% of the diagnoses were based on OGTT and diabetes 2-h values at both or one of the two examinations. Women with IGT at both OGTTs, in comparison with those with one impaired and one normal OGTT, had higher BMI, waist girth, and blood pressure. More than 40% of the women showed impaired glucose metabolism. CONCLUSIONS: Among these women, the prevalence of undetected diabetes was high and repeated OGTTs were needed to identify and not misclassify a considerable proportion of patients. The degree of glucose tolerance impairment and the number of abnormal OGTTs were directly associated with occurrence of components of the metabolic syndrome.     

Postpartum Diabetes Screening: Adherence rate and the performance of fasting plasma glucose versus oral glucose tolerance test

OBJECTIVE

To determine the rate of adherence to postpartum glycemic testing in women with gestational diabetes mellitus (GDM) and the performance of fasting plasma glucose (FPG) versus the 75-g oral glucose tolerance test (OGTT) in detecting postpartum glucose intolerance.

RESEARCH DESIGN AND METHODS

The study was a retrospective cohort of 1,006 women with GDM attending a pregnancy diabetes clinic.

RESULTS

Postpartum screening was completed in 438 (48%) women. Women nonadherent to testing had higher parity (1.10 vs. 0.87) and were less likely to require insulin for management of their GDM. Among women who were tested, 89 (21%) had an abnormal result, only 25 (28%) of whom were identified by FPG. Factors associated with abnormal postpartum diabetes screening include non-Caucasian ethnicity, previous GDM, higher A1C, and OGTT values during pregnancy and treatment with insulin.

CONCLUSIONS

The rate of postpartum diabetes screening is low, and FPG lacks sensitivity as a screening test in comparison with OGTT.Gestational diabetes mellitus (GDM) strongly predicts future development of type 2 diabetes (1), and abnormal glucose tolerance can persist postpartum leading to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (2). Compared with an oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) has greater reproducibility but may lack sensitivity to identify women with IGT or type 2 diabetes (3–5). The main study objectives were to assess adherence with postpartum testing, to identify factors associated with nonadherence, and to compare the sensitivity of FPG versus a 75-g OGTT in detecting postpartum glucose intolerance.     

2012～2013年合肥地区孕妇OGTT筛查结果分析

目的：调查合肥地区孕妇妊娠期糖代谢异常的发生率,探讨其相关高危因素,以及孕妇在妊娠期进行口服葡萄糖耐量试验（OGTT）筛查的意义。方法以1520例2012～2013年于该院门诊就诊的妊娠前无糖尿病、高血压、心脏病、肾脏疾病、血液系统疾病及其他系统疾病的孕妇为研究对象,进行75 g OGTT筛查,结合临床相关资料分析合肥地区孕妇妊娠期糖代谢异常发生的相关高危因素。结果1520例孕妇75 g OGTT筛查阳性率为5．78％,其中葡萄糖耐量降低发生率为2．50％,妊娠糖尿病（GDM）检出率为3．28％。高龄、孕前肥胖及糖尿病家族史为妊娠期孕妇糖代谢异常的相关高危因素。结论对孕妇进行OGTT筛查能够有效发现GDM高危孕妇,并可及早预防和减少GDM的相关并发症。     

Fasting Plasma Glucose at 24–28 Weeks to Screen for Gestational Diabetes Mellitus: New evidence from China

OBJECTIVE

To evaluate the usefulness of a fasting plasma glucose (FPG) at 24–28 weeks’ gestation to screen for gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined.

RESULTS

FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928.

CONCLUSIONS

FPG at 24–28 weeks’ gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.In 2011, the Ministry of Health (MOH) in China published the diagnostic criteria for gestational diabetes mellitus (GDM) based on a 75-g oral glucose tolerance test (OGTT) carried out between 24 and 28 weeks’ gestation (1). As a formal glucose tolerance test may be difficult to implement in low-resource rural areas in China, the MOH sought to assess whether a fasting plasma glucose (FPG) could be used as a screening tool to reduce the number of OGTTs required. The following cut points were suggested: if FPG ≥5.1 mmol/L, GDM can be diagnosed immediately; if FPG <4.4 mmol/L, GDM can be considered unlikely. Thus, the 75-g OGTT only needs to be performed for women with FPG values ≥4.4 mmol/L and <5.1 mmol/L. As there was no scientific evidence from China to support this approach, we conducted this study to test the hypothesis.     

