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Obstetrics & Gynecology 2003;101:1197-1203
© 2003 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Fasting Plasma Glucose Test at the First Prenatal Visit as a Screen for Gestational Diabetes

David A. Sacks, MD, Wansu Chen, MS, Girma Wolde-Tsadik, PhD and Thomas A. Buchanan, MD

From the Department of Obstetrics and Gynecology, Kaiser Foundation Hospital, Bellflower; Department of Research, Southern California Permanente Medical Group, Pasadena; and Departments of Internal Medicine, Obstetrics and Gynecology, and Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California.

Address reprint requests to: David A. Sacks, MD, Department of Obstetrics and Gynecology, Kaiser Foundation Hospital, 9400 East Rosecrans Avenue, Bellflower, CA 90740; E-mail: david.a.sacks{at}kp.org.


   ABSTRACT
TOP
ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: To determine whether the fasting plasma glucose test administered at the first prenatal visit could serve as an efficient screen for gestational diabetes.

METHODS: A total of 5557 women not known to have diabetes were offered a fasting plasma glucose test at their first prenatal visit. Results less than 100 mg/dL were blinded. A glucose tolerance test was requested immediately of those whose screening test result was 100–125 mg/dL and of all women not identified as having diabetes by their 23rd gestational week.

RESULTS: A total of 4507 women (81%) complied with the protocol. Of the 302 women found to have gestational diabetes, 46 (15%) were detected before 24 weeks. A false-positive rate of 57% was found at a threshold fasting glucose concentration giving a sensitivity of 80% for the detection of gestational diabetes.

CONCLUSION: The fasting plasma glucose screening test at the first prenatal visit has good patient compliance. However, its poor specificity (high false-positive rate) makes it an inefficient screening test for gestational diabetes.

First reported in 1973,1 the 50-g, 1-hour glucose challenge test is widely used as the standard screening test for gestational diabetes mellitus (GDM).2,3 Over time, a number of practical concerns have surfaced regarding this test’s clinical utility. Test results may vary depending upon the time elapsed since the last meal.4,5 Timing is critical, in that blood for glucose analysis must be drawn exactly 1 hour after ingestion of the glucose.2 The concentrated glucose load may induce unpleasant side effects, such as nausea, vomiting, and bloating, which may in turn lead to decreased compliance with requirements of the test.6,7 Postglucose challenge test results rise progressively throughout gestation.8–10 Therefore, a screening test threshold value derived from patients studied during the latter part of pregnancy may be less sensitive for the detection of gestational diabetes when applied early in gestation.11 Detection of gestational diabetes early in pregnancy is a desirable goal in that the application of diet, medication, and exercise throughout pregnancy may have a positive effect on maternal and fetal outcomes.12–14

Using the fasting plasma glucose as a screening test for diabetes early in gestation offers some theoretical advantages over a postglucose challenge. The fasting plasma glucose has been reported to vary little throughout gestation.8,15–21 Therefore, a given threshold fasting glucose value preceding a glucose tolerance test (GTT) should be applicable at any time during gestation. In addition, among women who have gestational diabetes, plasma glucose does not vary significantly between 4 and 9 hours after the last meal.22 A patient may, therefore, report for testing after an overnight fast of variable duration.

The purpose of this study was to determine whether the fasting plasma glucose test administered at the first prenatal visit would be sufficiently sensitive and specific for use as a screening test for gestational diabetes.


   MATERIALS AND METHODS
TOP
ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study patients were recruited between February 1, 1998, and July 31, 1999 from Kaiser Permanente Bellflower Medical Center. Our obstetric population consists predominantly of working-class Latina women. All pregnant women who were not known to have diabetes were asked at their first prenatal visit to participate. Those who enrolled were asked to return for both routine laboratory work and a venous plasma glucose test the next morning after a fast beginning no later than midnight. Those declining study participation were requested to have their routine prenatal laboratory work drawn at the initial visit. No advance laboratory appointments were required for study participants. All patients were made aware that they would receive a definitive (glucose tolerance) test for diabetes in midpregnancy (unless already diagnosed), regardless of study participation. This study was reviewed and approved by the Kaiser Permanente Institutional Review Board for the protection of human subjects. The conduct of this study was in conformity with the ethical standards for human experimentation established by the Declaration of Helsinki of 1975, revised in 1983.23 Written informed consent was obtained from each subject.

