OBSTETRICS Fasting Capillary Glucose as a Screening Test for Ruling Out Gestational Diabetes Mellitus Valerie Anderson,1 Chang Ye, MSc,1 Mathew Sermer, MD,2 Philip W. Connelly, PhD,3,4 Anthony J. G. Hanley, PhD,1,3,5 Bernard Zinman, CM MD,1,3,6 Ravi Retnakaran, MD1,3,6 1 Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto ON 2 Division of Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto ON 3 Division of Endocrinology, University of Toronto, Toronto ON 4 Keenan Research Centre in the Li Ka Shing Knowledge Institute of St . Michael’s Hospital, Toronto ON 5 Department of Nutritional Sciences, University of Toronto, Toronto ON 6 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON Abstract Résumé Objective: A common approach to screening for gestational diabetes mellitus (GDM) is the testing of all pregnant women with a one-hour, 50 g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (≥ 7 .8 mmol/L) . As only a small subset of those with a positive GCT will have GDM, many more women undergo the OGTT than may be necessary . In this context, we hypothesized that measurement of fasting capillary glucose (FCG) could provide a strategy for reducing the number of unnecessary OGTTs . Thus, we sought to identify a threshold level of FCG below which GDM could be ruled out following a positive GCT, without need for the OGTT . Objectif : Une approche courante pour le dépistage du diabète sucré gestationnel (DSG) consiste à soumettre toutes les femmes enceintes à une épreuve de charge en glucose (ECG, soit la glycémie une heure après l’ingestion de 50 g de glucose), suivie de la tenue d’une épreuve d’hyperglycémie provoquée par voie orale (EHPVO) diagnostique lorsque l’ECG s’avère positive (≥ 7,8 mmol/l) . Puisque seul un faible sous-ensemble des femmes ayant obtenu des résultats positifs à l’ECG présenteront un DSG, un grand nombre de femmes sont donc inutilement soumises à une EHPVO . Dans ce contexte, nous avons émis l’hypothèse selon laquelle la mesure de la glycémie capillaire à jeun (GCJ) pourrait fournir une stratégie qui permettrait de réduire le nombre d’EHPVO menées inutilement . Ainsi, nous avons cherché à identifier un seuil de GCJ en deçà duquel la présence possible d’un DSG pourrait être écartée à la suite de l’obtention de résultats positifs à l’ECG, sans devoir avoir recours à l’EHPVO . Methods: Following a positive GCT, 888 women underwent measurement of FCG prior to their OGTT . We evaluated the test characteristics of FCG for identifying the 209 women diagnosed with GDM on the OGTT . Results: Fasting capillary glucose was positively associated with each glucose measurement on the OGTT (all P < 0 .001) and inversely related to insulin sensitivity and pancreatic beta-cell function (both P < 0 .001) . As FCG increased, the prevalence of GDM progressively rose (P < 0 .001) . However, the area under the curve of the receiveroperating characteristic curve for FCG in predicting GDM was modest (0 .67) . Although using an FCG threshold of 4 .8 mmol/L could reduce the number of OGTTs by 28 .4%, this approach would miss 18 .2% of cases of GDM . Conclusion: Fasting capillary glucose is associated with glycemia, insulin sensitivity, and pancreatic beta-cell function . However, a single FCG measurement is insufficient for reliably ruling out GDM after an abnormal GCT . J Obstet Gynaecol Can 2013;35(6):515–522 Key Words: Fasting capillary glucose, gestational diabetes, screening, glucometer Competing Interests: None declared . Received on November 29, 2012 Accepted on February 15, 2013 Méthodes : Après avoir obtenu des résultats positifs à l’ECG, 888 femmes ont été soumises à la mesure de la GCJ avant la tenue d’une EHPVO . Nous avons évalué la valeur prévisionnelle de la GCJ pour ce qui