Diabetes in pregnancy: evaluating self-monitoring performance and glycemic control with memory-based reflectance meters

Reflectance meters modified by the addition of a memory microchip that stored glucose values were used to measure the difference between self-reported and actual blood glucose data in 34 pregnant diabetic women. Overall two thirds of the patients reported values that were significantly lower and less variable than those recorded in the memory meters.     

Capillary blood glucose screening for gestational diabetes: a preliminary investigation

Home glucose monitoring with the use of reflectance meters is an important adjunct in the care of pregnant women with insulin-dependent diabetes. The accuracy of reflectance meters for the assay of capillary glucose specimens has been well documented. The present preliminary study was undertaken to determine the utility of outpatient screening for gestational diabetes mellitus with the use of a reflectance meter (Accu-Chek, Boehringer Mannheim Co.). One hundred twenty-five patients in our high-risk practice had a standard 50 gm glucose load at 26 to 28 weeks' gestation. Capillary glucose values were measured on site with the Accu-Chek. Venous plasma glucose levels were measured by the central laboratory chemistry analyzer. While the laboratory (x) and meter (y) glucose determinations between the two sets of values were highly correlated (R = 0.89, p less than 0.001), there was a significant difference in their average values (x = 111.74, y = 136.35, p less than 0.0001). With the use of a receiver operator characteristic curve, a meter value of 160 mg/dl was determined as the optimal threshold for performing a 3-hour glucose tolerance test. The sensitivity and specificity with the use of a meter value of 160 mg/dl were 93% and 96%, respectively, for detecting an abnormal screening test in venous plasma (greater than or equal to 135 mg/dl). A total of 32 glucose tolerance tests were performed, with four patients included who had venous values less than 135 mg/dl. All eight patients with gestational diabetes mellitus were correctly identified. These data suggest that a glucose reflectance meter can be used for accurate outpatient screening of gestational diabetes mellitus. The potential advantages of capillary blood glucose screening include both cost and efficiency. Patients with abnormal screening values can be promptly identified and scheduled for a follow-up 3-hour glucose tolerance test.     

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.     

Neonatal morbidity in pregnancy complicated by diabetes mellitus: predictive value of maternal glycemic profiles

The relationship between glycemic control and perinatal outcome was assessed in a relatively uniform population of 75 White Class B through D pregnant diabetic women. All patients used glucose reflectance meter self-monitoring and performed a minimum of four determinations daily. Mean capillary blood glucose was calculated from a minimum of 16 weeks of determinations. Regression analysis confirmed a correlation between these values and third-trimester hemoglobin A1 (p less than 0.001). The study population was divided into two groups on the basis of mean capillary blood glucose values: group I, mean capillary blood glucose less than 110 mg/dl (43 patients) (mean = 96.8 +/- 7.1); group II, mean capillary blood glucose greater than 110 mg/dl (32 patients) (mean = 126 +/- 9.0). Of the 32 patients in group II, eight had mean capillary blood glucose greater than or equal to 130 mg/dl. The degree of maternal glycemic control appeared to affect perinatal outcome. At least one form of infant morbidity was present in 33% of group I infants compared with 53% of group II. Significant differences were observed for the incidence of hypoglycemia (p less than 0.05), macrosomia (p less than 0.05), and respiratory distress syndrome (p less than 0.01). One of six group I infants delivered at 35 to 36 weeks developed respiratory distress syndrome, compared with four of seven group II patients. The appearance of phosphatidylglycerol in amniotic fluid appeared delayed in group II patients at term. These data suggest that maintaining mean capillary blood glucose values less than 110 mg/dl may serve to reduce several major forms of morbidity in the infant of the diabetic mother. This information is helpful in establishing objectives for glycemic control in pregnant women using self-monitoring techniques.     

Insulin pump therapy for pregnancy: a primer

Current knowledge and advances in insulin formulations, insulin pump technology, and blood glucose monitoring techniques have improved practitioners’ ability to achieve diabetic people’s blood glucose targets. Practitioners and pregnant women should bear in mind that important differences exist in glucose metabolism during pregnancy and require a different approach from non-pregnant people to avoid pregnant women’s experience being adversely affected. Insulin pump therapy, if used skillfully by practitioners and their pregnant patients, can be especially beneficial for some diabetic women during their pregnancies. Women’s healthcare practitioners should endeavor to be familiar with this therapy, even if they are not experts in its full complexity.     

