The management of gestational diabetes

Figures & data

Table 1 Diagnostic criteria for GDM

	Glucose load	Glucose tolerance test (mmol/L)				Abnormal values for diagnosis
		Fasting	1 hour	2 hours	3 hours
ADA	75 g	5.3	10	8.6		Two or more
	100 g	5.3	10	8.6	7.8	Two or more
ADIPS	75 g	5.5		8.0		One
CDA	75 g	5.3	10.6	8.9		Two or more = GDM
						One value = IGT of pregnancy
WHO	75 g	7.0		11.1		One

Abbreviations: ADA, American Diabetes Association; ADIPS, Australasian Diabetes in Pregnancy Society; CDA, Canadian Diabetes Association; GDM, gestational diabetes mellitus; WHO, World Health Organisation.

Table 2 Recommended glucose targets

	Fasting	1 hr postprandial	2 hr postprandial
ADA	5.8	8.6	7.2
ADIPS	5.5	8.0	7.0
CDA	5.3	7.8	6.7

Abbreviations: ADA, American Diabetes Association; ADIPS, Australasian Diabetes in Pregnancy Society; CDA, Canadian Diabetes Association.

Table 3 Randomized trials comparing treatment of GDM with rapid acting insulin analogs and regular human insulin

Author, year	Subjects			Effect on HbA1c	Effect on hypos	Other comments
	Lispro	Aspart	Regular
Jovanovic et al 1999^Citation50	19	–	23	Lower 3rd trimester HbA1c with Lispro	Fewer hypos with lispro	Less 1 hr postprandial hyperglycemia with lispro
Mecacci et al 2003^Citation51	25	–	24	Not reported	Not reported	1 hr postprandial glucose higher with regular insulin
Pettitt et al 2007^Citation45	–	14	13	No difference	More minor, but not major hypos with aspart	Post-prandial glucose profile and maternal c-peptide lower with aspart
Di Cianni et al 2007^Citation52	33	31	32	No difference	No subjects had hypos	1 hr postprandial glucose and birthweight higher in regular insulin subjects

Abbreviation: Hb_A1c, glycated hemoglobin.

Table 4 Published studies of glyburide treatment for GDM

Author, year	Subjects on glyburide	Subjects on insulin	Nature of study	Effectiveness of glyburide compared to insulin	Safety of glyburide for neonate		Safety of glyburide for the mother	Failure of glyburide to achieve glycemic control
					Serious complications	Neonatal Hypoglycemia
Langer et al 2000^Citation57	201	203	RCT	No difference in glycemic control, macrosomia, or neonatal complications	No difference in fetal anomalies (2% in each group) or perinatal mortality (1% in each group)	No difference between groups (9% vs 6%, p = 0.25)	Glyburide less likely to result in maternal hypoglycemia (2% vs 20%, p = 0.03)	4%
Conway et al 2004^Citation58	75	–	Retrospective cohort	N/A	Not reported	Not reported	Not reported	16%
Kremer and Duff 2004^Citation59	73	–	Prospective cohort	19% required cesarean section vs 14%–17% in general obstetric population	Nil	Not reported	12% noticed side effects	19%
Chmait et al 2004^Citation60	69	–	Prospective cohort	N/A	1 achondroplasia and 1 intrauterine death attributed to knot in umbilical cord	2%	Not reported	18.8%
Bertini et al 2005a,^Citation61	24	27	RCT	Glycemic control not reported. 25% large for gestational age in Glyburide group, vs 4% in insulin group (p = 0.07)	Nil	33% in glyburide group, 4% in insulin group.	No maternal hypoglycemia	21%
Jacobson et al 2005^Citation62	236	268	Retrospective cohort	More women on glyburide achieved glycemic goals (86% vs 63%, p < 0.001). No difference in birth-weight, cesarean section, macrosomia	No difference in fetal anomalies (2% in each group). 3% in glyburide group had birth injuries (fractures and brachial plexus injury) compared to 1% in insulin group, p = 0.08)	No difference between groups (31% vs 27%, p = 0.42)	Glyburide higher incidence of pre-eclampsia (12% vs 6%, p = 0.02)	12%
Rochon et al 2006^Citation63	101	–	Retrospective cohort	N/A	9% shoulder dystocia	Not reported	Not reported	21%
Ramos et al 2007b,^Citation64	44	78	Retrospective cohort	No difference in birthweight, cesarean section, pre-eclampsia, prematurity, hyperbilirubinemia. Glyburide more macrosomia after adjustment for confounders (RR 3.5, (1.1–11.4)	Glyburide more congenital anomalies (9% vs 0%, p = 0.02)	Glyburide: more neonatal hypoglycemia (34% vs 14%, p = 0.01)	No problems reported	16%

Notes: ^aThis study included a 3rd arm of subjects randomized to receive Acarbose;

^b Subjects in the study of Ramos and colleagues were a subset of those in Jacobsen and colleagues, who had a 50 g glucose challenge test result ≥11.1 mmol/L and a fasting plasma glucose ≥5.8 mmol/L.

Abbreviation: GDM, gestational diabetes mellitus.

Table 5 Published studies of metformin therapy for gestational diabetes

Author, year	Subjects on metformin	Subjects on insulin	Nature of study	Effectiveness of metformin compared to insulin	Safety of metformin to the neonate		Safety of metformin for the mother	Inadequate glycemic control with metformin alone
					Major complications	Neonatal hypoglycemia
Hellmuth et al 2000a,^Citation68	50	42	Retrospective cohort	No comparison of glycemic control. Birthweight similar Increased pre-eclampsia	8% stillbirth compared to 2.3% with insulin (p = 0.042). 11.6% perinatal mortality compared to 1.3% with insulin or sulphonylurea (p < 0.02)	26% in metformin group, 33% insulin group	–	–
Moore et al 2007^Citation73	32	31	RCT	No difference in glycemic control, cesarean section, birthweight	1 shoulder dystocia and 1 stillbirth in metformin group attributed to other causes	No difference compared to insulin	–	0%
Rowan et al 2008^Citation72	363	378	RCT	No difference in primary composite outcome of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, Apgar score less than 7, or prematurity	One fetal death in insulin group. 11 congenital anomalies in metformin group compared to 18 in insulin group.	3.3% in metformin group had BGL < 1.6 mmol/L compared to 8.1% in insulin group (p = 0.008)	10.7% significant GI side-effects	46.3%
Tertti et al 2008^Citation74	45	45	Retrospective case control	No difference in birthweight or neonatal outcomes apart from hypoglycemia	1 Trisomy 13 with Metformin, 1 clavicle fracture in each group. 1 Erb’s palsy in insulin group	Higher in insulin group (p = 0.03)	–	18%

Notes: ^aGDM subjects in Metformin group included 19 with type 2 diabetes, and Insulin group had seven women with type 2 diabetes. There were an additional 68 women in a sulphonylurea group.

Abbreviations: GI, gastrointestinal; RCT, randomized, controlled trial.

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