Search

Type 1 diabetes is preceded by the appearance of islet autoantibodies. Seroconversion to islet autoantibodies is greatest around 1 yr of age and is more frequent in children born to fathers with type 1 diabetes as compared to children born to mothers with type 1 diabetes. Here we asked whether changes in beta-cell function in the neonate and infant reflect variations in the incidence of islet autoantibody seroconversion. Insulin, proinsulin, and c-peptide concentrations were measured in sequential samples taken from birth to age 2 yr in 103 children who had a first degree relative with type 1 diabetes and who had been followed for islet autoantibody seroconversion. Serum insulin and proinsulin concentrations were highest at birth declining by age 3 months and stable thereafter until age 2 yr. C-peptide concentrations, proinsulin/insulin, and proinsulin/c-peptide ratios were stable from age 3 months. No differences were observed between children who developed islet autoantibodies and children who remained islet autoantibody negative. Children born to a mother with type 1 diabetes had higher birth concentrations of insulin (p = 0.005) and proinsulin (p = 0.014) as compared with children of non-diabetic mothers. Increased insulin concentrations in children of type 1 diabetes mothers persisted until age 6 months. In conclusion, we could not relate excursions in beta-cell hormones to autoantibody development, but suggest that the higher exposure to insulin and proinsulin in neonates born to mothers with type 1 diabetes may be linked to the relative protection against islet autoantibody seroconversion observed in these children., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of the study was to evaluate the significance of the presence of thyroid peroxidase autoantibodies (anti-TPO Abs) in type 1 diabetes mellitus (DM1) pregnant women relative to the course of pregnancy and, especially, with regard to metabolic control, thyroid function, maternal complications and neonatal outcome., Methods: In a prospective observational study of 91 DM1 women with singleton pregnancies, anti-TPO, anti-thyroglobulin, thyroid-stimulating hormone (TSH), and free thyroxine index (T4/thyroid binding capacity) were measured in each trimester. At each visit, HbA1c, body mass index, and units of insulin per kilogram were recorded, as were complications and pregnancy outcome., Results: Twenty-one (27%) of the 78 women who met the inclusion criteria presented with positive anti-TPO Abs. There were no differences regarding glycemic control (HbA1c) or insulin dose. First-trimester TSH levels were significantly higher in the anti-TPO-positive group than in the anti-TPO-negative group. Finally, no differences were observed regarding diabetic or obstetric complications and neonatal outcome., Conclusion: One fourth of DM1 pregnant women presented with positive anti-TPO Abs. However, the presence of anti-TPO Abs does not seem to be related with worse metabolic control or adverse pregnancy outcome. Further investigation is needed; meanwhile, the effort for early treatment of thyroid dysfunction and strict metabolic control in all DM1 women should be continued.

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

The course of the diabetes type I at pregnants (n=120) with different levels of idiotypic (ABI) and antiidiotypic (AB2) antibodies to insulin was investigated. It is known that AB2 to insulin can interact with insulin receptor. It was shown that changes of levels AB1 and AB2 to insulin are often observed at pregnants suffered from diabetes type I. Isolated high levels of AB1 to insulin is relatively good prognostic sign of the course of the diabetes type I at pregnants. On the contrary, isolated high levels of AB2 to insulin lead to decompensation of the diabetes type I and deep glycohemia. High levels of AB1 and AB2 to insulin together lead to unstable course of the diabetes type I. The same situation is observed in case of abnormal low levels AB1 and AB2 to insulin, taking into consideration that serum of health people contains the certain level of autoantibodies (AB1 and AB2) to insulin. The conclusion about significance of detection AB1 and AB2 to insulin during pregnancy of patients with diabetes type I was made.

The levels of idiotypic (AB1) and antiidiotypic (AB2) antibodies were investigated in pregnants (n = 248) suffer from diabetes. It was proved that AB2 to insulin conditionally can be regards as antibodies to insulin receptor. It was shown that condition of newborns much depends on levels of these antibodies and their proportion. Condition of newborns from women with isolated high levels of AB1 to insulin was much better in comparison with ones from mothers with isolated high levels of AB2 to insulin. Conception about mechanisms of acting of AB1 and AB2 to insulin on fetus was represented.

