Insulin-dependent Diabetic Women Research Articles

Fatty acid compositions of serum lipids, erythrocytes, and platelets in insulin-dependent diabetic women.

The fatty acid composition of serum lipids, erythrocytes, platelets, and diet was studied in women with insulin-dependent diabetes (IDDM) and in normal subjects matched for age, sex, body weight, and serum lipid levels. The dietary intake of linoleic acid was higher in IDDM patients than in the normal subjects. The linoleic acid content of serum triglycerides, cholesterol esters, and phospholipids and of red cells and platelets were elevated in patients with IDDM proportionately to their dietary linoleate intake. The linoleic acid content of serum lipids, but not of diet, was significantly correlated with glycosylated hemoglobin A1c in IDDM patients. However, the serum lipid content of arachidonic acid and other n-6 polyunsaturated fatty acids, which are metabolites of linoleic acid, was decreased in IDDM patients, but these metabolites were normal or increased in their cell membranes. The contents of n-3 polyunsaturated fatty acids were decreased in serum and platelet lipids and tended to be increased in erythrocyte membranes of diabetic patients. The results suggest that elongation and desaturation of essential fatty acids, linoleic acid in particular, are decreased in women with IDDM.

Psychosocial childbearing stress and metabolic control in pregnant diabetics.

The authors tested the relationship between psychosocial childbearing stress factors and metabolic control in a research sample of 39 pregnant insulin-dependent diabetic women. Subjects were selected using rigorous exclusion criteria from a population of more than 200 pregnant diabetic patients assessed in a University National Institutes of Health Center. Metabolic control was determined by plasma levels of preprandial day, night, and early morning fasting glucose, urinary ketones, and glycosylation of hemoglobin. Differences in plasma glucose concentrations and urinary ketone levels at several times during the day and night were associated with psychosocial stress factors. A similar relationship between stress and levels of diabetic control could not be demonstrated by hemoglobin A1 assay, a result contradicting most prior studies of adolescent populations. These findings are compatible with a biopsychosocial model of diabetes mellitus and emphasize the importance of using several different measures of diabetic control to determine stress-control relationships.

Effect of normoglycemia before conception on early pregnancy hormone profiles.

Insulin-dependent diabetic women have been shown to have subnormal hormone levels in the first trimester of pregnancy. To determine whether these abnormalities were the result of poor diabetes control, testosterone, androstenedione, human chorionic gonadotropin (HCG), and prolactin were studied longitudinally in diabetic women made normoglycemic before conception (N = 11) and normal (N = 6) control subjects beginning at the fifth week of gestation. HCG levels rose normally in all 11 diabetic and six control subjects and then declined as expected, with peak levels between 8 and 12 wk of gestation. Prolactin levels similarly rose significantly (P less than 0.00001) during the period studied. Plasma androstenedione did not increase during the course of this study, but testosterone levels increased significantly (P = 0.0001). Androgen levels were consistently higher in diabetic subjects despite the normoglycemic state, although the differences reached statistical significance at only one point. This study demonstrates that when normoglycemia is achieved before conception, HCG and prolactin are normal at 5 wk after the last menstrual period. The possibility that androgen levels may be higher in insulin-requiring diabetic women, perhaps due to peripheral hyperinsulinemia, should be explored.

Glucose monitoring and insulin administration in the pregnant diabetic patient.

Over the past decade, it has been apparent that the degree of glycemic control achieved in the pregnant patient with diabetes mellitus significantly affects perinatal outcome. While several studies have documented excellent perinatal outcome with good glucose control, the incidence of neonatal morbidity still remains substantially greater than that observed in the general population. Physiologic or "tight" control appears to further reduce the incidence of macrosomia, hypoglycemia, and other indices of neonatal morbidity. The application of home glucose-monitoring techniques to pregnancies complicated by diabetes can result in optimal glucose control. While one small comparative series did not document improvement in perinatal morbidity, fewer admissions for diabetic control and decreased patient expense were observed in the group using home monitoring. After pregnancy, most patients continued to use home monitoring. This probably reflects the degree of patient enthusiasm and interest generated by self-care. Programs using home blood glucose monitoring and individualized insulin regimens in the management of diabetes may have their greatest impact if implemented prior to conception. The degree of glucose control during early embryogenesis appears to determine the incidence of congenital malformations in the offspring of insulin-dependent diabetic women. Continued careful assessment of the degree of glycemic control may enable the patient and her physician to plan the optimal time for attempting a pregnancy.

