The Child of the Diabetic Woman

Farquhar, James W.

doi:10.1136/adc.34.173.76

Cited by 111 publications

(22 citation statements)

References 64 publications

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“…Therefore, in the third trimester, statistically signifi- DISCUSSION A diabetes mellitus-like syndrome was consistently obtained after the administration of the pancreatic beta cell cytotoxin, streptozotocin, to rhesus monkeys before conception and during the first trimester of pregnancy. The conceptii of these streptozotocin-treated animals demonstrated changes similar to those encountered in pregnancies of women with diabetes mellitus (25,26). Specifically, these simian neonates and placentas were statistically significantly heavier than average for their gestational age, polyhydramnios was consistently encountered, and a well defined increase in the incidence of third trimester stillbirths for this colony was observed.…”

Section: Methodsmentioning

confidence: 64%

Subhuman Primate Pregnancy Complicated by Streptozotocin-Induced Diabetes Mellitus

Mintz¹,

Chez²,

Hutchinson³

1972

J. Clin. Invest.

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A B S T R A C T Polydipsia, polyuria, polyphagia, and glucosuria followed the administration of streptozotocin to 6 nonpregnant and 15 pregnant monkeys (Macaca mulatto) in the first trimester of pregnancy. The diabetogenic action of the drug was also reflected in an induced but variable deterioration in maternal intravenous glucose tolerance and a marked attenuation of maternal plasma insulin responsiveness to intravenous glycemic stimuli. The products of conception were examined in 29 pregnancies. The neonates and the placentas of the streptozotocin-treated pregnant animals were significantly heavier than average for the period of gestation, polyhydramnios was consistently present, and there was an increase in the incidence of third trimester stillbirths.The fetal and maternal plasma glucose, insulin, and growth hormone concentrations were examined after the intravascular administration of glucose or a solution of mixed amino acids to the fetus in the third trimester. The neonatal plasma responses to similar insulinogenic stimuli were also examined.Fetal and neonatal base line plasma insulin concentrations were significantly elevated compared to those of the controls. The administration of intravascular glucose to the fetus, mother, or neonate was associated with a prompt 2-to 5-fold increase in fetal or neonatal plasma insulin concentrations. These findings contrast to the unresponsiveness of the pancreatic islet tissue we reported in normal subhuman primate pregnancy.The intravascular infusion of a relatively low concentration of mixed amino acids (2 mg/min) to the con- ceptii from the streptozotocin-treated pregnancies was associated with an elevation in fetal and neonatal plasma insulin levels, whereas normal monkey fetuses and neonates required a 10-fold greater concentration of amino acids in the infusate for similar responses. The induced hyperaminoacidemia or hyperglycemia did not consistently alter plasma growth hormone concentrations in the conceptii from normal or streptozotocin-treated pregnancies.These data provide evidence that maternal glucose intolerance during pregnancy is associated with enhanced fetal and neonatal pancreatic islet cell responsiveness to glucose and mixed amino acids. Although the specific mechanism(s) that alters both the sensitivity and responsiveness of the normal pancreatic fetal islet to insulinogenic stimuli remains unclear, the data do indicate that insulin-dependent maternal hyperglycemia and hyperaminoacidemia, separately or in combination could contribute to the fetal hyperinsulinemia of pregnancies complicated by diabetes mellitus. Moreover, the overall experiences with these streptozotocin-treated animals suggest that a subhuman primate mnodel may be available to examine directly the antenatal pathophysiology of abnormal carbohydrate metabolism. INTRODUCTIONMaternal, fetal, and neonatal carbohydrate insulin and growth hormone metabolism in normal monkeys (Macaca mulatto) during the third trimester of pregnancy were detailed in previous studies from our laboratory...