Aims/hypothesis: The risk of type 1 diabetes is reduced in the children of mothers with type 1 diabetes compared with children of fathers with type 1 diabetes. We asked whether children of mothers with type 1 diabetes also have a decreased risk of developing islet autoantibodies, and which factors associated with maternal diabetes contribute to a reduced islet autoantibody risk in offspring., Methods: Singleton offspring of a mother (n = 1,008) or father with type 1 diabetes (n = 578) from the BABYDIAB study were included. Children were followed from birth for the development of islet autoantibodies defined as two or more autoantibodies to insulin, glutamic acid decarboxylase or insulinoma antigen 2 in two or more blood samples., Results: Islet autoantibody risk was lower in children of mothers with type 1 diabetes (5 year risk, 3.2% vs 5.7% in children of fathers with type 1 diabetes; p = 0.04). Among factors that differed between pregnancies from mothers with and without type 1 diabetes, birthweight was associated with islet autoantibody risk. Risk was reduced in children with birthweights in the lower (adjusted HR 0.33; 95% CI 0.14-0.75; p = 0.009) and upper (HR 0.45; 95% CI 0.21-0.97; p = 0.04) tertiles compared with the middle tertile. A sub-analysis of maternal HbA(1c) suggested that moderately elevated third trimester maternal HbA(1c) was also associated with a reduced islet autoantibody risk in children of mothers with type 1 diabetes (5.7-7%; HR 0.38; 95% CI 0.15-0.96; p = 0.04 vs children of mothers with HbA(1c) < 5.7%)., Conclusions/interpretation: The risk of islet autoimmunity is modified by maternally influenced events such as birthweight.

Objective: Human leukocyte antigen DQ (HLA-DQ) genetic factors and islet autoantibodies are strongly associated with type 1 diabetes (T1D) and are currently used to predict T1D. This study examined whether islet autoantibodies in the cord blood of newborns to nondiabetic mothers were associated with the (T1D) high-risk genotype HLA-DQ2/8, gestational infections or both., Study Design: Cord blood samples were taken from 33 683 newborns and used for HLA typing and analyses of islet autoantibodies. Parents completed questionnaires when the child was 2 months of age., Result: The prevalence of newborn islet autoantibodies consistently varied with season over 4 years (P<0.0001); lowest in first quarter (1.2%) and highest in third (2.4%). Cord blood islet autoantibodies were associated with HLA-DQ2/8 in the second (OR, 2.30; P=0.02), third (OR, 2.12; P=0.008) and fourth quarters (OR, 2.49; P=0.007), but not in the first (OR, 1.13). Reported gastroenteritis was additionally associated with islet autoantibodies in the third quarter (OR, 1.80, P=0.04)., Conclusion: An association between HLA and islet autoimmunity may depend on environmental exposure during pregnancy. Follow-up of mothers and children will determine risk of T1D.

Objective: In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome., Design/setting: Prospective study, Denmark., Population: Ninety-six consecutive pregnant women with type 1 diabetes. Twenty-five healthy pregnant controls., Methods: At 8, 14, 21, 27 and 33 weeks, the diabetic women self-monitored plasma glucose (SMPG) (8/day) for 3 days and had blood samplings obtained., Main Outcome Measures: Thyroid-stimulating hormone (TSH), free thyroxin (T4), hemoglobin A1C (HbA1C), anti-TPO, pregnancy outcome., Results: Anti-TPO was detected in 31 (32%) of the pregnant diabetic women compared with two women (8%) in the healthy controls (p=0.015). The presence of anti-TPO was associated with higher TSH at 8 (p<0.0001) and 14 weeks (p<0.05) and lower free T4 at 8 weeks (p<0.05) compared with anti-TPO negative women. Twenty untreated anti-TPO positive women had higher TSH compared with untreated, anti-TPO negative women (p<0.05), but comparable free T4. At inclusion, 25% had TSH above the recommended treatment goal for levothyroxine (TSH>2.5 mIU/l), most prevalently among anti-TPO positive women. Sixteen women (17%) were treated for thyroid disorder during pregnancy. No differences were detected between the diabetic women with and without anti-TPO regarding HbA1C, insulin dose, median SMPG or pregnancy outcome., Conclusions: Anti-TPO was present in one-third of pregnant women with type 1 diabetes and associated with slightly higher TSH, but not poorer glycemic control or adverse birth outcome. A total of 17% of women with type 1 diabetes were treated for thyroid disorder during pregnancy.