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women.

OBJECTIVE: To evaluate the mechanism of oxidative stress at glucose levels accompanying diabetic pregnancy. Specifically, we hypothesize that elevated glucose overwhelms hexose monophosphate shunt (HMS) down-regulation observed during pregnancy. METHODS: Peripheral blood cells from normal healthy pregnant women were exposed to heightened glucose levels to provide an in vitro model of the effects of diabetic pregnancy. Changes in NAD(P)H, reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated in single cells. RESULTS: Altered metabolic dynamics, as judged by NAD(P)H autofluorescence of neutrophils from both pregnant and non-pregnant women, were observed during incubation with 14 mM glucose, a pathophysiologic level. In parallel, increased production of ROS and NO was observed. The ROS and NO levels attained in cells from pregnant women were greater than those observed in cells from non-pregnant women. Inhibitors of the HMS and NAD(P)H oxidase blocked these effects. These metabolic and oxidant changes required approximately one minute, suggesting that transient glucose spikes during pregnancy could trigger this response. CONCLUSIONS: Elevated glucose levels enhance HMS activity and oxidant production in cells from pregnant women. This mechanism may be generally applicable in understanding the role of diabetes in materno-fetal health.     

Serum immunoglobulins in diabetic and healthy pregnant patients and their newborn infants

The immunoglobulin G, A, and M levels in maternal serum sampled at delivery and in umbilical cord serum of diabetic and normal pregnant women and their newborns had been estimated and compared. The aim of the diabetic control was to achieve normoglycemic blood glucose levels during pregnancy. IgG and IgM of diabetics were significantly lower, IgA levels were comparable to normal pregnant women. Excluding the 39th week gestation however both series of newborns divided in groups of same gestational age had comparable immunoglobulin levels. The data are discussed with those of other authors. According to these results immunological host defense due to placental IgG transport and fetal production of IgA and IgM in infants of well-controlled pregnant diabetics can be considered to be comparable to those of normal pregnant women.     

Effect of maternal hyperketonemia in hyperglycemic pregnant ewes and their fetuses

The fetus of the pregnant diabetic woman is exposed to hyperglycemia frequently accompanied by ketoacidosis. Previous studies have demonstrated that beta-hydroxybutyrate, a major ketone body, crosses the ovine placenta in significant amounts, leading to significant reductions in fetal PaO2 and increased fetal heart rate. In the present study the pregnant ewe was used to evaluate the maternal and fetal cardiovascular and metabolic responses to hyperketonemia in the presence of hyperglycemia and to determine if the combined diabetic insults were more detrimental to the fetus than hyperketonemia alone. A glucose priming dose of 25 gm was administered in the maternal femoral vein followed by a continuous glucose infusion of 200 mg/min to achieve steady maternal plasma glucose levels of 180 mg/dl. Once glucose levels were stable, beta-hydroxybutyrate was infused for 2 hours at a rate of 0.39 mmol/100 ml of uterine blood flow into both left and right uterine arteries. Infusion of glucose alone did not significantly alter fetal cardiovascular and blood gas parameters but did increase the fetal glucose level from 17 +/- 4 to 58 +/- 8 mg/dl. The simultaneous infusion of beta-hydroxybutyrate and glucose produced significant decreases in fetal PaO2 and oxygen content as were reported for hyperketonemia alone and significant time-related increases in fetal lactate levels and fetal heart rate. These data suggest that hyperketonemia in the pregnant ewe leads to quantitatively similar changes in oxygenation in both normoglycemic and hyperglycemic fetuses. These observations may in part help explain the increased perinatal mortality in the pregnant woman with uncontrolled diabetes.     

Management of diabetic pregnancies in the United Kingdom.

