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The prevailing concept of etiologic heterogeneity for the diabetes mellitus syndrome is one of multiple genetic factors interacting with a variety of environmental influences. Variation in expression of the disorder, particularly the need for insulin, does not correlate with known etiologic distinctions. There is much evidence for genetic heterogeneity, as well as phenotypic variation when etiology can be presumed to be identical. The vascular manifestations of diabetes include microangiopathy unique to diabetes and larger vessel disease that differs from that of normal aging only by its prematurity. There is as much evidence for heterogeneity of the vascular expression as there is for glucose intolerance. Approximately 25% of persons with insulin-dependent diabetes may never develop the microvascular disease. The pathogenesis of vascular disease in diabetes may involve a number of abnormalities of plasma, circulating cells, and vascular tissue. Were absolute control of glycemia possible, some of the contributing factors involved in vasculopathy would possibly be alleviated. In the absence of automated physiologic insulin replacement the potential deleterious effect of our current methods of treatment might be reduced by specific inhibition of excess catecholamine, growth hormone and/or glucagon responses.
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PMID:Nature and nurture in the expression of diabetes mellitus and its vascular manifestations. 33 1

Salbutamol infusion, 4 micrograms/kg in 5 ml of water infused for 20 minutes, was given to treat hyperkalaemia (potassium level > 6.0 mmol/l) in 10 critically ill preterm infants (median gestational age 26 weeks). Seven infants had acute renal failure, two had persistent metabolic acidosis without renal failure and the remaining infant had a combination of acute renal failure and persistent metabolic acidosis. No infant developed a tachycardia or became hyperglycaemic in response to the infusion. Seven of the 10 infants ultimately died but this was at a mean of 9 days following the infusion and as a consequence of complications due to their extreme prematurity or major congenital abnormality. In response to the infusion the potassium level fell in 7 infants with acute renal failure by a median of 1.1 mmol/l (range 0.7-1.8) at one hour but in the three infants with a persistent metabolic acidosis, the potassium level continued to rise. We conclude that salbutamol infusion achieves, without side-effects, at least a temporary reduction in hyperkalaemia in preterm infants with renal failure, but not metabolic acidosis. Its effect is of sufficient duration to allow ample time for definitive therapy to be instituted and thus may be a useful alternative for infants in whom the possible hypoglycaemic side-effects of glucose and insulin should be avoided.
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PMID:Salbutamol infusion to treat neonatal hyperkalaemia. 129 69

Among 58,187 women tested, 1002 had a maternal serum alpha-fetoprotein measuring greater than or equal to 2.5 multiples of the median after correction for race, weight, and insulin-dependent diabetes. They were stratified into three groups: group 1, 2.5 to 2.9; group 2, 3.0 to 5.0; group 3, greater than or equal to 5.0 multiples of the median. The initial risk of a serious abnormality detected by ultrasonography or amniocentesis was 17% (5%, 12% and 65% in groups 1, 2, and 3, respectively). After correction for twins and dates, this risk became 23% (7%, 18%, and 71% in groups, 1, 2, and 3, respectively). Among the women with high maternal serum alpha-fetoprotein levels, 556 (77%) had normal ultrasonographic and amniocentesis studies, and the risk of adverse pregnancy outcome ws 27% (19%, 29%, and 70% in groups 1, 2, and 3, respectively). There was a statistically significant increase in late fetal and perinatal death, prematurity and growth retardation, oligohydramnios, abruptio placentae, preeclampsia, and congenital abnormalities. The overall risk for abnormality or adverse outcome was 24% in group 1, 41% in group 2, and 91% in group 3.
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PMID:Risks associated with an elevated maternal serum alpha-fetoprotein level. 171 19

Before the discovery of insulin in 1921, pregnancies in women with diabetes mellitus were a rarity because most reproductive-age patients died soon after diagnosis of this illness. In the limited number of pregnancies reported in the pre-insulin era, both perinatal and maternal mortality were approximately 50%, with stillbirths being the primary cause of perinatal deaths. Insulin treatment restored the fertility of women with diabetes and was associated with a marked reduction in maternal mortality. Women with more severe disease had the opportunity to become pregnant; however, their pregnancies frequently resulted in neonatal death due to prematurity. Therefore, perinatal mortality was not substantially reduced.
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PMID:A story of two miracles: the impact of the discovery of insulin on pregnancy in women with diabetes mellitus. 173