Recent case-control studies reported an increased frequency of antibodies against Coxsackie virus (CV) antigens in patients with newly diagnosed type 1 diabetes and during pregnancy in mothers of diabetic offspring, suggesting a role for CV infections in the pathogenesis of type 1 diabetes (T1D). However, it is not known whether CV infections are causally related to the development of islet autoantibodies or merely represent secondary events in subjects already affected with established islet autoimmunity. Therefore we have prospectively evaluated CV infections from birth, prior to and in parallel with the appearance of islet autoantibodies in offspring of parents with T1D. Using indirect ELISAs, IgG-antibodies (abs) against a panel of CV, and IgG- and IgM-abs to CVB3, CVB4, and CVB5 were measured at 9 months, 2, 5, and 8 years in 28 offspring of mothers or fathers with T1D or of mothers with gestational diabetes who developed persistent islet antibodies (IAA, GADA, IA-2A), and compared to 51 islet autoantibody-negative offspring matched for place and date of birth. CV infections were also determined at delivery in 16 mothers whose offspring developed islet autoantibodies later in life and compared to 110 mothers (matched for HLA-DR, place and date of birth) whose offspring remained islet autoantibody-negative during early childhood. CV-antibodies were detected in only 2/28 (7.1%) offspring who developed islet autoantibodies during follow up and in 7/51 (13.7%) offspring without islet autoantibodies (median follow up time 3.0 years, range 2.0-8.7). CV-IgG abs were detected in one mother (6.3%), whose offspring developed islet autoantibodies during early childhood, compared to 15 mothers (13.6%) with islet autoantibody-negative offspring (P=0.5). Also, partum levels of CV-IgG and CVB3-, -4-, and -5-IgM abs were similar in both groups (median 35 U, 0.08 index (I), 0.08, 0.05 vs. 35 U, 0.06 I, 0.11, and 0.06, resp., P> 0.35 in each case). These data make it unlikely that CV infections during pregnancy or in early childhood play a major role in the induction of islet autoimmunity in offspring of mothers or fathers with T1D or of mothers with gestational diabetes., (Copyright 2001 Academic Press.)

We studied the pattern of type 1 diabetes-associated autoantibodies during pregnancy and the transplacental transfer of these autoantibodies to the fetal circulation and searched for possible signs of prenatal induction of beta-cell autoimmunity in newborn infants. The population comprised 208 mothers and their newborn infants. Seventy-four of the mothers (36%) had type 1 diabetes and 134 (64%) of the infants had an affected father or sibling. Blood samples were obtained from the mother at the end of the first trimester and at delivery, and from the cord blood of the newborn infant. Close to 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in early pregnancy, whereas the corresponding frequencies in the nonaffected mothers were 5.2%, 5.2% and 3.0%. No significant changes could be seen in autoantibody levels during pregnancy, and there was a close correlation between the two maternal samples. One third of the infants of mothers with type 1 diabetes tested positive for ICA, 50% for GADA and 51% for IA-2A. Six percent of the infants of nondiabetic mothers had ICA, 2.2% GADA and none had IA-2A. None of the infants of the antibody negative mothers had antibodies in their cord blood. These observations indicate that the immunomodulatory effect of pregnancy on signs of beta-cell autoimmunity is weak, but if diabetes-associated autoantibodies are present in the mother, most of them are transferred to the fetal circulation. Our data do not provide any support for fetal induction of beta-cell autoimmunity.

Accurate assessment of type 1 diabetes risk in young children requires discrimination between antibodies that are produced by the child and antibodies acquired through the placenta from an islet antibody-positive mother. We studied 682 offspring from mothers with type 1 diabetes and 329 offspring from fathers with type 1 diabetes and nondiabetic mothers for insulin (auto)antibodies, glutamic acid decarboxylase antibodies, and tyrosine phosphatase IA-2 antibodies before age 1 yr and again at age 2 yr to ascertain transience or persistence. Antibodies were detected at age 9 months in 5 (1.5%) offspring from fathers with type 1 diabetes; all were insulin (auto)antibodies only, all persisted and developed multiple antibodies, and 1 developed type 1 diabetes. In contrast, 31 (4.5%) offspring from mothers with type 1 diabetes had antibodies at 9 months; 12 (1.8%) persisted at age 2 yr, and 19 (2.8%) did not persist, suggestive of transient residual maternal antibodies. Multiple antibodies at 9 months were usually persistent (3 of 4 offspring), as were single insulin (auto)antibodies in offspring from mothers with type 1 diabetes (8 of 13 offspring), whereas persistent glutamic acid decarboxylase antibodies (1 of 12) and tyrosine phosphatase IA-2 antibodies (0 of 2) were rare. Offspring with persistent antibodies at age 9 months had a high type 1 diabetes risk (100% by age 5 yr for those with multiple antibodies and 27% for single antibodies at 9 months), whereas offspring with transient antibodies had 0% type 1 diabetes risk (P < 0.01). Transience was associated with very high antibody levels at birth. For insulin (auto)antibodies, the measurement of subclass was also informative. Residual maternal antibody was indicated by similar insulin (auto)antibodies subclasses at 9 months and at birth, whereas different subclasses were indicative of nonmaternal antibody. Moreover, the presence of IgG1-insulin (auto)antibodies was associated with antibody persistence and type 1 diabetes risk. These strategies are helpful in discriminating high and low risk antibodies before age 1 yr and should be important for prognosis and reducing unnecessary parent anxiety.

