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The usefulness of glycosuria and the influence of maternal blood pressure in screening for gestational diabetes
European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148
The usefulness of glycosuria and the influence of maternal blood pressure in screening for gestational diabetes Kai J. Buhlinga,*, Lennart Elzea, Wolfgang Henricha, Elizabeth Starra, Ursula Steina, Gerda Siebertb, Joachim W. Dudenhausena a
Clinic of Obstetrics, Charite´ Campus Virchow-Klinikum, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany b Institute for Medical Biometry, Humboldt University, Berlin, Germany Received 13 June 2002; received in revised form 13 May 2003; accepted 23 June 2003
Abstract Objective: Although gestational diabetes is among the most common diseases arising during pregnancy, glucose stix is the only screening test to date in Germany. Our goal was to evaluate the sensitivity of the glucose-stix for diabetes screening and the possible influence of other parameters. Methods: 1001 patients who underwent the 50 g glucose screening test between June 1, 1997 and January 5, 2000 as part of prenatal care were asked to participate. In accordance with the guidelines of the American Diabetes Association, patients with a screening test result 140 mg/dl underwent a oral glucose tolerance test (Carpenter/Coustan criteria). A urine sample was collected prior to the test. The glucose content of the urine was semiquantitatively analyzed using a test strip (Multistix 10 SG1 Bayer1, Munich, Germany). Blood pressure was measured in 349 consecutive cases according to the criteria of the National Institute of Health. Results: The overall frequency of gestational diabetes was 4.1% (37/912). 8.2% of the women presented with glycosuria (82/1001, 36 before screening, 46 based on the pregnancy medical records booklet). 30/82 (37%) of these patients had a pathological screening test (P ¼ 0:029). 7.1% (52/729) of the healthy patients and 10.8% (4/37) of the gestational diabetics had glycosuria at least once. Therefore, the sensitivity of glycosuria is 10.8%, the positive predictive value is 6.6%. The systolic blood pressure was 116 12 mmHg and the diastolic blood pressure 72 9 mmHg. Three of 349 (0.9%) patients were documented with preexisting hypertension, 14/349 (4.0%) patients with ‘‘pregnancy induced hypertension’’. Patients with glycosuria were both significantly more advanced in gestational age (34:4 2:8 versus 33:7 2:9, P ¼ 0:009) and had higher diastolic blood pressure (79 9 versus 71 9, P ¼ 0:005). The 50 g glucose screening test results showed only a tendency to differ (131 23 versus 127 24, P ¼ 0:073). A multivariate analysis of these factors showed a significant influence of the diastolic blood pressure (P ¼ 0:016) and the 50 g glucose screening test (P ¼ 0:032), whereas the gestational week had no influence (P ¼ 0:673). Conclusions: Urine glucose dip stick analysis is not useful in the detection of gestational diabetes because of its low sensitivity and negative predictive value. Our study suggests that glycosuria is not only dependent on the blood glucose level, but highly influenced by diastolic blood pressure. The results clearly underscore the need for standardized, routine testing of every pregnant woman. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Glycosuria; Gestational diabetes; Screening; Blood pressure
1. Objective Although gestational diabetes is among the most common diseases arising during pregnancy, no standard screening test involving the measuring of blood sugar is performed to date in Germany. The national maternal health guidelines (‘‘Mutterschaftsrichtlinien’’) only call for a urine glucose-stix check at every prenatal appointment. *
Corresponding author. Tel.: þ49-304505-64293; fax: þ49-304505-64901. E-mail address: [email protected] (K.J. Buhling).
