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ELSEVIER Diabetes Research and Clinical Practice 27 (1995) 147-151 The 75 g oral glucose tolerance in pregnancy F. Ian R. Martin*a, Sujiva Ratnaikeb, Andrew Woottonb, Peter Condosc, Philip E.N. SuterC “Department of Diabetes and Endocrinology, The Royal Melbourne Hospital and Essendon and Disrricr Memorial Hospital, C/ - Royal Melbourne Hospital Post Office, Victoria 3050, Australia bDepartment of Biochemistry, The Royal Melbourne Hospital and Essendon and Districr Memorial Hospital, C/ - Royal Melbourne Hospital POSI Office. Victoria 3050, Australia ‘Department of Obstetrics, The Royal Melbourne Hospita’l and Essendon and Districr Memorial Hospital, C/ - Royal Melbourne Hospital Post Office. Victoria 3050, Australia Received; revision received 2 December 1994;accepted I I January 1995 Abstract A 75 g oral glucose tolerance test was performed between 26 and 32 weeks gestation in 1371women attending an ante-natal clinic in Melbourne. Gestational diabetes according to various criteria was present in 4.2% (2 h plasma glucose L 8.0 mmol/l), 5.2% (2 h plasma glucose 2 7.8 mmoV1) and 5.5% by the proposed Australian criteria (fasting plasma glucose 2 5.5 mmol/l and/or 2 h plasma glucose 1 8.0 mmol/l). The long-term implications of gestational diabetes in the development of diabetes and metabolic abnormalities for both the mother and her child in addition to related infant morbidity emphasisethe urgent need for an agreed definition of this condition. Keywords: Gestational diabetes; 75 g Glucose tolerance test; Pregnancy; Diagnosis 1. Introduction The diagnosis of gestational diabetes has serious implications both for the fetus and the mother. Fetal embryopathy due to diabetes has long been recognised as a cause of still-birth and neonatal death but the significance of gestational diabetes as an important risk factor for permanent non- insulin-dependent diabetes has been documented l Corresponding author, Tel.: +61 3 3471550; Fax: +61 3 3428389. more recently [l]. Despite its world-wide impor- tance the definition of gestational diabetes is the subject of continuing controversy [2-71. Most coun- tries usethe World Health Organisation (WHO) de- finition of impaired glucose tolerance following a 75 g glucoseload although the 100g glucose toler- ance test is usual in North America and there is a very large experience of a 50 g glucose load at the Mercy Hospital in Melbourne. The recommended WHO criteria for gestational diabetes are the same as impaired glucose tolerance (IGT). The 1980 WHO definition of IGT; fasting plasma glucose 0168-8227/95/%09.50 0 1995Elsevier Science Ireland Ltd. All rights reserved SSDI 0168-8227(95)01035-C

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Page 1: The 75 g oral glucose tolerance in pregnancy

ELSEVIER Diabetes Research and Clinical Practice 27 (1995) 147-151

The 75 g oral glucose tolerance in pregnancy

F. Ian R. Martin*a, Sujiva Ratnaikeb, Andrew Woottonb, Peter Condosc, Philip E.N. SuterC

“Department of Diabetes and Endocrinology, The Royal Melbourne Hospital and Essendon and Disrricr Memorial Hospital, C/ - Royal Melbourne Hospital Post Office, Victoria 3050, Australia

bDepartment of Biochemistry, The Royal Melbourne Hospital and Essendon and Districr Memorial Hospital, C/ - Royal Melbourne Hospital POSI Office. Victoria 3050, Australia

‘Department of Obstetrics, The Royal Melbourne Hospita’l and Essendon and Districr Memorial Hospital, C/ - Royal Melbourne Hospital Post Office. Victoria 3050, Australia

Received; revision received 2 December 1994; accepted I I January 1995

Abstract

A 75 g oral glucose tolerance test was performed between 26 and 32 weeks gestation in 1371 women attending an ante-natal clinic in Melbourne. Gestational diabetes according to various criteria was present in 4.2% (2 h plasma glucose L 8.0 mmol/l), 5.2% (2 h plasma glucose 2 7.8 mmoV1) and 5.5% by the proposed Australian criteria (fasting plasma glucose 2 5.5 mmol/l and/or 2 h plasma glucose 1 8.0 mmol/l). The long-term implications of gestational diabetes in the development of diabetes and metabolic abnormalities for both the mother and her child in addition to related infant morbidity emphasise the urgent need for an agreed definition of this condition.