Congenital malformations in diabetic pregnancies. Clinical viewpoints.

A consecutive series of 2,587 newborn infants of diabetic mothers treated during pregnancy and delivery in the period 1926 to 1983 has been analysed. The malformation rate was 6.6%. The series has been divided into five consecutive periods each comprising around 500 infants. During the first four periods the frequency of congenital malformations (CM) was remarkably constant also when related to the severity of the maternal diabetes. During the latest period from 1979 to 1983 a significant decrease in the frequency and severity of CM in infants of diabetic mothers was seen, most marked in the group with more severe maternal diabetes (White's classes D + F). One hundred and thirty-five insulin-dependent diabetic women with regular menstrual histories were examined by ultrasonic scanning in the 7th to 14th week of pregnancy. As judged by the crown-rump length 53 fetuses were smaller than normal. The term early growth delay is used for this phenomenon. Nine of the 135 fetuses had major CM and seven of them were smaller than normal in early pregnancy. These observations show that fetuses that are significantly smaller than normal in early pregnancy carry a higher risk of being malformed and suggest a common mechanism behind early growth delay and induction of abnormal embryogenesis.

Glycosylated Albumin and Glycosylated Proteins: Rapidly Changing Indices of Glycaemia in Diabetic Pregnancy

Serial measurements of glycosylated albumin (GAlb), glycosylated plasma proteins (GPP) and glycosylated haemoglobin (GHb) were performed by affinity chromatography throughout the course of pregnancy in 14 insulin-dependent diabetic women. In patients whose glycaemic control improved markedly during pregnancy, the concentrations of GAlb and GPP decreased by more than 50 per cent after four weeks of good diabetic control. By contrast, the rate of decrease in GHb levels in the same patients was significantly less and did not indicate a comparable improvement in glycaemia until 12 weeks after good diabetic control was established. Elevated concentrations of GAlb or GPP decrease much more rapidly than GHb concentration when diabetic control is improved; thus measurement of glycosylated proteins is a valuable adjunct to serial blood glucose monitoring in clinical circumstances such as diabetic pregnancy, where early confirmation of good diabetic control is important.

140 MATERNAL DIABETIC CONTROL AND HYPERTROPHIC CARDIOMYO PATHY (HyC) IN INFANTS OF DIABETIC MOTHERS (IDM)

Transient HyC occurs frequently in IDM. This may result from fetal hyperinsulinemia secondary to maternal hyperglycemia in the 3rd trimester. Prospective study was designed to determine the incidence of IDM HyC and to investigate its relationship to 3rd trimester maternal diabetic control, measured by HbA1.20 insulin dependent diabetic women and their infants and 30 normal babies (controls) were enrolled in the study. Maternal HbA1 was obtained at the time of delivery and M-mode echocardiography was performed on all infants at 24-72 hrs.age. Cord blood glucose, follow-up glucose at q 30 min × 4 and chest x-ray were obtained in all IDM. Diagnosis of HyC was based on ratio of absolute ventricular septal thickness related to body weight (S/BW-mm/kg). No correlation existed between maternal HbA1 at term and incidence of neonatal HyC, macrosomia and hypoglycemia. These data do not support 3rd trimester hyperglycemia with consequent fetal hyperinsulinemia as a trigger mechanism for HyC.

Sera from diabetic pregnant women contain reduced titres of inhibiting factors on killer cell activity.

The presence of Fc-receptor-blocking factors in the sera of normal and insulin-dependent diabetic pregnant women was investigated by means of an antibody-dependent cell-mediated cytotoxicity assay. Sera from normal pregnant women induced a significant depression of antibody dependent cell-mediated cytotoxicity when compared with sera from normal and diabetic non-pregnant women (p less than 0.0001; p less than 0.002, respectively). The effect of sera from diabetic pregnant women, however, was not different from that observed with sera from normal and diabetic non-pregnant women. Thus, we confirm the presence of Fc-receptor-blocking factors in the sera of normal pregnant women. The higher cytotoxicity levels measured in the presence of sera from pregnant women with insulin-dependent diabetes suggests that the titres of such factors are reduced in this condition.

