History of GDM

The recorded history of diabetes in pregnancy over the past 200 years is essentially the story of the recognition of the adverse effects of hyperglycaemia on both mother and fetus. The aim of the Saint Vincent declaration to achieve an outcome similar to that of a non-diabetic pregnancy have been approached but never fully achievied. Much effort has been spent on the problem of categorising the degree of hyperglycaemia which would justify treatment, and how to identify the mother at risk.

The first documented evidence of the effects of hyperglycaemia in pregnancy in the moden era was in 1824, when Bennewitz recorded a case of severe fetal macrosomia and stillbirth in a 22 year old multigravida woman in Berlin. She had symptoms of severe hyperglycaemia, but he was only able to estimate this by boiling the urine to dryness[1]. The symptoms disappeared after the delivery. Until the discovery of insulin in 1923 there was no effective treatment for this condition, and the outcome of pregnancy for both mother and fetus was usually disastrous. These adverse effects have been gradually but not completely alleviated by intensive multidisciplinary care from both diabetologist and obstetrician, but complete normalisation of maternal glucose metabolism has not yet been achieved. By the 1940’s it was becoming recognised that lesser degrees of maternal hyperglycaemia were also a risk to pregnancy outcomes, with retrospective studies showing increases perinatal mortality some years before the diagnosis of overt diabetes mellitus. This led to the term ‘prediabetes in pregnancy’, and to poorly defined concepts of ‘temporary’ or ‘latent’ diabetes.

The first attempt to define the concept of ‘hyperglycaemia in pregnancy’ was over 50 years ago in Boston USA. This was an epidemiological study of an oral glucose tolerance test in 752 unselected normal pregnant women using a ‘two step’ procedure which has become the cornerstone of subsequent obstetrical guidelines in the USA, although not universally accepted elsewhere. For various reasons O’Sullivan used a 50g oral glucose load with a single one hour measurement as a first ‘screening’ test, administered on the afternoon of first registration of the pregnancy , followed by a three hour 100g oral glucose load with four samples [2]. He published the distribution curves of blood glucose at these four times, and considered it ‘expedient’ to require two or more values above the mean plus two standard deviations to be met or exceeded in deriving his proposed criteria for hyperglycaemia in pregnancy. These ‘O’Sullivan Criteria’ have remained in use since then, although concerns about the changing methodology of plasma glucose measurement led Carpenter and Coustan to alter the figures to take account of more modern technological processes [3].

A sub-committee of the World Health Organisation subsequently decided that the results of a two hour 75g oral glucose tolerance test derived from non-pregnant men and women could be used in pregnancy, with a cut-off point decided by consensus [4]. These two different sets of criteria have continued to be used in various parts of the world to the present day, but a major weakness has been their focus on the risk of subsequent diabetes in the mother rather than that of adverse fetal outcomes.

The term ‘Gestational Diabetes Mellitus’ (GDM) was not universally used until popularised by Freinkel in Chicago in a major paper in 1980. In this wide ranging presentation ‘Of Pregnancy and Progeny’ , incorporating several important insights into the pathophysiology of glucose metabolism in both mother and fetus, he developed his concepts of more subtle consequences of faulty maternal insulinisation. This led to an American Diabetes Association sponsored workshop, and a definition of gestational diabetes as ‘glucose intolerance with onset or first recognition during pregnancy’ [5]. Enlarging on the biochemical aspects Freinkel formulated his concept of ‘fuel mediated teratogenesis’, with potential adverse effects on the fetus in early, mid and late gestation. Gestational diabetes in this scenario would result in anthropometric/metabolic effects in the third trimester.

With the uncertainty about the actual glucose criteria used to categorise hyperglycaemia in pregnancy, and the absence of reliable studies of the fetal outcomes, the stage was set for the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study [6], which has resulted in an international consensus on diagnostic criteria [7], although this has not yet been fully accepted by some of the obstetrical community. To this end a new definition of the clinical problem is needed, on four points:

  1. “any degree” of glucose intolerance still includes mothers with unrecognised overt diabetes mellitus who need to be treated at once, so an upper as well as a lower limit of glycaemia is needed.
  2. ”glucose intolerance” by itself implies the need for a glucose tolerance test, which technically is unnecessary if the pregnancy risk is simply due to hyperglycaemia.
  3. “first recognition during pregnancy” serves to miss the pre-existing but unrecognised type 2 diabetic woman who should have been diagnosed and treated before the pregnancy. This problem is becoming more frequent.
  4. “diabetes” is an inappropriate term for a simple risk factor for the strong continuous associations of maternal glucose below those diagnostic of overt diabetes with increased birth weight and associated problems.

For these reasons the term used in the HAPO study should be preferred – Hyperglycaemia in Pregnancy should be defined as ‘Maternal hyperglycaemia less severe than that in diabetes mellitus, but associated with increased risk of adverse pregnancy outcome’.

It is with deep regret that we report the death of David Haddon on February 26th 2014. His obituary can be found at http://www.telegraph.co.uk/news/obituaries/10780540/Professor-David-Hadden-obituary.html

References

  1. ^ Bennetwitz HG. De diabete mellito, graviditatis symtomate, 1824. In Hadden DR, The first recorded case of diabetic pregnancy. Diabetologia 1989; 32: 625.

  2. ^ O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964; 13: 278-285.

  3. ^ Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982; 144: 763-773.

  4. ^ World Health Organisation. Technical Report Series (1965); 310: 12. WHO, Geneva.

  5. ^ Freinkel N. Of Pregnancy and Progeny – Banting Lecture 1980. Diabetes 1980; 29: 1023-1089.

  6. ^ Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJN, Persson B, Rodgers MS, Sacks DA. The HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcomes N Eng J Med 2008; 358; 1991-2002.

  7. ^ International Association of Diabetes and Pregnancy Study Groups. Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy. Diabetes Care 2010; 33: 676-682.

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