Keywords: Gestational diabetes; 75 g Glucose tolerance test; Pregnancy; Diagnosis

1. Introduction

The diagnosis of gestational diabetes has serious implications both for the fetus and the mother. Fetal embryopathy due to diabetes has long been recognised as a cause of still-birth and neonatal death but the significance of gestational diabetes as an important risk factor for permanent non- insulin-dependent diabetes has been documented

l Corresponding author, Tel.: +61 3 3471550; Fax: +61 3 3428389.

more recently [l]. Despite its world-wide impor- tance the definition of gestational diabetes is the subject of continuing controversy [2-71. Most coun- tries use the World Health Organisation (WHO) de- finition of impaired glucose tolerance following a 75 g glucose load although the 100 g glucose toler- ance test is usual in North America and there is a very large experience of a 50 g glucose load at the Mercy Hospital in Melbourne. The recommended WHO criteria for gestational diabetes are the same as impaired glucose tolerance (IGT). The 1980 WHO definition of IGT; fasting plasma glucose

0168-8227/95/%09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0168-8227(95)01035-C

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(FPG) < 8.0 mmol/l and 2-h plasma glucose (2PG) 1 8.0 mmol/l [S] was amended in 1985 to FPG < 7.8 mmol/l and 2PG 2 7.8 mmoyl [9]. This recommendation did not specifically include gesta- tional diabetes and there are many reports using the 1980 WHO standard to define gestational diabetes [lo-131.

In Australia a survey in 1988 confirmed that many different glucose loads and criteria for the diagnosis of gestational diabetes were in use [ 141 and subsequently an ad hoc committee proposed guide- lines for the diagnosis of gestational diabetes in Australia using the 75 g oral glucose load with values of plasma glucose at or above 5.5 mmol/l fast- ing and/or 8.0 mmol/l at 2 h as diagnostic [ 151.

In this report we describe the results of 75 g oral glucose tolerance tests performed on unselected women attending the ante-natal clinic at a public hospital in Melbourne.

2. Methods

In 1991 a screening programme for gestational diabetes was commenced for women attending the ante-natal clinics at the Essendon and District Memorial Hospital. As clinics were held in the morning, rather than use a glucose challenge screen- ing test, it was decided to perform a 75 g oral glu- cose tolerance test on all women between 26 and 32 weeks gestation as estimated by clinical indices often supplemented by ultrasound examination. The only exclusion criterion was women known to have diabetes mellitus before the test was performed. Women were instructed at the clinic visit before the test was scheduled to attend after an overnight fast with only water allowed and not to smoke cigarettes. The 75 g oral glucose load (in 200 ml orange- flavoured drink) was administered by the clinic nurse following venipuncture between 08:45 and 10.00 h. A second blood sample was taken 2 h later. During this time the women had had a normal con- sultation at the clinic but did not exercise. All patients were questioned that they were fasting and if not, the test was rescheduled within 1 week. Sim- ilarly, vomiting which occurred in 0.5% of women, negated the test. The clinic population was drawn from a mixed lower-middle class area of north-west Melbourne with a large Caucasian ethnic mixture, approximately 40% were of Mediterranean and

Table I Distribution of results of 75 g glucose tolerance tests in 1371 women between 26 and 32 weeks gestation

Fasting plasma glucose Percentile 10 25 50 75 90 95 97.5 IlllllOl/l 3.8 4.0 4.2 4.6 4.8 5.1 5.2 Mean 4.44 S.D. 0.45, Median 4.40

2 h Plasma glucose Percentile 10 25 50 75 90 95 97.5 mmol/l 4.0 4.7 5.4 6.2 7.0 7.8 8.3 Mean 5.64 S.D. 1.32, Median 5.60

Middle-Eastern origin and relatively few from Asia (2.4% had Vietnamese or Chinese surnames).