Early postpartum metabolic assessment in women with prior gestational diabetes.

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.     

Did publication of a clinical practice guideline recommendation to screen for type 2 diabetes in women with gestational diabetes change practice?

OBJECTIVE: To determine whether women with previous gestational diabetes mellitus (GDM) were screened postpartum for type 2 diabetes according to the Canadian Diabetes Association (CDA) guidelines. RESEARCH DESIGN AND METHODS: The 1998 CDA guidelines recommend that all women diagnosed with GDM be screened postpartum for type 2 diabetes using a 2-h 75-g oral glucose tolerance test (OGTT). The impact of and compliance with this expert opinion-based recommendation is unknown. All women who delivered at the Ottawa Hospital in 1997 (pre-guideline) and 2000 (post-guideline) with confirmed GDM were identified. Using population-based administrative databases, we determined the proportion of these women who had an OGTT, serum glucose test, or glycated hemoglobin (GHb) test in the first postpartum year. Women who had not undergone any blood work were excluded. RESULTS: There were 131 women in 1997 and 123 women in 2000 with confirmed GDM. Of these, only 69 women in 1997 and 52 women in 2000 had blood work recorded in the database. None of these women had an OGTT performed in either period. We found a significant increase in the measurement of serum glucose (50 women pre-guideline [72.1%], 48 women post-guideline [92.3%], P < 0.05) and GHb (8 women pre-guideline [11.6%], 20 women post-guideline [38.5%], P < 0.01). CONCLUSIONS: In our region, physicians are not following the CDA recommendations to screen women with GDM postpartum with an OGTT. However, we did find a significant increase in the measurement of serum glucose and GHb. Publication of expert opinion-based guidelines did not change the postpartum use of an OGTT in these women but may have increased the use of less reliable screening tests for type 2 diabetes.     

Gestational diabetes may represent discovery of preexisting glucose intolerance

A representative sample of 817 American women aged 20-44 yr who were not pregnant and had no medical history of diabetes were given 75-g 2-h oral glucose tolerance tests (OGTTs). Although these conditions are somewhat different from those recommended for pregnant women (100 g glucose, 3-h OGTT), 3.8% of the women might have been considered to have met O'Sullivan and Mahan criteria for gestational diabetes mellitus (GDM) had they been pregnant. Prevalence was 2-3% below age 35 yr, similar to that found in studies of pregnant women, and rose to 8% at age 40-44 yr. Rates of women meeting World Health Organization criteria for gestational impaired glucose tolerance (G-IGT) rose steadily from 5% at age 20-24 yr to 11% at age 40-44 yr. Risk factors for non-insulin-dependent diabetes mellitus (NIDDM) including parental history and obesity were more prevalent among women meeting these criteria than among women in the entire group; the same risk factors are also more prevalent among pregnant women with GDM. The similarity of rates in this study to rates of GDM and G-IGT, together with their association with risk factors for NIDDM, indicate that these entities are compatible with undiagnosed glucose intolerance occurring before pregnancy and discovered during the metabolic testing that generally accompanies prenatal care rather than conditions that have an etiologic relationship to pregnancy.     

Determinants of mild gestational hyperglycemia and gestational diabetes mellitus in a large dutch multiethnic cohort.

