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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During gestation, heterozygous C57BLKS/J-Lepr(db/+) mice develop spontaneous gestational diabetes mellitus (GDM), and the newborn fetuses are macrosomic compared with offspring from wild-type (+/+) mothers. To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). During pregnancy, fasting plasma glucose and hepatic glucose production were twofold greater in db/+ than +/+ mice, despite similar insulin levels. In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. Plasma leptin concentration increased 40-fold during pregnancy, from 2.2+/-0.5 to 92+/-11 ng/ml and 3.6+/-0.1 to 178+/-34 ng/ml in +/+ and db/+ mice, respectively (P<0.01), but was increased to only 23+/-3 ng/ml in pregnant db/+TG6 mice (P<0.001). Maternal fat mass and energy intake were greater in db/+ mice, and fat mass was reduced by GLUT4 overexpression, independent of food intake. Fetal body weight was increased by 8.1 and 7.9% in db/+ and db/+TG6 mothers, respectively (P<0.05), regardless of fetal genotype, whereas fetuses from db/+TG8 mothers (four- to fivefold overexpression) weighed significantly less compared with pups from +/+ or db/+ mothers (P<0.05). These results suggest that the single mutant db allele effects susceptibility to GDM through abnormalities in insulin receptor signaling, defective insulin secretion, and greater nutrient availability. GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. However, maternal hyperglycemia appears not to be the sole cause of fetal macrosomia. These data suggest that GDM is associated with defects in insulin receptor signaling in maternal skeletal muscle, and this may be an important factor provoking maternal and fetal perinatal complications.
Diabetes 1999 May
PMID:Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice. 1033 11

Shoulder dystocia is an infrequent and unexpected emergency requiring rapid and deft solution. Identifiable risk factors include maternal diabetes, fetal macrosomia (especially in the presence of diabetes), and maternal history of previous delivery of a large infant. Other reported risk factors include arrest and protraction disorders of labor and midpelvic operative delivery; however, more than 50% of shoulder dystocia occurs in instances without identifiable risk factors, and permanent neonatal injury is thus unpredictable. Therefore, all personnel in the delivery suite must be well versed in the timely and appropriate application of corrective measures. Although most instances of shoulder dystocia cannot be predicted, the judicious use of CS delivery in diabetic patients with expected birth weights of more than 4250 g should reduce the risk of shoulder dystocia in this subgroup of patients. A trial of labor for nondiabetic patients with suspected fetal macrosomia is recommended because predicting actual birth weights in this population remains difficult.
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PMID:Shoulder dystocia. 1039 67

Both our previously performed decision analysis and more recent clinical data considered in the context of our decision analytic framework support the claim that in the pregnancies of women without diabetes the level of intervention and the economic costs of prophylactic cesarean delivery for fetal macrosomia diagnosed by means of ultrasonography are predicted to be excessive. Under the most plausible assumptions, a prophylactic cesarean policy with either a 4000- or 4500-g macrosomia threshold would require more than 1000 cesarean deliveries and millions of dollars to avert a single permanent brachial plexus injury. In the pregnancies of diabetic women, although such policies would be expected to perform appreciably better, their use would nevertheless entail considerable intervention for any benefit achieved. Under most assumptions, hundreds of cesarean deliveries and hundreds of thousands of dollars would be required to avert a single permanent brachial plexus injury. In light of the available data, optimizing the management of shoulder dystocia seems at present to be the most immediate and tenable approach to the prevention of birth-related brachial plexus injury.
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PMID:Prophylactic cesarean delivery for fetal macrosomia diagnosed by means of ultrasonography--A Faustian bargain? 1045 78

Shoulder dystocia is one of the most dreaded complications of vaginal delivery encountered by the obstetrician. Although risk factors for shoulder dystocia exist, approximately 50% of cases do not demonstrate the classic predisposing signs. Obstetricians can help patients decrease their risk for fetal macrosomia by frequent attention to weight gain, nutrition, and exercise during pregnancy and by aggressive management of diabetes. All obstetricians must be familiar with the maneuvers used to effect delivery of impacted shoulders and must be prepared to institute these maneuvers immediately in a crisis situation.
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PMID:Shoulder dystocia: an obstetric emergency. 1047 64

The presence of insulin-dependent or non insulin-dependent diabetes mellitus in pregnant women has been associated with an adverse effect on the maternal an fetal outcomes of pregnancy. The incidence of obstetrical and diabetic complications is increased, and a continuum has been observed between maternal blood glucose levels and perinatal outcome. The incidence of congenital malformations, macrosomia and prematurity is increased in offspring of diabetic mothers. Programming and intensive collaborative follow-up improve the outcome of such pregnancies. Gestational diabetes mellitus is an heterogenous condition defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Short term complications are mainly represented by fetal macrosomia and high cesarean section rate. Women with a history of gestational diabetes mellitus are at increased risk of future diabetes, predominantly type 2. Obesity and type 2 diabetes are increased among their children.
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PMID:[Diabetes and pregnancy]. 1054 52

