Volume 198, Issue 3 , Pages 287.e1-287.e6, March 2008
Diet-treated gestational diabetes mellitus: comparison of early vs routine diagnosis
Article Outline
Objective
The purpose of this study was to compare pregnancy outcomes in women with diet-treated gestational diabetes mellitus (GDM) that was diagnosed at <24 weeks of gestation to those women who received the diagnosis at ≥24 weeks of gestation.
Study Design
This was a retrospective cohort study of 2596 women with diet-treated GDM who delivered between December 1999 and June 2005 at Parkland Hospital. Women with risk factors for GDM underwent immediate glucose screening; women without risk factors underwent universal glucose screening between 24 and 28 weeks of gestation. Women with diet-treated GDM that was diagnosed at <24 weeks of gestation (n = 339; 13.1%) were compared with those women who received the diagnosis at ≥24 weeks of gestation.
Results
Women with an earlier diagnosis of diet-treated GDM were at increased risk of preeclampsia and the delivery of large infants. Even after adjustment for differences in maternal characteristics and glycemic control, the risk of preeclampsia persisted (odds ratio, 2.4; 95% CI, 1.5, 3.8).
Conclusion
Women with an early diagnosis of diet-treated GDM have a 2-fold increased risk of preeclampsia.
Key words: diet, gestational diabetes mellitus, preeclampsia
Universal screening for gestational diabetes mellitus between 24 and 28 weeks of gestation has been adopted widely in the United States.1, 2 Earlier screening for gestational diabetes mellitus (at <24 weeks of gestation) may be prompted by risk factors such as a history of gestational diabetes mellitus in a previous pregnancy or glucosuria. Earlier screening thus may identify women with gestational diabetes mellitus during the first trimester or early in the second trimester. Previous studies have shown that women who are identified with gestational diabetes mellitus earlier in pregnancy are more likely to require insulin and experience preeclampsia.3, 4
Gestational diabetes mellitus has long been associated with an increased risk of preeclampsia and large-for-gestational age infants.5 A previous study from our institution identified a significant increase in hypertension among women with diet-treated gestational diabetes mellitus, compared with the general obstetric population. We also ascribed a 12% risk for overgrown infants to gestational diabetes mellitus after accounting for the effect of maternal obesity.6 We questioned whether patients who are identified with gestational diabetes mellitus earlier in pregnancy are at additional risk for adverse pregnancy outcomes, compared with patients who are diagnosed at the time of routine screening. The purpose of this study was to evaluate the effect of gestational age at diagnosis of gestational diabetes mellitus on pregnancy outcomes in women without fasting hyperglycemia and who are treated with diet alone.
Materials and Methods
This is a retrospective cohort study of women with diet-treated gestational diabetes mellitus who were delivered between December 1, 1999, and June 30, 2005. During the study period, pregnant women were screened for gestational diabetes mellitus between 24 and 28 weeks of gestation. Additionally, women with glucosuria, a random serum glucose concentration of ≥130 mg/dL (all antepartum women had serum glucose measured on evaluation for prenatal care), a history of gestational diabetes mellitus, or symptoms such as polydipsia or polyuria were screened immediately with a 50-g oral glucose screening test.
Those women whose serum glucose exceeded 140 mg/dL (but not >200 mg/dL) 1 hour after ingesting a 50-g oral glucose tolerance beverage (Allegiance Healthcare Corp, McGaw Park, IL) were given a 100-g, 3-hour oral glucose tolerance test after an overnight fast. Women with ≥2 abnormal values according to the National Diabetes Data Group thresholds were diagnosed with gestational diabetes mellitus.7 Women whose serum glucose exceeded 200 mg/dL after the 50-g glucose screen underwent a fasting capillary blood glucose measurement; those women with a glucose value of <105 mg/dL underwent a 100-g glucose tolerance test. All women who had a negative early 3-hour test result were tested again between 24 and 28 weeks of gestation.
