Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization

OBJECTIVE: This study was undertaken to compare the use of glyburide with insulin for the treatment of gestational diabetes mellitus (GDM) unresponsive to diet therapy. STUDY DESIGN: A retrospective study was performed among women with singleton pregnancies who had GDM diagnosed, with fasting plasma glucose 140 mg/dL or less on glucose tolerance testing, between 12 and 34 weeks who failed diet therapy from 1999 to 2002. We identified 584 women and compared those treated with insulin between 1999 and 2000 with women treated with glyburide between 2001 and 2002. Maternal and neonatal outcomes and complications were assessed. Statistical methods included univariate analyses and multivariable logistic regression. RESULTS: In 1999 through 2000, 268 women had GDM diagnosed and were treated with insulin; in 2001 through 2002, 316 women had GDM diagnosed of which 236 (75%) received glyburide. The 2 groups were similar with regard to age, nulliparity, and historical GDM risk factors; however, women in the insulin group had a higher mean body mass index (31.9 vs 30.6 kg/m 2 , P=.04), a greater proportion identified themselves as white (43%, 28%, P<.001) and fewer as Asian (24%, 37%, P=.001), and they had a significantly higher mean fasting on glucose tolerance test (105.4 vs 102.4 mg/dL , P=.005) compared with the glyburide group. There were no significant differences in birth weight (3599+/-650 g vs 3661+/-629 g, P=.3), macrosomia (24%, 25%, P=.7), or cesarean delivery (35%, 39 %, P=.4). Women in the glyburide group had a higher incidence of preeclampsia (12%, 6%, P=.02), and neonates in the glyburide group were more likely to receive phototherapy (9%, 5%, P<.05), and less likely to be admitted to the neonatal intensive care unit (NICU) (15%, 24%, P=.008) though they had a longer NICU length of stay (4.3+/-9.6 vs 8.0+/-10.1, P=.002). Posttreatment glycemic control data were available for 122 women treated with insulin and 137 women treated with glyburide. More women in the glyburide group achieved mean fasting and postprandial goals (86%, 63%, P<.001). These findings remained significant in logistic regression analysis. CONCLUSION: In a large managed care organization, glyburide was at least as effective as insulin in achieving glycemic control and similar birth weights in women with GDM who failed diet therapy. The increased risk of preeclampsia and phototherapy in the glyburide group warrant further study.     

Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome

OBJECTIVE: We sought to investigate the association between glyburide dose, degree of severity in gestational diabetes mellitus (GDM), level of glycemic control, and pregnancy outcome in insulin- and glyburide-treated patients. STUDY DESIGN: In a secondary analysis of our previous randomized study, 404 women were analyzed. The association among glyburide dose, severity of GDM, and selected maternal and neonatal factors was evaluated. Severity levels of GDM were stratified by fasting plasma glucose (FPG) from the oral glucose tolerance test (OGTT). Infants with birth weight at or above the 90th percentile were considered large-for-gestational age (LGA). Macrosomia was defined as birth weight > or =4000 g. Well-controlled was defined as mean blood glucose < or =95 mg/dL. The association between glyburide- and insulin-treated patients by severity of GDM and neonatal outcome was evaluated. RESULTS: The dose received for the glyburide-treated patients was 2.5 mg-32%; 5 mg-23%; 10 mg-17%; 15 mg-8%; and 20 mg-20%. Patients were grouped into low (< or =10 mg) and high (>10 mg) daily dose of glyburide. A comparison between severity of the disease (fasting plasma glucose categories) and highest dose of glyburide revealed a significant difference between the low-95 FPG and the other severity categories (P = .02). Of patients in the well-controlled glycemic group, only 6% required the high dose of glyburide (>10 mg). In patients with poor glycemic control (mean blood glucose >95 mg/dL), 38% received the high dose of glyburide (P = .0001). Comparison between the high glyburide (>10 mg) and the low glyburide dosages (< or =10 mg) revealed that the rate of macrosomia was 16% vs 5% and LGA 22% vs 8%, (P = .01), respectively. No significant difference was found in composite outcome, metabolic complications, and Ponderal Index between the 2 dose groups. Stratification by disease severity revealed a significantly lower rate of LGA for both the glyburide- and insulin-treated subjects. No significant difference was found between metabolic, respiratory, and neonatal intensive care unit (NICU) for patients within each fasting plasma glucose severity category. CONCLUSION: Glyburide and insulin are equally efficient for treatment of GDM in all levels of disease severity. Achieving the established level of glycemic control, not the mode of pharmacologic therapy, is the key to improving the outcome in GDM.     

