Undiagnosed asymptomatic hypoglycemia: diet, insulin, and glyburide for gestational diabetic pregnancy

OBJECTIVE: The role of maternal hypoglycemia during pregnancy has not yet been established. We sought to estimate the prevalence of undiagnosed, asymptomatic hypoglycemic events that occur in diabetic patients. METHODS: All patients were evaluated using a continuous glucose monitoring system for 72 consecutive hours. The continuous glucose monitoring system measures in subcutaneous tissue interstitial glucose levels within a range of 40-400 mg/dL every 5 minutes for a total of 288 measurements per day. All patients were instructed regarding diabetic diet and assigned to pharmacological treatment as needed. Patients documented the time of food intake, insulin or glyburide administration, and all clinical hypoglycemic events. An asymptomatic hypoglycemic episode was defined as more than 30 consecutive minutes of glucose value below 50 mg/dL detected only by continuous glucose monitoring system reading without patient awareness. RESULTS: An evaluation of 82 patients with gestational diabetes was performed; 30 were insulin-treated, 27 were managed by diet only, and 25 were patients treated with glyburide. For purposes of comparison, data were obtained from 35 nondiabetic gravid women. Asymptomatic hypoglycemic events were identified in 19 of 30 (63%) insulin-treated patients and in 7 of 25 (28%) glyburide-treated patients. No hypoglycemic events were identified in patients with gestational diabetes mellitus treated by diet alone or in nondiabetic subjects. The mean recorded hypoglycemic episodes per day was significantly higher in insulin-treated patients (4.2 +/- 2.1) than in glyburide-treated patients (2.1 +/- 1.1), P =.03. In insulin-treated patients, the majority of the hypoglycemic events were nocturnal (84%), whereas in glyburide-treated patients, episodes were identified equally by day and night. CONCLUSION: Our data suggest that asymptomatic hypoglycemic events are common during pharmacological treatment in gestational diabetic pregnancies. We speculate that this finding may be explained by treatment modality rather than by the disease itself.     

Continuous glucose monitoring for the evaluation and improved control of gestational diabetes mellitus

Objectives: To compare the daily glycemic profile reflected by continuous versus self-monitoring of blood glucose in women with gestational diabetes mellitus (GDM), and to evaluate possible differences in treatment strategy based on the two monitoring methods. Materials and methods: The study sample consisted of 57 women with gestational diabetes, 47 in Israel and ten in California. Gestational age ranged from 24 to 32 weeks in the Israeli women, and 32 to 36 weeks in the American women. Data derived from the Continuous Glucose Monitoring (CGM) System (MiniMed) for 72 h were compared to fingerstick glucose measurements (6-8 times a day). During continuous monitoring, patients documented the timing of food intake, insulin injections and hypoglycemic events. Results: In the Israeli group, 23 women were treated by diet alone, and 24 by diet plus insulin. An average of 763 ± 62 glucose measurements was recorded for each patient with continuous glucose monitoring. The mean total time of hyperglycemia (glucose level > 140 mg/dl) undetected by the fingerstick method was 132 ± 31 min/day in the insulin-treated group and 94 ± 23 min/day in the diet-treated group. Nocturnal hypoglycemic events (glucose levels < 50 mg/dl) were recorded in 14 patients, all insulin-treated. On the basis of the additional information provided by continuous monitoring, the therapeutic regimen (insulin therapy, diet adjustment, or both) was changed in 36 of the 47 patients. All ten American women were treated with insulin. The mean time of undetected hyperglycemia for a total group monitoring time of 30 days was 78 ± 13 min/day. Eight women had nocturnal hypoglycemia on at least one of the three nights of monitoring for a total of 12 nights. A change in insulin dosage was made in all women on the basis of the data provided by continuous glucose monitoring. Conclusion: Continuous glucose monitoring is helpful for monitoring women with GDM and for adjusting diabetes therapy. It can accurately detect high postprandial blood glucose levels and nocturnal hypoglycemic events that may go unrecognized by intermittent blood glucose monitoring. A large prospective study on maternal and neonatal outcome is needed to determine the clinical implications of this new monitoring technique.     

