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Jørgen Pedersen

ABSTRACT

In seven hospitalised obese patients (one diabetic, two with questionable diabetes, and four non-diabetic subjects) the average weight loss on a 1250 calorie diet was 20 per cent greater with than without metformin. The weight loss depended on the dosage of metformin.

Based on the present results and investigations the outline of a new investigation is presented.

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JØRGEN PEDERSEN

HISTORY

There has been some difference of opinion regarding the course of diabetes during pregnancy. During the pre-insulin era, diabetic coma was the outstanding feature (Offergeld, 1908; Joslin, 1924). Reports from the twenties emphasized mainly those cases in which an improvement occurred, and this gave rise to the idea that the foetal insulin production could in part replace that of the mother (Holzbach, 1926; Gray & Feemster, 1926). Pregnancy was then very uncommon among diabetics, but its incidence has increased, particularly during the past decade (Fig. 1). Most authors now report series of 30 to 50 cases, and it is generally held that the course of diabetes may vary (Skipper, 1933; Duncan & Fetter, 1934; White, 1937; Lawrence & Oakley, 1942; Andersson, 1950). In most cases an exacerbation takes place, particularly during the latter half of pregnancy. Improvement occurs in some instances and the condition remains unchanged in others. White

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Jørgen Pedersen

Not until the advent of modern micromethods during the second decade of this century, was it definitely established that liquor amnii normally contains glucose. From several investigations performed during the last 25 years it appears, that in normals the concentration of glucose varies considerably with a mean of about 30 mg.%, and a range from (0) 10 to 70 (90) mg.% (e. g. Mohs, 1931, Shrewsbury, 1933, Oakley & Peel, 1949, and Bevis, 1952). Mohs (1931) examined 100 normal women and found a mean of 27 mg.% and a range of 8 to 75 mg.% (Hagedorn-Jensen method). Bevis (1952) found 26 ± 8.1 mg.% (King's method) and Oakley & Peel (1949) who examined 10 normals, give a mean of 32 mg.% with a range of 11 to 51 mg.% (method not stated). Thus the concentration of glucose is far below that of the blood.

Although sugar was demonstrated in

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Jørgen Pedersen

The foetal mortality in pregnancies of diabetics is still high, and there is some disagreement as to the best treatment. This disagreement is due, among other things, to an unsatisfactory classification of the cases as well as to the small size of most series reported so far.

One of the points in dispute is the value of hormone therapy during pregnancy. White (1949, 1952) has reported a foetal mortality which is among the lowest obtained so far. She ascribes this success to the administration of stilbestrol and progesterone during pregnancy, but this explanation is not generally accepted.

As stated e. g. by Brandstrup & Okkels (1938) it would be very valuable to elucidate the rôle of the compensation of diabetes and the maternal hyperglycæmia. This applies not only to the foetal mortality, but also to the size, obesity, water content, etc. of the infants and their subsequent fate, int. al.

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Jørgen Pedersen

ABSTRACT

A series comprising 90 diabetic women with 99 pregnancies and 102 infants, from the 19 year period 1946–1964 has been analysed. The series includes all women whose first attendance in the department was at least 150 (150–250) days before the calculated term and who continued their pregnancy till the infants weighed 1000 g or more. There was a preponderance of severe cases.

The perinatal mortality was 14 deaths or 14 per cent; however, in 12 class-F cases there were 8 deaths, and in 90 non-F cases 6 deaths or 7 per cent. By comparison with the results of previous pregnancies in these women the series shows a very favourable progress in non-F cases. The new PBSP system of classification according to prognostically bad signs during pregnancy has been used and is of value. The PBSP complications seen were toxaemia and hyperpyretic pyelitis only.

In the 69 non-F cases also without any PBSP complication the foetal mortality was 4 per cent.

The investigation and treatment of latent and manifest urinary tract infection should be reinforced.

At present the therapeutic result in F cases is so poor that induced abortion and sterilisation should be advised more often.

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Jørgen Pedersen

SUMMARY

Birth weight and length of 122 surviving babies of diabetics, born in Rigshospitalet, Copenhagen 1926–1947, was compared to a control group of 122 infants of non-diabetics (matched controls). The groups were comparable, especially as to foetal age and parity of the mother, severe complications in the mothers, etc.

The average foetal age was 261 days (range 237–301). The average weight and length for the infants of non-diab. controls was 3045 gm. and 49.5 cm., for infants of diabetics 3600 gm. and 51.0 cm. Thus on average infants of diabetics weigh 550 gm. more and are 1.5 cm. longer than are infants of non-diab. Differences of the same magnitude were found in primiparae and in multiparae with and without obesity.

The frequency distribution curves for weight and length are nearly normal, but placed at higher levels than are those of non-diab. infants. Diabetics get big and small infants as others, but the whole population is bigger than that of non-diabetics' infants. There is an actual overgrowth.