Use of glyburide for the treatment of gestational diabetes: the San Antonio experience.

OBJECTIVES: Equivalent efficacy of glyburide and insulin for treatment of gestational diabetes (GDM) was demonstrated in a recent randomized trial. We describe our experience with glyburide in practice, and suggest factors that predict failure of glyburide treatment. METHODS: Women with GDM treated with glyburide were studied. They were divided into two groups: those who achieved adequate glycemic control with glyburide, and those who did not. The groups were compared in terms of baseline characteristics, including diabetes risk factors and glucose testing values. Receiver operating characteristics (ROC) curves were generated to identify thresholds for fasting plasma glucose and body mass index (BMI) that would predict glyburide failure. RESULTS: Seventy-five women were analyzed: 63 (84%) were successfully treated with glyburide, and 12 (16%) were not. Baseline characteristics were similar between the groups, except that failures had higher 3-h glucose tolerance test (GTT) values at all time points. ROC curves for fasting plasma glucose, pre-pregnancy BMI and BMI at diagnosis revealed no cut-off points for predicting failure of glyburide therapy. However, when fasting plasma glucose value on the GTT was > or = 110 mg/dl, 24% of women failed to respond to glyburide, compared to 12% at < 110 mg/dl (p = 0.15). CONCLUSIONS: In treatment of GDM, glyburide is successful in achieving good glycemic control in most women. Women with high fasting plasma glucose levels, however, may not respond adequately to glyburide therapy.     

Predictors of glyburide failure in the treatment of gestational diabetes

OBJECTIVE: Our objective was to identify among women with gestational diabetes mellitus (GDM) the patient characteristics that predict treatment failure with glyburide. METHODS: Historical cohort of 95 GDM women offered glyburide after dietary failure with defined entry criteria. RESULTS: From November 2000 to May 2005, 118 women had 124 pregnancies and were offered glyburide therapy by the 2 codirectors of our Diabetes Clinic. All but 2 women elected glyburide, and 27 pregnancies were excluded due to criteria defined a priori to the study. A cohort of 95 women with 95 pregnancies were included for analysis. Nineteen percent failed glyburide. Significant predictors of failure were maternal age (34 years compared with 29 years, P = .001), earlier diagnosis of GDM (23 weeks compared with 28 weeks, P = .002), higher gravidity (P = .01) and parity (P = .03), and a higher mean fasting blood glucose (112 compared with 100 mg/dL; P = .045) compared with those successfully treated. After adjustment in the multivariable logistic regression analysis, GDM women diagnosed at a gestational age less than 25 weeks were 8.3 times more likely to fail glyburide compared with those diagnosed after 25 weeks. Maternal and fetal outcomes were favorable with a cesarean delivery rate of 25% and macrosomia rate of 7%. CONCLUSION: Glyburide was more likely to fail in women diagnosed earlier in pregnancy, of older age and multiparity, and with higher fasting glucoses, suggesting that earlier glucose intolerance and a reduced capacity to respond to an insulin secretagogue may distinguish this group. The time for glyburide as an alternative treatment has come; however, it should be prescribed after careful consideration of these patient characteristics to minimize the likelihood of failure. LEVEL OF EVIDENCE: II-2.     

Management of fetal death after 20 weeks of gestation complicated by placenta previa

Objective.?To determine the frequency and risk factors associated with neonatal chemical hypoglycemia in neonates of mothers with type 2 diabetes and gestational diabetes mellitus (GDM).