OBJECTIVE: The purpose of this study was to identify independent determinants of mild gestational hyperglycemia (MGH) and gestational diabetes mellitus (GDM) and to assess the correlation between fasting glucose and C-peptide levels among control, MGH, and GDM women. RESEARCH DESIGN AND METHODS: A total of 1,022 consecutive women were evaluated with a 1-h 50-g glucose challenge test (GCT) at between 16 and 33 weeks of gestation. Women with a capillary whole-blood glucose > or =7.8 mmol/l in the GCT underwent a 3-h 100-g oral glucose tolerance test (OGTT). On the basis of a positive GCT, the women with a positive OGTT were classified as GDM, whereas the women with a negative OGTT were classified as MGH. The following data were collected for all women: age, prepregnancy BMI, ethnicity, clinical and obstetric history, pregnancy outcome, and C-peptide level. RESULTS: A total of 813 women (79.6%) were normal, 138 (13.5%) had MGH, and 71 (6.9%) had GDM. There was a stepwise significant increase in mean fasting glucose (3.6 +/- 0.4, 3.9 +/- 0.4, and 4.7 +/- 0.7 mmol/l, respectively) and C-peptide level (0.60 [0.1-2.4], 0.86 [0.3-2.0], and 1.00 [0.5-1.6] nmol/l, respectively) among the three diagnostic groups. Maternal age, non-Caucasian ethnicity, and prepregnancy BMI were associated with GDM, whereas only maternal age and prepregnancy BMI were associated with MGH. A positive correlation between levels of fasting glucose and C-peptide was found in control women (r = 0.39 [95% CI 0.31-0.46]). A similar result was seen in MGH women (r = 0.38 [95% CI 0.23-0.52]), whereas the correlation between fasting glucose and C-peptide was nearly lost in GDM women (r = 0.14 [CI -0.09 to 0.36]). The fasting C-peptide-to-glucose ratio was reduced by 60% in GDM patients versus control subjects and MGH patients (0.41 +/- 0.25 vs. 0.70 +/- 0.20 and 0.73 +/- 0.23, P < 0.001). CONCLUSIONS: Of the well-known independent determinants of GDM, only maternal age and prepregnancy BMI were associated with MGH. It appears that additional factors promoting loss of beta-cell function distinguish MGH from GDM. One of these factors appears to be ethnicity.     

Increasing incidence of diabetes after gestational diabetes: a long-term follow-up in a Danish population

OBJECTIVE: To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes. RESEARCH DESIGN AND METHODS: Women with diet-treated GDM during 1978-1985 (old cohort, n = 241, also followed up around 1990) or 1987-1996 (new cohort, n = 512) were examined in 2000-2002. Women were classified by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies. Historical data from index-pregnancy and anthropometrical measurements were collected. RESULTS: A total of 481 (63.9%) women were examined (median 9.8 years [interquartile range 6.4-17.2]) after index pregnancy. Diabetes and impaired glucose tolerance (IGT)/impaired fasting glucose were present in 40.0 and 27.0% of women, respectively. In the new cohort, 40.9% had diabetes compared with 18.3% in the old cohort at the 1990 follow-up (P < 0.0005). Prepregnancy BMI was significantly higher in the new compared with the old cohort (26.0 [22.5-30.8] vs. 22.9 kg/m2 [20.2-28.0], P < 0.0005). Among others, new-cohort membership, prepregnancy overweight (BMI > or = 25 kg/m2), and IGT postpartum were identified as independent predictors of diabetes by multiple logistic regression analyses. CONCLUSIONS: The incidence of diabetes among Danish women with previous diet-treated GDM was very high and had more than doubled over a 10-year period. This seems to be due to a substantial increase in BMI in women with GDM.     

Relationship between gestational diabetes mellitus and low maternal birth weight

OBJECTIVE: To study the relationship between low birth weight and the presence of gestational diabetes mellitus (GDM) or peripheral insulin resistance during pregnancy. RESEARCH DESIGN AND METHODS: We studied the relationship between peripheral insulin sensitivity (calculated by Matsuda and DeFronzo's oral glucose tolerance test (OGTT)-derived insulin sensitivity index [ISI(OGTT)]) or GDM prevalence and birth weight in 604 pregnant women, classified as normally glucose tolerant (n = 462) or affected with GDM (n = 142) after a 100-g 3-h oral glucose tolerance test. We then categorized these subjects into two groups: individuals with birth weight in the <10th percentile (<2,600 g; n = 68) and individuals with birth weight in the >10th percentile (n = 536). RESULTS: GDM prevalence was higher in the group in the lowest birth weight decile (<2,600 g; 24/68; 35%) than in the group with normal/high birth weight (118/536; 22%; chi(2) = 5.917; P = 0.01). Relative risk for GDM adjusted for age, parity, family history of diabetes, and prepregnancy body weight was about twofold in the group with low birth weight (odds ratio = 1.89 [95% CI 1.088-3.285; P = 0.023]), and the prevalence of low birth weight was about threefold higher in the first ISI(OGTT) decile. In 450 women whose newborn's weight was known, the delivery of macrosomic babies was associated with a twofold higher relative risk for GDM in women who themselves had low birth weight. In the latter, the relationships between their newborn's weight and either maternal glucose tolerance (positive) or ISI(OGTT) (negative) were amplified. CONCLUSIONS: Low maternal birth weight was associated with a twofold higher risk for GDM, independent of major confounders. Such a risk was highest in women with low birth weight who delivered macrosomic babies, and in the group with low birth weight, the relationship between maternal glucose tolerance or insulin resistance and offspring's neonatal weight was much more evident.     