Venous blood was collected into fluoride-heparin tubes. The samples were analysed at the Department of Biochemistry, Royal Melbourne Hospital on the Beckman Synchron CX5 (Beckman Instruments, USA) using the hexokinase method with reagents supplied by the manufacturer. The assay had inter- batch co-efficient of variations of 3.0 and 3.6% at glucose values between 3 and 20 mmol/I, respective- ly. In the second year of the study a slight positive bias in comparison with the Australian Quality Assurance Programme (AACB-RCPA) was cor- rected for.

3. Results

The results of 75 g glucose tolerance tests per- formed on 1371 women between 26 and 32 weeks gestation are shown in Table 1 and Fig. 1. At 120

1ZOmin Gluwse (ZE32wM

mMol/L

Fig. I. The distribution of venous blood glucose 120 min after 75 g glucose load in 1371 women between 26 and 32 weeks ges- tation.

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FAR. Martin et al. /Diabetes Research and Clinical Practice 27 (1995) 147-151 149

min after the glucose load in 21 (1.5%) venous PG was 1 9.0 mmol/l (111 .O mmol/l in 3) in 57 (4.2%) 1 8.0 mmol/l and in 71 (5.2%) > 7.8 mmol/l. In 23 (1.7%) FPG was 2 5.5 mmol/l. However in 18 of the women with FPG L 5.5 mmol/l, the 2PG was < 8.0 mmol/l although they claimed to be fasting. On the basis of the criteria recommended for diag- nosis of gestational diabetes in Australia (fasting glucose at or above 5.5 mmolil and/or 2 h plasma glucose at or above 8 mmol/l) 75 of 1371 women tested had gestational diabetes (5.5%).

4. Discussion

The use of the glucose tolerance test to define gestational diabetes is accepted world-wide but there are relatively few reports of results of the 75 g glucose tolerance test in pregnant women. A multicenter European study of unselected preg- nant women found that in the third trimester, ap- proximately 10% of women had a plasma glucose value 2 h after a 75 g oral glucose load of 8.0 mmolil or greater [5]. This study recommended the cut-off level for the diagnosis of gestational diabetes be 9.0 rnmol/l which was the 95 percentile value as the authors did not think it reasonable that 10% of pregnant women could have gestation- al diabetes. A series in England, which excluded women with any diabetic risk factors including obesity and age > 35 years, found that the 97.5 percentile geometric mean of plasma glucose at 2 h was 9.6 mmohl [ 161. In a recent report using both 1980 WHO and the proposed Australian cri- teria of diagnosis, the incidence of gestational diabetes in the Illawarra area of Australia was found to be 7.2% [13]. This series was not unselected and the authors did not clarify the numbers diagnosed by either criteria. The con- founding effect of different criteria of diagnosis in the determination of the prevalence of gestational diabetes was emphasised by the study of Li et al. in Hong Kong [lo] who compared the 75 g Gl’T directly with the 100 g G’IT using 1980 WHO and National Diabetes Data Group criteria for diagno- sis. In 216 women, they showed that 50% who had gestational diabetes with the 100 g GTT were nor- mal by WHO criteria using a 75 g glucose load. In Australia, Asian-born women have been found to have a higher prevalence of gestational diabetes

using 50 g, 75 g and 100 g glucose tolerance tests [13,17,18] so that it seems unlikely that the size of the glucose load is a critical determinant. Reports from Hong Kong, Saudia Arabia and Singapore using 1980 WHO criteria reported gestational diabetes in 9.0-l 1.5% of women tested and ques- tioned the validity of this definition [lo-121.