Research Design and Methods.?A retrospective cohort study of women with type 2 diabetes or GDM and their singleton neonates. The primary outcome measure was the presence of neonatal chemical hypoglycemia (capillary plasma equivalent glucose <45?mg/dl) within 1?h of birth. Statistical methods included bivariate and multivariate analyses.

Results.?242 mother infant dyads were identified. Sixty-eight (28%) were treated with diet, 110 (46%) with glyburide, and 64 (26%) with insulin. The incidence of neonatal chemical hypoglycemia was 18% (44/242). The incidence was significantly higher in those requiring pharmacotherapy (25% vs. 3%, p?p?=?0.58). The frequency of neonatal chemical hypoglycemia was statistically associated with birth weight, macrosomia and ponderal index (p?Conclusion.?Neonatal chemical hypoglycemia occurs more frequently in infants from women with type 2 diabetes and GDM treated with glyburide or insulin. An increased neonatal ponderal index is a strong predictor of significant neonatal chemical hypoglycemia.     

Macrosomic infants are not all equal

AIMS: To see whether macrosomic infants have different morbidity according to maternal screening results for gestational diabetes mellitus (GDM) and ethnicity. METHODS: After excluding infants of women with diabetes, the National Women's Hospital database identified 134 infants who were delivered in 2003 and weighed >or= 4500 g. Case notes were reviewed to record risk factors for macrosomia, delivery details and neonatal morbidity. Outcomes were analysed according to screening results for GDM and compared between Polynesian and Asian women. RESULTS: Body mass index (BMI) was calculated in 29% of women, and GDM screening was undertaken in 51%. Infants of women who had a screening glucose < 7.2 mmol/L compared to >or= 7.8 mmol/L had lower rates of admission to the neonatal intensive care unit (NICU) (6.4 vs 28.6%, P=0.049), had less respiratory distress (3.2 vs 23.8%P=0.033) and display a trend to less require intravenous dextrose (6.4 vs 23.8%P=0.10). Maternal BMI was lower in Asian (26.5 +/- 4.4 kg/m(2)) compared to Polynesian women (35.2 +/- 8.1 kg/m(2), P=0.008). More Asian women had a Caesarean delivery (73.3 vs 25%P<0.001) and their infants were more likely to be admitted to NICU (33.3 vs 7.7%P=0.02), require intravenous dextrose (20 vs 1.9%P=0.03) and have respiratory distress (26.7 vs 3.8%P=0.02). CONCLUSION: Risk factors for macrosomia are not assessed adequately, which may contribute to morbidity. Using a birthweight >or= 4500 g to define macrosomia is associated with disparate morbidity between ethnicities that have different body compositions.     

One hour versus two hours postprandial glucose measurement in gestational diabetes: a prospective study.

OBJECTIVE: To compare the rate of adverse perinatal outcomes among women with gestational diabetes mellitus (GDM), monitored by 1 versus 2 hour-postprandial glucose (PPG) measurements. METHODS: A total of 112 women diagnosed with GDM, by the criteria of Carpenter-Coustan, were included in the study population. Women were recruited from two different treatment settings, but were managed by the same team of health-care professionals using a standardized protocol. Allocation to treatment group was based on treatment setting. Glucose levels were measured fasting, and either 1 hour (1-hour monitoring group-target values <140 mg/dl) or 2 hours (2-hour monitoring group-target values <120 mg/dl) postprandially. Demographic data and perinatal outcomes were collected from their medical records. RESULTS: In all, 66 women were assigned to 1-hour monitoring group (1 h-PPG) and 46 women to 2-hour monitoring group (2 h-PPG). There were no differences in parity, family history of diabetes, rate of GDM in previous pregnancies, weight gain, pregestational BMI and 50-g-glucose challenge test (GCT) and 100-g oral glucose challenge test (OGTT) results. As expected, there was a significant difference in mean blood glucose levels between the two groups (108.1+/-19.2 and 94.9+/-21.2 mg/dl, 1- and 2 hours, respectively, p<0.0001); however, HbA1C levels were similar in the two groups. Perinatal outcomes were defined as gestational week at delivery; fetal weight (3325+/-471 vs 3309+/-608 g, respectively) and percentile (47.2+/-27 vs 49.6+/-30, respectively), and were similar for both groups. Insulin therapy was initiated more frequently in 2-hour monitoring group (28 and 40% of women in groups 1 and 2, respectively; p<0.05). Rates of macrosomia (7.5 versus 10.6%), large for gestational age (7.4 versus 15.2%), and delivery by cesarean section (24 versus 30%) were increased in group 2 (2 h-PPG) but these differences did not reach statistical significance. CONCLUSION: These data suggest that diet control in women with GDM managed by 1-hour PPG measurements is associated with a decreased rate of insulin therapy. However, neonatal and obstetrical outcomes are not determined by the timing of their glucose determinations.     