Continuous subcutaneous insulin therapy during early pregnancy

Intensive metabolic control of diabetes is probably important during formation of the embryo early in pregnancy. The purpose of this study was to determine the efficacy and complications of continuous subcutaneous insulin infusion therapy during the fifth to the tenth week of gestation. Twenty-four insulin-dependent subjects were trained to use blood glucose self-monitoring and the Auto Syringe portable insulin infusion pump (AS6C). Regular insulin was administered as a basal infusion of 18 +/- 8 U/24 hours (+/- SD) (12.2 +/- 3.9 mU . kg-1 . h-1) and as bolus injections of 6 +/- 3 U before meals and 1.2 +/- 1 U before snacks. Reasonable control of fasting (119 +/- 30 mg/dL) and postprandial (133 +/- 34 mg/dL) hyperglycemia was achieved, accompanied by an average of 2.2 +/- 1.5 symptomatic hypoglycemic episodes per week. The frequency of complications with this new therapy declined as the authors gained experience in teaching the system. The persistence of good diabetic control in many of the subjects after they returned to conventional insulin therapy points to the need for a controlled trial of continuous subcutaneous insulin infusion therapy versus intensive conventional therapy in pregnancy.     

Pen injector for insulin-requiring diabetic patients.

To compare the metabolic control and acceptability of a pen injector to the traditional syringe used in diabetes, 12 non-insulin-dependent diabetes mellitus (NIDDM) patients and six insulin-dependent diabetes mellitus (IDDM) patients were followed-up at the outpatient clinic of the Taipei Municipal Yang-Ming Hospital. All patients participated in a four-week run-in period and 24-week randomized cross-over design study. Human NPH insulin (Protaphane HM) in vials and in penfills were used in each 12-week experimental period, respectively. Metabolic control was assessed by a biochemical examination (before and after seven months of treatment) and HbA1c levels (at Weeks 1, 4, 16 and 28) and was found to be unchanged. The overall mean blood glucose declined slightly in both treatment modalities but not to a significant level (mean +/- SE; run-in: 175 mg/dL +/- 10 mg/dL; pen: 159 mg/dL +/- 8 mg/dL; syringe: 156 mg/dL +/- 7 mg/dL). The number of hypoglycemic episodes and self-adjustments of insulin dosage did not differ significantly between pen and syringe treatments. At the end of the study, a questionnaire revealed that eight patients would choose pen injectors, nine patients syringes and one was unsure of what to use as a future preference. The limitation of 36 units per injection of insulin is a drawback for those NIDDM patients with insulin resistance. An insulin delivery device that would allow an injection of a larger quantity of insulin is desirable for some patients.     

Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women

OBJECTIVE: A paucity of data exists concerning the normal glycemic profile in nondiabetic pregnancies. Using a novel approach that provides continuous measurement of blood glucose, we sought to evaluate the ambulatory daily glycemic profile in the second half of pregnancy in nondiabetic women. STUDY DESIGN: Fifty-seven obese and normal weight nondiabetic subjects were evaluated for 72 consecutive hours with continuous glucose monitoring by measurement interstitial glucose levels in subcutaneous tissue every 5 minutes. Subjects were instructed not to modify their lifestyle or to follow any dietary restriction. For each woman, mean and fasting blood glucose values were determined; for each meal during the study period, the first 180 minutes were analyzed. RESULTS: For the study group, the fasting blood glucose level was 75 +/- 12 mg/dL; the mean blood glucose level was 83.7 +/- 18 mg/dL; the postprandial peak glucose value level was 110 +/- 16 mg/dL, and the time interval that was needed to reach peak postprandial glucose level was 70 +/- 13 minutes. A similar postprandial glycemic profile was obtained for breakfast, lunch, and dinner. Obese women were characterized by a significantly higher postprandial glucose peak value, increased 1- and 2-hour postprandial glucose levels, increased time interval for glucose peak, and significantly lower mean blood glucose during the night. No difference was found in fasting and mean blood glucose between obese and nonobese subjects. CONCLUSION: Glycemic profile characterization in both obese and normal weight nondiabetic subjects provide a measure for the desired level of glycemic control in pregnancy that is complicated with diabetes mellitus.     

Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus

OBJECTIVE: This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism. STUDY DESIGN: This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations. RESULTS: Oral glucose tolerance tests were done at a mean (+/-SD) of 24.9 +/- 5.7 and 30.7 +/- 3.2 weeks' gestation, and amniotic fluid insulin measurements were done at 31.1 +/- 3.2 weeks' gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs 180 mg/dL; 9.3 vs 10.0 mmol/L; P = .0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 microU/mL; >42 pmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P = .002) during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test. CONCLUSION: Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal.     

