Objective
Screening for gestational diabetes mellitus commonly uses an oral glucose challenge test with a 50-g glucola beverage and subsequent venous puncture. However, up to 30% of pregnant women report significant side-effects, and the beverage is costly. We hypothesized that equivalent glucose loads could be achieved from a popular candy twist (Twizzlers; The Hershey Company, Hershey, PA) and tested it as cost-effective, tolerable alternative with a test of equivalency.
Study Design
The glucose equivalent of the 50-g glucola was calculated as 10 candy twists. We initially used a triple crossover design in nonpregnant patients whereby each subject served as her own control; this ensured the safety and equivalency of this load before using it among pregnant subjects. We then recruited pregnant women with an abnormal screening at 1 hour (glucose challenge test) in a double crossover design study. Subjects consumed 10 candy twists with a 1-hour venous blood glucose assessment. All subjects subsequently completed the confirmatory 3-hour glucose tolerance test. Sensitivity, specificity, positive predictive values, negative predictive values, false-referral rates, and detection rates were calculated.
Results
At ≥130 mg/dL, the sensitivity (100%) was the same for candy twists and glucola. However, the false-referral rate (82% vs 90%), positive predictive value (18% vs 10%), and detection rate (18% vs 10%) were improved for candy twists when compared with the 50-g glucola beverage.
Conclusion
Our results indicate that strawberry-flavored candy twists are potentially an equally effective screening test, compared with the gold standard glucola beverage but lead to fewer false-positive screens and therefore could be a cost-effective alternative.
To meet the metabolic demands of a developing fetus, pregnancy occurs in a state of relative insulin resistance. A nondiabetic pregnant woman experiences mild fasting hypoglycemia, postprandial hyperglycemia, and mild hyperinsulinemia. In contrast, according to the American College of Obstetricians and Gynecologists, gestational diabetes mellitus (GDM) is defined as “carbohydrate intolerance that begins or is first recognized during pregnancy.” Although the prevalence of GDM varies accordingly with population risk factors and prevalence of type II diabetes mellitus in most populations, the commonly accepted point prevalence varies from 2-5% but can be as high as 14%. Of note, almost 40% of all women with GDM will continue to have elevated glucose values after pregnancy. Given the epidemic of obesity at a population-wide level, it is reasonable to anticipate ongoing increased prevalence of GDM in the coming years.
The current commonly used sequence of screening for GDM uses a 50-g oral glucose challenge test (GCT) performed between 24 and 28 weeks’ gestation. A positive screen is defined as a venous blood glucose level of either 130 or 140 mg/dL at 60 minutes. The 140 mg/dL cutoff is 10% less sensitive than the 130 mg/dL cutoff but is also less likely to produce a false-positive result. When 130 mg/dL is used as the screening threshold, roughly 25% of all pregnant women will ‘screen positive’ for GDM. Once a positive screen has been established, the patient then undergoes a fasting 100-g 3-hour glucose tolerance test (GTT) with a 100-g glucose beverage. Venous blood glucose is measured fasting and then at 1-, 2-, and 3-hour intervals after the 100-g glucose drink. Two sets of criteria exist for then definitively diagnosing GDM: the National Diabetes Data Group Criteria and the Coustan Criteria. Although the cutoff values differ in these criteria sets, both require at least 2 of the 4 values to be elevated to diagnose the patient with GDM.
Notably, up to 30% of pregnant women cannot tolerate the traditional 50-g glucola screening test. Reported side-effects include nausea, emesis, bloating, abdominal pain, diarrhea, sweating, and headache. Given this side-effect profile, pregnant women may be unwilling or unable to complete screening for GDM with the glucola beverage. There are limited reports (PubMed, 1990-present) that provide viable alternatives to the glucola beverage. For example, studies that have investigated jelly beans demonstrated lower sensitivity than the glucola (80% sensitivity when the ‘screen positive’ cutoff is a blood glucose value of 140 mg/dL, 90% sensitivity when the ‘screen positive’ cutoff is a blood glucose value of 130 mg/dL). However, subjects documented that jelly beans were better tolerated by the study participants than the glucola drink.
The effects of hyperglycemia/GDM are well-known in obstetric populations. Infants of mothers with diabetes mellitus are at higher risk of macrosomia, fetal malformations, shoulder dystocia, hypoglycemia, hypocalcemia, respiratory distress syndrome, and thus neonatal intensive care unit admissions. As adults, children of mothers with diabetes mellitus are at higher risk of obesity and the development of type II diabetes mellitus. This is thought to be secondary to “metabolic memory” from an intrauterine diabetic milieu. The mothers, themselves, are at higher risk for hypertension, preeclampsia, future type II diabetes mellitus, shoulder dystocia, and operative/cesarean delivery. Furthermore, maternal obesity is associated independently with adverse pregnancy outcomes and greater severity of outcomes, and treatment of even mild GDM results in improved maternal and fetal morbidity. Ergo, it is imperative that the cost-effective and well-tolerated means of screening are used.
In this study, we sought to identify an alternative, possibly better tolerated, screening method for GDM. We chose to substitute an equivocal 50-g glucose load with the use of strawberry-flavored twist candy (Twizzlers; The Hershey Company, Hershey, PA) as an alternative to the glucola beverage. To establish safety, we initially tested and confirmed equipoise in a nonpregnant cohort. In this study, we hypothesized that strawberry twists would demonstrate equipoise in screening for GDM when compared with the glucola beverage in pregnant women but at a fraction of the cost.
