Use of glycosylated hemoglobin as a screen for macrosomia in gestational diabetes

Glycosylated hemoglobin and blood sugar levels in the fasting state and two hours after oral 100 g glucose load were measured in 180 patients. Glycosylated hemoglobin was measured by cation exchange column chromatography, and blood sugar was measured by hexokinase reaction. Patients with an elevated postprandial and/or fasting blood sugar level (positive screen) subsequently underwent three-hour glucose tolerance test. The mean value of glycosylated hemoglobin in patients with a negative screen and normal hemoglobin was 6.17 +/- 0.61%; and the value for glycosylated hemoglobin in patients with class A diabetes and normal hemoglobin electrophoresis was 6.85 +/- 0.73% (P less than .001). A glycosylated hemoglobin value greater than 6.78 (mean + 1 SD) was considered elevated. Glycosylated hemoglobin values were elevated in 21 of 33 patients with gestational diabetes and in 27 of 147 patients with normal blood sugar levels. The sensitivity and specificity of glycosylated hemoglobin for the diagnosis of gestational diabetes were 63.6 and 81.6%, respectively. Fifty percent of patients with an initially elevated glycosylated hemoglobin value delivered macrosomic infants, whereas no patient with a normal glycosylated hemoglobin value had a macrosomic infant. An elevated glycosylated hemoglobin value may alert the obstetrician of a potentially elevated mean blood sugar level and may warrant aggressive management of gestational diabetes.     

Verified self-monitored blood glucose data versus glycosylated hemoglobin and glycosylated serum protein as a means of predicting short- and long-term metabolic control in gestational diabetes

Glycosylated hemoglobin and glycosylated serum protein have been suggested as tools for evaluation of long- and short-term glycemic control, respectively. Twenty-six patients with gestational diabetes were prospectively studied to determine the relationship of glycosylated hemoglobin and glycosylated serum protein to metabolic control. To verify the accuracy of blood glucose data, a memory-based reflectance meter was used for subjects with gestational diabetes who tested 6.5 +/- 1 times per day. Our analysis revealed that despite a statistically positive correlation between glycosylated hemoglobin, glycosylated serum protein, and verified data, their use as a clinical tool is limited because of their poor predictability.     

Glycosylated serum protein level as a screening and diagnostic test for gestational diabetes mellitus

Glycosylated serum protein assay was examined as an alternative to standard glucose screening and glucose tolerance testing. In a comparison of two groups of gravid women having abnormal 1-hour 50 gm glucose screening tests, there was no difference in glycosylated protein level in the group with abnormal glucose tolerance test results (9.4% +/- 2.0%, mean +/- SD; n = 8) versus normal results (9.2% +/- 1.07%, mean +/- SD; n = 11). Furthermore, correlation of glycosylated serum protein level with glucose screening test results was poor (r = 0.185, p = 0.23, n = 17). Glycosylated serum protein assay is not useful in detecting mild metabolic aberrations associated with gestational diabetes.     

Fructosamine as a screening-test for gestational diabetes mellitus: a reappraisal.

Fructosamine, glycosylated hemoglobin (HbA1c) and serum total proteins were measured in normal nondiabetic pregnant women (n = 170) at three stages of pregnancy (14-18, 24-28, and 32-40 weeks of gestation). No significant correlation was found between fructosamine and either HbA1c or total plasma proteins. Only early in pregnancy (less than 20 weeks of gestation) was a correlation found between fructosamine and fasting blood glucose (r = 0.40, P less than 0.05). There was also no correlation between either tests (i.e. fructosamine and HbA1c) and fetal birthweight. The value of fructosamine measurement in the detection of diabetes in pregnancy was further tested in a group of high-risk patients (n = 98) for developing carbohydrate intolerance. It is concluded that fructosamine has limited value as a screening test for gestational diabetes mellitus, particularly for the mild form of the glucose intolerance.     