The postprandial glucose profile in the diabetic pregnancy

OBJECTIVE: A controversy exists regarding the time to monitor blood glucose in the diabetic pregnancy (60 or 120 minutes after meals). Using a novel approach that provides continuous measurement of blood glucose, we sought to determine postprandial glucose profile in the diabetic pregnancy. STUDY DESIGN: Subjects were connected to a continuous glucose monitoring system for 72 consecutive hours. A continuous glucose monitoring system measures the interstitial glucose levels in subcutaneous tissue every 5 minutes. Women were instructed to record the time of each meal during the study period. For each meal, the first 240 minutes were analyzed. RESULTS: Sixty-five women participated in the study: 26 women were treated by diet alone; 19 women received insulin therapy, and 20 women had type 1 diabetes mellitus. The time interval from meal to peak postprandial glucose levels was similar in all the evaluated types of diabetic pregnancies and in good and poor control insulin-treated patients with gestational diabetes mellitus (approximately 90 minutes). Failure to return to preprandial glucose values within a 3-hour observation period was identified in approximately 50% of the patients. A similar postprandial glucose peak time was obtained for breakfast, lunch, and dinner in all study groups. Postprandial hypoglycemia events were noted in approximately 10% of the meals and occurred about 160 minutes after mealtime. CONCLUSION: The time interval for postprandial glucose peak in diabetic pregnancies is approximately 90 minutes after meals throughout the day and is not affected by the level of glycemic control. This information should be considered in the treatment of diabetes mellitus in pregnancy.     

Diurnal variation of insulin sensitivity in NIDDM patients and normal subjects.

A modified insulin suppression test was adopted to assess the diurnal variation in insulin sensitivity and insulin clearance in 14 non-insulin-dependent diabetes mellitus (NIDDM) patients and eight age-, sex- and weight-matched normal subjects. The modified insulin suppression test was combined with an infusion of regular insulin, 30 mU/min x m2; glucose, 6 mg/kg x min; and somatostatin, 500 micrograms/h, for 120 minutes followed by only a somatostatin infusion for 60 minutes. Blood samplings were performed at appropriate times to obtain data on steady-state plasma insulin (SSPI), steady-state plasma glucose (SSPG as an index of insulin sensitivity), metabolic clearance and the half disappearance time (T1/2) of insulin. Blood specimens were also obtained during SSPI for measurement of erythrocyte insulin receptor binding. Each subject took the insulin suppression test twice. One test was started at 8 am and the other at 4 pm; each test was preceded by 16 hours of fasting. The order of the insulin suppression tests in each subject was randomized and balanced. In normal subjects, the SSPG level was lower in the morning than in the afternoon (118.0 +/- 43.6 vs 150.3 +/- 34.2 mg/dL, p less than 0.05). The NIDDM patients had a higher SSPG in the morning (217.7 +/- 51.4 vs 188.3 +/- 40.6 mg/dL, p less than 0.01). There was no diurnal difference in insulin clearance or the T1/2 in either normal subjects or NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

妊娠合并糖代谢异常孕妇产程中血糖监测的前瞻性研究

目的　探讨妊娠合并糖代谢异常孕妇在产程中行血糖监测和处理后对新生儿血糖变化的影响。方法　选择妊娠合并糖代谢异常孕妇 4 0例 ,其中妊娠期糖尿病孕妇 30例 ,糖耐量低减孕妇8例 ,糖尿病合并妊娠孕妇 2例。产程中对其进行血糖动态监测 ,血糖异常者及时使用低剂量短效胰岛素静脉滴注 ,观察分娩后新生儿的血糖水平变化。结果　产程中糖代谢异常孕妇的血糖波动范围为 3 8～ 11 2mmol/L。其中 ,17例进行了胰岛素静脉滴注 (胰岛素用量范围为 1 5～ 3 0U) ,占糖代谢异常孕妇总数的 4 2 5 % (17/40 ) ,分娩后新生儿即刻血糖水平平均为 (4 0± 1 5 )mmol/L ,分娩后 2 4h的新生儿血糖水平为 (3 9± 1 0 )mmol/L ,发生新生儿低血糖 2例 ;2 3例未用胰岛素孕妇的新生儿生后即刻血糖水平平均为 (4 2± 1 5 )mmol/L ,分娩后 2 4h的新生儿血糖水平为 (3 9± 1 0 )mmol/L ,发生新生儿低血糖 1例。结论　妊娠合并糖代谢异常孕妇 ,在产程中行血糖监测和控制 ,可避免新生儿低血糖的发生。     

