Hypoglycemia in glyburide-treated gestational diabetes: is it dose-dependent?
OBJECTIVE
To estimate whether there is a relationship between glyburide dose and the rate of hypoglycemic episodes in women with gestational diabetes mellitus (GDM).


METHODS
We studied 674 women with GDM who were treated with glyburide and diagnosed from 2000 to 2009. Glucose data were downloaded from memory-based meters at each visit and analyzed to estimate the incidence of recorded episodes of hypoglycemia and the association with concurrent dose of glyburide therapy (2.5, 5, 10, 15, or 20 mg). Hypoglycemia was defined as a blood glucose of less than 50 mg/dL, further classified as "severe hypoglycemia" if the event required the assistance of another person for resuscitation, "symptomatic hypoglycemia" if it was associated with typical neurogenic symptoms, or "asymptomatic hypoglycemia" if the biochemical reading was less than 50 mg/dL with no symptoms or accompanied by mild symptoms that did not impair the patient's ability to function.


RESULTS
Patients recorded a mean of 272 glucose values. Sixty-seven percent of the patients experienced no blood glucose values in the hypoglycemic range. 33% had 1-7% of their total blood glucose values within the hypoglycemic range. All recordings of hypoglycemic episodes were asymptomatic; no patient reported a severe or symptomatic hypoglycemic episode. A significant association was found between the incidence of asymptomatic hypoglycemia and mean blood glucose (P<.001). No association was found between glyburide dose and incidence of asymptomatic hypoglycemia. No association between glyburide dose or mean blood glucose value and the incidence of neonatal hypoglycemia was found.


CONCLUSIONS
Incremental increases in glyburide dose are not associated with an increase in the incidence of hypoglycemic episodes.


METHODS
II.
From the Department of Obstetrics and Gynecology, St. Luke's Roosevelt Hospital Center, New York, New York.
Lois
L
Brustman
Oded
O
Langer
Sophia
S
Scarpelli
Manal
M
El Daouk
Anna
A
Fuchs
Barak
B
Rosenn
D000328:Adult; D016640:Diabetes, Gestational / Q000188:drug therapy*; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D011247:Pregnancy; D012189:Retrospective Studies
D007004:Hypoglycemic Agents; D005905:Glyburide
Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003;102:857–68.
Saade G. Gestational diabetes mellitus: a pill or a shot? Obstet Gynecol 2005;105:456–7.
Greene MF. Oral Hypoglycemic drugs for gestational diabetes. N Engl J Med 2000;343:1178–9.
Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 2007;30(suppl 2):S251–60.
Kremer CJ, Duff P. Glyburide for the treatment of gestational diabetes. Am J Obstet Gynecol 2004;190:1438–9.
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes. N Engl J Med 2000;343:1134–8.
Brunton LB, Lazo JS, Parker KL, editors. Goodman & Gilman's The pharmacological basis of therapeutics. 11th ed. New York (NY): McGraw-Hill; 2005.
Carpenter MW, Coustan DR. Criteria for screening tests of gestational diabetes. Am J Obstet Gynecol 1982;144:763–8.
Langer O, Brustman L, Anyaegbunam A, Mazze R. The significance of one abnormal glucose tolerance test value on adverse outcome in pregnancy. Am J Obstet Gynecol 1987;157:758–63.
Langer O, Anyaegbunam A, Brustman L, Divon M. Management of women with one abnormal oral glucose tolerance test value reduces adverse outcome in pregnancy. Am J Obstet Gynecol 1989;161:593–9.
Langer O, Yogev Y, Xenakis EM, Rosenn B. Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. Am J Obstet Gynecol 2005;192:134–9.
Langer O, Berkus M, Brustman L, Anyaegbunam A, Mazze R. Rationale for insulin management in gestational diabetes mellitus. Diabetes 1991;40(suppl 2):186–90.
American Diabetes Association Workgroup on Hypoglycemia. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005;28(5):1245–9.
Yogev Y, Ben-Haroush A, Chen R, Rosenn B, Hod M, Langer O. Undiagnosed asymptomatic hypoglycemia: diet, insulin, and glyburide for gestational diabetic pregnancy. Obstet Gynecol 2004;104:88–93.
Freinkel N, Metzger BE, Nitzan M, Hare JW, Shambaugh GE 3rd, Marshall RT, et al. “Accelerated starvation” and mechanisms for the conservation of maternal nitrogen during pregnancy. Israel J Med Sci 1972;8:426–39.
Hebert MF, Ma X, Naraharisetti SB, Krudys KM, Umans JG, Hankins GD, et al. Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.Clin Pharmacol Ther 2009;85:607–14.