Women with gestational diabetes mellitus were treated in a special obstetrics clinic held weekly at Parkland Hospital and received dietary counseling, which includes instructions regarding daily caloric intake (35 kilocalories per kilogram) and food types to avoid. Women with diet-treated gestational diabetes mellitus routinely were given an Accucheck Advantage or Advantage II blood glucose monitor (Boehringer Manheim Corp, Indianapolis, IN) on diagnosis. Women who were given these monitors were instructed to test their capillary blood glucose 4 times per day, beginning with a fasting value in the morning. All women with persistent fasting glucose values of ≥105 were initiated on insulin. Women with gestational diabetes mellitus and fasting glucose values of <105 mg/dL were treated with diet therapy. Glucose values from these self blood glucose monitors were downloaded routinely to a computerized database.
Those women who were identified with diet-treated gestational diabetes mellitus and delivered of singleton, cephalic infants without major fetal malformations were included in this analysis. Noncephalic gestations were excluded from analysis because noncephalic presentation may affect delivery outcomes that are independent of gestational diabetes mellitus. Women with persistent fasting hyperglycemia (≥105 mg/dL) after dietary counseling and who were treated ultimately with insulin were excluded from this analysis.
Pregnancy outcomes for all women who were delivered at Parkland Hospital are entered routinely into a computerized operations database. Antepartum data on women with gestational diabetes mellitus were entered into a separate database and linked electronically to pregnancy outcome data. Women with diet-treated gestational diabetes mellitus were classified according to gestational age at diagnosis. Those women who were diagnosed at <24 weeks of gestation were considered to have “early” diet-treated gestational diabetes mellitus and were compared with those with the diagnosis at ≥24 weeks of gestation who were considered to have “routine” diet-treated gestational diabetes mellitus. The Institutional Review Board of the University of Texas Southwestern Medical Center determined that this study was exempt in accordance with federal regulations. Large for gestational age was defined by the 90th percentile birthweight for gestational age distribution for our population and reported by McIntire et al.8 Shoulder dystocia was identified when a maneuver such as McRoberts’ or suprapubic pressure was required to effect delivery.
A standardized protocol for the intravenous administration of magnesium sulfate for seizure prophylaxis was used for patients with blood pressure of at least 140/90 mm Hg and ≥1 of the following findings: proteinuria of ≥2+ as measured by dipstick in a catheterized urine specimen, a serum creatinine of ≥1.2 mg/dL, platelets <100,000/μL, aspartate transaminase elevated 2 times above the upper limit of the normal range or persistent headache, scotomata, or mid-epigastric or right-upper quadrant pain.9, 10, 11
Statistical analysis was performed with SAS statistical software (version 9.1; SAS Institute Inc, Cary, NC). Statistical analyses that were performed included chi-square, Student t test, Wilcoxon rank-sum test, Shapiro-Wilk test, and multiple logistic regression. The demographic covariables that were entered for adjustment into the regression model were age, maternal weight (as continuous linear effects), race (classified as black, white, Hispanic, and other) and nulliparity (yes or no). To assess glycemic control between the 2 groups, differences in mean fasting and postprandial glucose levels and changes in fasting blood sugars over the course of therapy were evaluated. Differences in glycemic control were added as a covariables into the regression model. Results are presented as mean ± SD, frequency (percent), and odds ratios with 95% CIs. Probability values of <.05 were considered statistically significant.
Results
Between December 1999 and June 2005, information relating to maternal characteristics and perinatal outcomes was collected prospectively on 87,057 women delivered of singleton, cephalic infants (Figure 1). Of these, 3334 women (3.8%) were diagnosed with gestational diabetes mellitus. A total of 2596 women (78%) were treated with diet alone; 2257 of the women (87%) with diet-treated gestational diabetes mellitus at delivery were identified after 24 weeks of gestation. Twenty-two percent (n = 737) of the 3334 women who were diagnosed with gestational diabetes mellitus were identified before 24 weeks of gestation, and 339 of these women (46%) were without fasting hyperglycemia (fasting blood sugar, ≤ 105 mg/dL) and were treated with diet only.