妊娠早期空腹血糖测定结果回顾性分析

目的 探讨妊娠早期空腹血糖（FPG）测定水平与妊娠中期75g葡萄糖口服糖耐量试验（OGTT）结果 的关系。方法 选取2012年8月至2013年4月在孕12周时来该院建立孕册行空腹血糖检测,并于24～28周行75g葡萄糖OGTT试验的孕妇1107例,对其临床资料进行回顾性分析。以国际妊娠合并糖尿病研究组（IADPSG）2010年提出的新诊断标准按OGTT结果 将孕妇分为4组。A组为OGTT结果 正常组,B组为OGTT结果 有1项异常,C组为OGTT结果 有2项异常,D组为OGTT结果 有3项异常。比较4组孕妇空腹血糖结果 的差异。结果 A、B、C、D组的孕早期空腹血糖均值呈递增变化,A组孕早期FPG≥5．1mmol／L的孕妇有65例占5．9％（65／1107）,OGTT异常组有7例孕妇早期FPG≤4mmol／L。结论 孕早期空腹血糖升高是预警信号,提示孕中期发生妊娠糖尿病（GDM）的可能性增大。但将孕早期FPG≥5．1mmol／L作为GDM的诊断标准尚存疑问。处于任何一个空腹血糖区间,均有可能发生糖耐量异常,设立1个空腹血糖值而排除GDM的方法 不准确。     

Lack of concordance between the 75-g and 100-g glucose load tests for the diagnosis of gestational diabetes mellitus

BACKGROUND: Gestational diabetes mellitus (GDM) is common and can have a substantial impact on fetal growth, birth weight, and morbidity. The American Diabetes Association recommends GDM testing with either a 3-h, 100-g glucose load (100 g) (criteria according to Am J Obstet Gynecol 1982;144:768-73) or a 2-h, 75-g glucose load (75g). We investigated the comparability of the 75 g and the 100g tests in the diagnosis of GDM. METHODS: From January 1997 to December 1999, in 1061 consecutive Caucasian nonobese and nondiabetic pregnant women who attended the Maternal-Fetal Medicine Unit, we performed GDM testing with a 75-g load during 2 periods of pregnancy: early (16-20 weeks) and late (26-30 weeks). Because we assumed there would be few GBM cases in women with a 1-h plasma glucose <1300 mg/L in the 75 g test, we did not retest these women. We retested the remaining women with possible or diagnosed GDM with a 100-g load within a week. RESULTS: GDM was diagnosed in 41 of 227 women with the 100-g load and 15 of 227 with the 75-g load (11 concordant); the kappa index was 0.21. At 26-31 weeks of pregnancy, 484 of 976 women (49.9%) underwent both tests. GDM was diagnosed in 60 of 484 woman with the 100-g load and in 26 of 484 with the 75-g load (13 concordant); the kappa index was 0.18. CONCLUSIONS: Among women with possible GDM in both early and late periods of pregnancy, there was only weak diagnostic agreement between results determined with 75-g and 100-g glucose loads.     

Clinical Outcomes of Pregnancies Complicated by Mild Gestational Diabetes Mellitus Differ by Combinations of Abnormal Oral Glucose Tolerance Test Values

OBJECTIVE

To examine the association between levels of hyperglycemia, determined by each prenatal oral glucose tolerance test (OGTT) value (fasting, 1 and 2 h), and maternal and perinatal outcomes and to determine whether the risk for these outcomes differs for women whose value(s) equaled or exceeded the thresholds for gestational diabetes mellitus (GDM) established by the International Association of Diabetes in Pregnancy Study Groups (IADPSG).