During pregnancy, the absorption capacity of the kidneys for glucose is reduced. This is caused by the elevated glomerular filtration rate (GFR) and the decrease in glucose carriers in the kidney [1,2]. The German national maternal health guidelines do not contain any regulations regarding semi-quantitative measuring methods, although the cut-off values vary depending on the manufacturer. The wide variety of commercially available test strips is listed in Table 1 [3,4]. Few studies have examined the sensitivity of glycosuria regarding gestational diabetes [5]. The consensus is that the two frequently occur simultaneously, however the
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.06.013
146
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148
Table 1 Cut-off levels of various glucose stix (selection) [2,3] Manufacturer
Cut-off value (mg/dl)
Diastix (Bayer1, Leverkusen, Germany) Clinistix (Bayer1, Leverkusen, Germany) Multistix 10 SG (Bayer1, Leverkusen, Germany) Diabur-Test 5000 (Roche1, Mannheim, Germany) Combur (Roche1, Mannheim, Germany)
75–125 75–125 75–125 100 40
diagnostic value of regular testing with glucose-stix during pregnancy has not been adequately proven. In the following prospective study, the sensitivity of the glucose-stix was tested in comparison with the 50 g glucose screening test.
2. Patients and methods
equaled or exceeded 140 mg/dl. Within the next few days, an OGTT using 75 g oligosaccharide was given to patients in the fasted state. The OGTT was technically analyzed like the 50 g screening test and the cut-off values of O’Sullivan (90/ 165/145 mg/dl) were used [8]. For comparative purposes, the OGTT results were also evaluated using the criteria of Carpenter/Coustan which correspond with those of the German Diabetes Association and the German Society for Gynecology and Obstetrics (90/180/155 mg/dl) [6,9]. 2.3. Glycosuria A urine sample was collected from patients prior to administration of the screening test. The test strips (Multistix 10 SG1 Bayer1, Munich, Germany) were used to semiquantitatively measure the amount of glucose in the fresh urine sample. In accordance with the manufacturer’s specifications, the number of colored squares was recorded (‘‘trace’’, ‘‘single positive’’, ‘‘double positive’’) [3].
2.1. Patients 2.4. Blood pressure All patients receiving prenatal care in our clinic between June 1, 1997 and January 5, 2000 who had not been previously tested for gestational diabetes, were included in our study following informed consent. The number of prenatal visits and the frequency of glycosuria was taken from the pregnancy medical records booklet (Mutterpass) issued to every pregnant woman in Germany (Fig. 1).
The blood pressure was measured in a sitting position using the sphygmomanometer of boso1 (Jungingen, Germany) according to the criteria of the National Institute of Health [10]. Patients with repeated systolic measurements above 140 mmHg or diastolic measurements above 90 mmHg were classified as having ‘‘pregnancy induced hypertension’’.
2.2. Diagnostics
2.5. Statistics
In accordance with the criteria of the American Diabetes Association (ADA) and the Deutschen Diabetes Gesellschaft (DDG), the 50 g glucose screening test was carried out independent of the time of day or any previous meals [6,7]. Capillary whole blood was analyzed with the hexokinase method. An oral glucose tolerance test (OGTT) was recommended to all patients whose one hour test result
For statistical analysis of abnormally distributed data, we used a nonparametric test (Kruskal–Wallis-test) and for nominal data, the Chi-square test. A P-value below 0.05 was considered significant.
3. Results 3.1. Patients
Glukosuria 4%
1001 pregnant women were included in the evaluation. The mean age was 28:5 5 years, and the testing was carried out in the 33:8 3 weeks of gestation. The average body-mass-index was 23.6 kg/m2 (4.4). Prior to the testing in our clinic, patients had an average of 8:2 2:3 prenatal visits. Patients with a positive screening test result were somewhat older, had a higher body mass index, a somewhat higher systolic blood pressure, and a lesser weight gain than pregnant women with a normal screening test (Table 2).
p=0.008 3%
2%
1%
3.2. Fifty gram glucose screening test and oral glucose tolerance test
0% 1. Trimester
2. Trimester
3. Trimester
Fig. 1. Frequency of glycosuria in the various trimesters.