Fetal hyperinsulinism and maternal one-hour postload plasma glucose level

OBJECTIVE: Fetal insulin concentrations reflect the intrauterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160-179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. RESULTS: Of the 930 patients who entered the study, 570 (61.3%) were assigned to group I, 76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL; range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 microU/mL; range, < 3-61 microU/mL). CONCLUSION: Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL.     

Insulin during pregnancy, labour and delivery

Optimal glycaemic control is of the utmost importance to achieve the best possible outcome of a pregnancy complicated by diabetes. This holds for pregnancies in women with preconceptional type 1 or type 2 diabetes as well as for pregnancies complicated by gestational diabetes. Glycaemic control is conventionally expressed in the HbA1c value but the HbA1c value does not completely capture the complexity of glycaemic control. The daily glucose profile measured by the patients themselves through measurements performed in capillary blood obtained by finger stick provides valuable information needed to adjust insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the woman with tight glycaemic control in the run-up to pregnancy. Repetitive hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with prevention of hypoglycaemia. A delicate balance should be struck between preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform across the day: it is low during the night with a more or less pronounced rise at dawn, followed by a gradual decrease during the remainder of the day. A basal amount of insulin is needed to regulate the endogenous glucose production, short-acting insulin shots are needed to handle exogenous glucose loads. Insulin therapy means two choices: the type of insulin used and the method of insulin administration. Regarding the type of insulin, the choice is between human and analogue insulins. The analogue short-acting insulin aspart has been shown to be safe during pregnancy in a randomised trial and has received registration for this indication; the short-acting analogue insulin lispro has been shown to be safe in observational studies. No such information is available on the long-acting insulin analogues detemir and glargine and both are prescribed off-label with human long-acting insulin as obvious alternatives. Randomised trials have not been able to show superiority of continuous subcutaneous insulin administration (CSII (insulin pump)) over intensive insulin injection therapy (multiple-dose insulin (MDI)) on any maternal or foeto-neonatal end point. However, group sizes were far too small to allow assessment of superiority and issues such as manageability of the disease and quality of life were never assessed. These two issues are of major importance to patients. The first trimester is often the period of most hypoglycaemic events, and insulin therapy should be especially closely monitored and adjusted in this period. After midterm, insulin requirements increase. Continuous glucose monitoring can offer better insights into the glycaemic profile than self-monitoring of blood glucose levels by the patients but the place of these new monitoring techniques has yet to be established more clearly. Insulin therapy during labour means short-acting insulin adjusted to achieve glucose levels between 4 and 8 mmol l(-1) to prevent neonatal hypoglycaemia as much as possible. After delivery, glycaemic control must be relaxed to prevent hypoglycaemia, especially in women who breastfeed.     

New technologies for the management of pregestational diabetes mellitus

Purpose of the Review: The purpose of this review is to understand new modalities available to treat and manage type 1 and type 2 diabetes during pregnancy. Recent Findings: The use of new insulin analogs and oral agents, as well as new technologies to deliver insulin and monitor glucose during pregnancy remains controversial. This review will outline the advantages and disadvantages, as well as the safety profiles of these new medications and therapeutic options. Summary: There are many effective treatments for diabetes during pregnancy. New insulin analogs seem to be safe to use in pregnancy and offer the potential for better glycemic control compared with older agents. Oral hypoglycemic medications also seem to be safe and may be an option for a select group of pregnant patients with type 2 diabetes. Insulin pumps and continuous glucose monitoring systems may be beneficial in certain patients, but adequate data are not yet available in terms of outcomes and cost-effectiveness to support widespread use. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this CME activity, physicians should be better able to revise glycemic goals for pregnant patients with pregestational diabetes to be in line with our current understanding of glycemic profiles in normal pregnant women. Use new insulin analogs to treat pregnant women with abnormalities in glucose homeostasis and choose which patients will benefit from advanced technologies for diabetes management, such as insulin pumps and continuous glucose monitoring systems.     