RESEARCH DESIGN AND METHODS

This article discusses a retrospective study of 8,711 women, delivering at ≥20 weeks'' gestation, who had a prenatal 2-h 75-g OGTT without a prior 50-g challenge and were not treated with insulin, glyburide, diet, and/or exercise during pregnancy. Associations between adverse outcomes and elevated OGTT values are reported.

RESULTS

After excluding treated women, 19.4% of the remaining women had IADPSG-defined GDM. Continuous fasting, 1- and 2-h OGTT measures, and GDM (yes/no) were significantly associated with most adverse outcomes. However, the magnitude and significance of risk for these outcomes differed by various combinations of abnormal glucose values. Women with normal fasting and elevated postload values were at higher risk for preterm delivery, gestational hypertension, and having an infant with hyperbilirubinema, whereas women with elevated fasting and normal postload values were at higher risk of having a large-for-gestational-age infant, compared with women without GDM.

CONCLUSIONS

Risks for different adverse outcomes vary depending on which single or combined IADPSG-defined OGTT thresholds are equaled or exceeded. Prospective studies are needed to determine whether changing pre- and postprandial glucose targets during pregnancy will more uniformly reduce adverse outcomes.Gestational diabetes mellitus (GDM) is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” (1). The diagnosis of GDM is typically based on the results of a 2-h 75-g or 3-h 100-g oral glucose tolerance test (OGTT), which measures maternal fasting plasma glucose (FPG) and postload glucose concentrations, administered between 24 and 28 weeks of gestation. American Diabetes Association (ADA) guidelines confer a GDM diagnosis if at least two 75-g or 100-g OGTT values meet the following thresholds: ≥95 mg/dl FPG, 1-h glucose ≥180 mg/dl, 2-h glucose ≥155 mg/dl, and 3-h glucose ≥140 mg/dl (2). These thresholds were initially established to identify women at high risk for type 2 diabetes following pregnancy (3).GDM is associated with increased risk for adverse maternal and perinatal outcomes, such as macrosomia, shoulder dystocia and birth injury, primary cesarean delivery, preeclampsia, preterm delivery, and fetal and neonatal mortality (4–7). However, risk for these outcomes among women with modest hyperglycemia during pregnancy has only recently been studied. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study investigated quantitative associations between maternal glycemia and adverse outcomes and, after excluding women with FPG ≥105 and/or 2-h ≥200 mg/dl, reported significant associations between increasing glucose and adverse events, including birth weight >90th percentile, preterm delivery, shoulder dystocia/birth injury, primary cesarean delivery, preeclampsia, and hyperbilirubinemia (8,9). These findings formed the basis for the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations that GDM be identified by at least one abnormal 75-g 2-h OGTT value: FPG ≥92 mg/dl, 1-h glucose ≥180 mg/dl, or 2-h glu≥153 mg/dl (10).In the present study, we examined the association between each of the 75-g OGTT glucose values (fasting, 1-h and 2-h glucose) and several adverse maternal and perinatal outcomes in untreated women, taking into account differences in maternal demographics, prepregnancy BMI, and gestational weight gain. Additionally, we explored associations between adverse outcomes and categories of hyperglycemia that result in GDM diagnosis under IADPSG criteria to determine whether the level of risk is similar for each abnormal OGTT result and combinations thereof.     

Abnormal carbohydrate metabolism during pregnancy : association with endothelial dysfunction

OBJECTIVE: To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endothelium-independent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. High-resolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured. RESULTS: FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 +/- 1.1% in the IGT group and 4.1 +/- 0.9% in the GDM group vs. 10.9 +/- 1.1% in control subjects, P < 0.04 and P < 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P < 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r=-0.60, P < 0.0001). CONCLUSIONS: Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women.     