267/1001(27%) of the patients had an elevated screening test. 178 (67%) of these patients underwent further
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148 Table 2 Comparison of the medical histories of pregnant women with positive and negative screening test results 50 g Test Negative (n ¼ 734) Age (years) Parity (% prima parity) Body-mass-index (kg/m2) Weight gain (kg) Gestational week at time of screening Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) 50 g glucose screening test (mg/dl)
28 53 23.4 13.7 33.7
5 4.2 5.1 3.0
115 12 72 9 116 15
147
n 800
p=0.049
P 600
Positive (n ¼ 267) 29 41 24.2 12.6 33.8
5 4.7 5.2 2.8
0.006 0.002 0.029 0.001 0.668
118 13 72 9 159 16
0.067 0.887 <0.001
400
Glukosuria 200
no yes
0
normal
pathological
50g glucose screening test
diagnostic measures and were included in the analysis. 37/ 178 (21%). The overall frequency of gestational diabetes was 4.1% (37/912). The sensitivity of the 50 g glucose screening test for this test group was 97.3%. However, the positive predictive value was only 21%.
Fig. 2. Correlation between glycosuria and the 50 g glucose screening test.
(8.2%). 30/82 (37%) of these patients had a pathological screening test (P ¼ 0:029). 3.4. Glycosuria and the oral glucose tolerance test
3.3. Glycosuria and the 50 g glucose screening test The rate of glycosuria increases with the gestational week. 1–13 weeks of gestational age (GA): 0.9%, 13–26 weeks of GA: 2.3%, and 26–40 weeks of GA: 2.6% (P ¼ 0:008). Immediately preceding the 50 g glucose screening test, 3.6% (36/1001) patients had a positive glucose stix reading. Based on the pregnancy medical records booklet, 4.6% (46/1001) additional patients were identified as having glycosuria at least once during their pregnancy. Thus, 8.2% (82/1001) pregnant women had glycosuria at a prenatal visit or preceding their screening test. The demographic data are shown in Table 3. Of those patients with a positive glucose stix reading directly preceding the screening test, 18 (50%) had a pathological 50 g glucose screening test (P ¼ 0:012, Fig. 2). Adding the positive glucose stix readings to the documented reading in the pregnancy medical records booklet, the frequency of at least one-time glycosuria was 82/1001
The evaluation of the glycosuria rates among gestational diabetics (pathological OGTT) and metabolically healthy pregnant patients (negative screening) produced the following results: 7.1% (52/729) of the healthy patients and 10.8% (4/37) of the gestational diabetics had glycosuria at least once. Therefore, the sensitivity of glycosuria is 10.8%, the positive predictive value is 6.6%. 89.2% of the patients would have unnecessarily undergone an OGTT based on the glycosuria. 3.5. Blood pressure Blood pressure measurements were recorded in 349 consecutive cases. The mean systolic blood pressure was rate of glucosuria 20% 18%
Table 3 Comparison of the medical history data of pregnant women with positive and negative urine-stix Urine-stix Negative Age (years) Parity (% prima parity) Body-mass-index (kg/m2) Weight gain (kg) Gestational week at time of screening Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) 50 g glucose screening test (mg/dl)
28.5 49 23.6 13.4 33.7
5.1 4.4 5.1 2.9
116 12 71 9 127 24
P Positive 28.8 56 23.6 13.8 34.4
5.6
p=0.025
16% 14% 12% 10%
4.4 4.8 2.8
0.732 0.852 0.953 0.612 0.009
120 16 76 9 131 23
0.128 0.005 0.073
8% 6% 4%
lowest thru 70
71-80
81 thru highest
diastolic blood pressure (mm Hg) Fig. 3. Rate of glycosuria grouped by diastolic blood pressure.