est de l’identification des 209 femmes ayant obtenu un diagnostic de DSG à la suite de l’EHPVO . Résultats : La glycémie capillaire à jeun a été positivement associée à chacune des mesures de la glycémie obtenues au moyen de l’EHPVO (toutes P < 0,001) et s’est avérée inversement proportionnelle à l’insulinosensibilité et à la fonction des cellules β pancréatiques (toutes deux P < 0,001) . La GCJ s’est avérée directement proportionnelle à la prévalence du DSG (P < 0,001) . Toutefois, la surface sous la courbe de la fonction d’efficacité du récepteur pour ce qui est de la valeur prévisionnelle de la GCJ en matière de DSG était modeste (0,67) . Bien que l’utilisation d’un seuil de GCJ de 4,8 mmol/l puisse réduire le nombre de EHPVO de 28,4 %, 18,2 % des cas de DSG passeraient alors inaperçus . Conclusion : La glycémie capillaire à jeun est associée à la glycémie, à l’insulinosensibilité et à la fonction des cellules β pancréatiques . Toutefois, une seule mesure de la GCJ ne s’avère pas suffisante pour écarter de façon fiable la présence possible du DSG à la suite de l’obtention de résultats anormaux à l’ECG . JUNE JOGC JUIN 2013 l 515 OBSTETRICS INTRODUCTION S creening for gestational diabetes mellitus has become a standard element of obstetrical practice because of the adverse maternal and neonatal outcomes associated with exposure to maternal hyperglycemia.1,2 These outcomes include increased rates of macrosomia, birth trauma, shoulder dystocia, and Caesarean section.1–4 Although protocols for GDM screening vary by jurisdiction, a common approach is the universal testing of all pregnant women in the late second trimester with a one-hour 50 g glucose challenge test, followed by referral for a diagnostic oral glucose tolerance test in those in whom the GCT is positive. In the general population, however, the GCT has been shown to have a false-positive rate as high as 83%.5 Thus, many more pregnant women undergo the diagnostic OGTT than may be necessary. As the test is costly, timeconsuming, and unpleasant for many women, strategies directed towards refining the screening process to reduce the number of unnecessary OGTTs could hold significant clinical implications. Measurement of fasting capillary glucose, using a pointof-care hand-held glucometer, might be one such strategy. The advantages of capillary glucose measurement by glucometer include the immediacy of results, the ease of use, and the minimal invasiveness compared with venous blood draw. Of note, there has been limited previous evaluation of FCG as a screening test for GDM and only in specific ethnic populations at very high6 or very low7 risk of GDM. In this context, we hypothesized that for GDM screening in the general obstetric population a possible strategy would be to use FCG to reduce the number of unnecessary OGTTs following initial GCT screening. Thus, our objective in this study was to identify in women ABBREVIATIONS AUC area under the curve FCG fasting capillary glucose GCT glucose challenge test GDM gestational diabetes mellitus IADPSG International Association of Diabetes and Pregnancy Study Groups HOMA-IR Homeostasis Model Assessment of Insulin Resistance 1/HOMA-IR inverse of the HOMA-IR IGI/HOMA-IR insulinogenic index divided by HOMA-IR ISSI-2 Insulin Secretion-Sensitivity Index-2 NDDG National Diabetes Data Group NGT normal glucose tolerance OGTT oral glucose tolerance test ROC receiver-operating-characteristic 516 l JUNE JOGC JUIN 2013 with a positive GCT a threshold level of FCG below which GDM could be ruled out without need for the OGTT. METHODS This analysis was conducted as part of an ongoing observational study in which a cohort of women recruited at the time of antepartum screening for GDM is undergoing metabolic