Spontaneous abortion among insulin-dependent diabetic women

A prospective study was undertaken to evaluate the frequency of spontaneous abortion in clinically apparent pregnancies among insulin-dependent diabetic women evaluated prior to pregnancy. The study was done in 132 pregnancies occurring in 91 diabetic women. The spontaneous abortion rate was 30%; 70% of the pregnancies progressed beyond 20 weeks. The abortion rates for Classes B, C, D, and F through RT were 0%, 25%, 44%, and 22%, respectively. Initial serum levels of the beta-subunit of human chorionic gonadotropin above 6000 mIU were usually associated with favorable outcome while levels below 6000 mIU were not predictive of outcome. Data from this study suggest that the risk of spontaneous abortion among insulin-dependent diabetic women may be substantially higher than for the general population. Higher abortion rates were generally associated with more advanced White classification of diabetes. Age at diagnosis was the only factor which showed a significant contribution to the risk of abortion.

Somatomedins and insulin in diabetic pregnancies: effects on fetal macrosomia in the human and rhesus monkey.

The concentrations of the somatomedins (SMs) insulin-like growth factors I and II (SM-C/IGF-I and IGF-II) were measured by RIA in six normal and seven insulin-dependent diabetic pregnant women and their infants at delivery. SM-C/IGF-I and IGF-II levels in the two groups of women were similar. Maternal IGF-II concentrations correlated with maternal hemoglobin AIc levels (r = 0.68) and infant birth weight ratios (actual birth weight/expected 50th percentile sex-corrected birth weight for gestation age; r = 0.54). SMC/IGF-I and IGF-II levels in umbilical plasma in infants of diabetic mothers did not differ from those in control infants, but were lower than the corresponding maternal values. In contrast, umbilical plasma levels of C-peptide immunoreactivity were significantly elevated in the infants of diabetic mothers (2.25 +/- 1.85 (+/-SD) vs. 0.34 +/- 0.15 pmol/ml; P less than 0.01). The infant birth weight ratio was logarithmically correlated with the umbilical plasma C-peptide immunoreactivity (r = 0.78). SM levels were also measured by radioreceptor assay in five normal and five hyperinsulinemic rhesus monkey fetuses. When chronic hyperinsulinemia was produced by continuous SC infusion of insulin in the fetal rhesus monkey, the fetal birth weight ratio was also found to be logarithmically correlated with the fetal plasma insulin concentration (r = 0.81). The fetal SM peptide content was elevated only in the fetuses with plasma insulin levels greater than 3000 microU/ml. The fetal weight gains in response to hyperinsulinemia in the human and rhesus are similar. Since fetal SM levels in the humans and monkeys were not significantly different in the two groups, our data suggest that insulin plays the predominant role in stimulating human and subhuman primate excess fetal weight gain of the infant of the diabetic mother during the latter part of gestation.

Subpopulations of lymphocytes in maternal peripheral blood during pregnancy

The fetus can be considered an allograft with up to one-half of its MHC antigens being potentially recognized by the mother as foreign. This study compares expression of OKT3, OKT4, OKT8, Kappa, Lambda and Ia antigens on lymphocytes in the peripheral blood of normal non-pregnant women, normal pregnant women, patients who are chronic spontaneous aborters and pregnant insulin-dependent diabetic women. Monoclonal antibodies and cytofluorometric analyses were used for these determinations. There were no significant differences ( P = 0.01) between these groups for T-cell markers. A statistically significant ( P = 0.001) increased ratio of cells bearing surface immunoglobulin to those expressing Ia antigen (K&L/Ia) was observed between normal non-pregnant controls and women with a history of chronic spontaneous abortion. It is concluded that T-lymphocytes in the peripheral blood do not demonstrate a phenotypic abnormality that would account for the non-rejection of the fetal allograft; however, women with chronic spontaneous abortion may have abnormal B-cell differentiation or T-cell activation that mediates chronic spontaneous abortion.

POOR REPRODUCTIVE OUTCOME IN INSULIN-DEPENDENT DIABETIC WOMEN ASSOCIATED WITH LATER DEVELOPMENT OF OTHER ENDOCRINE DISORDERS IN THE MOTHERS

In a prospective study of insulin-dependent diabetic women who in the 1950s were involved in a drug trial, 13(14%) of those who were still alive 27 years later were reported to have acquired thyroid disease or pernicious anaemia during the follow-up period. This suggests that their diabetes mellitus was a manifestation of a more generalised polyendocrine disorder. The pregnancy history of these 13 women differed strikingly from that of the other 82 insulin-dependent diabetic women: in the diabetic women who subsequently acquired other endocrine disease 69% of pregnancies resulted in a fetal or infant death, compared with 44% in other insulin-dependent diabetic women (p<0·01). This risk increased with pregnancy order, the odds ratio of an unfavourable outcome in women who later acquired thyroid disease or pernicious anaemia, compared with the other diabetic women, being 1·2 for the first pregnancy, 3·1 for the second pregnancy, 7·3 for the third pregnancy, and 14·0 for the fourth pregnancy. The mean birthweight of offspring of the women with other endocrine disease was substantially lower than the mean birthweight of offspring of other diabetic mothers (2977 g and 3430 g, respectively). These differences in birthweight and mortality could not be explained by the severity of the mothers' diabetes at the time of their pregnancies, and were evident even before the diabetes was diagnosed.