Glyburide in gestational diabetes – prediction of treatment failure

Objective.?To identify factors predicting failure of glyburide treatment in women with gestational diabetes mellitus (GDM).

Methods.?A retrospective study of all women with GDM that were treated with glyburide in a single tertiary referral center. Patients were switched from glyburide to insulin if they failed to achieve glycemic goals, and were then classified as glyburide failure.

Results.?Overall, 124 women with GDM treated with glyburide were included in the study, of which 31 (25%) failed to achieve glycemic control. Women in the failure group were characterized by a higher weight gain during pregnancy, higher rates of GDM on previous pregnancies, and a glucose challenge test (GCT) result. On multivariate logistic regression analysis, a GCT value of >200?mg/dl (OR=7.1, 95% CI 2.8–27.6) and weight gain ≥12?kg (OR=3.9, 95% CI 1.2–13.0) were the only significant and independent predictors of glyburide failure. Most women who were successfully treated with glyburide required a daily dose of 5?mg or less and the time required to achieve glycemic control in these cases was 12.4±4.9 days (range 5–24 days). Of the women who failed to achieve glycemic control with gluburide, 26/31 were switched to insulin, of them only 12 (46%) achieved desired level of glycemic control.

Conclusion.?Most women with GDM achieved desired level of glycemic control under glyburide treatment.     

Influence of the degree of carbohydrate metabolism imbalance in gestational diabetes on pregnancy and newborns condition

The aim of our study was the evaluation of the correlation between carbohydrate metabolism imbalance at the moment of gestational diabetes mellitus (GDM) diagnosis and regulation of glycemia during pregnancy, pregnancy complications, time and mode of delivery and conditions of the newborns. MATERIAL: 231 women with GDM delivered in our hospital between 1993-1996 were investigated. This population was divided into 6 groups, according to glycemia levels. METHOD: The term of diagnosis of the GDM, medical treatment (diet or diet and insulin), the degree of metabolic regulation archived, mode and time of delivery, as well as state of newborns were analysed. RESULTS: In groups I and VI we noticed the greatest percentage of patients treated with insulin (68%, 67%), versus 26% in group II and 17% in group III. In group VI in all cases treated with insulin we begun this therapy shortly after marking GDM. Glycemia in 24 hrs period after GDM diagnosis in group I were 122.7 +/- 28.6 mg/dl, in group VI 112.0 +/- 23.6 mg/dl, while we noticed 90.3 +/- 15.6 mg/dl in group II and 87.7 +/- 15.9 mg/dl in group III. Blood glucose level < 100 mg/dl in first determination of 24 hrs profiles we noticed in 5% in group I, 2% in group VI while 20% in group II and 51% in group III. Average levels of glycemia in last 24 hrs profiles before delivery in group I were 93.0 +/- 15.8 mg/dl, in group VI 96.2 +/- 21.1 mg/dl while 87.8 +/- 13.5 mg/dl in group II and 86.8 +/- 14.1 mg/dl in group III. Blood glucose level < 100 mg/dl of daily profile before the end of pregnancy was discovered in 8% in group I, 47% in group III. The greatest amount of complications (pregnancy induced hypertension and imminent premature delivery) was diagnosed in group VI-75% and in group III-55%. Surgical delivery took place in group I in 50%, in group V in 46%, in group VI in 67% while 17% in group II, 35% in group III and 30% in group IV. Macrosomy of newborns (> 4000 g) was diagnosed in group I in 36% in group V in 23% and in group VI in 42% while 9%, 6% and 15% in groups, II, III and IV respectively. The condition of newborns in the 1st minute of life was determined as good (8-10 points in Apgar scale) in significant percentage, in 87%, 75%, 70% in groups II, III, IV while only 59%, 62%, 58% in groups I, V, VI respectively. CONCLUSION: Serious intensification of carbohydrates metabolism disorders at the moment of diagnosing GDM, such as fasting glycemia > 140 mg/dl and the result after 2 hours > 200 mg/dl in 75 g OGTT more often requires insulin treating connect with numerous difficulties both in pregnancy monitoring and also has inadventageous influence on obstetrics outcomes-increasing percentage of surgery deliveries and macrosomies, that change the condition of newborns for worse.     