妊娠期妇女葡萄糖筛查2870例结果临床分析

目的初步了解本地区妊娠期糖尿病（GDM）的患病率,探讨不同孕期妇女的50 g葡萄糖负荷试验（GCT）对筛查GDM的临床意义,以及GDM与孕妇伴随有高危因素和孕期的关系。方法 2010年1—12月,来我院行葡萄糖筛查孕妇2 870例,按不同孕期分为孕24~28周组、孕〉28周组;按其是否伴有高危因素分为伴高危因素组、无高危因素组。进行分组对照研究。结果妊娠伴有高危因素的孕妇GCT和75 g口服葡萄糖糖耐量试验（OGTT）的异常检出率明显高于妊娠无高危因素组,两组比较差异有统计学意义（χ2=63.52、109.51,P〈0.05）;而不同孕周两组比较差异无统计学意义（χ2=1.00、0.27,P〉0.05）。结论本地区GDM有一定的患病率,伴有高危因素的孕妇GDM发生率高。对伴有高危因素的孕妇应尽早进行GCT筛查,对临床早期诊断、治疗GDM、改善妊娠结局具有重要意义。     

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 (AUC_gluc) 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 AUC_gluc, 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.It is now recognized that many physiologic functions, including energy metabolism, exhibit 24-h circadian rhythms generated by light/dark cycles (1–3). For example, in nonobese humans, glucose tolerance decreases in the afternoon and evening, as detected by oral or intravenous glucose tolerance tests (4,5). Reduced insulin sensitivity and β-cell responsivity to glucose both account for this deterioration in glucose tolerance later in the day (4). The potential importance of this type of circadian cycle is highlighted by the increased risk of obesity and diabetes in shift workers (2). Moreover, sleep restriction or misalignment of circadian rhythm by scheduling a 28-h day diminishes insulin sensitivity in humans (6,7).A clinical setting in which these circadian changes in glucose metabolism may be particularly relevant is antepartum screening for gestational diabetes mellitus (GDM). Owing to the obstetrical risks associated with maternal hyperglycemia and subsequent fetal overgrowth, screening for GDM has become a standard element of obstetrical practice. Although protocols may vary, a common approach to screening is the universal testing of all pregnant women in the late second trimester with a 1-h, 50-g glucose challenge test (GCT), followed by referral for a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (defined as 1-h postchallenge plasma glucose ≥7.8 mmol/L). More important, the GCT is performed throughout the day and without regard to fasting or fed state. Sermer et al. (8) demonstrated that the duration of elapsed time since the last meal could affect the result of the GCT. However, despite emerging recognition of circadian changes in glucose metabolism, there has been limited study of the effect of time of day on the performance of the GCT (9,10). Thus, in this context, we sought to assess the clinical and metabolic phenotype of pregnant women with a positive screening GCT at varying times of the day to better understand the clinical implications of performing this test without regard to time of day.     

The clinical usefulness of glucose tolerance testing in gestational diabetes to predict early postpartum diabetes mellitus.

We examined the clinical usefulness of antepartum clinical characteristics, along with measures of glucose tolerance, in Dutch multiethnic women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes within 6 months of delivery (early postpartum diabetes). The present study comprised a cross-sectional 5-year investigation (1998-2003) of a consecutive series of 168 women with GDM identified by a two-stage protocol at 16-33 weeks of gestation. The following data were collected for all women: age and gestational age at entry into the study; prepregnancy body mass index (BMI); ethnicity; obstetric and clinical history, including the onset of early postpartum diabetes; pregnancy outcome; level of fasting C-peptide; and glycemic parameters of 50-g 1-h glucose challenge test and 100-g 3-h oral glucose tolerance test (diagnostic OGTT). We used receiver operating characteristic (ROC) curve analysis to test the clinical usefulness of the glycemic parameters. A total of 11 women (6.5%) developed early postpartum diabetes. Apart from family history of diabetes (p = 0.052), anthropometric, maternal, and neonatal clinical parameters showed no association with early postpartum diabetes in univariate analyses. The level of fasting glucose, and both the glucose challenge test and diagnostic OGTT post-load glucose levels and glucose areas were associated with early postpartum diabetes. ROC curve analysis identifiedall three glucose challenge-test parameters, including fasting glucose concentration, as poor diagnostic tests, with a positive predictive value of approximately 22%, whereas the positive predictive value associated with the area under the diagnostic OGTT curve increased progressively over monitoring time from 20.6% to 100%. Using a 3-h OGTT glucose area threshold of 35.7 mmol.h/L resulted in 100% sensitivity and 100% specificity, identifying the 11 women who developed early postpartum diabetes. In summary, we can conclude from the present analysis that early postpartum diabetes is rare in GDM women (6.5%), and that the clinical usefulness of the total area under the diagnostic 3-h OGTT is superior to all other glycemic parameters for detecting early postpartum diabetes.