characterization in pregnancy. The study protocol has been described previously.8,9 In brief, the standard obstetrical practice at our institution is for all pregnant women to undergo screening for GDM at 24 to 28 weeks’ gestation. This screening consists of a one-hour 50 g GCT, followed by a diagnostic OGTT if the result of the GCT is abnormal (defined as a plasma glucose level ≥ 7.8 mmol/L at one hour after ingestion of the glucose load). In this study, women are recruited either before or after the GCT, and all participants undergo a three-hour 100 g OGTT regardless of the GCT result. All participants provide written informed consent. The current analysis was restricted to women with a singleton pregnancy and a GCT ≥ 7.8 mmol/L (n = 888). On the morning of their OGTT, participants came to the hospital laboratory after an overnight fast. They completed interviewer-administered questionnaires that provided data pertaining to demographic information (age, ethnicity), medical history (medications, comorbidities), reproductive and obstetrical history (parity, previous GDM), the current pregnancy (complications, illnesses, medications), and family history. Anthropometric measurements of height (to nearest 0.5 cm) and weight (to nearest 0.1 kg) were obtained using a medical scale. Fasting capillary glucose was measured by Lifescan SureStepFlexx glucose meter (LifeScan Canada Ltd, Burnaby BC). For the three-hour 100 g OGTT, venous blood samples were drawn for measurement of plasma glucose and insulin at baseline (fasting) and at 30, 60, 120, and 180 minutes after ingestion of the 100 g glucose load. Specific insulin was measured using the Roche Modular system and the electrochemiluminescence immunoassay kit (Roche, Montreal, QC). The plasma glucose and insulin measurements on the OGTT enabled assessment of glucose tolerance status and the pathophysiologic determinants of diabetes: insulin sensitivity and pancreatic beta-cell function. As previously described,8 glucose tolerance status on the OGTT was classified as follows: GDM, defined by two or more glucose values above National Diabetes Data Group criteria10; gestational impaired glucose tolerance, defined as only one glucose value exceeding NDDG criteria; or normal glucose tolerance. Insulin sensitivity was assessed Fasting Capillary Glucose as a Screening Test for Ruling Out Gestational Diabetes Mellitus by the Matsuda index, a validated measure of insulin action that can be obtained from the OGTT.11 The inverse of the Homeostasis Model Assessment of Insulin Resistance was determined as a secondary measure of insulin sensitivity.12 Pancreatic beta-cell function was assessed by the Insulin Secretion-Sensitivity Index-2, a validated measure that can be obtained from the OGTT.13,14 The insulinogenic index divided by HOMA-IR was determined as a secondary measure of beta-cell function.15 All analyses were conducted with SAS 9.2 software (SAS Institute, Cary, NC). The study population was stratified into four groups based on the FCG. For each group, we identified the median and interquartile range of continuous variables and the proportions of categorical variables. Continuous variables were compared across the groups by Kruskal-Wallis test. Categorical variables were compared by chi-square test or Fisher exact test. Spearman correlation analysis was performed to evaluate the associations of FCG with measures of metabolic function. The test characteristics of FCG for prediction of GDM were determined by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio associated with different thresholds of FCG. In addition, we determined the proportion of OGTTs that could be averted by not performing the test in women whose FCG was below each of these