The aim of this postal questionnaire survey was to identify facilities currently available for the care of pregnant diabetic women in the United Kingdom and determine how closely these reflect the standards recommended by The St Vincent Declaration Action Programme. A questionnaire was sent to a physician and an obstetrician in each of the 255 obstetric hospitals in the UK. Two hundred and forty-five (96.1%) hospitals replied, with most of these managing 20 or less insulin dependent diabetics per year. Of the hospitals, 58.4%, had a special combined diabetic antenatal clinic; 86.6% of the units had a single physician responsible for diabetic care, whilst more than one obstetrician was involved in 50.6% of the units. Prepregnancy counselling was provided in 87.4% of the hospitals. Home blood glucose monitoring was used in 97.9% of the units. Ideal mean pre- and postprandial blood glucose concentrations were 6.0 mmol/1 (SD 0.82) and 7.9 mmol/l (SD 0.91), respectively. Ultrasound was routinely used to assess fetal growth in 98.7% of the units. The mean gestational age for elective caesarean section was 38.2 weeks (SD 0.55), compared with 39.0 weeks (SD 0.35) for planned vaginal delivery. During labour, 98% of the units used a dextrose and insulin infusion, but only 53.7% of the units maintained an intrapartum maternal blood glucose of between 4 and 6 mmol/l. We conclude that there is widespread variation in the management of the pregnant diabetic patient, and much practice is suboptimal. Many of the recommendations of the St Vincent Declaration are not being met by current UK practice.     

The relationship between large-for-gestational-age infants and glycemic control in women with gestational diabetes

In this prospective study 246 women with gestational diabetes were followed up to determine the characteristics of metabolic control associated with large-for-gestational-age infants. Memory-based reflectance meters were used for self-monitoring blood glucose. Ambulatory glucose profiles were produced to characterize glycemic control levels throughout pregnancy. With these novel approaches to the collection and representation of glucose data, the severity of glucose intolerance (hyperglycemia) was found to be associated with both maternal and neonatal morbidity in terms of infant size and cesarean section rate. By use of hierarchical cluster analysis to identify three groups on the basis of control levels (low less than 87 mg/dl, mid 87 to 105 mg/dl, high greater than 105 mg/dl) we were able to show a positive outcome in the low group with reduced rates of large-for-gestational-age (2%) and macrosomatic (0%) infants. Furthermore, we showed that as mean blood glucose levels and instability in glycemic control increased from group to group, incidence of large-for-gestational-age and macrosomatic infants increased. Whereas obesity increased the relative risk of adverse neonatal outcome, type of treatment (insulin versus diet) did not appear to be significant. Appropriately monitored toward stability within a narrow range to achieve tight metabolic control, ambulatory glycemia in pregnancy is associated with a decreased risk of maternal and fetal complications.     

Decreased bone mineral content in infants of diabetic mothers

The present study was conducted to test the hypothesis that infants of diabetic mothers (IDMs) have decreased bone mineral content at birth, and whether or not decreased infant bone mineral content in IDMs correlates with poor control of diabetes during pregnancy, maternal bone mineral content, and the development of neonatal hypocalcemia. Forty-five pregnant diabetic women and their infants were enrolled in a prospective trial. In addition, 55 normal newborn infants of nondiabetic mothers were used as controls. Bone mineral content was measured before delivery in all diabetic pregnant patients and at birth in all infants by photon absorptiometry. Bone mineral content was significantly decreased in infants of diabetic mothers compared with control infants and correlated inversely with mean first trimester maternal capillary blood glucose; it did not correlate with cord serum 1,25-dihydroxyvitamin D concentrations. By stepwise multiple regression analysis, in infants of diabetic mothers, bone mineral content correlated inversely with mean first trimester capillary blood glucose and maternal bone mineral content, but did not correlate with maternal blood glycosylated hemoglobin, infant gestational age, infant birthweight or weight percentile, or development of neonatal hypocalcemia.     

Peripheral blood neutrophils reactive oxygen intermediates (ROI) production in early pregnancy complicated by diabetes mellitus type I

The components of maternal innate immune system are activated in pregnancy. Increased number of circulating neutrophils and monocytes, reactive oxygen intermediate production (ROI), increased expression of the adhesion molecules can be observed. The activation status and neutrophils response to stimulators in pregnant diabetic women's comprise, to some extend, both situations pregnancy and diabetes, combined effect of both seems to be very intriguing. AIM OF STUDY: Evaluation production of ROI on peripheral blood neutrophils in early pregnancy of diabetic mothers. MATERIAL: 12 pregnant diabetic women demonstrating good glycemic control and without major complications before pregnancy were studied at 8-12 weeks of first gestation, 11 healthy pregnant women match for weeks of gestation, age and parity; 11 healthy non-diabetic women; 13 diabetic, non-pregnant women, were also studied. METHODS: ROI production was evaluated with chemiluminescence method using standard stimuli fMLP, PMA, OZ and also after 15 min. priming with TNF-alpha. We used MLX Microtiter Plate Luminometr DYNEX, USA. with computer program Revelation 97. For statistic analysis Fisher, Kolmogorow-Smirnow and Wilcoxon tests were used (p < 0.05). RESULTS: 1. Peripheral blood neutrophils of healthy pregnant, diabetic and pregnant diabetic women independently from the stimuli used showed an increase in ROI production 2. Peripheral blood neutrophils change their activity, evaluate by ROI production during pregnancy, diabetes and pregnancy complicated by diabetes. 3. Peripheral blood neutrophils of pregnant diabetes women do not show expected impairment of their function. CONCLUSIONS: Diabetes type 1 with good glycemic control and pregnancy, change the production of ROI by peripheral blood neutrophils but these events do not sum up in diabetic pregnancies.     