Upon presentation for the test, the subjects’ time of last oral intake was recorded. Women who had ingested anything other than water after midnight were rescheduled. Both patients and practitioners were blinded to the fasting plasma glucose results below 100 mg/dL (the lower limit value used to define GDM on the GTT).18 Results that were greater than or equal to that value were unblinded. Women whose results were 100–125 mg/dL were asked to have a GTT immediately. Those whose fasting plasma glucose concentration was greater than or equal to 126 mg/dL were asked to return for a second fasting glucose test. Patients whose results were again greater than or equal to 126 mg/dL were referred for care for diabetes.2 At their first visit after their 23rd gestational week, all women not identified as having diabetes were advised to schedule a 75-g, 2-hour GTT. The testing procedure followed was in accord with the recommendations of the American Diabetes Association.2 Gestational diabetes was diagnosed if two or more values of the GTT equaled or exceeded the mean + two standard deviations derived from our patient population (fasting 100 mg/dL, 1-hour 195 mg/dL, and 2-hour 160 mg/dL).18 Women with gestational diabetes were referred for management with diet, insulin, or both, as determined by the diabetes in pregnancy team.

Prepregnancy weight and ethnicity were self-reported. Gestational age was determined by ultrasound examination. When no sonographic examination had been done, gestational age was calculated from the date of onset of the last menstrual period. Maternal body mass index was calculated from the formula: body mass index = weight (kg)/[height (m)]2. Prepregnancy overweight was defined by a body mass index of 27.3 or greater.24 Women were categorized as compliant with the study protocol if they had had both a fasting plasma glucose and at least one GTT, or if their fasting plasma glucose result equaled or exceeded 126 mg/dL. Data were recorded for analysis at the time of delivery. Women were excluded from the study if they had 1) transferred their care to another institution, and/or 2) begun their prenatal care elsewhere and had been screened for gestational diabetes before transfer, and/or 3) had a spontaneous abortion after enrollment for prenatal care. Unless stated otherwise, for women who had two GTTs the results of the second test were used.

Venous blood was collected in tubes containing sodium fluoride and then centrifuged and the plasma separated within 30 minutes of collection. Plasma glucose was assayed by an automated glucose oxidase method (Beckman Synchron LX20; Beckman Instruments, Brea, CA) within 30 minutes of separation. Interassay and intraassay coefficients of variation for normal controls were respectively 2.4% and 2.1%.

The purpose of a screening test is to detect a large proportion of patients at risk for a disease. Therefore, the balance struck between sensitivity and specificity should tilt toward sensitivity. The threshold glucose value selected by O’Sullivan et al for the 50-g, 1-hour glucose screening test had a sensitivity of 0.79.1 Based on these data, we decided that the fasting glucose value selected for the screening test should provide a sensitivity of at least 0.70. We then used this sensitivity to estimate the study sample size because this sample size estimate is the most conservative (largest) one for any sensitivity between 0.70 and 0.99. Assuming a specificity of 0.50 and a tolerance of ±0.05 (length of the 95% confidence interval 0.10) for estimating the sensitivity, we estimated the necessary number of women having gestational diabetes to be 321.25 Assuming a population incidence of 3.2%,18 10,032 subjects would have been needed. A 1-year interim analysis found the actual incidence of gestational diabetes to be 6.6%. The targeted number of subjects was accordingly adjusted to 4864.