Fetal macrosomia is an heterogeneous condition in terms of definition and etiologic factors. Recent findings suggest that macrosomia should not be classified on the basis of birth weight and gestational age alone. The ponderal index delineates a symmetric and an asymmetric subtype of macrosomia. The relationship between maternal diabetes and fetal macrosomia has been extensively investigated. However, eighty percent of macrosomic infants are born to mothers who are not hyperglycemic, and various factors have been associated. Maternal factors explain approximately 50% of the variance in birth weight, whereas paternal factors have no significant effect. The predisposition to excessive fetal growth may be shared within the intra uterine environment and the fetal genome. The respective roles of lipids, amino acids, hormones such as leptin, and growth factors need to be evaluated. Perinatal morbidity and long term consequences such as obesity and glucose intolerance might be associated with some of the factors leading to fetal overgrowth.
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PMID:[Etiopathogeny of fetal macrosomia]. 1067 72

This article provides the reader with relevant information regarding the association between level of glycemia and perinatal outcome in preexisting diabetes. Although the glycemic profile is a continuum in nature, different thresholds of glucose are associated with fetal complications such as stillbirth, spontaneous abortion, congenital anomalies, fetal macrosomia, and metabolic and respiratory complications. For each complication, a different targeted threshold of normality is required. Thus, although it is not always possible to achieve optimal glycemic control in all patients, any improvement will be beneficial because it will reduce the rate of complications for a given glucose threshold.
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PMID:Level of glycemia and perinatal outcome in pregestational diabetes. 1075 33

Diabetes in pregnancy is unique because of the diversity of problems that can affect the embryo/fetus beginning with conception. Considerable effort has been devoted to understanding the basic developmental biology from observing young embryos in vitro or in vivo. Maternal glucose control has been identified as an important event. The preponderance of evidence indicates that rigid glucose control will minimize the incidence of anomalies incurred before 9 weeks of pregnancy. Later events are related to fetal hyperinsulinemia. These include fetal macrosomia, respiratory distress syndrome, neonatal hypoglycemia, neonatal hypocalcemia, and neonatal hypomagnesemia. Control of maternal metabolism can have a significant impact on each of the above. Finally, the long-term effects of maternal diabetes are as diverse as the pathogenetic events during pregnancy. Surprisingly, there is a significant transmission rate of 2% of type I diabetes if the mother has insulin-dependent diabetic mother, whereas the rate is 6% for the father. The Diabetes in Early Pregnancy Study showed that good maternal control was associated with normal neurodevelopmental outcome.
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PMID:Effects of diabetic pregnancy on the fetus and newborn. 1080 68

The authors examined the impact of universal screening on the diagnosis of gestational diabetes and its complications. All mothers and newborns registered by the Canadian Institute for Health Information from 1984 to 1996 (even-numbered fiscal years only) were included in the analysis. Over this time period, the proportion of women with gestational diabetes increased ninefold (from 0.3% to 2.7%) while the proportion with prepregnancy diabetes fell from 0.7% to 0.4%. As rates of gestational diabetes increased, a corresponding reduction in the risks of complications (polyhydramnios, amniotic cavity infection, cesarean delivery, and preeclampsia) occurred for women with gestational diabetes. The incidence of gestational diabetes fell in Metro-Hamilton (where screening was discontinued in 1989) but remained high in the rest of Ontario (where screening continued in most areas). No related temporal trends for fetal macrosomia, cesarean delivery, or other diabetes-related complications were observed, regardless of screening policy. The authors concluded that the substantial increase in gestational diabetes in Canada is an artifact caused by universal screening, with no evidence of beneficial effects on pregnancy outcomes.
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PMID:Impact of prenatal glucose screening on the diagnosis of gestational diabetes and on pregnancy outcomes. 1111 9

Even though the role of fetal hyperinsulinemia in the pathogenesis of fetal macrosomia in patients with overt diabetes and gestational diabetes mellitus seems plausible, the molecular mechanisms of action of hyperinsulinemia remain largely enigmatic. Recent indications that hyperinsulinemia "primes" various tissues to the mitogenic influence of growth factors by increasing the pool of prenylated Ras proteins prompted us to investigate the effect of fetal hyperinsulinemia on the activitiy of farnesyltransferase (FTase) and the amounts of farnesylated p21 Ras in fetal tissues in the ovine experimental model. Induction of fetal hyperinsulinemia by direct infusion of insulin into the fetus and by either fetal or maternal infusions of glucose resulted in significant increases in the activity of FTase and the amounts of farnesylated p21 Ras in fetal liver, skeletal muscle, fat, and white blood cells. An additional infusion of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and completely prevented these increases, specifying insulin as the causative factor. We conclude that the ability of fetal hyperinsulinemia to increase the size of the pool of farnesylated p21 Ras may prime fetal tissues to the action of other growth factors and thereby constitute one mechanism by which fetal hyperinsulinemia could induce macrosomia in diabetic pregnancies.
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PMID:Fetal hyperinsulinemia increases farnesylation of p21 Ras in fetal tissues. 1144 Aug 96


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