Quantitativ-histologische Untersuchungen des fetalen menschlichen Pankreas von stoffwechselgesunden Frauen und insulinabhängigen Diabetikerinnen

Human fetal pancreases from nondiabetic (n = 26) and insulin-dependent diabetic women (n = 14) between the 13th and 26th week of pregnancy were investigated morphologically. There was in enhanced islet cell volume in fetuses from diabetic patients compared to those from nondiabetics, mainly caused by nesidioblastosis. This phenomenon could be caused by the metabolic state of the insulin-dependent diabetic patients. There were also single beta cells or groups of beta cells, which could be found between the exocrine pancreatic tissue, already at an early stage in pregnancy. It is assumed, that the nesidioblastosis in fetuses from diabetic women is caused by a continuous stimulation of the fetal endocrine pancreas during pregnancy. These results are in a good correlation to the in vitro results of the insulin secretion of human fetal pancreatic slices after incubation.

Fibrin generation during the diabetic pregnancy.

Fibrin catabolism was measured during the pregnancy of insulin-dependent diabetic women in both a longitudinal and cross sectional fashion. Samples of maternal peripheral venous blood were obtained in 20 pregnant diabetic women between 26 and 38 weeks' gestational age. Fibrinopeptide A, the first peptide cleaved from fibrinogen during thrombin-mediated catabolism, was measured by radioimmunoassay. Intra-assay and interassay variation for fibrinopeptide A in this laboratory were 2% and 4% respectively. Antithrombin III activity was determined by the method of Odegaard. The patients ranged from 23 to 36 years. Overall blood glucose control was good as reflected in near-normal HbA1 fasting plasma glucose values. The mean HbA1 +/- 1 standard deviation was 7.1% +/- 1.2%. The mean fasting plasma glucose concentration was 101.9 mg% +/- 21.5 mg%. Mean FPA for the diabetic women exceeded control values at each gestational period. Significant differences were found in four of the seven intervals. While the highest FPA was noted in a patient with advanced diabetic vasculopathy, exclusion of this patient did not alter the overall findings. The findings were striking and suggest the need for a prospective study designed to account for White's classification of diabetes and the degree of glucose control. Because complications of the diabetic pregnancy include an increased risk of hypertension in the mother and sudden, unexplained fetal loss, two complications associated with abnormal clotting, the increase in fibrin catabolism in patients in tight metabolic control would suggest that events other than glucose regulation impact upon fibrin catabolism and possibly pregnancy outcome in the diabetic mother.

Reduced short-term variability of fetal heart rate in association with maternal hyperglycemia during pregnancy in insulin-dependent diabetic women

The differential index, which describes the short-term component of fetal heart rate variability, and maternal blood glucose levels were measured 109 times in 19 insulin-dependent diabetic mothers in the second half of gestation. An abnormal differential index was observed more often with maternal hyperglycemia (11/45) than with normoglycemia (5/64). A significant negative linear correlation was found between the differential index and the blood glucose level of the mother.

Insulin and glucose requirements during the first stage of labor in insulin-dependent diabetic women

Studies utilizing glucose-controlled insulin infusion systems were undertaken to more accurately define the glucose and insulin requirements during the first stage of labor induced by oxytocin in 12 insulin-dependent diabetic women in whom normoglycemia had been maintained before delivery. Insulin requirements decreased to zero during active stage 1 labor, while the glucose infusion rate necessary to maintain a blood glucose level of 70 to 90 mg/dl (or 3.9 to 5.0 mmol/liter) was constant at 2.55 mg/kg per minute. The findings were confirmed in 40 additional studies of oxytocin-induced labor. Studies of six women undergoing spontaneous labor and one nonpregnant woman receiving oxytocin confirmed that the decrement in the insulin requirement during stage 1 labor was not influenced by oxytocin infusion. The changes occurred regardless of whether epidural anesthesia was employed. Insulin requirements returned during the second stage of labor. Active stage 1 labor in diabetic women thus appears to be associated with a predictable decrease in the need for insulin and a constant glucose requirement.

