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Query: UMLS:C0011849 (diabetes)
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We assessed the factors influencing the birth weight of infants born to 83 women with insulin-dependent diabetes mellitus (IDDM) over a 5-yr period. Maternal glycosylated hemoglobin (HbA1) concentrations at delivery correlated with the percentile birth-weight ratios (r = .43, P less than .001) and indicated that approximately 18% of variance in the birth weight could be ascribed to glycemic control in the third trimester. Fetal macrosomia occurred in 22 (27%) pregnancies. When 20 of these pregnancies were compared closely with 20 nonmacrosomic pregnancies in diabetic women, the mothers of macrosomic infants were found to be more obese, have a history of previous macrosomic birth, and have higher concentrations of serum human placental lactogen and urinary estriols in the third trimester. Macrosomic pregnancy was further distinguished by accelerated fetal growth (judged by serial ultrasonography) from the 32nd wk of gestation and by biochemical (but asymptomatic) hypoglycemia in the neonate. In our study, no serious neonatal morbidity could be attributed to macrosomic pregnancy. Good glycemic control was attained in both groups, and no significant differences between the groups in overall glycemic control throughout pregnancy were noted. Thus, despite good glycemic control, macrosomia remains comparatively common in modern pregnancy complicated by IDDM, and factors other than maternal hyperglycemia must contribute to its etiology.
Diabetes Care
PMID:Macrosomia in pregnancy complicated by insulin-dependent diabetes mellitus. 367 77

Using a 1982-4 computerized data base from a perinatal network, 511 pregnancies in women whose age was 40 or more years at delivery were studied. The oldest woman was 52 years of age. This represented 1.2% of the 41,335 women delivering. Their pregnancy outcomes were compared with those in 26,759 whose age at delivery was 20 to 30 years. The older women were more parous and had higher weights. There was also an increased frequency of hypertension, diabetes mellitus, and placenta previa in the older women. These changes had a significant impact on the fetus for the older women had an increase in infant macrosomia, male sex, stillbirths, and low Apgar scores. They also had a higher incidence of cesarean section and fewer forcep deliveries. The older women whose weight was less than 67.5 kg at delivery did not show any difference in hypertension, fetal macrosomia, fetal death rates, or low infant Apgar scores. Also older of low parity did not have an increase in placenta previa. The older women of normal weight and low parity showed a higher frequency of diabetes mellitus and cesarean section delivery, but their infant outcomes were not different from the control groups. Thus older women of low parity and normal weight managed by modern obstetric methods can expect a good pregnancy outcome.
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PMID:Pregnancy after 40 years of age. 374 89

Nonhuman primate models of gestational diabetes have produced fetopathies most similar to those of the human infant of the mother with gestational diabetes (IGDM). Fetal hyperglycemia, hyperinsulinemia, macrosomia, selective organomegaly, intrauterine death, and placental hyperplasia are hallmarks of the fetopathy of the IGDM. The chronic infusion of insulin into the fetus of a normal pregnant rhesus monkey results in fetal hyperinsulinemia with normal to low plasma metabolic substrate concentrations. Under these conditions, fetal hyperinsulinemia is sufficient to cause fetal growth and hormone changes observed in the human IGDM. Our studies provide evidence that the soft tissue hyperplasia in the fetal macrosomia syndromes in humans and nonhuman primates in which fetal hyperinsulinemia is observed is the direct result of that chronic in utero hyperinsulinemia.
Diabetes 1985 Jun
PMID:Effects of hyperinsulinemia in the primate fetus. 388 40

The maternal antepartum, intrapartum, and neonatal characteristics of 158 patients with gestational diabetes mellitus (GDM) attending a large teaching hospital between 1979 and 1983 were described and compared with a matched nondiabetic control group. The primary cesarean section rate in patients with GDM (18%) was significantly greater than in the control group (11%, P less than 0.04). Neonatal macrosomia, as reflected in mean birthweight (P less than 0.04), the number of neonates weighing greater than 4 kg (P less than 0.05) and large-for-gestational-age infants (P less than 0.05), and the birthweight adjusted for gestational age (K-score, P less than 0.01) was significantly increased in the diabetic group. The characteristics of patients with GDM treated with diet alone and diet and insulin together were examined. The insulin-therapy group was characterized by more patients older than 25 yr (P less than 0.01) and a higher mean birthweight (3743 +/- 677 g) (P less than 0.02) than the diet-alone group. This may reflect an increased magnitude of glucose intolerance in the insulin-treated group. Obese patients with GDM delivered heavier neonates than the nonobese patients with GDM (P less than 0.01). Although there was no difference between the groups, perinatal mortality was present in this study. These data indicate that the major perinatal morbidity in GDM included increased cesarean section for fetal macrosomia. Early diagnosis with strict diagnostic criteria and rigid antenatal surveillance may result in further improvements in outcome.
Diabetes 1985 Jun
PMID:Gestational diabetes mellitus. Is further improvement necessary? 388 43