Prematurity in Indian births is modeled, based on the hypothesis that reduced protein and glucose and aminoacids and maternal anemia and preeclampsia lead to placental dysfunction which is also affected by metabolic disturbance and fetal circulation related to cellular growth and questions about genetics. There may be an ethnic propensity for early maturation of the fetus which affects the higher stillbirth rates and perinatal mortality. It was observed that among, for instance, black and Indian racial groups there may be meconium release and fetal distress. The significance is that physicians should increase antenatal surveillance before 40 weeks. Maternal nutrition should be advanced and hyperalimentation by cordocentesis. Other interventions such as glucose, oxygen, and aspirin administration are still very experimental. The evidence that velocity of growth is different and low birth weight is due to abnormal growth and shortened gestation is currently being researched among different ethnic groups. The discussion is concerned with reports of ethnic variation among Indian and Malay babies in Singapore and babies of French or African ancestry in France. In these studies findings were that the Indians and Malays in Singapore vs. the Chinese had higher mortality, and black African ancestry in mixed ancestry babies was related to higher infant mortality. Another study on neonatal mortality in India led to the recommendation that 2000 gm be established as the limit for defining low birth weight. In the 1501- 2000 gm birth weight groups, 30-45% are preterm, and the remainder are term or postterm. Low birth weight may transcend generations in India even with emigration. Experimental studies show that intrauterine weight is related to placental volume. Reduced growth and lower fetal insulin/glucose ratio with elevated fetal glycine/valine ratio was found to be related to reduced glucose supply among fetuses with fetal hypertriglyceridemia. Fat seems to be lacking among low birth weight fetuses. Studies of somatomedin and somatostatin in metabolism are helping to provide greater understanding of fetal growth processes.
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PMID:The prematurity paradox of the small Indian baby. 180 Mar 24

The purpose of the present study was to determine the risk of neonatal morbidity in infants of diabetic mothers in relation to birth weight percentiles, maternal White classification and metabolic control during pregnancy. The subjects consisted of 51 infants of gestational and Type II diabetic women and 148 infants of insulin-dependent diabetic women. The following neonatal symptoms commonly associated with maternal diabetes were analyzed: macrosomia, hypoglycemia, erythremia, hyperbilirubinemia, hypocalcemia, prematurity and hyaline membrane disease. The incidence of the symptoms was as follows: hypoglycemia in the first hour of life 34.3% macrosomia 24.6%, hyperbilirubinemia 23.7%, prematurity 18.1%, hypoglycemia after the first hour of life 16.6%, hypocalcemia 11.1%, erythremia 7.6%, and hyaline membrane disease 2.0%. There were statistically significant differences in the symptoms "hypoglycemia after the first hour of life" and "erythremia" between the birth weight percentile groups, i.e. the incidence of these symptoms increased with higher birth weights. The risk of neonatal morbidity among infants of insulin-treated gestational diabetics was higher than that of infants of diet-controlled gestational diabetic women. The incidence of macrosomia and hypocalcemia was significantly higher in the first group. Newborns of insulin-dependent diabetic women with proliferative retinopathy and/or nephropathy (White class FR) had an increased risk of neonatal morbidity in comparison to infants of White classes B, C, and D, especially with regard to prematurity and associated problems. Neonatal morbidity varies with the quality of metabolic control in women with insulin-dependent diabetes. Infants of poorly-controlled mothers were more often macrosomic and premature than infants of well-controlled mothers.
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PMID:[Neonatal morbidity of children of diabetic mothers]. 234 9

From Jan. 1, 1983, through Dec. 31, 1987, 420 gravidas with insulin-requiring diabetes antedating pregnancy delivered on the Joslin Clinic service. Among them, 110 pregnancies (26.2% of the total) delivered before 37 completed weeks of gestation compared with a 9.7% incidence (906/9368) for the general population at the Brigham and Women's Hospital during calendar year 1985. Thirty-three percent of all premature deliveries were the result of the development of preeclampsia. The relative risk of prematurity for diabetic patients with any hypertensive complication was 2.0 (95% confidence interval, 1.40 to 2.87) compared with normotensive diabetic subjects. Compared with the general population, most of the excess risk of prematurity was confined to hypertensive diabetics and normotensive patients of more advanced White class. A history of having had a previous premature delivery, increasing duration of diabetes antedating pregnancy, and carrying a male fetus in the index pregnancy were significantly associated with premature delivery. Future efforts to reduce the incidence of prematurity among diabetic gravidas should be directed toward reducing the incidence of preeclampsia.
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PMID:Prematurity among insulin-requiring diabetic gravid women. 266 91