In a personal series from 1946–1953 75 infants of long-term treated (1. t.) were compared to 91 infants of short-term treated (sh. t.) diabetics. The foetal age was 237 days or more, on average 260 days. Average weight and length for 1. t. infants was 3380 gm. and 50.5 cm., for sh. t. 3570 gm. and 51.3 cm. Thus the 1. t. infants on average weighed 190 gm. less and were 0.8 cm. shorter than sh. t. infants. So far these differences are not statistically significant, but an inverse correlation between the length of the last consecutive stay of the mother in Department B and the infants' weight and length could be demon

I. Published in extenso in Acta endocrinol. 16, 330, 1954.

strated. As the length of stay increases, weight and length decreases. This indicates the differences found to be due to the length of our treatment.

As there is a positive correlation between the maternal pregnancy level of blood sugar (foetal glucose supply) during the last 6–7 weeks of pregnancy and the birth weight and length of infants of non-diabetic controls, 1. t. and sh. t. diabetics, the maternal pregnancy level may play a part of its own for the differences found in weight and length of the infants in these 3 groups.

The maternal blood sugar level may influence weight and length of the infants directly (foetal glucose consumption) but also indirectly (foetal insulin turn-over rising with a rising supply of glucose), as foetal insulin may act as a growth stimulating factor.

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Jørgen Pedersen

At birth, infants of diabetic women are held to be bigger, fatter and more oedematous than those born of normal mothers. This is indicated especially by the works of Fischer (1935) and White & Hunt (1943) in which the foetal age is noticed. Some of the babies are truly giant infants, but others may be small, and the majority of literature does not afford any clear impression of the weight distribution and relation of these babies. The matter is complicated by the limited empirical material and the praemature occurrence of most deliveries, in connection with the great natural variance of birth weights.

The excessive weight of the infants has been attributed to the maternal hyperglycaemia, which entails an increased supply and foetal content of glucose. Hitherto, no one has succeeded in or even tried to demonstrate a correlation between the foetal glucose supply and the weight of the infant, difficult

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Jørgen Pedersen and Lars Mølsted Pedersen

ABSTRACT

In order to improve the possibilities of predicting the outcome of pregnancy in diabetics, we analysed a consecutive series of 304 pregnancies in 263 diabetic women in the Royal Maternity Department B, Rigshospitalet, Copenhagen, during the 5-year period 1959-1963. The period of supervision and treatment during pregnancy varied greatly. The perinatal mortality in the 306 infants was 17.9%.

According to the results of this analysis, patients with a poor prognosis were divided into the following four groups: Pregnant women who developed (1) hyperpyretic pyelitis, (2) pre-coma or severe acidosis, (3) toxaemia, or patients who could be so described, (4) »neglectors« These four groups, and the classification, are designated PBSP (Prognostically Bad Signs during Pregnancy).

The mothers of 130 infants belonged to one or more of the four groups of PBSP, and among the infants of these mothers the perinatal mortality was 31.5% as compared with 7.9% in the group of 176 infants without PBSP during pregnancy.

The poor prognosis for the pregnancies with PBSP applies to all foetal weight groups. In addition, these pregnancies terminate in premature delivery twice as often as the others. It is demonstrated that from the prognostic point of view, nothing is gained by including hydramnios in PBSP.

The risk involved by a PBSP complication to the foetus depends on the White (1949) class in which it occurs. A combination of White's classification of pregnant diabetics with regard to foetal prognosis used together with the present classification improves the possibility of predicting the foetal prognosis in a series of pregnant diabetics which is mixed as regards the length of treatment during pregnancy.

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Jørgen Pedersen and Mogens Osler

As is well-known, newborn infants of diabetic mothers (diab. infants) are characterized by a larger size and weight than infants born of normal mothers. We have found, for instance, that diab. infants born 3 weeks before term were on an average 550 gm. heavier and 1.5 cm. longer than control infants of the same gestational age (Pedersen, 1954). It is the general impression that the diab. infants are premature in spite of their large size, but little has been published on this important aspect.

For this reason, we studied the development of the ossification centres in newborn diab. infants by X-rays, comparing the findings with those in normal infants as well as in control infants of the same gestational age as the diab. infants.

PREVIOUS INVESTIGATIONS

Normal Infants.

Recently, Hartley (1957) has published careful X-ray studies on the development of the ossification centres in infants before and shortly after birth.

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Jørgen Pedersen and Christian Hamburger

A distinction is usually made between two kinds of virilizing ovarian tumours: arrhenoblastoma and 'adrenal-like tumour of the ovary'. The last-mentioned tumour is very uncommon, and there is a great diversity of opinion as to the histogenesis and classification; the tumour is accordingly known by many different names. e. g. adrenal cell tumour, adrenal cell rest tumour, hypernephroma of the ovary, luteoma, masculinovoblastoma, etc. It is generally believed that the tumour originates from adrenal cells, located in the ovary, but some tumours of this category have recently been classified as Leydig cell tumours of the ovary (Berger, 1942, Teilum, 1944, 1951, Pedersen, 1947 a, Sternberg, 1949, Waugh et al., 1949, and Sachs & Spiro, 1951).

In studying the present case, we have tried to find out, whether the tumour was of an adrenal or testicular nature.

In 1947 (a), Pedersen reported clinical, hormonal and pathological studies in a patient with