The effect of maternal obesity on pregnancy outcomes of women with gestational diabetes controlled with diet only, glyburide, or insulin

Objective To examine the effect of obesity on maternal and neonatal outcomes in women diagnosed with gestational diabetes mellitus (GDM) and managed with diet only, glyburide, or insulin.Study Design Women with singleton gestations enrolled for outpatient services diagnosed with GDM and without history of pregnancy-related hypertension at enrollment or in a prior pregnancy were identified in a database. Women with GDM controlled by diet only (n = 3918), glyburide (n = 873), or insulin without prior exposure to oral hypoglycemic agents (n = 2229) were included. Pregnancy outcomes were compared for obese versus nonobese women within each treatment group and also compared across treatment groups within the obese and nonobese populations.Results Within each treatment group, obesity was associated with higher rates of cesarean delivery, pregnancy-related hypertension, macrosomia, and hyperbilirubinemia (all p < 0.05). Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in women receiving glyburide.Conclusion Obesity adversely affects pregnancy outcome in women with GDM. Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in pregnant women receiving glyburide.     

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     

妊娠期糖尿病孕妇血清肿瘤坏死因子α水平变化与胰岛素抵抗关系的研究

目的　探讨妊娠期糖尿病孕妇血清肿瘤坏死因子α(TNF α)水平变化与胰岛素抵抗的关系。方法　采用酶联免疫吸附试验测定 4 2例妊娠期糖尿病孕妇 (GDM组 )、4 0例正常妊娠晚期孕妇 (正常妊娠组 )空腹血清TNF α水平 ;同时测定两组孕妇空腹血糖、C肽、胰岛素、糖化血红蛋白(HbA1c)水平。并且根据公式计算两组孕妇的胰岛素敏感指数 (ISI) ,以评价胰岛素抵抗程度。结果(1)GDM组孕妇空腹血清TNF α水平为 (5 2± 1 6 )ng/L ,正常妊娠组孕妇为 (4 5± 0 5 )ng/L ,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇ISI为 - 4 3± 0 4 ,正常妊娠组为 - 3 8± 0 3,两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )GDM组孕妇空腹血糖、胰岛素、C肽水平分别为 (5 5± 0 7)mmol/L、(13 4± 3 8)mU/L、(1 6± 0 4 )nmol/L ,正常妊娠组孕妇空腹血糖、胰岛素、C肽水平分别为(4 9± 0 4 )mmol/L、(9 3± 2 5 )mU/L、(1 2± 0 3)nmol,两组比较 ,差异有极显著性 (P <0 0 1) ;GDM组孕妇HbA1c为 (5 6± 0 5 ) % ,正常妊娠组孕妇为 (5 3± 0 5 ) % ,两组比较 ,差异有显著性(P <0 0 5 )。 (3)GDM组孕妇空腹血清TNF α水平与ISI呈显著负相关 (r=- 0 70 3,P <0 0 1) ,分别与空腹血糖、C肽、HbA1c呈显著正相关 (r     