thresholds. Receiveroperating-characteristic analysis was performed to assess the discriminative capacity of FCG for predicting GDM. The Mount Sinai Hospital Research Ethics Board approved the study protocol. RESULTS Relationship Between Fasting Capillary Glucose and Metabolic Function The study population consisted of 888 pregnant women with an abnormal GCT, of whom 209 had GDM on the OGTT. The characteristics of the study population were stratified into the following four groups: FCG ≤ 4.5 mmol/L (n = 132), FCG between 4.6 and 5.0 mmol/L inclusive (n = 309), FCG between 5.1 and 5.5 mmol/L inclusive (n = 237), and FCG ≥ 5.6 mmol/L (n = 210) (Table 1). The GDM clinical risk factors of age, pre-pregnancy BMI, and prevalence of family history of diabetes progressively increased from the lowest to the highest FCG group (P = 0.008, P < 0.001, and P = 0.032, respectively). Gestational age at the time of the OGTT was slightly higher in women with FCG between 4.6 and 5.0 mmol/L inclusive (P = 0.049). Otherwise, there were no significant differences between the groups with respect to ethnicity, parity, previous GDM, and weight gain in pregnancy to the time of the OGTT. Importantly, the four groups displayed clear metabolic differences with respect to insulin sensitivity, pancreatic beta-cell function, and glucose tolerance. Notably, both insulin sensitivity (Matsuda index and 1/HOMA-IR, both P < 0.001) and beta-cell function (ISSI-2 and IGI/HOMA-IR, both P < 0.001) progressively decreased across the groups as FCG increased. Furthermore, each of the plasma glucose values on the OGTT (fasting, 1 hour, 2 hour, 3 hour) showed a continuous increase across the four groups (all P < 0.001). Most importantly, the FCG groups differed markedly with respect to glucose tolerance status on the OGTT (P < 0.001). Indeed, as FCG rose across the groups, the prevalence of GDM increased (from 12.9% to 16.2% to 22.4% to 42.4%), while the prevalence of NGT decreased (from 69.7% to 67.3% to 56.1% to 36.7%). On Spearman correlation analysis, FCG was positively associated with fasting venous glucose (r = 0.78, P < 0.001) and with each post-challenge glucose value on the OGTT (1 hour glucose: r = 0.39, P < 0.001; 2 hour glucose r = 0.24, P < 0. 001; 3 hour glucose: r = 0.14, P < 0.001). Moreover, FCG was inversely related to both insulin sensitivity (Matsuda index: r = −0.44, P < 0.001; 1/HOMA-IR: r = −0.51, P < 0.001) and beta-cell function (ISSI-2: r = −0.56, P < 0.001; IGI/HOMA-IR: r = −0.55, P < 0.001). Fasting Capillary Glucose and Screening for GDM Having demonstrated that FCG is associated with metabolic function, we next sought to characterize its potential as a screening test for ruling out GDM. The distribution of FCG in the women who had GDM on the OGTT (n = 209) and those who did not have GDM (n = 679) is shown in Figure 1. Of note, there was considerable overlap in the distribution of FCG between these two patient populations, suggesting that there was no clear threshold level of FCG that can be used to rule out GDM. Indeed, even at a threshold as low as 4.5 mmol/L, there were still 13 women with FCG at or below this level who had GDM on the OGTT. To formally evaluate the potential capacity of FCG for ruling out GDM, we determined its test characteristics in this regard. Different thresholds of FCG for predicting GDM and their associated sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the percentage of OGTTs that could be averted if they were not performed in women whose FCG was below this level are shown in Table 2. For example, an FCG threshold of 4.8 mmol/L could eliminate the need for an OGTT in 28.4% of women JUNE JOGC JUIN 2013 l 517 518 l JUNE JOGC JUIN 2013 9 .8 8 .4 GCT, mmol/L 0 .9 1/HOMA-IR 14 .7 IGI/HOMA-IR (4 .9–7 .5) 7 .8 6 .1 2-hour glucose, mmo/L 12 .9 GDM 16 .2 16 .5 67 .3 6 .7 8 .0 9 .2 4 .4 11 .5 767 .9 0 .7 4 .8 8 .4 10 22 .7 4 .2 9 .4 33 .7 57 IQR: interquartile range; DM: diabetes mellitus; GIGT: gestational impaired glucose tolerance . 