الفهرس 
DIABETES MELLITUSOnly 14 pages are availabe for public view
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Abstract
The use of oral antidiabetic drugs to control diabetes with pregnancy was controversial. Some studies suggest a possible link between the use of oral antidiabetics and fetal anomalies, fetal macrosomia and neonatal hypoglycemia whereas others have demonstrated no such relationship.
Glibenclamide dose not cross the human placenta from the maternal to the fetal circulation in significant amount, and recent studies have shown that glibenclamide is transferred from the fetal to maternal circulation against its concentration gradient. So, the question of its safety from the standpoint of the fetus is greatly diminished and its use in the management of GDM becomes a possibility.
Studies have suggested the potential safety of this drug in pregnancy and its ability to maintain adequate glycemic control in pregnancy. In the present study, the aim was to evaluate the effectiveness of glibenclamide in patients with GDM during pregnancy who failed to achieve adequate glucose control on diet therapy alone.
The present study included 30 pregnant women who have been diagnosed as gestational diabetics at 15 - 33 weeks gestation with singleton pregnancy. They had FBG level ranging from 95-130 mg / dl or 2 hours postprandial blood glucose level ranging from 120-180 mg / dl. The exclusion criteria included pregnant women with preexisting DM and underlying diseases known to affect fetal growth or drug clearance.
All patients were followed up during their antenatal visits in the specialized outpatient Diabetic Clinic of Ain Shams University Maternity Hospital every week. The HbA1c was measured before the initiation of therapy and late in the third trimester. During each visit, fasting and 2-hPP blood glucose levels were assessed for every patient and fructosamine level was assessed every two weeks. Glibenclamide was started at an oral dose of 2.5 mg daily in the morning and the dose was titrated up to total of 20 mg /day. According to their response to the treatment, women treated with glibenclamide were divided into two groups: success group in which patients succeeded to achieve satisfactory glucose control for the remainder of the pregnancy (FBG: 60-90 mg/dl & 2-hPP: less than 120 mg/dl) and failure group in which patients failed to achieve satisfactory glucose control on maximum dose of glibenclamide for two weeks.
Comparison of the baseline characteristics was performed between both groups and it was found that women in the failure group had older age, higher BMI, earlier gestational age at the start of treatment and positive family history of DM more than those in the success group. These differences were of statistical significance.
Additionally, it was noticed that women in the failure group had findings suggesting increased glucose intolerance than the success group. They had significant higher mean fasting and 2- hPP blood glucose levels than women in the success group either before or during treatment with glibenclamide. Furthermore, fructosamine level in the failure group was significantly higher than its level in the success group during treatment.
Analysis of the results revealed that glibenclamide was an effective medication for control of blood glucose in women with GDM who failed to achieve euglycemia with diet. Although there was significant decrease of the mean fasting, postprandial blood glucose and glycosylated hemoglobin levels during treatment with glibenclamide than before in all patients, approximately 80% of them achieved the desired range of blood glucose control. Of those who responded to medication, more than 90% were controlled with daily doses 7.5 mg or less.
Because it can take several weeks for patients to fail while their doses are being adjusted, one could be concerned that these pregnancies would be at increased risk for adverse pregnancy outcomes because of exposure to longer periods of hyperglycemia. Nevertheless, the findings suggest that glibenclamide failure is not associated with increased risk of adverse pregnancy outcomes where the maternal and neonatal outcomes show no significant differences between both groups and this compare favorably with many studies.
To identify the most sensitive predictors of glibenclamide failure, different parameters were included in the stepwise logistic multi-regression analysis. It was found that glibenclamide was more likely to fail in women started treatment earlier in pregnancy (less than 27 weeks), and those requiring dose > 7.5 mg/day.
The time for glibenclamide as an alternative treatment has come; however, it should be prescribed after careful consideration of these patient characteristics to minimize the likehood of failure.