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。     

Perinatal outcomes and the use of oral hypoglycemic agents

OBJECTIVE: To compare neonatal results from patients with gestational diabetes mellitus (GDM) who were treated with insulin, glyburide and acarbose. RESULTS: Seventy patients diagnosed with GDM who needed therapy to complement diet and physical activities were included in the study. One group was assigned to insulin therapy (n = 27), a second group was assigned to glyburide therapy (n = 24) and a third group was assigned to acarbose therapy (n = 19). Maternal characteristics were similar in the three groups. Glucose control was not achieved in five (20.8%) of the patients using glyburide and in eight (42.1%) of patients using acarbose. No statistical difference was observed in fasting and post-prandial glucose levels or in average newborn weight in the three groups. The rate of large for gestational age (LGA) fetuses was 3.7, 25 and 10.5% in the groups treated with insulin, glyburide and acarbose, respectively. Neonatal hypoglycemia was observed in eight newborns, six of which from the glyburide group. CONCLUSION: We believe that glyburide and acarbose can be promising alternative therapies for the treatment of GDM. Glyburide controlled glucose levels in most patients and it was more efficient than acarbose. Glyburide showed a higher rate of macrosomia and neonatal hypoglycemia as compared to other therapies.     

A ten-year gestational diabetes mellitus cohort at a university clinic of the mid-Anatolian region of Turkey

OBJECTIVE: The study attempts to analyze a 10-year retrospective cohort of gestational diabetes mellitus (GDM) cases, elucidating the maternal complications and perinatal morbidity and mortality. STUDY DESIGN: The study participants were 110 diabetic singleton pregnancies receiving obstetric care at the Department of Obstetrics and Gynecology, Osmangazi University School of Medicine in Eskisehir, Turkey from January 1995 to December 2004. In 70 of the GDM cases, mean age, diagnostic criteria used to define GDM, gestational age at delivery, presence of additional risk factors, method of clinical management, mode of delivery, fetal birthweights and newborn characteristics were assessed. RESULTS: The prevalence of GDM in the past ten-year period was 3.1% (110/3548). Mean age of enrolled GDM cases was 32.6 +/- 5.3 years. With regard to diagnostic criteria of GDM, 24 (37.1%) cases were diagnosed based on a 100 g, three-hour oral glucose tolerance test (OGTT), while 18 (25.7%) cases were referred to our unit without any information on the specific criteria of GDM diagnoses. In less than a third of the cases (25.7%), a one-hour 50 g glucose challenge test (GCT) resulted > or =185 mg/dl completing the diagnoses. More than half of the cases (57.1%) revealed controlled glucose homeostasis on diet, while 30 (42.9%) pregnant women needed insulin therapy to control blood glucose levels to within normal physiologic limits. Fetal macrosomia was present in 18 (25.7%) pregnancies. Meanwhile, most of the fetuses (62.9%) were within the normal growth percentiles throughout the pregnancy. There was no difference detected in body mass index (BMI) of women undergoing cesarean section and spontaneous vaginal births (25.1 +/- 1.2 vs 26.2 +/- 2.3 kg/m2, respectively, p = 0.45). Vacuum extraction and forceps applications were indicated in 10% of all GDM groups. Fetuses born to women having cesarean section were heavier at birth compared to those of women having vaginal births (3940 +/- 320 g vs 430 +/- 117 g, p = 0.08) Most frequent neonatal morbidity was hyperbilirubinemia in 25 (35.7%) newborns. Interestingly, of those women with GDM, only ten (14.3%) cases consented to follow-up evaluation of glucose intolerance between six and eight weeks postpartum. CONCLUSIONS: Proposed risks from abnormal glucose intolerance in pregnancy are multiple. Early diagnosis, patient education, proper follow-up and postpartum testing in women with GDM will certainly decrease poor perinatal outcomes, enabling also a secondary prevention of type 2 diabetes in the long term.     

The association between glucose challenge test, obesity and pregnancy outcome in 6390 non-diabetic women.