69 .7 17 .4 NGT GIGT Glucose tolerance status, % 3-hour glucose, mmol/L (6 .4–8 .9) 8 .4 1-hour glucose, mmol/L (7 .4–9 .6) 4 .1 (4 .0–4 .3) (11 .2–21 .5) (768 .8–1099) (0 .6–1 .5) (3 .7–9 .6) (8 .1–9 .0) (7 .0–13 .6) Fasting glucose, mmol/L OGTT 915 .3 ISSI-2 Beta-cell function 6 .2 Matsuda Index Insulin sensitivity 22 .2 Pre-pregnancy BMI (kg/m ) Weight gain in pregnancy, kg 10 .6 >1 2 .3 34 .9 1 Previous GDM, % 54 .6 0 Parity, % 56 .6 15 .2 13 .6 Family history of DM, % 51 .5 13 .6 Other 14 .9 72 .7 69 .9 29 34 (5 .6–7 .6) (7 .1–9 .0) (8 .2–10 .2) (4 .2–4 .5) (8 .6–16 .1) (655 .5–915 .7) (0 .5–0 .9) (3 .3–6 .3) (8 .0–9 .1) (7 .7–13 .0) (21 .0–25 .7) (28–31) (31–37) IQR 4 .6 ≤ FCG ≤ 5 .0 mmol/L n = 309 Asian (20 .2–25 .4) (28–30) (30–35) IQR White 2 29 Mean weeks’ gestation Ethnicity, % 33 Mean age, years n = 132 FCG ≤ 4 .5 mmol/L Table 1. Characteristics of study population stratified by fasting capillary glucose level 42 .4 22 .4 36 .7 7 .1 8 .8 10 .5 5 .1 5 .2 524 .2 0 .3 2 .8 8 .8 10 26 8 .1 13 .8 36 .7 49 .5 66 .2 20 .5 14 .3 65 .2 29 34 21 .0 (5 .4–7 .7) (7 .2–9 .4) (8 .5–10 .7) (4 .5–4 .8) (5 .8–12 .9) (555 .5–816 .9) (0 .3–0 .7) (2 .7–5 .2) (8 .1–9 .1) (6 .8–13 .6) (21 .5–28 .8) (28–30) (31–37) (6 .1–8 .1) (7 .8–9 .9) (9 .3–11 .7) (4 .9–5 .4) (3 .2–7 .5) (424 .9–619 .3) (0 .2–0 .5) (2 .0–4 .2) (8 .2–9 .4) (6 .5–13 .0) (22 .9–30 .5) (28–30) (31–38) IQR FCG > 5 .5 mmol/L n = 210 21 .5 56 .1 6 .7 8 .3 9 .6 4 .6 8 .8 668 .6 0 .5 3 .8 8 .5 9 .5 23 .7 7 .2 14 .8 33 .8 51 .5 55 .7 17 .7 13 .1 69 .2 29 34 IQR 5 .1 ≤ FCG ≤ 5 .5 mmol/L n = 237 P <0 .001 <0 .001 <0 .001 <0 .001 <0 .001 <0 .001 <0 .001 <0 .001 <0 .001 0 .002 0 .501 <0 .001 0 .059 0 .428 0 .032 0 .662 0 .049 0 .008 OBSTETRICS Fasting Capillary Glucose as a Screening Test for Ruling Out Gestational Diabetes Mellitus Figure 1. Histogram showing the distribution of fasting capillary glucose in women who had GDM (n = 209) and women who did not have GDM (n = 679) with an abnormal GCT but would miss 18.2% of cases of GDM. Similarly, a threshold of 4.6 mmol/L could reduce the need for OGTTs in 14.9% of this patient population but at a cost of still missing 8.1% of GDM cases. Lastly, the ROC curve for FCG as a screening test for GDM is shown in Figure 2. This curve shows no clear threshold for optimizing test characteristics, consistent with the modest AUC ROC of 0.67. DISCUSSION In this study, we have demonstrated that FCG in pregnancy is associated with metabolic function as measured on the OGTT. Specifically, FCG was positively associated with each glucose measurement on the OGTT and inversely related to insulin sensitivity and pancreatic beta-cell function. Moreover, the prevalence of GDM progressively increased as FCG increased within the study population. However, despite these findings, its test characteristics for predicting GDM were such that a single FCG measurement after an abnormal GCT was insufficient for reliably ruling out GDM in practice. There has been limited previous study of FCG as a screening test for GDM.6,7 In a low-risk population of 3616 Swedish women, of whom only 55 had GDM, Fadl et al.7 reported that FCG was a useful screening test for GDM. However, the authors noted that the GCT offered better screening test characteristics than did FCG.7 Agarwal et al.6 studied a high-risk population of 1465 women in the United Arab Emirates, of whom 196 had GDM. They reported that FCG had an AUC ROC of 0.83 for the prediction of GDM and could be used as a screening test to