The distribution of continuous variables was tested for normality with the Shapiro and Wilk test. Nonparametric tests were used when data did not meet the assumptions of normal distribution. For continuous variables, all comparisons between compliant and noncompliant women were made with the Wilcoxon rank-sum test. Comparisons between the fasting plasma glucose screen and the fasting component of the GTT, and those between the first and second GTTs were performed using the Wilcoxon signed rank test. The {chi}2 or Fisher exact tests were used to compare categoric variables. Results were presented as median with range for continuous variables and cell size, and as percent and exact 95% confidence interval for categoric variables, unless otherwise stated. The exact confidence intervals were calculated using binomial distribution. The area under the receiver operating characteristic (ROC) curves and the standard errors were estimated using the method of Hanley and McNeil.26 All analyses were two tailed and were conducted with SAS software 8.02 for Windows (SAS Institute, Cary, NC). Statistical significance was set at the 0.05 level.


   RESULTS
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
There were 5557 women who delivered during the study period and who met criteria for inclusion. Although none requested blood testing at the prenatal class, 4507 (81%) met criteria for compliance. Demographic differences were found between compliant and noncompliant women (Table 1Go). The latter were more likely to be younger, parous, and black, and to have enrolled later for prenatal care. Of the 1050 noncompliant patients, 663 (63%) had only the fasting plasma glucose screening test, 241 (23%) had only the GTT, and 146 (14%) had neither a screening test nor a definitive test for glucose tolerance during pregnancy. Thus, of all 5557 patients, only 3% had neither a screening nor a definitive test for GDM.


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  		Table 1. Demographics of Women Who Had Both Fasting Plasma Glucose Screening and a Subsequent Glucose Tolerance Test (Compliant Patients) Compared With Those Who Did Not (Noncompliant Patients)
 
Of the 4507 patients who met criteria for compliance, 4143 (92%) had their gestational ages established by ultrasound examination. Ninety-five percent (4259) delivered after their 36th week. The mean (standard deviation) gestational age at the time of the fasting plasma glucose screening test was 10.7 (4.9) weeks. Seventy-seven percent of all screens were performed during the first trimester and 96% before 23 weeks.

Gestational diabetes was identified in 302 subjects (6.7% of compliant women). Of these, 12 were diagnosed based on an initial fasting plasma glucose greater than or equal to 126 mg/dL. An additional 34 were diagnosed before 24 weeks by a GTT after a fasting plasma glucose screen equal to or exceeding 100 mg/dL. The mean fasting plasma glucose screen was significantly greater for women who had gestational diabetes than for those found not to have diabetes (94 mg/dL versus 84 mg/dL, P < .001).

The ROC curves for all 4507 patients were constructed using the numerical criteria to define gestational diabetes derived at our institution18 as well as those of the American Diabetes Association.2 As shown in Figure 1Go, the shapes of the curves were virtually identical, and the areas under the curves were not significantly different (respectively 0.67, standard error 0.013 and 0.70, standard error 0.017, P = .19). The proportions of the former group who equaled or exceeded different fasting plasma glucose screening threshold values and their respective true-positive rate (sensitivity) and false-positive rate (1 – specificity) and positive and negative predictive values are reported in Table 2Go. A false-positive rate of 57% was found at a threshold fasting glucose concentration giving a sensitivity of 80% for the detection of gestational diabetes.



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  		Figure 1. Receiver operating characteristic curves for all 4507 subjects. The area under the curve generated by the American Diabetes Association criteria2 (open circles) is not significantly different from that generated by our institution-specific criteria18 (closed circles) (respectively 0.67, standard error 0.013 and 0.70, standard error 0.017, P = .19). Numbers on curves are fasting plasma glucose threshold values in mg/dL.

Sacks. Fasting Plasma Glucose Screening Test. Obstet Gynecol 2003.