Assessment of self monitoring of blood glucose (SMBG) and continuous subcutaneous insulin infusion (CSII) in diabetic pregnant women

We instructed pregnant women with insulin dependent diabetes mellitus (IDDM) or noninsulin dependent diabetes mellitus (NIDDM) how to monitor their own blood glucose concentrations and evaluated the efficiency and feasibility of continuous subcutaneous insulin infusion (CSII) therapy. Self-monitored glucose concentrations with a reflectance meter correlated with those of hospital laboratory measurements (hexokinase method) with a coefficient of more than 0.9. Glycosylated hemoglobin (HbA1) levels of the patients were normalized with insulin treatment based on the self-monitored glucose concentrations. In pregnant women with NIDDM who monitored their blood glucose concentrations before breakfast, the fasting glucose concentrations could be lowered by insulin administration and the duration of hospitalization could be shortened compared to non-monitored patients. Although diurnal variations were prominent in pregnant women with IDDM and precise control of their blood glucose concentrations was difficult with conventional insulin administration, even if the patients had monitored their glucose concentrations 7 times a day, the mean glucose concentrations and M values could be kept in the optimum range in patients treated with CSII. These methods have contributed to the improvement in maternal and infant complications.     

Self-monitoring of blood glucose in pregnant diabetics. A comparative study of the blood glucose level and course of pregnancy in pregnant diabetics on an out-patient regime before and after the introduction of methods for home analysis of blood glucose

Sixty-one pregnant patients with insulin-dependent diabetes mellitus completed a self-monitoring program consisting of five daily blood glucose tests at least twice weekly during the ambulatory periods of their pregnancies. Either a reflectometer method, Eyetone, glucometer--reflectometer, or Haemoglucotest 1-44 test strips were used. Of 1 834 glucose profiles, 45% were optimal, with all blood glucose values between 3.9 and 8.3 mmol/l. The 61 pregnancies were compared with 62 pregnancies where the diabetic control and therapy principles were identical, but where self-monitoring blood glucose methods were not employed. The self-monitoring regime resulted in a significant drop in mean blood glucose levels, from 7.8 +/- 1.3 to 6.4 +/- 1.0 mmol/l, compared with the period before the self-monitoring program was introduced. Furthermore, a decline in the number of diabetes-conditioned extra hospitalizations during pregnancy in the self-test group could be registered.     

Perinatal outcome of pregnancies complicated by diabetes and by maternal daily hyperglycemia not related to diabetes. A retrospective 10-year analysis

We analyzed the perinatal outcome of 1,086 pregnancies classified according to the response to the 3-hour 100-gram glucose tolerance test and the diurnal glycemic profile into the Rudge groups corresponding to control pregnant women, class A gestational diabetic women, class A/B to FRH pregnant women and women with daily hyperglycemia. Despite treatment, the diabetic pregnant women and those with daily hyperglycemia presented higher mean blood glucose levels compared to controls (76.6+/-10.2 mg/dl). The pregnancies complicated by diabetes and by daily hyperglycemia were characterized by a high incidence of prematurity, macrosomia, large for gestational age newborn infants, malformation and fetal and neonatal death, with consequent perinatal mortality. The perinatal mortality of women with daily hyperglycemia was 10 times higher than that of the controls and was similar to that of the diabetic patients. These adverse perinatal results emphasize the need for the diagnosis and control of intrauterine hyperglycemia both in diabetic pregnant women and in women with an altered diurnal glycemic profile.     