reduce the number of OGTTs required for diagnosis of GDM.6 It should be recognized, however, that the generalizability of JUNE JOGC JUIN 2013 l 519 OBSTETRICS Table 2. Test characteristics of different thresholds of FCG for prediction of GDM FCG, mmol/L Sensitivity, % Specificity, % PPV, % NPV, % LR+ LR− OGTTs averted, % ≥ 4 .1 99 .0 2 .1 23 .7 87 .5 1 .01 0 .46 1 .8 ≥ 4 .2 99 .0 4 .0 24 .1 93 .1 1 .03 0 .24 3 .3 ≥ 4 .3 97 .6 6 .5 24 .3 89 .8 1 .04 0 .37 5 .5 ≥ 4 .4 94 .3 9 .9 24 .4 84 .8 1 .05 0 .58 8 .9 ≥ 4 .5 93 .8 13 .5 25 .0 87 .6 1 .08 0 .46 11 .8 ≥ 4 .6 91 .9 16 .9 25 .4 87 .1 1 .11 0 .48 14 .9 ≥ 4 .7 86 .6 24 .2 26 .0 85 .4 1 .14 0 .55 21 .6 ≥ 4 .8 81 .8 31 .5 26 .9 84 .9 1 .19 0 .58 28 .4 ≥ 4 .9 79 .0 39 .2 28 .5 85 .8 1 .30 0 .54 34 .9 ≥ 5 .0 70 .3 50 .1 30 .2 84 .6 1 .41 0 .59 45 .3 ≥ 5 .5 45 .5 79 .8 40 .9 82 .6 2 .25 0 .68 73 .9 ≥ 6 .0 21 .1 95 .3 57 .9 79 .7 4 .47 0 .83 91 .4 ≥ 6 .5 8 .6 99 .1 75 .0 77 .9 9 .75 0 .92 97 .3 PPV: positive predictive value; NPV: negative predictive value; LR+: positive likelihood ratio; LR-: negative likelihood ratio; Percentage of OGTTs averted = (true negative + false negative) / total number of subjects . Figure 2. Receiver operating characteristic curve for fasting capillary glucose as a screening test for GDM (with FCG thresholds of 4.6 to 5.0 mmol/L inclusive labelled) 520 l JUNE JOGC JUIN 2013 Fasting Capillary Glucose as a Screening Test for Ruling Out Gestational Diabetes Mellitus the findings of these two previous studies is limited by the fact that their respective patient populations represented extremes in the risk and prevalence of GDM. In this context, our study extends this literature in three key ways. First, unlike the previous studies, we have evaluated FCG in relation to clinical risk factors and pathophysiologic determinants of GDM. Specifically, we found that FCG is associated with clinical risk factors for GDM such as prepregnancy BMI, family history of diabetes mellitus, and maternal age. Furthermore, in showing its associations with insulin resistance and beta-cell dysfunction, we demonstrate that FCG is a marker of the pathophysiology that leads to GDM. Second, we have studied the use of FCG in a multi-ethnic Canadian population. This population may be more representative of a typical intermediate-risk obstetric population than the high- and low-risk ethnic groups studied previously.6,7 For example, in a similar vein, previous studies have suggested that the relative benefits of fasting plasma glucose measurement (i.e., from venous blood sample) for identifying GDM may differ between women from the United Arab Emirates and those from Canada.16–18 Lastly, we tested the measurement of FCG after initial screening with the GCT. This approach enabled evaluation of FCG in a specific clinical setting in which it has not been previously studied, but one which may facilitate a reduction in the number of OGTTs needed for GDM screening. The rationale for evaluating the use of FCG in women who have had an abnormal GCT relates to the pathophysiology of GDM. GDM develops in women who have a chronic defect in pancreatic beta-cell function such that they are unable to secrete sufficient insulin to maintain euglycemia in the setting of the severe insulin resistance of late pregnancy.3 Evaluation of beta-cell function is generally more reliable under stimulatory test conditions (i.e., such as a glucose challenge), as opposed to static test conditions such as a fasting measurement.13,15 Therefore, we reasoned that FCG likely could not take the place of the GCT for initial GDM screening. Indeed, this hypothesis is supported by the mixed results of previous studies comparing fasting plasma glucose with the GCT for GDM screening.19–21 