Prospective study of an inverse relationship between maternal glycosylated hemoglobin and serum alpha-fetoprotein concentrations in pregnant women with diabetes

A hypothesized inverse relationship between the concentration of glycosylated hemoglobin and serum alpha-fetoprotein was observed in a prospective study of 39 pregnant women with insulin-dependent diabetes as well as seven pregnant women with diabetes who did not require insulin (r = -0.434, p less than 0.002). No similar correlation was found among a selected population of healthy pregnant women (r = -0.129). Because the level of glycosylated hemoglobin in pregnancy correlates with poor outcome, including the occurrence of fetal anomaly, it may be important to quantify glycosylated hemoglobin in pregnancies with low alpha-fetoprotein levels. These results also suggest that the maternal concentration of glycosylated hemoglobin can be used to adjust serum alpha-fetoprotein values before their interpretation in the screening of pregnant women with diabetes.     

Glycosylated hemoglobin concentration in early gestation associated with neonatal outcome

Previous studies have indicated an association of fetal macrosomia with mild degrees of glucose intolerance in late pregnancy. To determine whether glycosylated hemoglobin concentration in early gestation was related to fetal outcome, 48 pregnant women with normal glucose tolerance and 21 women with gestational diabetes were studied. Glycosylated hemoglobin concentration was determined by a specific aminophenylboronic acid assay, and mean glycosylated hemoglobin concentration was calculated from two or three determinations before 17 weeks' gestation. The incidence of infants large for gestational age was 10% in nondiabetic women with glycosylated hemoglobin concentration of less than 6.0%. With glycosylated hemoglobin concentration of 6.0% to 6.9%, the incidence of infants who were large for gestational age was increased in both nondiabetic women (75%, p less than 0.01) and diabetic women (40%, p less than 0.01). With glycosylated hemoglobin concentration of greater than 7.0%, 36% of infants of diabetic women were large for gestational age. The incidence of hyperbilirubinemia was 2.5% in the infants of nondiabetic women with glycosylated hemoglobin concentration of 6.0%. With glycosylated hemoglobin concentration of 6.0% to 6.9%, hyperbilirubinemia was increased in both the infants of nondiabetic women (38%, p less than 0.01) and diabetic women (30%, p less than 0.01). With glycosylated hemoglobin concentration of greater than 7.0%, hyperbilirubinemia was present in 27% of infants of diabetic mothers. The current study suggests that glycosylated hemoglobin concentration elevation in early gestation is associated with perinatal morbidity.     

The effects of first-trimester diabetes control on the incidence of macrosomia.

OBJECTIVE: The aim of this study was to explore the association between glycosylated hemoglobin concentrations during pregnancy and macrosomia. STUDY DESIGN: One hundred thirty-six pregnancies in 120 women with type 1 or type 2 diabetes were studied longitudinally between January 1, 1991, and December 31, 1996. Glycosylated hemoglobin concentration and several maternal variables of mothers of neonates who were large for gestational age were compared with those of neonates who were appropriate for gestational age. Receiver-operator characteristic curves and regression analyses were used to determine a threshold related to macrosomia and to assess its predictive value. RESULTS: Glycosylated hemoglobin concentrations throughout pregnancy were higher in mothers of neonates who were large for gestational age (n = 65) than in mothers of neonates who were appropriate for gestational age (n = 71, P <. 001). A first-trimester glycosylated hemoglobin concentration of >/=5.5% (3 SD above the normal mean) was established by receiver-operator characteristic curves as the strongest predictor of macrosomia and yielded an odds ratio of 24 in multiple logistic regression analysis. CONCLUSION: Macrosomia is determined mainly by first-trimester diabetes control.     

Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes

We studied the impact of a training program on glucose tolerance in gestational diabetes mellitus. Women with gestational diabetes mellitus (N = 19) were randomized into either group I, a 6-week diet alone group (24 to 30 kcal/kg/24 hours; 20% protein, 40% carbohydrate, 40% fat), or group II, which followed the same diet plus exercise (20 minutes three times a week for 6 weeks). An arm ergometer was used to maintain heart rate in the training range. Glycemic response was monitored by glycosylated hemoglobin, a 50 gm oral glucose challenge with a fasting and 1-hour plasma glucose, and blood glucose self-monitoring, fasting and 1 hour after meals. Week 1 glycemic parameters were the same for both groups. Week 6 data (mean +/- SD) were as follows: group I glycosylated hemoglobin, 4.7% + 0.2% versus group II, 4.2% +/- 0.2%; p less than 0.001. The group I glucose challenge fasting value was 87.6 +/- 6.2 versus 70.1 +/- 6.6 mg/dl, p less than 0.001 for group II. The group I 1-hour plasma glucose challenge result was 187.5 +/- 12.9 mg/dl versus 105.9 +/- 18.9 mg/dl for group II, p less than 0.001. The glycemic levels diverged between the groups at week 4. We conclude that arm ergometer training is feasible in women with gestational diabetes mellitus and results in lower glycosylated hemoglobin, fasting, and 1-hour plasma glucose concentrations than diet alone. Arm ergometer training may provide a useful treatment option for women with gestational diabetes mellitus and may obviate insulin treatment.     

Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes

OBJECTIVES: We sought to determine the types of congenital anomalies affecting infants of women with gestational diabetes mellitus or type 2 diabetes and to examine the relationship between those malformation types and measures of initial glycemia of women at entry into prenatal care with type 2 diabetes or at time of diagnosis in women with gestational diabetes mellitus. STUDY DESIGN: A total of 4,180 pregnancies complicated by gestational diabetes mellitus (n = 3764) or type 2 diabetes (n = 416) that were delivered after 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as being absent, minor, major, genetic syndromes, or aneuploidies. Major anomalies were further categorized by the number and type of affected organ systems. In addition to maternal clinical and historical parameters, the initial fasting serum glucose either from the diagnostic glucose tolerance test (gestational diabetes mellitus) or at entry to prenatal care (type 2 diabetes) and the initial glycosylated hemoglobin before insulin therapy were examined for a relationship to anomalies. RESULTS: The initial fasting serum glucose and glycosylated hemoglobin levels were significantly higher in pregnancies with major (n = 143) and minor (n = 112) anomalies and genetic syndromes (n = 9) compared with pregnancies with no anomalies (n = 3895). Of those pregnancies with major anomalies, the most commonly affected organ systems were the cardiac (37.6%), musculoskeletal (14.7%), and central nervous systems (9.8%) and anomalies involving multiple organ systems (16%). There was no increased predominance of any specific organ system involvement seen with increasing fasting serum glucose levels in pregnancies with major congenital anomalies. Pregnancies with major anomalies affecting multiple organ systems had significantly higher initial fasting serum glucose levels (166 +/- 64 mg/dL) compared with pregnancies in which one organ system was affected (141 +/- 55 mg/dL, P <.04) or no organ systems were affected (115 +/- 38 mg/dL, P <.0001). CONCLUSION: Congenital anomalies in offspring of women with gestational and type 2 diabetes affect the same organ systems that have been previously described in pregnancies complicated by type 1 diabetes. Increasing hyperglycemia at diagnosis or presentation for care was associated with an increasing risk of anomalies in general and with anomalies involving multiple organ systems without a preferential increase in involvement of specific organ system.     

Clinical usefulness of estimation of serum fructosamine concentration as screening test for gestational diabetes