Comparison of capillary and plasma glucose values in screening and oral glucose tolerance testing in pregnancy

The substitution of capillary reflectance meter glucose values for plasma or serum glucose values would be practical and cost saving. A direct comparison was performed of simultaneous capillary reflectance meter and plasma glucose values in routine screening and oral glucose tolerance testing in a pregnant population. The use of capillary glucose in 50-g glucola screening had a sensitivity of 82.6% and specificity of 98.1% as compared to the standard plasma method. Even though our data demonstrate a good correlation (r = 0.897) between capillary and plasma glucose values, our results do not support the direct substitution of plasma glucose values with capillary reflectance meter glucose values in screening for or diagnosing glucose intolerance in an obstetric population.     

Perinatal significance of diagnosing glucose intolerance during pregnancy with portable glucose meter

OBJECTIVE: To evaluate the effect on perinatal outcome of replacing glucose measurements for the diagnosis of gestational diabetes mellitus in central laboratories with those obtained by portable glucose meter. STUDY DESIGN: Simultaneously, venous blood samples were taken at the 100-g glucose tolerance test, and finger capillary blood glucose levels were also measured with a portable glucose meter in 180 pregnant patients. Patient management was according to the venous plasma glucose results. Following deliveries, the women were reallocated to diagnostic groups by both methods of measurements and by using the same cutoff values, and the outcome data were compared. RESULTS: By using glucose values obtained by portable glucose meters instead of the results attained in the central laboratory, more women were diagnosed with gestational diabetes (33 vs 25) and the perinatal outcome was comparable. CONCLUSIONS: Obstetricians have to identify glucose intolerance during pregnancy in order to prevent macrosomia and its perinatal complications. These goals can be achieved with at least the same efficacy by performing the 100-g glucose tolerance test with a portable glucose meter as with current laboratory methods. Such an approach is time and resource saving and more convenient for both patients and health providers.     

Placental lactogen,progesterone, total estriol and prolactin plasma levels in pregnant women with insulin-dependent diabetes mellitus

Fifteen insulin-dependent diabetic (White's class B-C) and 10 healthy pregnant women were examined from the 12th to the 36th wk. Every 4 wk, a blood sample was drawn to determine total estriol, progesterone, placental lactogen and prolactin.Throughout the pregnancy, total estriol and progesterone in diabetic and non-diabetic women are very similar. On the contrary, the PRL levels are constantly lower in diabetic pregnant women, even though the difference is statistically significant only for the 24th wk determination. The hPL level is instead significantly lower in diabetic pregnant women at the 12th, 20th, 24th, 32nd and 36th wk. A negative correlation exists between the hPL value and the mean blood glucose level, performed the same day as the hormonal test. This correlation is statistically significant at the 12th, 16th, 20th, 28th and 36th wk. No significant difference is found between the two groups examined for the delivery week, the placental weight, the birth weight and the fetal body weight index.To conclude, while estriol and progesterone are not affected by the higher variability of glucose levels during pregnancy in diabetics, compared to normals, hPL and perhaps also PRL may be influenced by the mild hyperglycemia consequent to diabetes.     

Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects

Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these cases require insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of less than 2.6 mmol/L. These results suggest that when both the oral glucose tolerance test and fructosamine level are used, only 30% of women with gestational diabetes need to undergo amniocentesis to assess fetal insulin homeostasis.     

Antenatal nonstress test in complicated and uncomplicated pregnancies in type-1-diabetic women

111 pregnant women with type-1 diabetes were cared for at the Karolinska Hospital from 1979 to 1986. As routine fetal monitoring, a non-stress test (NST) was performed twice weekly from the 35th or 36th week of gestation to delivery. If pregnancy complications occurred, an NST was still used for fetal monitoring, but more frequently. The median gestational age at delivery was 270 days. The mean maternal blood glucose during the third trimester was 6.0 mmol/l. In 88 of the totally 111 women the only indication for an NST was the patient's diabetes. In this routinely monitored group, 2/88 patients had abnormal NSTs and cesarean sections were performed. The neonatal outcome was good in both cases. Twenty-three had such complications as pre-eclampsia or IUGR, and in these cases the frequency of an NST was individualized. Four of these 23 had abnormal NSTs leading to cesarean sections. There were no signs of asphyxia among these four infants. Thus, in diabetic pregnancies with a well-regulated blood glucose, intervention due to abnormal fetal monitoring is more associated with acute pregnancy complications than the diabetes per se. The results of this study suggest that antenatal NSTs twice a week from week 35-36 is sufficient in well blood-glucose regulated type-1-diabetic women with a well-regulated blood glucose. If pregnancy complications occur, the NST, in an individualized frequency, seems to be a safe way of fetal monitoring.