The incidence of spontaneously occurring premature labor in insulin-dependent diabetic pregnancies is unclear, because previous studies have been confounded by a high rate of iatrogenic prematurity. The purpose of this study was to determine, in a large population of insulin-dependent diabetic pregnant women, the rate of spontaneous occurrence of premature labor and the various factors that may affect it. We hypothesized a priori that spontaneously occurring premature labor occurs at a high rate in insulin-dependent diabetic pregnant women, mainly because of poor control of diabetes during pregnancy, and is related to the presence of polyhydramnios and hypomagnesemia. One hundred forty-five insulin-dependent diabetic women undergoing 181 pregnancies were recruited since 1978 in an interdisciplinary prospective study. The goals of glucose control were a fasting blood glucose less than 100 mg/dL and a 90-minute postprandial glucose less than 140 mg/dL. The rate of spontaneous premature labor, 31.1%, was significantly higher (P less than .01) than that in a control population managed by the same obstetricians in similar clinical settings (20.2%). The following variables were not significantly associated with the onset of premature labor: maternal age, parity, gravidity, diabetic class according to White, presence of renal disease or retinopathy, previous elective abortion, chronic hypertension or pregnancy-induced hypertension, cigarette smoking, first-trimester or post-20 weeks' gestation vaginal bleeding, maternal serum magnesium concentration, or polyhydramnios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High spontaneous premature labor rate in insulin-dependent diabetic pregnant women: an association with poor glycemic control and urogenital infection. 339 60

This paper describes criteria used to assess maturity of the newborn foal and their clinical application to field cases of prematurity and dysmaturity. Premature and mature foals may be clearly distinguished by their behavioural and physical characteristics. Measurement of haematological parameters (mean cell volume, total white cell and differential counts), pancreatic beta cell activity (plasma glucose and insulin levels), adrenocortical-medullary function (plasma cortisol, adrenocorticotrophic hormone and catecholamines) and the renin-angiotensin system (plasma renin substrate concentrations) were found useful in evaluating the status of the newborn foal. Confirmation of the initial diagnosis can be made by response to various challenge tests eg, glucose tolerance test, short acting synthetic adrenocorticotrophic hormone (ACTH1-24) and frusemide. In the present investigation a small number of individuals appeared to be intermediate in maturity to the other two groups, indicating that a third state of maturity may be identified. The clinical implications of this work suggest that cortisol replacement therapy and administration of long acting synthetic ACTH1-24 may be of benefit.
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PMID:Studies on equine prematurity 6: Guidelines for assessment of foal maturity. 609 Jan 20

We studied the risk of a large group of jaundiced neonates for bilirubin encephalopathy by serial assessment of their reserve serum albumin binding capacity as measured by the saturation index test. In 1271 infants with serum bilirubin concentration greater than 10 mg/dl, 12% had a saturation index (SI) of 7% or greater and therefore were clinically at or near risk for bilirubin encephalopathy. Treatment with glucose infusion (1 gm/kg over one hour) was highly effective in lowering the SI (delta = -3.7%. P less than 0.001). In none of the infants did SI rebound to 7% or greater within 24 hours after the infusion. In a detailed study of 19 infants who received glucose, the highly significant (P less than 0.001) fall in SI (delta = -3.7%) was accompanied by an equally significant rise in serum values for insulin (delta = +21.6 mcu/ml) and fall in serum free fatty acids (delta = -0.51 mEq/L). Many factors in the study, such as prematurity, hemolysis, acidosis, and hypoxemia, could have predisposed the infants to the risk of bilirubin encephalopathy. However, the facility by which most (93%) of the infants with high SI, including those who were premature or had evidence of hemolysis or respiratory insufficiency, responded to infusion of glucose indicates that serum free fatty acids may be the principal factor contributing to the high saturation index and therefore an underestimated factor in bilirubin binding to albumin.
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PMID:Influence of free fatty acids and glucose infusion on serum bilirubin and bilirubin binding to albumin: clinical implications. 682 17


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