 

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  		Table 2. True-Positive Rate (Sensitivity), False Positive Rate (1 – Specificity), and Positive and Negative Predictive Values for Selected Fasting Plasma Glucose Screening Thresholds
 
To better understand the influence of the time interval from screening to definitive test (GTT) on the sensitivity and specificity of the fasting plasma glucose screening test, the data were initially broken into five time intervals (less than 90 days, 90–109 days, 110–124 days, 125–139 days, and 140 days or more). These intervals were selected to produce approximately equal sample sizes within each cell. The area under the curve for the first interval was 0.84, whereas those among the second to fifth intervals ranged from 0.60 to 0.70. The latter were therefore combined and compared with those whose intertest interval was less than 90 days. The area under the ROC curve for those whose fasting plasma glucose-to-GTT interval was less than 90 days was significantly greater than that of women whose interval was 90 days or more (0.84 versus 0.64, respectively, P < .001). However, because of protocol design, women whose fasting plasma glucose screening results were 100 mg/dL or greater were more likely to have been tested with GTT within a shorter time of the fasting plasma glucose screening and to have been tested twice during pregnancy with GTTs. To minimize bias, a comparison was therefore made of the areas under the ROC curves for only those women whose fasting plasma glucose screening result was less than 100 mg/dL. Among the latter, there was no statistically significant difference in areas under the ROC curves for those whose intertest interval was either more or less than 90 days (0.68 versus 0.62, respectively, P = .27).

For women who both did and did not have gestational diabetes, the fasting plasma glucose value was significantly greater at the time of the GTT than at the time of screening. At each of those examinations, the fasting plasma glucose value was higher for women who had diabetes than for those who did not (Table 3Go). To compare the differences over time between the fasting plasma glucose and the plasma glucose after a glucose load, the results of the 155 patients who had two GTTs were analyzed. Although no statistically significant differences were noted between median fasting plasma glucose results, both the 1-hour and 2-hour postglucose load results were significantly greater on the test performed later in gestation than on that performed earlier (Table 4Go).


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  		Table 3. Fasting Plasma Glucose at the Time of Screening and at the Time of Second or Only Glucose Tolerance Test
 

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  		Table 4. Results of Subjects Who Had Two Glucose Tolerance Tests During Pregnancy (n = 155)
 

   DISCUSSION
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Identification of gestational diabetes early in gestation is a desirable goal. In this study, 12 women (4% of all who had gestational diabetes) whose diabetes likely antedated their pregnancies were identified at their first prenatal visits with the use of the fasting plasma glucose screening test. Because of the increase in postchallenge maternal glucose concentration with advancing pregnancy,8–11 we concluded that we would detect a greater proportion of gestational diabetics by deferring definitive (glucose tolerance) testing till 23 weeks or later.

To be clinically useful, a screening test should satisfy certain requirements. The test should be easy to perform and acceptable to those being tested. The threshold value selected for the screening test should be sufficiently sensitive so that a large proportion of those affected by the disease will be selected to undergo the definitive test. Only a small proportion of those who do not have the disease should exceed the screening test threshold. If a large number of patients who do not have the disease exceed the threshold, they will unnecessarily undergo the definitive test. The latter seems to be the case in the present study.

Although no convention has been established regarding appropriate sensitivity and specificity for a screening test for gestational diabetes, the original study which proposed the use of the 50-g, 1-hour glucose screening test selected a threshold glucose concentration that gave a sensitivity of 79% and a false-positive rate of 13%.1 Others27–29 have studied the fasting glucose component of the GTT as a predictor of GDM. In those reports, the false-positive rates corresponding to sensitivities above 80% are markedly lower than those found in the present study27–29 (Table 5Go). Differences in populations studied, sample sizes, and definitions of gestational diabetes could explain the differences in study findings. The prevalence of GDM is enhanced when the patients studied came from ethnic groups where the prevalence of nongestational diabetes is high, if the study participants are selected on the basis of having risk factors, and if the numerical threshold values used to define GDM are low. A high prevalence of GDM would, in turn, enhance the positive predictive value of the screening test. Another important distinction between the design of the current study and that of prior reports is that we administered the fasting plasma glucose screening test independent of the administration of the GTT. The use of the fasting component of the GTT as a predictor of GDM, as was done in the earlier reports,27–29 assumes perfect reproducibility of the fasting plasma glucose. The day-to-day reproducibility of the fasting plasma glucose during pregnancy has not been reported. An increase in fasting plasma glucose concentrations over time (Table 3Go) may also have contributed to the decreased efficiency of the screening test.