148
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148
116 12 mmHg and the diastolic blood pressure 72 9 mmHg. Three (0.9%) of the patients were documented with preexisting hypertension. Fourteen (4.0%) patients were classified as having ‘‘pregnancy induced hypertension’’. 3.6. Influence of blood pressure on glycosuria The rate of glycosuria increased with the value of diastolic blood pressure (Fig. 3). A comparison of the medical histories and anthropometric data of the pregnant patients with and without glycosuria showed that both groups differ significantly with respect to gestational age and diastolic blood pressure. Patients with glycosuria had both significantly higher gestational age (34:4 2:8 versus 33:7 2:9, P ¼ 0:009) and diastolic blood pressure (79 9 versus 71 9, P ¼ 0:005, Table 3). The 50 g glucose screening test results showed only a tendency to differ (131 23 versus 127 24, P ¼ 0:073). A multivariate analysis of these factors showed a significant influence of the diastolic blood pressure (P ¼ 0:016) and the 50 g glucose screening test (P ¼ 0:032), whereas the gestational week had no influence (P ¼ 0:673).
maintained. Usually the resorption of glucose takes place in the distal tubulus, less in the proximal part. Additionally the capacity of the resorption is influenced negatively by human placental lactogen which is the reason for a more frequently (physiological?) glycosuria in the second half of pregnancy [11]. On the other hand the renal filtration is influenced positively by the blood pressure [12]. We found no studies on glycosuria and gestational diabetes which took blood pressure into consideration. Our study suggests the rate of glycosuria is not only dependent on blood glucose levels, but also highly influenced by diastolic blood pressure. The results clearly underscore the need for standardized, routine testing of every pregnant woman measuring blood glucose directly.
Acknowledgements We thank Bayer1 and Roche1 (Mannheim, Germany) for generously supplying the materials for this study. Also thanks to the study nurse Christiana for careful reading of the glucose stix. K.J.B. is supported by a University Lecturing Qualification Grant from the Charite´ .
4. Discussion This prospective study examined the coexistence of glycosuria, hypertension, and gestational diabetes in a population of 1001 pregnant patients who sought prenatal care in our clinic as part of the German national maternal health guidelines. Only patients who had not yet been diagnosed as gestational diabetics were recruited for the study. All patients underwent the 50 g glucose screening test. The rate of positive test results and pathological glucose tolerance tests was equivalent to that of other studies. We therefore conclude that our test population was not at a higher risk. Glycosuria is, indeed, a risk factor for gestational diabetes (OR 1.5), however, glycosuria is not a suitable screening parameter. Our examination shows the low sensitivity of glycosuria (10.8%) with respect to gestational diabetes. In addition, only 37% of patients with glycosuria had a pathological glucose screening test which produces a very low positive predictive value of 6.6%. To our knowledge, this is the first study reporting an independent relationship between the glycosuria rate and blood pressure during pregnancy. Renal function is dependent upon generous blood flow to the kidneys. As previously mentioned, blood flow to the kidneys is dependent on the systemic blood pressure. However, actual renal perfusion, and hence adequate glomerular perfusion, is further dependent on intra-renal vascular resistance. Auto regulatory mechanisms monitoring changes in vascular resistance, ensure that over a wide range of perfusion pressures renal blood flow remains stable and glomerular filtration can be
References [1] Davison JM, Hytten FE. The effect of pregnancy on the renal handling of glucose. Br J Obstet Gynaecol 1972;82:374–81. [2] Schroder W. Glycosuria in Pregnancy Gynakologe 1991;24:228–9. [3] Bayer1 Vital Product Information. Bayer1, Munich, Germany; 2002. [4] Roche1 Product Information. Roche Diagnostics1, Mannheim, Germany; 2001. [5] Hooper DW. Detecting GD and preeclampsia. Effectiveness of routine urine screening for glucose and protein. J Reprod Med 1996; 41:885–8. [6] Deutsche Diabetes Gesellschaft. Leitlinien der Arbeitsgemeinschaft Diabetes und Schwangerschaft (also available at http://www. deutsche-diabetes-gesellschaft.de updated June 2001). [7] American Diabetes Association: Clinical Practice Recommendations: Gestational Diabetes mellitus. Diabetes Care 24 (Suppl 1):S77–S79; 2001 (also available at http://www.diabetes.org/clinicalrecommendations/Supplement101/S77.htm updated January 2001). [8] O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1963;13:278–85. [9] Carpenter MW, Coustan DR. Criteria for screening test for gestational diabetes. Am J Obstet Gynecol 1982;144:768–73. [10] NIH: National High Blood Pressure Education Program—Working Group Report on High Blood Pressure in Pregnancy 2000 (http:// www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_preg.pdf last update July 2000). [11] Feige A, Mitzkat HJ, Jakobitz K. Investigations into the influence of pregnancy on carbohydrate and lipid metabolism of the mother—part 1: the kinetics of individual parameters of carbohydrate and lipid metabolism and of various hormones as a function of gestational age. Z Geburtsh u Perinat 1984;188:136–42. [12] Guyton A.C., Hall J.E., Textbook of medical physiology. 10th ed., 2000.