Glucose kinetics in nondiabetic and diabetic women during the third trimester of pregnancy

Glucose kinetics were measured with 78% enrichedd-[U-13C] glucose by the prime constant infusion technique during the third trimester of pregnancy in nine nondiabetic women, nine insulin-dependent diabetic women, six gestational diabetic women, and five control women (nonpregnant, nondiabetic) after an overnight fast. The patients not dependent on insulin were diagnosed as diabetic by oral glucose tolerance tests with the use of O'Sullivan and Mahan's criteria as modified by Carpenter and Coustan during the third trimester. The turnover studies were repeated post partum (6 weeks to 5 months after delivery) in 14 of the 24 pregnant subjects. All pregnant groups had a progressive fall in plasma glucose concentration during the study, but there was a steady state of plasma glucose concentration during the turnover period. In comparison to the control subjects, both the pregnant nondiabetic and pregnant insulin-dependent diabetic women had significantly higher plasma insulin concentrations throughout the study (p < 0.05). There were no differences in the glucose turnover rate between any of the pregnant groups (1.7 ± 0.2 mg · kg−1min−1 in pregnant nondiabetic women; 1.5 ± 0.2 mg · kg−1min−1 in pregnant insulin-dependent diabetic women; and 2.1 ± 0.4 mg · kg−1min−1 in gestational diabetic women) and the control group of women (1.8 ± 0.2 mg · kg−1min−1) (mean ± SEM). When the pregnant patients were studied post partum, the glucose turnover rate was similar when referenced to body weight; however, because of a 9.6% to 14.5% fall in weight post partum, the absolute values were higher in the pregnant women. We conclude that, in the basal state after an overnight fast, (1) both nondiabetic and diabetic patients accelerated their glucose turnover rate during pregnancy to provide for increased maternal and fetoplacental metabolic requirements, and (2) in the diabetic subjects the nearly normal plasma glucose and insulin concentrations and other metabolic parameters, as well as the glucose turnover rate, suggested good metabolic control during pregnancy in most of the insulin-dependent and in all of the gestational diabetic patients.

Spontaneous abortion and diabetes mellitus.

In 58 consecutive pregnancies in insulin-dependent diabetic women, glycosylated haemoglobin levels were abnormally high in 78% at the time of booking for antenatal care. Spontaneous abortion was the outcome in 15 pregnancies, 10 occurring before the 15th week of gestation. Glycosylated haemoglobin levels were significantly higher in those women who aborted spontaneously than in women who delivered successfully (12.8 +/- 1.8% v. 11.2 +/- 2.3%, mean +/- s.d.). These results emphasise the inadequacy of diabetic control in the first trimester and lend further support to the importance of good control at this critical time in insulin-dependent diabetes.

Prevention of Congenital Malformations in Infants of Insulin-dependent Diabetic Mothers

From April 1977 to April 1981, 420 deliveries of infants of insulin-dependent diabetic women were performed in our department. Of the infants delivered, 23 had congenital malformations (5.5%). The malformation rate was 1.4% for infants of 420 nondiabetic women. Strict metabolic control was begun after 8 wk gestation in 292 of the diabetic women who delivered 22 infants with congenital malformations (7.5%). Intensive treatment was begun before conception in 128 diabetic women planning pregnancy. There was only one malformation in infants of this group (0.8%), a significant reduction from the anomaly rate in the late registrants (X2 = 7.84; P less than 0.01). These observations indicate that reasonable metabolic control started before conception and continued during the first weeks of pregnancy can prevent malformations in infants of diabetic mothers.

Sexual responsiveness in diabetic women.

Sexual responsiveness in 82 Type 1 (insulin-dependent) diabetic women was compared with that of 47 normal control subjects, using an interview method for rating various aspects of sexual response, and attitude questionnaires. The diabetic women were questioned about symptoms of autonomic neuropathy, and cardiovascular autonomic nerve function tests were performed. There were differences between the two groups in the reports of vaginal lubrication, but in most other respects the groups were similar. The diabetic women were not less orgasmic, and reported significantly fewer unpleasant feelings during sexual intercourse. They saw themselves and their husbands as less 'potent' than did the normal subjects. The possible enhancing effect of diabetes on the marriage of some diabetic women possibly counteracted the relatively mild physiological deficits involved. There was very little difference in sexual response between women with and without symptomatic autonomic neuropathy.