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  		Table 5. Threshold Fasting Glucose Concentration and False-Positive Rate (1 – Specificity) Corresponding to True-Positive Rate (Sensitivity) Between 80% and 90%
 
A salient finding of this study is a 57% false-positive rate (1 – specificity) to achieve a sensitivity of 80% (Table 5Go). In clinical terms, over half of all patients who did not have GDM underwent a GTT to be able to identify 80% of those who did. We therefore conclude that when given at the first prenatal visit, the fasting plasma glucose is not an efficient screening test for gestational diabetes.


   Footnotes
 
doi:10.1016/S0029-7844(03)00049-8

Received September 25, 2002. Received in revised form December 7, 2002. Accepted December 18, 2002.


   REFERENCES
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. O’Sullivan JB, Mahan CM, Charles DM, Dandrow RV. Screening criteria for high-risk gestational diabetic patients. Am J Obstet Gynecol 1973;116:895–900.[Medline]

2. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2001;24 Suppl 1:S5–20.

3. American College of Obstetricians and Gynecologists. Gestational diabetes. ACOG practice bulletin no. 30. Washington: American College of Obstetricians and Gynecologists, 2001.

4. Coustan DR, Widness JA, Carpenter MW, Rotondo L, Pratt DC, Oh W. Should the fifty-gram, one-hour plasma glucose screening test for gestational diabetes be administered in the fasting or fed state? Am J Obstet Gynecol 1986;154:1031–5.[Medline]

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15. Gillmer MDG, Beard RW, Brooke FM, Oakley NW. Carbohydrate metabolism in pregnancy. Part I—Diurnal plasma glucose profile in normal and diabetic women. Br Med J 1975;3:399–404.

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17. Assel A, Rossi K, Kalhan S. Glucose metabolism during fasting through human pregnancy: Comparison of tracer method with respiratory calorimetry. Am J Physiol 1993; 265:351–6.

18. Sacks DA, Greenspoon JS, Abu-Fadil S, Henry HM, Wolde-Tsadik G, Yao JFF. Toward universal criteria for gestational diabetes: The 75-gram glucose tolerance test in pregnancy. Am J Obstet Gynecol 1995;172:607–14.[Medline]

19. Weiss PAM, Haeusler M, Kainer F, Furstner P, Haas J. Toward universal criteria for gestational diabetes: Relationships between seventy-five and one hundred gram glucose loads and between capillary and venous glucose concentrations. Am J Obstet Gynecol 1998;178:830–5.[Medline]

20. Mills JL, Jovanovic L, Knopp R, Aarons J, Conley M, Park E, et al. Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: The Diabetes in Early Pregnancy Study. Metabolism 1998;47:1140–4.[Medline]

21. Agardh C-D, Aberg A, Norden NE. Glucose levels and insulin secretion during a 75g glucose challenge test in normal pregnancy. J Intern Med 1996;240:303–9.[Medline]

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23. Sacks DA, Chen W, Wolde-Tsadik G, Buchanan TA. When is fasting really fasting? The influence of time of day, interval after a meal, and maternal body mass on maternal glycemia in gestational diabetes. Am J Obstet Gynecol 1999;181:904–11.[Medline]

24. Kuczmarski RJ, Fiegal KM, Campbell SM, Johnson CL. Increasing prevalence of overweight among US adults. JAMA 1994;272:205–11.[Abstract]

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28. Reichelt AJ, Spichler ER, Branchtein L, Nucci LB, Franco LJ, Schmidt MI. Fasting plasma glucose is a useful test for the detection of gestational diabetes. Diabetes Care 1998; 21:1246–9.[Abstract]

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30. World Health Organization. Prevention of diabetes mellitus: Report of a WHO Study Group. Technical report series no. 844. Geneva: World Health Organization, 1994.




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