The usefulness of glycosuria and the influence of maternal blood pressure in screening for gestational diabetes Kai J. Buhlinga,*, Lennart Elzea, Wolfgang Henricha, Elizabeth Starra, Ursula Steina, Gerda Siebertb, Joachim W. Dudenhausena a
Clinic of Obstetrics, Charite´ Campus Virchow-Klinikum, Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany b Institute for Medical Biometry, Humboldt University, Berlin, Germany Received 13 June 2002; received in revised form 13 May 2003; accepted 23 June 2003
Abstract Objective: Although gestational diabetes is among the most common diseases arising during pregnancy, glucose stix is the only screening test to date in Germany. Our goal was to evaluate the sensitivity of the glucose-stix for diabetes screening and the possible influence of other parameters. Methods: 1001 patients who underwent the 50 g glucose screening test between June 1, 1997 and January 5, 2000 as part of prenatal care were asked to participate. In accordance with the guidelines of the American Diabetes Association, patients with a screening test result 140 mg/dl underwent a oral glucose tolerance test (Carpenter/Coustan criteria). A urine sample was collected prior to the test. The glucose content of the urine was semiquantitatively analyzed using a test strip (Multistix 10 SG1 Bayer1, Munich, Germany). Blood pressure was measured in 349 consecutive cases according to the criteria of the National Institute of Health. Results: The overall frequency of gestational diabetes was 4.1% (37/912). 8.2% of the women presented with glycosuria (82/1001, 36 before screening, 46 based on the pregnancy medical records booklet). 30/82 (37%) of these patients had a pathological screening test (P ¼ 0:029). 7.1% (52/729) of the healthy patients and 10.8% (4/37) of the gestational diabetics had glycosuria at least once. Therefore, the sensitivity of glycosuria is 10.8%, the positive predictive value is 6.6%. The systolic blood pressure was 116 12 mmHg and the diastolic blood pressure 72 9 mmHg. Three of 349 (0.9%) patients were documented with preexisting hypertension, 14/349 (4.0%) patients with ‘‘pregnancy induced hypertension’’. Patients with glycosuria were both significantly more advanced in gestational age (34:4 2:8 versus 33:7 2:9, P ¼ 0:009) and had higher diastolic blood pressure (79 9 versus 71 9, P ¼ 0:005). The 50 g glucose screening test results showed only a tendency to differ (131 23 versus 127 24, P ¼ 0:073). A multivariate analysis of these factors showed a significant influence of the diastolic blood pressure (P ¼ 0:016) and the 50 g glucose screening test (P ¼ 0:032), whereas the gestational week had no influence (P ¼ 0:673). Conclusions: Urine glucose dip stick analysis is not useful in the detection of gestational diabetes because of its low sensitivity and negative predictive value. Our study suggests that glycosuria is not only dependent on the blood glucose level, but highly influenced by diastolic blood pressure. The results clearly underscore the need for standardized, routine testing of every pregnant woman. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Glycosuria; Gestational diabetes; Screening; Blood pressure
1. Objective Although gestational diabetes is among the most common diseases arising during pregnancy, no standard screening test involving the measuring of blood sugar is performed to date in Germany. The national maternal health guidelines (‘‘Mutterschaftsrichtlinien’’) only call for a urine glucose-stix check at every prenatal appointment. *
Corresponding author. Tel.: þ49-304505-64293; fax: þ49-304505-64901. E-mail address: [email protected] (K.J. Buhling).