OBJECTIVE: To evaluate the association between obesity, glucose challenge test (GCT) and pregnancy outcome. METHODS: A prospective cohort study of 6854 consecutive gravid patients screened for gestational diabetes (GDM) using 50-gram GCT, at 24-28 weeks' gestation was performed. A screening value 130 mg/dl was followed by 100 gr oral GTT. Patients who were diagnosed with GDM were excluded. For purpose of analysis patients were categorized by prepregnancy BMI and by different GCT thresholds. Maternal outcome was defined by rate of preeclampsia, gestational age at delivery, cesarean section (CS) rate and the need for labor induction. Neonatal outcome was defined by fetal size (macrosomia/LGA), arterial cord pH, respiratory complications and neonatal intensive care unit (NICU) admission. RESULTS: Overall, a positive GCT result (GCT > or = 130 mg/dl) was identified in 2541/6854 (37%) women. GDM was further diagnosed in 464/6854 (6.8%) of subjects. In both groups of screening results ( > 130 mg/dl and < 130 mg/dl), the obese women were significantly older, gained more weight during pregnancy and had a lower rate of nulliparity in comparison to the non obese women. The obese women had higher rates of macrosomia, LGA and induction of labor. No difference was found in mean birth weight, the total rate of cesarean section, preterm delivery, 5 minute Apgar score < or = 7, mean arterial cord pH, NICU admission and a need for respiratory support in comparison to non obese women in both groups of screening results. A gradual increase in the rate of macrosomia, LGA and cesarean section was identified in both obese and non-obese women in relation to increasing GCT severity categories. CONCLUSION: Fetal size and cesarean section rate are associated with the degree of carbohydrate intolerance (screening results). Furthermore, obesity remains the main contributor impacting fetal size.     

Maternal obesity not maternal glucose values correlates best with high rates of fetal macrosomia in pregnancies complicated by gestational diabetes

AIM: The current therapeutic strategies to reduce macrosomia rates in gestational diabetes (GDM) have focused on the normalizing of maternal glucose levels. The aim of our study was 1.) to compare maternal glycemic values with the presence of fetal macrosomia at different gestational ages (GA) and with LGA at birth in a cohort of women with glucose intolerance and standard diabetic therapy. METHODS: 306 women with GDM and 97 with impaired glucose tolerance underwent ultrasound examinations at entry and, after initiation of therapy, monthly in addition to standard diabetic therapy. Measurements from the entry diagnostic oGTT, glucose profile and HbA1c and from subsequent glucose profiles obtained within 3 days of the ultrasound at 5 categories of GA age (20-23, 24-27 etc) were retrospectively compared between pregnancies with and without fetal macrosomia, defined as an abdominal circumference (AC) > or = 90th percentile. Maternal prepregnancy BMI was adjusted for and BMI > or = 30 kg/m2 was defined as obesity. RESULTS: At entry, neither the hourly oGTT values, HbA1c, nor the entry glucose profile differed significantly between pregnancies with and without fetal macrosomia. In a total of 919 pairs of ultrasound/glucose profiles there was no significant difference in glucose levels at every GA category neither in lean nor in obese woman except for the fasting glucose of 32-35 GA. The fetal macrosomia rate in each GA category and the rate of LGA were significantly higher in obese women: e.g. 14.5 vs 28% at diagnosis, 15.7 vs 26.7% at 32-35 weeks, 15.5 vs 25.0% at birth (p < 0.05 for each comparison). CONCLUSION: The association of maternal glucose values and fetal macrosomia was limited to the fasting glucose values between 32-35 weeks while maternal obesity appeared to be a strong risk factor for macrosomia throughout pregnancies with GDM. In obese women the high fetal macrosomia rate did not appear be normalized by therapy based on maternal euglycemia.     

50gram oral glucose challenge test combined with risk factor-based screening for gestational diabetes