Serum fructosamine levels and fructosamine/protein ratios were measured in 100 pregnant women who underwent glucose tolerance tests because of clinical risk. Compared with normal pregnant women, the 13 study participants with gestational diabetes had higher fructosamine/protein levels (39 +/- 3.9 mumol/gm versus 37 +/- 3.2 mumol/gm, p less than 0.05), fasting serum glucose levels (107 +/- 13.7 mg/dl versus 82 +/- 8.6 mg/dl, p less than 0.001), and area under curve of glucose tolerance test (36 +/- 5 gm x min x dl-1 versus 22 +/- 3.6 gm x min x dl-1, p less than 0.001). The serum fructosamine levels were not significantly different between the two groups of participants (2.3 +/- 0.26 mmol/L versus 2.2 +/- 0.17 mmol/L); 10 of the 13 women with diabetes had a fructosamine/protein ratio within 2 SD of the mean of the groups of normal pregnant women. Spontaneous caloric intakes (r = 0.72, p less than 0.005) and the hospital mean daily capillary glucose levels during diabetic diet (r = 0.72, p less than 0.005) correlated better with the fructosamine/protein ratio than with fasting serum glucose levels (r = 0.58, p less than 0.05) and area under curve (r = 0.57, p less than 0.05). Consequently, serum fructosamine and fructosamine/protein ratio levels should be considered insensitive as a screening test in pregnant patients with clinical risk of gestational diabetes.     

Effect of dietary fiber on the oral glucose tolerance test in pregnancy

Paired oral glucose tolerance tests (GTTs) were performed during the third trimester of pregnancy to determine whether soluble fiber, which is known to blunt the rise in postprandial serum glucose in nonpregnant subjects, demonstrated similar effects in pregnancy. Normal pregnant women (n = 14) and gestational diabetic patients (n = 4) were first given a standard 100 gm oral GTT, and serum levels of glucose and insulin were determined in the fasting state and at 60, 120, and 180 minutes after ingestion of the glucose load. Several days later, a second GTT was done. In this test, glucose was combined with 15 gm guar gum, a purified soluble dietary fiber. Improved glucose tolerance was documented in all but one patient. Guar gum produced a significant reduction in mean serum glucose levels at 1 hour (p less than 0.005), 2 hours (p less than 0.005), and 3 hours (p less than 0.005), and each of the four gestational diabetic patients tested showed a normal glucose tolerance curve. The soluble dietary fiber, guar gum, did limit the postchallenge rise in serum glucose in pregnant subjects. Furthermore, the improvement in glucose tolerance in gestational diabetic patients is sufficient to suggest a potential clinical value for dietary fiber in the treatment of gestational diabetes.     

Glycosylated hemoglobin and fructosamine. Indicators of glycemic control in pregnancies complicated by diabetes mellitus

In 50 gravidas with insulin-dependent diabetes mellitus, mean preprandial whole blood glucose levels over a two-week period were compared with serum glycosylated hemoglobin (HbA1c) and fructosamine values. Although there was a statistically significant correlation between mean glucose levels and both HbA1c (r = .44, P less than .01) and fructosamine (r = .37, P less than .01), the wide range of HbA1c and fructosamine observed at all levels of mean blood glucose limited the usefulness of those assays in the management of pregnant diabetics.     

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.     

Glycosylated serum protein levels in diabetic and nondiabetic pregnant patients: an indicator of short-term glycemic control in the diabetic patient

Measurement of the level of nonenzymatic glycosylation of blood proteins with more rapid turnover times than hemoglobin has been suggested as an indicator of time-averaged glucose control in nonpregnant diabetic patients. Using affinity chromatography, we have measured the levels of glycosylated serum proteins during pregnancy in 14 normal volunteers and 15 insulin-dependent diabetic patients. No relationship was noted between the percentage of glycosylated serum proteins in serum from normal patients and the gestational age at the time of sampling in the second and third trimesters of pregnancy. When the relative frequency distribution of glycosylated serum protein levels in normal patients was compared with that in diabetic patients, a significant difference was noted between the two groups, with a higher percentage of glycosylated serum protein levels in diabetic patients being at elevated values compared to those in normal patients. Normal patients had measured glycosylated serum protein levels of 12.5% +/- 2.2% whereas diabetic patients had glycosylated serum protein levels of 14.0% +/- 3.6%. When peak fasting serum glucose and high Chemstrip glucose levels were compared with glycosylated serum proteins in the diabetic population, a significant correlation for each was noted. The best correlation resulted from a comparison of an average Chemstrip glucose level (mean of 49 glucose values during the previous week) and the glycosylated serum protein value obtained at the end of that week. This inexpensive assay can be adapted to any clinical laboratory and should provide an objective means to evaluate short-term glycemic control, complementing the evaluation provided by self-glucose monitoring (immediate control) and intermittent assay of glycosylated hemoglobin (long-term control).     