FIGURE 1.
Gestational diabetes mellitus screening outcomes
Outcomes of screening for gestational diabetes mellitus in women who were examined for prenatal care and delivered singleton, cephalic infants between December 1, 1999, and June 30, 2005.
Hawkins. Diet-treated gestational diabetes mellitus. Am J Obstet Gynecol 2008.
Maternal demographic characteristics for women with diet-treated gestational diabetes mellitus are listed in Table 1. Women with early diagnosis were more likely to be older, multiparous, and obese, when compared with women with diet-treated gestational diabetes mellitus that was diagnosed at ≥24 weeks of gestation. Table 2 shows glucose test results in these women, according to gestational age at diagnosis. Women with early diagnosis had significantly higher mean results for the 50-g glucose screen. Approximately one-half of the women (n = 182) who received the diagnosis early had glucose screens of ≥200 mg/dL, compared with 16% in women who were diagnosed routinely (P < .001). Analysis of glycemic control in women with early and routine diagnosis of diet-treated gestational diabetes mellitus revealed that women with early diagnosis had higher mean fasting glucose values (96.1 vs 91.6 mg/dL; P < .001) but a greater decrease in fasting glucose values over the course of therapy (13 vs 10 mg/dL; P = .005). Mean postprandial glucose values were similar between the 2 groups.
TABLE 1. Maternal demographic characteristics, according to gestational age at diagnosis in women with diet-treated gestational diabetes mellitus
| Characteristic | Diagnosis | P value | |
|---|---|---|---|
| <24 weeks of gestation (n = 339) | ≥24 weeks of gestation (n = 2257) | ||
| Age (y)a | 31.1 ± 5.4 | 29.7 ± 5.9 | <.001 |
| Race (n) | |||
| Black | 29 (9%) | 125(6%) | .068 |
| White | 1(0%) | 24(1%) | |
| Hispanic | 300(89%) | 2027(90%) | |
| Other | 9(3%) | 81(4%) | |
| Multiparity | 291(86%) | 1671(24%) | <.001 |
| Body mass index (kg/m2)a | 34.4 ± 6.1 | 32.8 ± 5.4 | <.001 |
aData are presented as mean ± SD. |
TABLE 2. Glucose testing results in women with diet-treated gestational diabetes mellitus, according to the gestational age at diagnosis
| Variable | Diagnosis | P value | |
|---|---|---|---|
| <24 weeks of gestation (n = 339) | ≥24 weeks of gestation (n = 2257) | ||
| 50 gram screen (mg/dL)a | 198±33 | 95.2±16.1 | <.001 |
| 50 gram screen > 200 mg/dL (n) | 182(54%) | 355(16%) | <.001 |
| 3-hour 100-g glucose tolerance test (mg/dL)a | |||
| Fasting blood sugar | 97.1±16.4 | 95.2±16.1 | .10 |
| 1 hour | 205.3±35.8 | 206.4±29.5 | .68 |
| 2 hour | 178.5±39.0 | 184.6±32.4 | .04 |
| 3 hour | 137.3±36.2 | 140.9±34.6 | .16 |
| Meter analysis | |||
| Mean fasting values (mg/dL)a | 96.1±1.3 | 91.6±11.0 | <.001 |
| Mean postprandial values (mg/dL)a | 110.7±12.9 | 111.2±12.9 | .62 |
| Reduction in fasting glucose values with diet therapy (mg/dL)b | 13 (2-25) | 10 (2-19) | .005 |
aData are presented as mean ± SD. |
bData presented as median (interquartile range) |
Selected pregnancy outcomes are shown in Table 3. Women with an early diagnosis of gestational diabetes mellitus had higher rates of preeclampsia, when compared with women who were identified after 24 weeks of gestation. This increase in preeclampsia that was treated with magnesium sulfate accounted for the earlier gestational age at delivery and remained statistically significant, even after adjustment for maternal age, race, parity, weight, and differences in glycemic control (odds ratio, 2.4; 95% CI, 1.5, 3.8). Women with an earlier diagnosis of gestational diabetes mellitus also had a higher rate of repeat cesarean deliveries but fewer cesarean deliveries for dystocia. Neonatal outcomes are listed in Table 4. Infants of women who were identified with early diet-treated gestational diabetes mellitus were more likely to be overgrown and require phototherapy for hyperbilirubinemia. However, the increased rate of large-for-gestational age and macrosomic infants did not persist after adjustment for demographic characteristics and weight (Figure 2).