During pregnancy, the absorption capacity of the kidneys for glucose is reduced. This is caused by the elevated glomerular filtration rate (GFR) and the decrease in glucose carriers in the kidney [1,2]. The German national maternal health guidelines do not contain any regulations regarding semi-quantitative measuring methods, although the cut-off values vary depending on the manufacturer. The wide variety of commercially available test strips is listed in Table 1 [3,4]. Few studies have examined the sensitivity of glycosuria regarding gestational diabetes [5]. The consensus is that the two frequently occur simultaneously, however the
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2003.06.013
146
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148
Table 1 Cut-off levels of various glucose stix (selection) [2,3] Manufacturer
Cut-off value (mg/dl)
Diastix (Bayer1, Leverkusen, Germany) Clinistix (Bayer1, Leverkusen, Germany) Multistix 10 SG (Bayer1, Leverkusen, Germany) Diabur-Test 5000 (Roche1, Mannheim, Germany) Combur (Roche1, Mannheim, Germany)
75–125 75–125 75–125 100 40
diagnostic value of regular testing with glucose-stix during pregnancy has not been adequately proven. In the following prospective study, the sensitivity of the glucose-stix was tested in comparison with the 50 g glucose screening test.
2. Patients and methods
equaled or exceeded 140 mg/dl. Within the next few days, an OGTT using 75 g oligosaccharide was given to patients in the fasted state. The OGTT was technically analyzed like the 50 g screening test and the cut-off values of O’Sullivan (90/ 165/145 mg/dl) were used [8]. For comparative purposes, the OGTT results were also evaluated using the criteria of Carpenter/Coustan which correspond with those of the German Diabetes Association and the German Society for Gynecology and Obstetrics (90/180/155 mg/dl) [6,9]. 2.3. Glycosuria A urine sample was collected from patients prior to administration of the screening test. The test strips (Multistix 10 SG1 Bayer1, Munich, Germany) were used to semiquantitatively measure the amount of glucose in the fresh urine sample. In accordance with the manufacturer’s specifications, the number of colored squares was recorded (‘‘trace’’, ‘‘single positive’’, ‘‘double positive’’) [3].
2.1. Patients 2.4. Blood pressure All patients receiving prenatal care in our clinic between June 1, 1997 and January 5, 2000 who had not been previously tested for gestational diabetes, were included in our study following informed consent. The number of prenatal visits and the frequency of glycosuria was taken from the pregnancy medical records booklet (Mutterpass) issued to every pregnant woman in Germany (Fig. 1).
The blood pressure was measured in a sitting position using the sphygmomanometer of boso1 (Jungingen, Germany) according to the criteria of the National Institute of Health [10]. Patients with repeated systolic measurements above 140 mmHg or diastolic measurements above 90 mmHg were classified as having ‘‘pregnancy induced hypertension’’.
2.2. Diagnostics
2.5. Statistics
In accordance with the criteria of the American Diabetes Association (ADA) and the Deutschen Diabetes Gesellschaft (DDG), the 50 g glucose screening test was carried out independent of the time of day or any previous meals [6,7]. Capillary whole blood was analyzed with the hexokinase method. An oral glucose tolerance test (OGTT) was recommended to all patients whose one hour test result
For statistical analysis of abnormally distributed data, we used a nonparametric test (Kruskal–Wallis-test) and for nominal data, the Chi-square test. A P-value below 0.05 was considered significant.