Most studies of gestational diabetes mellitus (GDM) have reported a marked reduction in perinatal mortality with appropriate dietary regimens and good medical and obstetrical surveillance. Nevertheless, fetal morbidity, including macrosomia, has remained high and appears to be linked to factors other than plasma glucose control. In a review of six investigations in which insulin therapy was combined with an appropriate diet, the incidence of fetal macrosomia was reduced in five studies as compared with diet-only treatments. Again, the improvement did not always correlate with altered plasma glucose profiles. Other studies suggest that maternal plasma substrate disturbances other than glucose may contribute to the development of fetal macrosomia. To what extent insulin administration reduces morbidity by containing circulating maternal fuels, such as lipids and amino acids, in a more normal range remains to be determined. Moreover, the role of diet, maternal obesity, and weight gain during pregnancy adds to the complexity of factors influencing obstetrical outcome in gestational diabetes. Until the relative importance of all of these variables is adequately assessed, criteria for selection of women with pregnancy-onset diabetes for insulin therapy are most likely to be based on fasting and postprandial plasma glucose concentrations.
Diabetes 1985 Jun
PMID:Therapeutic results of insulin therapy in gestational diabetes mellitus. 388 49

This study of 74 diabetic pregnant women shows that tight maternal blood glucose control before the 32nd week of gestation significantly reduces the incidence of fetal macrosomia (11%) when compared with that of patients with fair to poor control before the 32nd week of gestation (44%, P less than .05) or with those whose good diabetic control was not achieved until after the 32nd week of gestation (34%, P less than .05). The macrosomic infant produced by a diabetic mother is associated frequently with an elevated amniotic fluid C-peptide level, which shows the evidence of intrauterine fetal hyperinsulinism. The use of tight diabetic control early in pregnancy to reduce the risk of fetal macrosomia and/or neonatal complications is of clinical importance in the management of diabetes in pregnancy.
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PMID:Good diabetic control early in pregnancy and favorable fetal outcome. 394 Mar 38

The AA. report the results of 14 years' screening for diabetes type 2 in their Health District (Emilia Romagna, North Italy), according to Pavel's method, for early diagnosis of clinical diabetes and impaired glucose tolerance (IGT). The AA. found in a first screening 1.03% of clinical diabetes and 2.65% of IGT cases in the population examined (200,000 subjects). Statistically significant correlations existed in relation to the various risk factors (hereditary factors, obesity, fetal macrosomia, job). The follow-up after 6 years for IGT subjects showed a 25.5% return to normal oral glucose tolerance test (OGTT) values, 21.7% improvement, 19% unchanged, 33.8% impairment. There was a correlation between these results and life-style (diet, physical exercise, weight loss). Fourteen years after these screening, a 2.7% negative incidence was observed for diabetes type 2 in this Health District.
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PMID:Pavel's "dynamic screening" for diabetes type 2: 14 years results in a district of northern Italy. 399 42

The authors report the results of a 12-year screening for type II diabetes in their Health District (Emilia-Romagna, Northern Italy). The method consisted of two steps, following Pavel and Sdrobici, for early diagnosis of clinical diabetes and IGT. The authors found 1.03% of clinical diabetes and 2.65% of IGT cases in the population examined (200,000 subjects). Statistically significant correlations existed with regard to the various risk factors (familiarity, obesity, fetal macrosomia, occupation). Follow-up after 6 years for IGT subjects showed a 25.5% return to normal of OGTT values, 21.7% improvement, 19% unchanged, 33.8% deterioration. There was a correlation between these results and life-style (diet, reduction in calorie intake, weight loss). Twelve years after these screenings, a 2.7% drop in incidence was observed for type II diabetes in this Health District.
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PMID:Long-term results in preventive medicine for type II diabetes. 407 68

To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.
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PMID:Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers. 635 86

One of the hallmarks of the hyperglycemic-hyperinsulinemic infant of the diabetic mother (IDM) is macrosomia and selective organomegaly. Primary hyperinsulinemia, with insulin levels similar to those observed in human IDMs at delivery, was produced in the fetal rhesus monkey during the last third of gestation. The effects of this physiologically relevant hyperinsulinemia, in the absence of hyperglycemia, on fetal growth were studied. Fetal macrosomia, with a 23% increase in total body weight, was observed in physiologically hyperinsulinemic fetuses. A similar 27% increase in weight was produced by fetal insulin levels that were 10 times higher. A logarithmic correlation was observed between fetal birth weight ratio and fetal plasma insulin concentration. In contrast to this increase in weight, skeletal growth, as measured by crown-heel length and head circumference, was not affected by hyperinsulinemia. Only cardiomegaly was found in the low-dose hyperinsulinemic fetuses, whereas cardiomegaly, hepatomegaly, and splenomegaly were produced by hyperinsulinemia in which insulin levels were in the highest range. Compositional analysis of heart and skeletal muscle indicated no differences in the protein, RNA and DNA concentration, or in the protein-to-DNA ratio in hyperinsulinemic fetuses. We interpret these data as indicating that fetal insulin plays the predominant role in controlling the normal, as well as the augmented, fetal weight characteristic of the human infant of the diabetic mother.
Diabetes 1984 Jul
PMID:Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiologic hyperinsulinemia on fetal growth and composition. 637 21


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