Clinical outcomes of pregnancy in women with type 1 diabetes(1)

OBJECTIVE:To evaluate predictors of neonatal hypoglycemia and macrosomia in 107 consecutive pregnancies in type 1 diabetic women. METHODS:We conducted a case record analysis of singleton type 1 diabetic pregnancies between January 1994 and January 1999 following institution of standardized management. RESULTS:The duration of diabetes in the women was 12.9 +/- 6.8 years, and 44 were primigravidas. The mean HbA1c throughout pregnancy was 7.2 +/- 0.8%. There was no relationship between neonatal blood glucose (checked before the second feed) and HbA1c at any point in pregnancy or mean pregnancy HbA1c (R = 0.20, P >.1). However, there was a negative correlation between neonatal blood glucose and maternal blood glucose during labor (R = -0.33, P <.001). When maternal blood glucose during labor was greater than 8 mM (144 mg/dL), neonatal blood glucose was usually less than 2.5 mM (mean 1.7 +/- 0.4 mM or 31 mg/dL). There was no relationship between mean HbA1c and birth weight (R = 0.02, P >.1) or between maximum insulin dose and birth weight (R = 0.09, P >.1). Fetal abdominal circumference measured by ultrasound at 34 weeks correlated strongly with birth weight (R = 0.72, P <.001). CONCLUSION:Neonatal hypoglycemia correlates with maternal hyperglycemia in labor, not with HbA1c during pregnancy. Macrosomia does not correlate with HbA1c during pregnancy.     

Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial

OBJECTIVE: This study was undertaken to compare preprandial and postprandial capillary glucose monitoring in pregnant women with type 1 diabetes. STUDY DESIGN: Sixty-one women with type 1 diabetes were randomly assigned at 16 weeks' gestation to preprandial or postprandial blood glucose monitoring using memory-based glucose reflectance meters throughout pregnancy. Serial measurements of hemoglobin A1c and fructosamine were obtained throughout pregnancy. Insulin, glucose, and insulin-like growth factor-I (IGF-I) were measured in cord blood at delivery. Neonatal anthropometric measures were performed within 72 hours of delivery RESULTS: Maternal age, parity, age of onset of diabetes, number of prior miscarriages, smoking status, social class, weight gain in pregnancy, and compliance with therapy were similar in the two groups. The postprandial monitoring group had a significantly reduced incidence of preeclampsia (3% vs 21%, P<.048), a greater success in achieving glycemic control targets (55% vs 30%, P<.001) and a smaller neonatal triceps skinfold thickness (4.5+/-0.9 vs 5.1+/-1.3, P=.05). CONCLUSION: Postprandial capillary blood glucose monitoring in type 1 diabetic pregnancy may significantly reduce the incidence of preeclampsia and neonatal triceps skinfold thickness compared with preprandial monitoring.     

Insulin resistance and β-cell function influence postprandial blood glucose levels in Japanese patients with gestational diabetes mellitus

Abstract

Aims/introduction: The aim of this study in patients with gestational diabetes mellitus (GDM) was to evaluate the relationship of insulin resistance and secretion to area-under-the-sensor glucose concentration–time curve from before to 120?min postmeal (CGM-AUC_0–120?min) as determined with continuous glucose monitoring (CGM).

Materials and methods: Immunoreactive insulin and HbA1c were determined in 22 Japanese patients with GDM undergoing a 75?g oral glucose tolerance test. Patients underwent CGM within 3 weeks of receiving a diagnosis of GDM.

Results: HbA1c (NGSP) was 5.5?±?0.4%, BMI was 24.8?±?5.3?kg/m², mean sensor glucose by CGM was 94.2?±?10.3?mg/dL, standard deviation was 17.5?±?4.4?mg/dL, and CGM-AUC_0–120?min was 204.2?±?23.8?h?mg/dL. The insulin resistance indices the homeostasis model assessment ratio (HOMA-R), quantitative insulin sensitivity check index (QUICKI), and the Matsuda Index were correlated with CGM-AUC_0–120?min. The disposition index (DI), which was used to evaluate insulin secretion, was negatively correlated with CGM-AUC_0–120?min.

Conclusions: Not only insulin resistance but also beta cell dysfunction contributes to postprandial hyperglycemia in Japanese patients with GDM.     