3. Results 3.1. Patients
Glukosuria 4%
1001 pregnant women were included in the evaluation. The mean age was 28:5 5 years, and the testing was carried out in the 33:8 3 weeks of gestation. The average body-mass-index was 23.6 kg/m2 (4.4). Prior to the testing in our clinic, patients had an average of 8:2 2:3 prenatal visits. Patients with a positive screening test result were somewhat older, had a higher body mass index, a somewhat higher systolic blood pressure, and a lesser weight gain than pregnant women with a normal screening test (Table 2).
p=0.008 3%
2%
1%
3.2. Fifty gram glucose screening test and oral glucose tolerance test
0% 1. Trimester
2. Trimester
3. Trimester
Fig. 1. Frequency of glycosuria in the various trimesters.
267/1001(27%) of the patients had an elevated screening test. 178 (67%) of these patients underwent further
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148 Table 2 Comparison of the medical histories of pregnant women with positive and negative screening test results 50 g Test Negative (n ¼ 734) Age (years) Parity (% prima parity) Body-mass-index (kg/m2) Weight gain (kg) Gestational week at time of screening Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) 50 g glucose screening test (mg/dl)
28 53 23.4 13.7 33.7
5 4.2 5.1 3.0
115 12 72 9 116 15
147
n 800
p=0.049
P 600
Positive (n ¼ 267) 29 41 24.2 12.6 33.8
5 4.7 5.2 2.8
0.006 0.002 0.029 0.001 0.668
118 13 72 9 159 16
0.067 0.887 <0.001
400
Glukosuria 200
no yes
0
normal
pathological
50g glucose screening test
diagnostic measures and were included in the analysis. 37/ 178 (21%). The overall frequency of gestational diabetes was 4.1% (37/912). The sensitivity of the 50 g glucose screening test for this test group was 97.3%. However, the positive predictive value was only 21%.
Fig. 2. Correlation between glycosuria and the 50 g glucose screening test.
(8.2%). 30/82 (37%) of these patients had a pathological screening test (P ¼ 0:029). 3.4. Glycosuria and the oral glucose tolerance test
3.3. Glycosuria and the 50 g glucose screening test The rate of glycosuria increases with the gestational week. 1–13 weeks of gestational age (GA): 0.9%, 13–26 weeks of GA: 2.3%, and 26–40 weeks of GA: 2.6% (P ¼ 0:008). Immediately preceding the 50 g glucose screening test, 3.6% (36/1001) patients had a positive glucose stix reading. Based on the pregnancy medical records booklet, 4.6% (46/1001) additional patients were identified as having glycosuria at least once during their pregnancy. Thus, 8.2% (82/1001) pregnant women had glycosuria at a prenatal visit or preceding their screening test. The demographic data are shown in Table 3. Of those patients with a positive glucose stix reading directly preceding the screening test, 18 (50%) had a pathological 50 g glucose screening test (P ¼ 0:012, Fig. 2). Adding the positive glucose stix readings to the documented reading in the pregnancy medical records booklet, the frequency of at least one-time glycosuria was 82/1001
The evaluation of the glycosuria rates among gestational diabetics (pathological OGTT) and metabolically healthy pregnant patients (negative screening) produced the following results: 7.1% (52/729) of the healthy patients and 10.8% (4/37) of the gestational diabetics had glycosuria at least once. Therefore, the sensitivity of glycosuria is 10.8%, the positive predictive value is 6.6%. 89.2% of the patients would have unnecessarily undergone an OGTT based on the glycosuria. 3.5. Blood pressure Blood pressure measurements were recorded in 349 consecutive cases. The mean systolic blood pressure was rate of glucosuria 20% 18%
Table 3 Comparison of the medical history data of pregnant women with positive and negative urine-stix Urine-stix Negative Age (years) Parity (% prima parity) Body-mass-index (kg/m2) Weight gain (kg) Gestational week at time of screening Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) 50 g glucose screening test (mg/dl)
28.5 49 23.6 13.4 33.7
5.1 4.4 5.1 2.9
116 12 71 9 127 24
P Positive 28.8 56 23.6 13.8 34.4
5.6
p=0.025
16% 14% 12% 10%
4.4 4.8 2.8
0.732 0.852 0.953 0.612 0.009
120 16 76 9 131 23
0.128 0.005 0.073
8% 6% 4%
lowest thru 70
71-80
81 thru highest
diastolic blood pressure (mm Hg) Fig. 3. Rate of glycosuria grouped by diastolic blood pressure.