OBJECTIVE: Our aim was to study whether universal screening of all pregnant women by Oral Glucose Challenge Test (OGCT) would identify a higher number of women with Gestational Diabetes (GDM) than risk factor based screening. STUDY DESIGN: A 50 g OGCT test was performed prospectively in 532 unselected women at 26-28 weeks of gestation. The 1-h venous plasma glucose concentration of >7.3 mmol/l was considered as a positive screening result. Patients with a positive OGCT underwent a 75 g 2-h OGTT, which was used as the actual diagnostic test for GDM. When two or all three of the glucose concentrations in OGTT (measured at fasting state and 1 and 2 h after the 75 g glucose load) were above the 97.5th percentile the patient was considered as having GDM. In addition, women with risk factors for GDM also underwent a 75 g OGTT regardless of the result of the OGCT. RESULTS: A positive 50 g OGCT was obtained in 123 (23%) of the women. In 15 (12%) of these, a diagnosis of GDM was established by the subsequent OGTT. Out of the 409 remaining women with a normal OGCT, 148 (36%) had risk factors for GDM. An OGTT performed in these patients identified 4 additional women with a GDM. Seventy-nine percent of GDM was thus found with 50g OGCT without regarding risk factors. Forty-seven percent of the women with GDM would have been missed in screening by risk factors only. CONCLUSIONS: In our population 50 g OGCT appears to identify a higher number of GDM than risk factor based screening. Combined with risk factor screening a few more cases of GDM would be found.     

Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus.

OBJECTIVE: To establish parameters associated with therapeutic success in gestational diabetics treated with glyburide. STUDY DESIGN: A total of 69 gestational diabetics who failed dietary therapy were treated with glyburide. Inadequate glycemic control on maximum dose glyburide (10 mg b.i.d.) was considered treatment failure. The glyburide failure rate was calculated and factors that might predict success with glyburide were analyzed between the success and failure groups using chi(2) or Student'st-tests. RESULTS: The glyburide failure rate was 18.8%. Gestational age at glyburide initiation (p<0.01), pretreatment fasting blood sugars (p<0.001), and 1-hour postprandial values (p<0.001) were the only statistically significant factors between the two groups. Glyburide success was predicted if dietary failure occurred after 30 weeks, or fasting blood sugars were <110 mg/dl and 1-hour postprandials were <140 mg/dl (sensitivity 98%, specificity 65%). CONCLUSION: Gestational diabetics who fail dietary therapy after 30 weeks gestation or have fasting blood sugars <110 mg/dl and 1-hour postprandials <140 mg/dl do well on glyburide therapy.     

Total plasma homocysteine correlates in women with gestational diabetes

AIM: We aim to assess serum total homocysteine (tHcy) associations with metabolic syndrome components and B-vitamins in women with gestational diabetes mellitus (GDM). METHODS: We studied 61 consecutive pregnant women, 44 with GDM and 17 with normal glucose tolerance (CG). Serum homocysteine levels were analyzed by ELISA, using Bio-Rad reagents. Serum folates and vitamin B(12) concentrations were determined by chemiluminescent immunoassay, free fatty acids (FFA) and lipids enzymatically. RESULTS: Serum homocysteine levels were similar in both the GDM and the CG groups (8 +/- 2.0 vs 7.4 +/- 1.1 mumol/l, respectively). Women with GDM in comparison to CG women were characterized by higher values of homeostasis model of insulin resistance (HOMA-IR) (2.8 +/- 1.7 vs 1.6 +/- 0.9, P < 0.01), serum triglycerides (2.7 +/- 0.9 vs 1.9 +/- 0.5 mmol/l, P < 0.01) and FFA (0.6 +/- 0.2 vs 0.46 +/- 0.2 mmol/l, P < 0.05). In GDM women serum tHcy correlated with vitamin B(12) (r = -0.47, P < 0.01) and folates (r = -0.51, P < 0.001); in CG women with HOMA-IR, a marker of insulin resistance (r = -0.49, P < 0.05). In multiple regression analysis with serum tHcy as a dependent variable, folate and vitamin B(12) entered the analysis in GDM women (beta = -0.42 and -0.34, respectively, P < 0.05), whereas in CG cystatin C and HOMA-IR entered the analysis (P < 0.05). CONCLUSIONS: In women with GDM, serum homocysteine is significantly associated with vitamin B(12) and folate levels, while in healthy pregnant women with HOMA-IR and with kidney function. The results suggest the importance of the B-group vitamins in regulation of serum tHcy levels in women with insulin resistance/gestational diabetes, what might be relevant in protection against pregnancy complications associated with elevated tHcy in GDM women.