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Section: Methodsmentioning

confidence: 64%

Subhuman Primate Pregnancy Complicated by Streptozotocin-Induced Diabetes Mellitus

Mintz¹,

Chez²,

Hutchinson³

1972

J. Clin. Invest.

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“…However, in the diabetic group, birthweight corrected for gestational age (birthweight SDS) was correlated with weight, height and triceps skinfold thickness. Several reports indicate that the offspring of diabetic women are taller [24,25] than non-diabetic offspring but other studies report them as normal or short [26,27,28]. Reduced growth could result from cases of intra-uterine growth retardation caused by poor glycaemic control.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and metabolic abnormalities in the offspring of diabetic pregnancy

et al. 2002

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Aims/hypothesis. Maternal fuel metabolism is known to exert long range effects on the later development of children of diabetic mothers. Recently cardiovascular disease in adult life has been linked retrospectively with foetal malnutrition. The aim of this study was to identify whether markers for fuel-related cardiovascular programming exist for the offspring of diabetic pregnancy. Methods. Sixty-one children aged 5 to 11 years, of mothers with Type I (insulin-dependent) diabetes mellitus were compared with 57 randomly selected control children of non-diabetic mothers similar in age, sex and social class. Fasting blood was taken for plasma glucose, insulin, lipids, IGF-1, plasminogen activating inhibitor 1 (PAI-1) and the adhesion molecules ICAM-1, VCAM-1 and E-Selectin. Results. Fasting glucose and insulin were similar in the two groups. Differences existed between the offspring of diabetic and non-diabetic pregnancies (mean ± SD) for total cholesterol (4. with diabetic pregnancy is the consequence of foetal hyperinsulinism secondary to excess maternal glucose and other fuels. While subsequent data would generally support this concept, the relatively few studies which have examined the question are poorly comparable and focus almost exclusively on growth and glucose regulation [3,4]. Confounding factors include variation in the number of subjects, year of birth, age at follow up, type of diabetes (pregestational, gestational), adequate control subjects and assessment of morbidities. During the intervening four decades, the management of pregnant women and their newborns has improved markedly.Recently others have shown provocative epidemiological evidence that coronary heart disease, and several other chronic adult diseases have their originsThe proposal that maternal fuel metabolism might exert long range effects on human development was first suggested more than 40 years ago [1]. The hypothesis, with minor modification [2], is now widely accepted and envisages that excess foetal growth associated

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“…A characteristic spectrum of clinical, metabolic, and morphologic abnormalities have been reported in infants born to diabetic mothers (2,3,5,11). While various hypotheses have been advanced to explain the pathogenesis of these abnormalities, considerable controversy remains (I I).…”

Section: Speculationmentioning

confidence: 99%

Transplacental Passage of Islet Cell Antibody in Infants of Diabetic Mothers

et al. 1979

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SummaryThe incidence of pancreatic islet cell antibody (ICAb) was assessed in the cord blood and sera of infants of diabetic mothers (IDM). ICAb activity was detected in the cord blood of 10 of 36 (27.8%) consecutive IDM studied and in 0 of 111 (0%) cord bloods of normal control infants. In aU instances, ICAb activity in the cord sera was of the immunoglobulin (I&) class and was associated with ICAb in maternal sera at the time of delivery. No correlation was obsened between the incidence of ICAb in IDM and alterations in fetal growth parameters, congenital malformation rates, cord blood insulin levels, or the incidence of neonatal complications. The evidence would support transplacental passage of ICAb from diabetic mothers to their offspring, but would not support a primary pathogenetic role for ICAb in the clinical or metabolic alterations observed in these infants. SpeculationThe detection of ICAb in the cord blood of IDM at birth would suggest a possible role for transplacentally-acquired ICAb in the pathogenesis of the clinical, metabolic, and morphologic abnormalities observed in these infants.

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The Child of the Diabetic Woman

Cited by 111 publications

References 64 publications

Subhuman Primate Pregnancy Complicated by Streptozotocin-Induced Diabetes Mellitus

Subhuman Primate Pregnancy Complicated by Streptozotocin-Induced Diabetes Mellitus

Cardiovascular and metabolic abnormalities in the offspring of diabetic pregnancy

Transplacental Passage of Islet Cell Antibody in Infants of Diabetic Mothers

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