148
K.J. Buhling et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 113 (2004) 145–148
116 12 mmHg and the diastolic blood pressure 72 9 mmHg. Three (0.9%) of the patients were documented with preexisting hypertension. Fourteen (4.0%) patients were classified as having ‘‘pregnancy induced hypertension’’. 3.6. Influence of blood pressure on glycosuria The rate of glycosuria increased with the value of diastolic blood pressure (Fig. 3). A comparison of the medical histories and anthropometric data of the pregnant patients with and without glycosuria showed that both groups differ significantly with respect to gestational age and diastolic blood pressure. Patients with glycosuria had both significantly higher gestational age (34:4 2:8 versus 33:7 2:9, P ¼ 0:009) and diastolic blood pressure (79 9 versus 71 9, P ¼ 0:005, Table 3). The 50 g glucose screening test results showed only a tendency to differ (131 23 versus 127 24, P ¼ 0:073). A multivariate analysis of these factors showed a significant influence of the diastolic blood pressure (P ¼ 0:016) and the 50 g glucose screening test (P ¼ 0:032), whereas the gestational week had no influence (P ¼ 0:673).
maintained. Usually the resorption of glucose takes place in the distal tubulus, less in the proximal part. Additionally the capacity of the resorption is influenced negatively by human placental lactogen which is the reason for a more frequently (physiological?) glycosuria in the second half of pregnancy [11]. On the other hand the renal filtration is influenced positively by the blood pressure [12]. We found no studies on glycosuria and gestational diabetes which took blood pressure into consideration. Our study suggests the rate of glycosuria is not only dependent on blood glucose levels, but also highly influenced by diastolic blood pressure. The results clearly underscore the need for standardized, routine testing of every pregnant woman measuring blood glucose directly.
Acknowledgements We thank Bayer1 and Roche1 (Mannheim, Germany) for generously supplying the materials for this study. Also thanks to the study nurse Christiana for careful reading of the glucose stix. K.J.B. is supported by a University Lecturing Qualification Grant from the Charite´ .
4. Discussion This prospective study examined the coexistence of glycosuria, hypertension, and gestational diabetes in a population of 1001 pregnant patients who sought prenatal care in our clinic as part of the German national maternal health guidelines. Only patients who had not yet been diagnosed as gestational diabetics were recruited for the study. All patients underwent the 50 g glucose screening test. The rate of positive test results and pathological glucose tolerance tests was equivalent to that of other studies. We therefore conclude that our test population was not at a higher risk. Glycosuria is, indeed, a risk factor for gestational diabetes (OR 1.5), however, glycosuria is not a suitable screening parameter. Our examination shows the low sensitivity of glycosuria (10.8%) with respect to gestational diabetes. In addition, only 37% of patients with glycosuria had a pathological glucose screening test which produces a very low positive predictive value of 6.6%. To our knowledge, this is the first study reporting an independent relationship between the glycosuria rate and blood pressure during pregnancy. Renal function is dependent upon generous blood flow to the kidneys. As previously mentioned, blood flow to the kidneys is dependent on the systemic blood pressure. However, actual renal perfusion, and hence adequate glomerular perfusion, is further dependent on intra-renal vascular resistance. Auto regulatory mechanisms monitoring changes in vascular resistance, ensure that over a wide range of perfusion pressures renal blood flow remains stable and glomerular filtration can be
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