TABLE 3. Pregnancy outcomes according to the gestational age at diagnosis in women with diet-treated gestational diabetes mellitus
| Variable | Diagnosis | P value | |
|---|---|---|---|
| <24 weeks of gestation (n = 339) | ≥24 weeks of gestation (n = 2257) | ||
| Preeclampsia treated with magnesium (n) | 42(12%) | 140(6%) | <.001 |
| Estimated gestational age at delivery (wk)a | 38.9 ± 1.9 | 39.3 ± 1.6 | <.001 |
| Labor induction(n) | 58(17%) | 314(14%) | .12 |
| Third- or fourth-degree laceration (n) | 13(4%) | 128(6%) | .16 |
| Shoulder dystocia (n)b | 9(3%) | 32(1%) | .09 |
| Cesarean delivery (n) | 128(38%) | 797(35%) | .38 |
| Repeat | 88(26%) | 426(19%) | .002 |
| Dystocia | 10(3%) | 137(6%) | .02 |
aData are presented as mean ± SD. |
bShoulder dystocia was defined as requiring a maneuver such as McRoberts or suprapubic pressure to affect delivery. |
TABLE 4. Neonatal outcomes according to the gestational age at diagnosis in women with diet-treated gestational diabetes mellitus
| Variable | Diagnosis | P value | |
|---|---|---|---|
| <24 weeks of gestation (n = 339) | ≥24 weeks of gestation (n = 2257) | ||
| Birthweight (g)a | 3485 ± 668 | 3448 ± 570 | .66 |
| Birthweight ≥4000 g (n) | 70(21%) | 3356(16%) | .02 |
| Large for gestational age (n)b | 76(22%) | 390(17%) | .02 |
| 5-minute Apgar score <4 (n) | 2(0.6%) | 15(0.7%) | .87 |
| Umbilical artery pH ≤7.0 (n) | 2(0.6%) | 18(0.8%) | .92 |
| Erb’s palsy (n) | 2(0.6%) | 15(0.7%) | .87 |
| Fractured clavicle (n) | 6(1.8%) | 33(1.4%) | .66 |
| Intensive care nursery admission (n) | 9(2.7%) | 44(2.0%) | .39 |
| Hyperbilirubinemia (n) | 16(4.7%) | 48(2.1%) | .004 |
| Stillbirth (n) | 2(0.6%) | 11(0.5%) | .80 |
| Neonatal death (n) | 0 | 3(0.1%) | .50 |
aData are presented as mean ± SD. |
bDefined as birthweight ≥90th percentile for gestational age. |
FIGURE 2.
Adjusted odds ratios
Adjusted odds ratios for selected pregnancy outcomes in women with diet-treated gestational diabetes mellitus, according to gestational age at diagnosis (adjusted for maternal age, race, parity, weight, and glycemic control).
Hawkins. Diet-treated gestational diabetes mellitus. Am J Obstet Gynecol 2008.
Comment
This retrospective analysis of women who were diagnosed with gestational diabetes mellitus early in pregnancy includes several notable findings. First, 1 of 5 women (22%) with gestational diabetes mellitus was identified before the time of routine screening, and almost one-half of these women (46%) were treated successfully with diet alone. In comparison, approximately 87% of routinely diagnosed women were treated successfully with diet. Second, our initial evaluation of pregnancy outcomes that are associated typically with gestational diabetes mellitus revealed an increased risk for overgrown infants in women who were identified early, as compared with those women who were diagnosed at the time of routine screening. These differences, however, did not persist after adjustment for maternal demographic characteristics. The third important finding was that women with diet-treated gestational diabetes mellitus who were identified early were at a 2-fold increased risk for the development of preeclampsia, even after adjustment for differences in maternal characteristics and glycemic control.