Accordingly, we reasoned that it may be more appropriate to use the FCG in conjunction with the GCT, rather than supplanting the GCT. Specifically, it may be possible to use FCG measurement as a means for reducing the number of unnecessary OGTTs required after an abnormal GCT. Using this strategy, however, yielded an AUC ROC of only 0.67 for predicting GDM. Furthermore, although the single FCG measurement could reduce the number of OGTTs, it does so at the cost of missing a substantial number of women with GDM. These data thus suggest that a single FCG measurement is insufficient to rule out GDM. Nevertheless, it should also be recognized that its associations with glycemia, insulin resistance, and betacell dysfunction indicate that FCG still holds potential for playing a role in GDM screening. For example, it may be that multiple FCG measurements are required to reliably rule out GDM after an abnormal GCT. In other words, if the initial FCG is below a given threshold, then repeat sampling at specified intervals (such as 3 days later) may be warranted so that the OGTT is only triggered when the FCG is consistently above a certain threshold. Such an approach might improve the capacity of this test to reliably rule out GDM. Thus, further study (ideally by randomized controlled trial) is indicated to evaluate strategies for using serial FCG measurements to reduce the number of OGTTs required after an abnormal GCT.A potential limitation of this study is that GDM was diagnosed using NDDG criteria for the three-hour 100 g OGTT, since protocols for GDM screening vary by jurisdiction. Recently, the International Association of Diabetes and Pregnancy Study Groups has proposed the use of lower glycemic thresholds for diagnosing GDM by two-hour 75 g OGTT.1 It should be recognized, however, that since the NDDG thresholds are more stringent than the recent IADPSG criteria (and hence identify more severe dysglycemia), the observed insufficiency of the single FCG measurement to rule out GDM is likely to apply to the IADPSG criteria as well. The IADPSG has also recommended that all pregnant women undergo an OGTT at 24 to 28 weeks’ gestation without prior screening by GCT. Our findings relating FCG to glycemia, insulin resistance, and beta-cell dysfunction are notable in light of previous criticism that the IADPSG criteria will lead to an increase in the number of OGTTs performed.22,23 Specifically, our findings suggest that strategies for using serial FCG measurements to reduce the number of OGTTs required with the IADSPG approach may warrant consideration. CONCLUSION Fasting capillary glucose showed significant associations with metabolic parameters on the OGTT, including glycemia, insulin resistance, and pancreatic beta-cell dysfunction. Even though the findings of this study indicate that a single FCG measurement could not be used to reliably rule out GDM, its associations with the metabolic parameters described suggest that FCG holds potential for use in GDM screening. Indeed, strategies may exist whereby FCG could be used to reduce the number of unnecessary OGTTs associated with GDM screening. Further study of serial FCG measurement during pregnancy is warranted to refine the screening process for GDM. JUNE JOGC JUIN 2013 l 521 OBSTETRICS ACKNOWLEDGEMENTS The authors wish to thank Mount Sinai Hospital Department of Pathology and Laboratory Medicine and Patient Care Services. This study was supported by operating grants from the Canadian Institutes of Health Research (CIHR) (MOP-84206) and the Canadian Diabetes Association (CDA) (OG-3–08–2543-RR). Anthony J. G. Hanley holds a Tier-II Canada Research Chair in Diabetes Epidemiology. Bernard Zinman holds the Sam and Judy Pencer Family Chair in Diabetes Research at Mount Sinai Hospital and University of Toronto. Ravi Retnakaran holds an Ontario Ministry of Research and Innovation Early Researcher Award. REFERENCES 1. Metzger BE. Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, et al. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82. 2. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of Diabetes in Canada. Can J Diabetes 2008;32(Suppl 1):S168–S180. 3. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest 2005;115(3):485–91. 4. 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–S260. 5. Van Leeuwen M, Louwerse MD, Opmeer BC, Limpens J, Serlie MJ, Reitsma JB, et al. Glucose challenge test for detecting gestational diabetes mellitus: a systematic review. BJOG 2012;119(4):393–401. 6. Agarwal MM, Dhatt GS, Othman Y, Gupta R. Gestational diabetes: fasting capillary glucose as a screening test in a multi-ethnic, high-risk population. Diabet Med 2009;26(8):760–5. 7. Fadl H, Ostlund I, Nilsson K, Hanson U. Fasting capillary glucose as a screening test for gestational diabetes mellitus. BJOG 2006;113(9):1067–71. 8. Goldberg RJ, Ye C, Sermer M, Connelly PW, Hanley AJ, Zinman B, et al. Circadian variation in the response to the glucose challenge test in pregnancy: implications for screening for gestational diabetes. Diabetes Care 2012;35(7):1578–84. 522 l JUNE JOGC JUIN 2013 9. Retnakaran R, Ye C, Hanley AJ, Sermer M, Connelly PW, Zinman B, et al. Effects of maternal weight, adipokines, glucose intolerance and lipids on infant birthweight in women without gestational diabetes mellitus. CMAJ 2012;184(12):1353–60. 10. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039–57. 11. Matsuda M, Defronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70. 12. Mathews DR, Hosker GP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9. 13. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B. Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity 2008;16(8):1901–7. 14. Retnakaran R, Qi Y, Goran MI, Hamilton JK. Evaluation of proposed oral disposition index measures in relation to the actual disposition index. Diabet Med 2009;26:1198–1203. 15. Kahn SE. The relative contributions of insulin resistance and b-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003;46:3–19. 16. Agarwal MM, Dhatt GS, Shah SM. Gestational Diabetes Mellitus: Simplifying the International Association of Diabetes and Pregnancy diagnostic algorithm using fasting plasma glucose. Diabetes Care 2010;33(9):2018–20. 17. Mahdavian M, Hivert MF, Baillargeon JP, Menard J, Ouellet A, Ardilouze JL. Gestational Diabetes Mellitus: Simplifying the International Association of Diabetes and Pregnancy diagnostic algorithm using fasting plasma glucose: comment on Agarwal, Dhatt, and Shah. Diabetes Care 2010;33:e145. 18. Agarwal MM, Dhatt GS, Shah SM. Gestational Diabetes Mellitus: Simplifying the International Association of Diabetes and Pregnancy diagnostic algorithm using fasting plasma glucose: response to Mahdavian et al. Diabetes Care 2010;33:e146. 19. Rey E, Hudon L, Michon N, Boucher P, Ethier J, Saint-Louis P. Fasting plasma glucose versus glucose challenge test: screening for gestational diabetes and cost effectiveness. Clin Biochem 2004;37:780–4. 20. Sacks DA, Greenspoon JS, Fotheringham N. Could the fasting plasma glucose assay be used to screen for gestational diabetes? J Reprod Med 1992;37:907–9. 21. Sacks DA, Chen W, Wolde-Tsadik G, Buchanan TA. Fasting plasma glucose test at the first prenatal visit as a screen for gestational diabetes. Obstet Gynecol 2003; 101(6):1197–203. 22. Ryan EA. Diagnosing gestational diabetes. Diabetologia 2011; 54(3):480–6. 23. Long H. Diagnosing gestational diabetes: can expert opinions replace scientific evidence? Diabetologia 2011; 54(9):2211–3.