Correlation between amniotic fluid glucose concentration and amniotic fluid volume in pregnancy complicated by diabetes

OBJECTIVE: Pregnancies complicated by diabetes are frequently characterized by an increased volume of amniotic fluid, and the pathophysiologic mechanism of this increase is not known. Our goal was to evaluate the relationship between amniotic fluid glucose concentration and the amniotic fluid index in pregnancies complicated by insulin-treated diabetes and to compare it with that seen in normal pregnancies. STUDY DESIGN: Amniotic fluid index and amniotic fluid glucose levels were measured before elective repeated cesarean delivery in 41 women with insulin-treated diabetes and in 35 women without diabetes. Only singleton gestations without anomalous fetuses were included. Women with diabetes were hospitalized for approximately 4 weeks before delivery, during which time glycemic control was optimized. Amniotic fluid index and amniotic fluid glucose concentration were correlated with each other and were compared between the groups with and without diabetes. RESULTS: The mean amniotic fluid index was significantly increased in the diabetes group (16.6 +/- 5.0 cm in the diabetes group vs 13.4 +/- 3.5 cm in the control group; P =.002). The amniotic fluid glucose concentration was also significantly greater in the diabetes group than in the control group (39 +/- 17 mg/dL in the diabetes group vs 24 +/- 11 mg/dL in the control group; P <.001). Among women with diabetes the amniotic fluid glucose concentration was significantly correlated with the amniotic fluid index (r = 0.32; P =.04), a correlation not found among the control women. The mean fasting blood glucose concentration among the women with diabetes for the week before amniocentesis was 82 +/- 11 mg/dL. CONCLUSION: The amniotic fluid index parallels the amniotic fluid glucose level among women with diabetes. This finding raises the possibility that the hydramnios associated with diabetes is a result of increased amniotic fluid glucose concentration.     

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.     

Gestational diabetes and screening during pregnancy

The oral glucose tolerance test is an unreliable test in screening for diabetogenic fetal disease. In diabetogenic fetopathy due to gestational diabetes (White class A diabetes), the insulin content in the umbilical cord blood as well as in the fetal urine is considerably raised. As increased amounts of insulin pass into the amniotic fluid via the fetal urine, the fetal disease can be diagnosed from the amniotic fluid insulin content. In 75 pregnant women with potential diabetes, the blood sugar value was below 160 mg/dL at maximum under glucose loading in 28 patients; it was over 200 mg/dL in 25 patients. However, diabetogenic fetopathy was present in only 14 patients. The endangered and the healthy fetus could be distinguished in each case by amniotic fluid insulin content. The mean amniotic fluid insulin values in diabetogenic fetopathy were about seven times the normal.     

Can glucose tolerance test predict fetal hyperinsulinism?

Objective To establish cut off levels for oral glucose tolerance test in pregnancy using fetal hyperinsulinism as a clinical endpoint.
Design Capillary blood glucose levels at 0, 1, and 2 hours after the ingestion of either 1 g/kg or 75 g glucose, at 28 (SD 5) weeks of gestation were analysed in 220 women with elevated amniotic fluid insulin levels [≥ 42 pmol/L (≥ 7 μU/mL)] after a mean (SD) of 31 weeks (3) and in 220 nondiabetic controls.
Results In women with elevated amniotic fluid insulin levels the mean (SD) capillary blood glucose values at 0, 1, and 2 hours were 5.2 mmol/L (1.0) [94 mg/dL (18)], 10.5 mmol/L (1.4) [189 mg/dL (25)] and 8.2 mmol/L (2.0) [147 mg/dL (36)], respectively. The one-hour value had the highest sensitivity to predict elevated amniotic fluid insulin levels. The 5th centile of the one-hour blood glucose levels representing a detection rate of 95% was 8.9 mmol/L (160 mg/dL).
Conclusion Glucose cut off levels in most established oral glucose tolerance test criteria are too high, to accurately predict amniotic fluid hyperinsulinism. A one-hour test may be sufficient for detecting amniotic fluid hyperinsulinism. Since different loads (1 g/kg, 75 g or 100 g) and blood fractions (venous plasma or capillary blood) have minimal impact on oral glucose tolerance test results, a single one-hour cut off of 8.9 mmol/L (160 mg/dL), independent of the sampling method, may be appropriate for the diagnosis of gestational diabetes mellitus severe enough to cause amniotic fluid hyperinsulinism.