Our finding that 22% of patients with gestational diabetes mellitus were diagnosed early is similar to that of other studies, which reveal that 27%-29% of patients with gestational diabetes mellitus (including both insulin treated and diet treated) were diagnosed early.3, 4 Both studies found that women with an early diagnosis of gestational diabetes mellitus more often required insulin and had a higher rate of hypertensive disorders of pregnancy. Our analysis corroborates these findings, even in women who were treated with diet alone. The severity of glucose intolerance has been reported to influence the rate of preeclampsia.12 In some studies, less severe forms of glucose intolerance, even in women who were not diagnosed with gestational diabetes mellitus, have been associated with preeclampsia.13, 14, 15, 16 Hyperinsulinemia, which is often associated with glucose intolerance, may also contribute to the pathogenesis of essential hypertension 17, 18, 19, 20, 21 or development of preeclampsia.22, 23, 24, 25, 26, 27, 28 Other investigators have found that demographic variables that include race, age, and weight also confer an increased risk of preeclampsia.29, 30, 31 Even after adjustment for these demographic characteristics and differences in glycemic control, data indicate a persistent increased risk for preeclampsia in women who are identified with diet-treated gestational diabetes mellitus early in pregnancy compared with women who are diagnosed after 24 weeks of gestation.
Excessive fetal growth that leads to traumatic delivery has been a primary concern for obstetricians who treat women with gestational diabetes mellitus. Although improved glycemic control can reduce fetal size and theoretically reduce the risk of a difficult delivery,32, 33 maternal obesity is also a potent risk factor for oversized babies.34, 35 In our study, there was a tendency toward large-for-gestational-age and macrosomic birthweights in women with earlier diagnosis that did not persist after adjustment for maternal demographic characteristics, especially maternal weight. This finding supports the previous claim that fetal overgrowth and the potential for a difficult delivery are associated more strongly with maternal size and adiposity rather than glycemic control.36, 37 Diet-treated gestational diabetes mellitus has been shown to have a 12% attributable risk for overgrown infants.6 In comparing women with diet-treated gestational diabetes mellitus who were diagnosed early to women who were diagnosed after 24 weeks of gestation, we found no increased risk for overgrown infants or difficult delivery that was related to early diagnosis. This seems consistent with previous findings that indicated that fetal overgrowth that is attributable to diabetes mellitus is influenced most strongly by maternal glycemia in the third trimester,38 particularly after 32 weeks of gestation.39, 40
We believe that women with relative hyperinsulinemia at an earlier point in pregnancy may manifest vascular changes that predispose them to a higher rate of preeclampsia.22, 23, 24, 25, 26, 27, 28 Although our report is retrospective in design, this population-based study includes a large cohort of patients with gestational diabetes mellitus that was diagnosed early in pregnancy (before routine screening) and treated with diet. Such women face a 2-fold increased risk of the development of preeclampsia that requires magnesium sulfate prophylaxis (12% vs 6%; odds ratio, 2.4; 95% CI, 1.5, 3.8). This information is of practical significance in the counseling and treatment of women with gestational diabetes mellitus that is identified early in pregnancy and may explain the reason that observational studies have not demonstrated consistently an increased risk for preeclampsia in women with gestational diabetes mellitus.41
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Cite this article as: Hawkins JS, Lo JY, Casey BM, McIntire DD, Leveno KJ. Diet-treated gestational diabetes mellitus: Comparison of early vs routine diagnosis. Am J Obstet Gynecol 2008;198:287.e1-287.e6.
PII: S0002-9378(07)02233-8
doi:10.1016/j.ajog.2007.11.049
© 2008 Mosby, Inc. All rights reserved.
Volume 198, Issue 3 , Pages 287.e1-287.e6, March 2008