We have found that there was a significant vari- ation in the prevalence of gestational diabetes from 4.2 to 5.5% in 1371 women of Caucasian ori- gin using different criteria of diagnosis. The 1985 WHO revision of IGT criteria from 2PG L 8.0 mrnol/l to 2PG r 7.8 mmovl was made without any apparent reference to its significance in rela- tion to the prevalence of gestational diabetes [9]. The proposed Australian criteria [ 151 include women with an FPG r 5.5 mmoY1 but a 2PG 2: 8.0 mmol/l. Although it is possible that some women could be included who were not fast- ing, it was thought that an elevation of the fasting glucose above normal was probably indicative of a more severe abnormality of basal insulin produc- tion [21]. In the present series, the number of Asian-born women was too small to confirm a higher rate of gestational diabetes. Furthermore, as there was no difference between Australian- born and southern European women in the Il- lawarra survey [13], it is unlikely that any ethnic group contributed significantly to the overall prev- alence of gestational diabetes. The distribution of both the fasting and post-load glucose values ap- proached normal and the mean and median values were not significantly different and we believe that these results provide an estimate of the prevalence of gestational diabetes in women in Melbourne.

In the context of modem obstetric care, the importance of the recognition and management of gestational diabetes has been questioned as not cost-effective for either infant morbidity or mor- tality, particularly with only slight degrees of glu- cose intolerance [7,19,20]. However, these critics assume the general availability of high standard obstetric care which is not the case in many coun- tries. Furthermore, the recent demonstration in both animals [22,23] and man [24] that children of mothers with hyperglycaemia during pregnancy are significantly more likely to have abnormalities of glucose metabolism suggest that the effects on the children may be permanent. Thus, the diagno-

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sis of gestational diabetes has now assumed as much importance in predicting the long-term health of the mother and her baby as for the well- being of the fetus and neonate. The possibility of preventing the onset of permanent diabetes by either diet and exercise programmes or phar- macological intervention needs to be examined prospectively in women who have had gestational diabetes and in their children.

131

141

151

The Third International Workshop Conference in 1990 did not reach agreement on the definition of gestational diabetes and Coustan pointed out that consensus may not be possible without agree- ment on the objectives of diagnosis [25]. These ob- jectives include epidemiological and preventative studies as well as the health of individual women and their children and may have different empha- sis in different countries. In the context of modem obstetric care in Melbourne we did not find any difference in neonatal outcome between a preva- lence of 4.2 to 5.5% of gestational diabetes deter- mined by the three criteria used. However, the ultimate effect on both the women and their child- ren can only be determined by long-term follow- up. As the number of women and children affected by gestational diabetes will continue to increase world-wide, an agreed international definition of diagnosis is a necessity to formulate coherent policies which would take account of ethnic and geographic differences in prevalence. This presents an urgent challenge to both the World Health Organisation and the International Diabetes Federation.

161

[71

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[91

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1111

1121

[I31

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Acknowledgements WI

1161 The assistance of the nursing staff of the Essen-

don and District Memorial Hospital and Sally Reason in the Biochemistry laboratory is grateful- ly acknowledged.

1171

References 1181

[l] O’Sullivan, J.B. (1991) Diabetes mellitus after GD. Diabetes 40 (Suppl. 2), 131-135.

121 Second International Workshop Conference on Gesta- tional Diabetes Mellitus (1985). Summary and Recom- mendations. Diabetes 34 (Suppl. 2), 123-126.

