The 75 g oral glucose tolerance in pregnancy

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

ELSEVIER

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 noninsulin-dependent diabetes has been documented l Corresponding author, Tel.: +61 3 3471550; Fax: +61 3 3428389.

more recently [l]. Despite its world-wide importance the definition of gestational diabetes is the subjectof continuing controversy [2-71. Most countries usethe World Health Organisation (WHO) definition of impaired glucose tolerance following a 75 g glucoseload although the 100g glucose tolerance 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

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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 gestational diabetesand there are many reports using the 1980WHO standard to define gestational diabetes [lo-131. In Australia a survey in 1988 confirmed that many different glucose loads and criteria for the diagnosisof gestationaldiabeteswerein use[ 141and subsequentlyan ad hoc committee proposed guidelines for the diagnosis of gestational diabetes in Australia using the 75 g oral glucose load with valuesof plasmaglucoseat or above 5.5 mmol/l fasting 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 diabeteswas commencedfor women attending the ante-natal clinics at the Essendon and District Memorial Hospital. As clinics were held in the morning, rather than usea glucosechallengescreening test, it was decided to perform a 75 g oral glucose tolerance test on all women between 26 and 32 weeks gestation as estimated by clinical indices often supplementedby 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 scheduledto attend after an overnight fast with only water allowed and not to smokecigarettes. The 75 g oral glucose load (in 200 ml orangeflavoured drink) was administered by the clinic nurse following venipuncture between 08:45 and 10.00h. A secondblood samplewas taken 2 h later. During this time the women had had a normal consultation at the clinic but did not exercise. All patients were questioned that they were fasting and if not, the test was rescheduledwithin 1 week. Similarly, vomiting which occurred in 0.5% of women, negated the test. The clinic population was drawn from a mixed lower-middle classarea 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 3.8 4.0 4.2 4.6 4.8 5.1 5.2 Mean 4.44 S.D. 0.45, Median 4.40

IlllllOl/l

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 sampleswereanalysedat 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 assayhad interbatch co-efficient of variations of 3.0 and 3.6% at glucosevalues between3 and 20 mmol/I, respectively. In the second year of the study a slight positive bias in comparison with the Australian Quality Assurance Programme (AACB-RCPA) was corrected for. 3. Results The results of 75 g glucose tolerance tests performed on 1371women 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 120min after 75 g glucoseload in 1371women between 26 and 32 weeks gestation.

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

min after the glucose load in 21 (1.5%) venous PG was 1 9.0 mmol/l (111 .Ommol/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 recommendedfor diagnosis 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 pregnant women found that in the third trimester, approximately 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 recommendedthe 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 gestational 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 1980WHO and the proposed Australian criteria 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 confounding effect of different criteria of diagnosis in the determination of the prevalence of gestational diabetes was emphasisedby 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 1980WHO and National Diabetes Data Group criteria for diagnosis. In 216 women, they showed that 50% who had gestational diabetes with the 100g GTT were normal 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

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using 50 g, 75 g and 100 g glucose tolerance tests [13,17,18]so that it seemsunlikely 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 questioned the validity of this definition [lo-121. We have found that there was a significant variation in the prevalence of gestational diabetes from 4.2 to 5.5% in 1371women of Caucasian origin 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 relation 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 somewomen could be included who were not fasting, it was thought that an elevation of the fasting glucose above normal was probably indicative of a more severeabnormality of basal insulin production [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 Australianborn and southern European women in the Illawarra survey [13], it is unlikely that any ethnic group contributed significantly to the overall prevalence of gestational diabetes. The distribution of both the fasting and post-load glucose values approached normal and the mean and median values were not significantly different and we believe that theseresults 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 managementof gestational diabetes has been questioned as not cost-effective for either infant morbidity or mortality, particularly with only slight degreesof glucose intolerance [7,19,20]. However, these critics assume the general availability of high standard obstetric care which is not the casein many countries. 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 wellbeing of the fetus and neonate. The possibility of preventing the onset of permanent diabetes by either diet and exercise programmes or pharmacological intervention needs to be examined prospectively in women who have had gestational diabetes and in their children. The Third International Workshop Conference in 1990did not reach agreement on the definition of gestational diabetes and Coustan pointed out that consensusmay not be possible without agreement on the objectives of diagnosis [25]. These objectives include epidemiological and preventative studies as well as the health of individual women and their children and may have different emphasis in different countries. In the context of modem obstetric care in Melbourne we did not find any difference in neonatal outcome between a prevalence of 4.2 to 5.5% of gestational diabetes determined by the three criteria used. However, the ultimate effect on both the women and their children can only be determined by long-term followup. 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 differencesin prevalence.This presents an urgent challenge to both the World Health Organisation and the International Diabetes Federation. Acknowledgements

The assistanceof the nursing staff of the Essendon and District Memorial Hospital and Sally Reason in the Biochemistry laboratory is gratefully acknowledged. References [l] O’Sullivan, J.B. (1991) Diabetes mellitus after GD. Diabetes 40 (Suppl. 2), 131-135. 121 Second International Workshop Conference on Gestational Diabetes Mellitus (1985). Summary and Recommendations. Diabetes 34 (Suppl. 2), 123-126.

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[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 environment. Diabetes 37, 622-628. [25] Coustan D. (1991) Diagnosis of gestational diabetes what are our objectives? Diabetes 40 (Suppl. 2) 14-17.