Maternal Glucose Tolerance and Obstetric ... - Diabetes Care

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Maternal Glucose Tolerance and Obstetric Complications in Pregnancies in Which the Offspring Developed Type I Diabetes NORMAN A. BEISCHER, MD PETER W E I N , FRACOG MARY T. SHEEDY, B APP SC

GEORGE A. WERTHER, FRACP HUGO GOLD, FRCP

OBJECTIVE — To identify possible in utero risk factors in children who develop type I diabetes and to determine the risk of development of type I diabetes in the children of women with gestational diabetes. RESEARCH DESIGN A N D M E T H O D S — All known children with type I diabetes born at the Mercy Hospital for Women whose mothers had glucose tolerance tests (GTTs) performed during pregnancy were identified. The results of the mothers' GTTs were compared with those of the hospital population, as were their obstetric complications. RESULTS — We identified 38 children with type I diabetes born at this hospital whose mothers had GTTs performed during pregnancy. Only one of these mothers had gestational diabetes, compared with 5.6% in the overall hospital population (adjusted odds ratio 0.69, 95% confidence interval 0.12-3.84, P = 0.99). There were no differences in the blood glucose levels between the mothers of the children who developed diabetes and the general hospital population. The birth weights of the children destined to develop diabetes also showed no deviation from the expected distribution, and there were no outstanding features of the mothers' obstetric histories. CONCLUSIONS — Maternal blood glucose level is not an important determinant of the child's risk of developing type I diabetes.

From the Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne; the Department of Endocrinology and Diabetes, Royal Children's Hospital; and the Department of Paediatric Endocrinology and Diabetes, Monash Medical Centre, Melbourne, Australia. Address correspondence and reprint requests to Norman Beischer, MD, Mercy Hospital for Women, 126-158 Clarendon Street, East Melbourne 3002, Australia. Received for publication 15 July 1993 and accepted in revised form 17 February 1994. GDM, gestational diabetes mellitus; GTT, glucose tolerance test; OR, odds ratio; Cl, confidence interval; BMI, body mass index.

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he prevalence of type I diabetes has increased by a factor of two or three in a number of developed countries in the last two decades (1,2), which suggests that environmental, possibly nutritional, factors are important in the etiology of type I diabetes. The prevalence of gestational diabetes mellitus (GDM) using the same methodology and criteria for diagnosis has trebled, from 3.1% during 1971-1980 to 9.2% during 1990-1992 at the Mercy Hospital for Women in Melbourne, Australia (3). As we aim to perform glucose tolerance tests (GTTs) on all prenatal patients at the Mercy Hospital for Women, we are in a position to determine whether abnormalities of maternal carbohydrate metabolism during pregnancy influence the risk of the offspring developing type I diabetes. Type I diabetes is considered to have an important genetic component in its etiology, although the concordance rate for diabetes in identical twins is only - 3 0 % (1). Data from the Joslin Diabetes Center involving 244 offspring of 88 men and 175 offspring of 99 women with type I diabetes revealed that, by 20 years of age, 6.1% of the men's offspring and 1.3% of the women's offspring had diabetes (4). Although the destruction of pancreatic /3-cells that occurs in patients with type I diabetes is autoimmune in nature, a dietary factor such as cow's milk has been implicated as a possible trigger of the autoimmune response in genetically susceptible individuals (5). This theory is in accord with the observed increase in prevalence of type I diabetes observed in Indian subcontinent immigrants to the United Kingdom (1). From the above, it seems possible that dietary factors and maternal hyperglycemia may affect the predisposition of a fetus to type I diabetes in later life. Accordingly, we have analyzed and presented here the data obtained from GTTs performed at 28-34 weeks gestation at the Mercy Hospital for Women from 1971 to 1992 in women carrying fetuses destined to develop type I diabetes, to as-

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sess the risk of diabetes in the offspring of mothers with GDM compared with those having normal glucose tolerance. The obstetric complications in these pregnancies were also scrutinized.

RESEARCH DESIGN AND METHODS— At the Mercy Hospital for Women in Melbourne, since the hospital opened in 1971, we have attempted to screen all prenatal patients at 28-34 weeks gestation with a 3-h GTT and have succeeded in doing so in 68,859 of the 103,391 pregnancies (66.6%), resulting in confinements in our hospital from 1971 to December 1992. We obtained the register of all known children with type I diabetes in the state of Victoria from the files of the Royal Children's Hospital and Monash Medical Centre Departments of Endocrinology and gathered all those born since the Mercy Hospital for Women opened in 1971. These two centers review the management of >90% of children and adolescents with type I diabetes in metropolitan Melbourne. The names and dates of births of these children were matched against all women who delivered at the Mercy Hospital for Women. The histories of the women thus identified were examined to select whether a GTT had been performed during the pregnancy that resulted in a child with type I diabetes. The GTTs of these women were studied to note the prevalence of GDM, and mean plasma glucose values fasting and at 1, 2, and 3 h. At the Mercy Hospital for Women, pregnant women having a GTT attend following an overnight fast and no other dietary modification. Capillary plasma glucose is measured fasting and at 1, 2, and 3 h after an oral 50-g glucose load. Glucose measurements were performed using the Beckman Autoanalyzer. GDM was diagnosed by the combination of a 1-h glucose value of >9.0 mM and a 2-h value of ^7.0 mM. The hospital reference ranges for plasma glucose values were calculated from the mean ± 2 SDs of the total population.

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The case notes of the identified women were also studied for the presence of prenatal complications and fetal growth retardation or macrosomia. Fetal growth retardation was defined as birth weight