v91

1201

Hadden, D.R. (1985) Geographic, ethnic and racial vari- ations in the incidence of gestational diabetes mellitus. Diabetes 34 (Suppl. 2) 8-12. Naylor, C.D. (1989) Diagnosing gestational diabetes. Is the gold standard valid? Diabetes Care 8, 565-572. Lind, T. (1989) For the diabetic pregnancy study group of the European Association for the study of diabetes. A prospective multi-center study to determine the influence of pregnancy upon the 75 g oral glucose tolerance test (OGTT). In: H.W. Sutherland, J.M. Stowers, D.W. Pear- son (Eds.), Carbohydrate Metabolism in Pregnancy and the Newborn. Springer-Verlag, Berlin, pp. 209-226. Keen, H. (1991) Gestational diabetes, can epidemiology help? Diabetes 40 (Suppl. 2), 3-7. Jarret, R.J. (1993) Gestational diabetes mellitus - a non- entity. Br. Med. 1. 306, 37-38. World Health Organization Expert Committee on Diabetes Mellitus (1980) Technical Report Series 646, WHO, Geneva. World Health Organization Expert Committee on Diabetes Mellitus (1985) Technical Report Series 727, WHO, Geneva. Li, D.F.H., Wong, V.C., O’Hoy, K.M. and Ma, H.K. (1987) Evaluation of the WHO criteria for 75 g oral glu- cose tolerance test in pregnancy. Br. J. Obstet. Gynaecol. 94, 847-850. Al-Shawaf, T., Akiel, A. and Moghraby, S.A. (1988) Gestational diabetes and impaired glucose tolerance of pregnancy in Riyadh. Br. J. Obstet. Gynaecol. 95,84-90. Cheng, L. and Salmon, Y.M. (1993) Are the WHO (1980) criteria for the 75 g oral glucose tolerance test appropri- ate for pregnant women. Br. J. Obstet. Gynaecol. 100, 645-648. Moses, R.G., Grifliths, R.D. and McPherson, S. (1994) The incidence of gestational diabetes mellitus in the Il- lawarra area of New South Wales. ANZ J. Obstet. Gynecol. 34, 425-427. Hunter, A., Doery, J.C.G. and Miranda, V. (1990) Diag- nosis of gestational diabetes in Australia. A national sur- vey of current practice. Med. J. Aust. 153, 290-292. Martin, F.I.R. (1991) The diagnosis of gestational diabetes. Med. J. Aust. 155, 112. Hattem, M., Anthony, F., Hogston, P., Rowe, D. and Dennis, K. (1988) Reference values for 75 g oral glucose tolerance test in pregnancy. Br. Med. J. 296, 676-678. Doery, J.C., Edis, K., Healy, D., Bishop, S. and Tippet, C. (1989) Very high prevalence of gestational diabetes in Vietnamese and Cambodian women. Med. J. Aust. 151, 111-112. Henry, O.A., Beicher, N.A., She&y, M.T. and Walstab, J.E. (1993) Gestational diabetes and follow-up among immigrant Vietnam-born women. Aust. NZ J. Obstet. Gynecol. 33, 109-114. Ales, K.L. and Santini, D.L. (1989) Should all pregnant women be screened for gestational glucose intolerance. Lancet i, 1187-l 190. Li, D.E.H., Wong, V.C.W., O’Hoy, K.M.K.Y., Yeung,

Page 5: The 75 g oral glucose tolerance in pregnancy

F.I.R. Martin et al. /Diabetes Research and Clinical Practice 27 (1995) 147-151 151

C.Y. and Mah, H. (1987) Is treatment needed for mild impairment of ghtcose tolerance in pregnancy. A ran- domised control trial. Br. J. Obstet. Gynaecol. 94, 851-854.

[21] Ross, G. (1992) Screening for gestational diabetes. Med. J. Aust. 157, 567.

[22] Van Assche, F.A., Aerts, L. and Holemans, K. (1991) Metabolic alterations in adulthood after intra-uterine de- velopment in mothers with mild diabetes. Diabetes 40 (Suppl. 2), 106-108.

[23] Gauguier, D., Bi Hareau, M., Ktorza, A., Berthault, M. and Picon, L. (1990) Inheritence of diabetes mellitus as a consequence of gestational hyperglycaemia in rats. Diabetes 39, 734-739.

[24] Pettit, D.J., Kirk, A., Aleck, H. et al. (1988) Congenital susceptibility to NIDDM. Role of intrauterine environ- ment. Diabetes 37, 622-628.

[25] Coustan D. (1991) Diagnosis of gestational diabetes - what are our objectives? Diabetes 40 (Suppl. 2) 14-17.