妊娠早期母体一般特征联合多项指标预测妊娠期糖尿病发生的可行性

目的:探讨采用妊娠早期母体一般特征联合多项常规孕早期保健血液检查指标的方法预测妊娠期糖尿病(GDM)发生的可行性。方法:回顾分析2013年1月至2014年12月在上海市第一妇婴保健院建卡产检资料完整的8513例单胎妊娠妇女(已排除糖尿病合并妊娠妇女234例)相关资料,包括母体一般特征及孕11~18周抽血化验结果。根据孕24~28周75g糖耐量检查结果分为病例组(GDM组,1087例)及对照组(正常组,7426例)。结果:两组的年龄、体质量指数(BMI)、白细胞总数、血红蛋白量、谷丙转氨酶、血清铁蛋白、促甲状腺素、空腹血糖、糖化血红蛋白和乙肝病毒e抗原比较,差异均有统计学意义(P0.05)。将这些相关指标建立模型进行GDM的预测,准确性为74.79%,假阳性为46%。利用该式对100例排除了糖尿病合并妊娠的早孕妇女进行前瞻性预测,其准确性为81.25%,假阳性率为57.14%。结论:联合分析孕早期母体一般特征及一些常规孕前保健的血液检查结果,可有效预测GDM发生,通过加强对预测阳性孕妇的早期宣教,或可降低GDM发生。     

A reassessment of maternal serum alpha-fetoprotein in diabetic pregnancy

We assessed maternal serum alpha-fetoprotein (AFP) concentrations in 227 diabetic women who belonged to different groups of White's classification but found no difference either between the insulin-dependent and the normative population or between the former and diabetics who were not insulin-dependent. By contrast, we found in maternal blood a marked, statistically significant inverse correlation between maternal serum AFP and the concentration of glycosylated hemoglobin in maternal blood assayed within 6 weeks of each other in mid-gestation (r = -0.4, p less than 0.05), but not when glycosylated hemoglobin was determined in the first two months of pregnancy (r = 0.05). These data indicate that the decrease in maternal serum AFP found in pregnant diabetic women is related to the efficacy of diabetic control but not to the diabetic status. A correction in maternal serum AFP should therefore be applied only to values obtained for women with poor glycemic control. Decreased maternal serum AFP in poorly controlled diabetics may indicate reduced synthesis of other fetal proteins which, in turn, may correlate with fetal growth retardation and the occurrence of malformation.     

Effect of dietary therapy on pancreatic beta cell function in noninsulin-dependent diabetes mellitus

Twenty-four noninsulin-dependent diabetics, who were newly diagnosed or had discontinued therapy for at least 10 months, were studied for the effect of dietary therapy on pancreatic beta cell function. The mean fasting plasma glucose (176 +/- 14 vs 212 +/- 16 mg/dl, p less than 0.01) and glycosylated hemoglobin (HbA1c, 8.6 +/- 0.5 vs 9.4 +/- 0.6%, p less than 0.001) decreased significantly after 1 month of dietary control, although there was no significant change in mean body weight (57.4 +/- 2.0 vs 57.7 +/- 2.0 kg, p greater than 0.5). The mean incremental serum C-peptide (delta CP) response to oral glucose stimulation (OGTT) increased (4.6 +/- 0.6 vs 3.5 +/- 0.7 ng/ml, p less than 0.01), but that to intravenous glucagon (GT) did not (2.5 +/- 0.2 vs 2.7 +/- 0.2 ng/ml, p greater than 0.1). In 12 patients whose glycemic control improved after dietary treatment, there was a good correlation between the decrement in fasting plasma glucose and the increment in delta CP response to OGTT (r = 0.66, p less than 0.05). In conclusion: after 1 month of dietary therapy in noninsulin-dependent diabetics, (1) the serum C-peptide response to OGTT, but not to GT, improved; (2) the beta cell secretion increased only in those patients with improved glycemic control; (3) there was a good correlation between glycemic control and beta cell function.     

妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖关系的研究

目的　探讨妊娠期糖代谢异常孕妇血清瘦素水平及其与胰岛素和血糖的关系。方法　采用放射免疫法 ,测定 36例妊娠期糖代谢异常孕妇 (糖代谢异常组 )和 2 4例正常孕妇 (正常妊娠组 )的空腹及口服 50g葡萄糖后 3h的血清瘦素水平 ;采用电化学发光法测定两组孕妇的空腹血清胰岛素水平 ;采用低压液相色谱分析法测定两组孕妇的糖化血红蛋白 ;采用葡萄糖氧化酶法测定两组孕妇的口服 50g葡萄糖后 1h的血糖水平。结果　 (1 )糖代谢异常组孕妇血清瘦素水平为 (1 4 9± 4 3) μg/L ,正常妊娠组为 (1 0 0± 1 8) μg/L ,两组比较 ,差异有极显著性 (P <0 0 1 ) ;(2 )糖代谢异常组孕妇空腹血清胰岛素、糖化血红蛋白、服糖后 1h血糖水平分别为 (1 2 9± 4 3)mU/L、 (6 1± 1 1 ) %、(1 1 0±1 4)mmol/L ;正常妊娠组孕妇分别为 (8 6± 3 2 )mU/L、(4 5± 1 0 ) %、(7 8± 1 2 )mmol/L。糖代谢异常组孕妇血清瘦素水平与空腹血清胰岛素、糖化血红蛋白、服糖后 1h的血糖水平呈明显的正相关关系 ,相关系数 (r)分别为 0 835、0 758、0 561。结论　妊娠期糖代谢异常孕妇空腹血清瘦素水平升高 ,其瘦素水平的高低与空腹血清胰岛素及血糖水平相关     

Lack of predictive value of HbA1 for impaired glucose tolerance in polycystic ovary syndrome

Twenty-seven women with polycystic ovary syndrome (PCO) and 17 control women had a 75 g oral glucose tolerance test (oGTT) performed. Although glucose tolerance was impaired in the obese (body mass index greater than 25 kg/m2) women with PCO, glycosylated hemoglobin (HbA1) concentrations did not exceed the normal upper limit (7.2%). In all 44 women, there was no correlation between HbA1 and fasting glucose (r = 0.082, p = 0.63) but there was a significant correlation between HbA1 and summed glucose levels through the oGTT (r = 0.389, p = 0.02). HbA1 measurement does not predict the presence of impaired glucose tolerance in women with PCO.     

Low sensitivity of serum fructosamine as a screening parameter for gestational diabetes mellitus.

Oral glucose tolerance testing (OGTT) and quantification of serum fructosamine levels were performed in 190 asymptomatic women in weeks 24-28 of pregnancy. OGTT identified 10 of the 190 women as having gestational diabetes, but serum fructosamine quantification failed to do so because none of these 10 women exhibited levels exceeding the normal limit of 2.76 mmol/l. The mean fructosamine level in this group was 1.72 +/- 0.25 mmol/l compared to 1.60 +/- 0.15 mmol/l in the other 180 women without gestational diabetes. Fructosamine was found to correlate only with postload glucose values in excess of 180 mg/dl at 2 h (r = 0.87; p = 0.01), i.e. with the highest overall glucose values, but not with fasting glucose or milder postprandial hyperglycemia of under 180 mg/dl. We conclude that quantification of fructosamine detects only the rather severe cases of gestational hyperglycemia, but is too insensitive to uncover mild asymptomatic gestational diabetes mellitus, and we do not consider fructosamine to be a useful parameter for the diagnosis of this condition.