Materials and Methods
Study cohort
After institutional review board approval (Institutional Review Board Project# H-26324, renewal approved on June 24, 2013), recruitment for the study was open to all pregnant women seen at the high-risk obstetrics clinic at Ben Taub General Hospital between July and October of 2013 who underwent either universal or risk-based screening with the 50-g 1-hour GCT and screened positive, thus requiring a confirmatory 3-hour GTT. Written informed consent was obtained, and subjects were reimbursed for their participation. Mean gestational age at the time of testing was 24.6 weeks n for glucola and 28.2 weeks for candy twists. In our institution, a positive screen is defined as 140 mg/dL. Demographics of our study cohort are presented in Table 1 . We did not exclude women with a history of GDM.
| Demographic | Subjects (n = 20), n |
|---|---|
| Age, y | |
| 17-30 | 9 |
| 31-40 | 9 |
| 41-50 | 2 |
| Body mass index, kg/m 2 | |
| <25 | 3 |
| 25-29.9 | 3 |
| ≥30 | 14 |
| Parity | |
| Nulliparous | 3 |
| Parous | 17 |
| Race/ethnicity | |
| White | 1 |
| Black | 2 |
| Asian | 1 |
| Hispanic | 16 |
Choice and amount of candy
To calculate the oral intake necessary to achieve a 50-g load, nutritionists who specialized in diabetes mellitus consulted product information regarding calories, total and saturated fat, carbohydrates, sugars (including sugar alcohols), and protein in candy twists in a per piece calculation. This yielded 50-g calculated consumption of 10 strawberry-flavored candy twists in 5 minutes. Nutritional calculations were confirmed with the University of Minnesota Nutrition Data System for Research ( http://www.ncc.umn.edu/products/ndsr.html ). Ten strawberry-flavored candy twists yielded 47.408 g of sugars, mostly comprised of sucrose. Other major sugars in the composition were fructose, maltose, and glucose; 91.968% of the calories were derived from carbohydrates; 4.527% of the calories were derived from fat, and 3.515% of the calories were derived from protein. In the pilot study population, there was no significant difference in the mean serum glucose after consumption. Initially, a nonpregnant cohort was assembled to investigate this hypothesis. We found that candy twists provide an equivalent screening alternative to the glucola beverage in nonpregnant women. In this study, we set out to test these findings in a pregnant population.
Study protocol
Subject recruitment was limited to those who had already ‘screened positive’ for GDM based up a 50-g 1-hour GCT (Azer Scientific, Morgantown, PA ) and who were already scheduled to undergo a confirmatory 3-hour 100-g GTT. This way subjects served as their own controls. At our institution, we use a cutoff of 140 mg/dL as a positive screen. Subjects consumed 10 strawberry-flavored candy twists within 5 minutes. One hour later, 5 mL of venous blood was drawn for testing of blood glucose and insulin concentrations. Screen-positive values for blood glucose values after candy twists consumption were set as ≥130 mg/dL to ensure that any and all subjects with GDM were captured in our cohort. After candy twists, blood glucose values were blinded to providers; subjects proceeded with the 3-hour GTT as scheduled. Results of the 3-hour confirmatory GTT were interpreted according to Coustan and National Diabetes Data Group diagnostic criterion. By limiting our cohort to those who already required a 3-hour GTT, we minimized cost and discomfort for the patient.
Sample size calculation and statistical analysis
The decision regarding sample size of this double crossover study was made with the goal of achieving at least 80% power to detect equivalence between 50-g glucola and candy twists with the use of a paired t test where each subject is compared with her own ‘control.’ Previous data have shown the available estimates of mean (90 mg/dL) and standard deviation (10 mg/dL) for serum glucose values with the glucola beverage. We estimated that a sample size of 20 pairs will achieve 87% power to detect equivalence when the margin of equivalence is ±8 (hence between 82 and 98 mg/dL). The actual difference is 0; correlation between 50-g glucola and candy twists test for serum glucose is 0.4 (our pilot data), with a significance of .05. This estimate was based on 2000 Monte Carlo simulations. All statistical analyses were performed in SPSS statistical software (SPSS Inc, Chicago, IL). Sensitivity, specificity, positive predictive values, negative predictive values, false-referral rate, and detection rate were calculated with venous blood glucose cutoffs of 130 mg/dL to ensure maximum detection of GDM. We defined false-referral rate as the proportion of test subjects who test positive but do not have the disease and the detection rate as the proportion of participants who test positive and have the disease.
Results
Subject demographics
Most study participants were Hispanic. The mean body mass index in our cohort was 33.8 kg/m 2 ; the mean age was 30.3 years. Overall, the demographic breakdown in the study was reflective of our clinic population. The remainder of the demographic data can be found in Table 1 .
Glucose challenge test
Each participant served as her own control in our double crossover study design, whereby all subjects were screened by the standard glucola GCT and the 50-g load of candy twists (calculated at 10 individual twists), followed with a confirmatory diagnostic 100-g GTT. The comparison of venous glucose values after the candy twists and glucola consumption can be seen in Table 2 . Two participants were diagnosed with GDM by both the Coustan diagnostic criteria and the National Diabetes Data Group; these subjects screened positive by both candy twists and glucola. The median difference in gestational age between the glucola GCT and the candy twists challenge was 2 weeks. No adverse side-effects were reported in women after completion of the candy twists challenge. In addition to calculating the serum glucose after consumption of the glucola and the candy twists, we also calculated the insulin concentration after candy twists consumption. There is no discernible correlation between venous blood glucose values after candy twists consumption and insulin levels measured on the same samples ( R 2 = 0.131).
| Variable | Mean glucose, mg/dL ± standard deviation | Minimum glucose, mg/dL | Maximum glucose, mg/dL |
|---|---|---|---|
| Candy twists | 130.6 ± 31.7 | 69.5 | 212.9 |
| Glucola | 154.4 ± 14.6 | 139 a | 188 |
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