A high incidence of autoimmune Type 1 diabetes mellitus (DM) has been clearly established in Sardinia. Although systematic epidemiological studies are still not available, an increased prevalence of thyroid autoantibodies (ATA) has been documented in the Sardinian adult population as compared to other Italian regions, suggesting that thyroid autoimmune disease may also have increased. We carried out a preliminary study with the aim of determining the prevalence of serological markers of thyroid (anti-thyroperoxydase antibodies, TPOAb) and islet cell (ICA) autoimmunity in a large number (no.=2249) of sera obtained from cord-blood of Sardinian pregnant women at delivery. The prevalence of TPOAb was 11.9%, while ICA were detected in 59 cases (2.6%). A higher prevalence of TPOAb (6/17=35.3%) was found in sera with high ICA titers (> or = 20 JDF-U), as compared to sera with low ICA titers (5-19 JDF-U) and to ICA-negative sera (3/42=7,1%; chi2=5.4, p=0.02 and 258/2190=11,8%; chi2=6.8, p=0.009 respectively). Fourteen women (all ICA-negative) were diabetic: 4 had Type 1 and 10 had gestational DM; due to the low number, no correlation could be established between DM type and TPOAb prevalence and/or titer. These preliminary data indicate that ATA are frequently observed in the general population of Sardinian pregnant women at term. As a consequence, even the frequency of postpartum thyroiditis is expected to be high. Although ATA were not increased in women with clinical overt diabetes, a higher prevalence of ATA was found in women with high titers of circulating ICA. Our results also confirm that Sardinia represents, perhaps for its peculiar genetic characteristics, an ideal place to study organ-specific autoimmunity.

The elimination of maternally acquired, diabetes-associated antibodies from the peripheral circulation of infants was studied in a population of 47 mothers and their newborn infants from families in which at least 1 first degree relative had type 1 diabetes. Blood samples were taken from the placental cord; from the infant at follow-up visits at the ages of 3, 6, 9, 12, 18, and 24 months; and from the mother at the time of delivery. The samples were analyzed for cytoplasmic islet cell antibodies (ICA), insulin antibodies (IA), autoantibodies to the 65-kDa isoform of glutamic acid decarboxylase (GADA), and autoantibodies to the protein tyrosine phosphatase-related IA-2 antigen (IA-2A). The mean elimination times for ICA, IA, GADA, and IA-2A were 3.1, 3.1, 4.5, and 4.3 months (P = NS), respectively. The initial levels of IA, GADA, and IA-2A in the cord blood correlated closely with the elimination time (r(s) = 0:84-0.91; P < 0.001). The mean proportions of ICA, IA, GADA, and IA-2A still detectable were 18%, 21%, 30%, and 20%, respectively, at 3 months; 2.2%, 14%, 10%, and 6% at 6 months; and 0.3%, 15%, 2.3%, and 5.1% at 9 months. One infant still tested positive for GADA at the age of 12 months, whereas all of the other antibodies had been eliminated by that age. When observing the natural history of beta-cell autoimmunity or when screening for secondary prevention in young children, cross-sectional autoantibody analyses do not provide sufficient information. Repeated testing is to be recommended in young children. In infancy, increasing antibody levels most likely reflect de novo synthesis of diabetes-associated autoantibodies.

Free insulin cannot cross the placenta but insulin complexed to anti-insulin antibodies has been demonstrated in cord blood. We studied whether antibody-bound insulin in diabetic patients can evoke fetal macrosomia independently of maternal metabolic control. In 457 non insulin-treated controls and 173 insulin-treated diabetic patients we measured 1187 anti-insulin antibody levels and maternal blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide, cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody levels in maternal blood and cord blood were significantly higher in insulin treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml) with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood) anti-insulin antibody levels were above the 97th percentile. There was a high significant correlation between maternal and cord blood anti-insulin antibodies (R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and fetal metabolic parameters correlated with birth weight neither maternal nor cord blood anti-insulin antibody levels correlated with birth weight. These findings do not support the hypothesis that maternal anti-insulin antibodies independently influence fetal weight.

Objective: To study whether the presence of antithyroid peroxidase antibodies (TPO-Abs) before gestation in IDDM affects thyroid function and metabolic control during pregnancy and early postpartum as well as neonatal outcome., Research Design and Methods: A prospective study at an outpatient endocrine-obstetric unit was carried out in 20 pregnant IDDM women. Free T4 (thyroxine), thyroid-stimulating hormone (TSH), TPO-Abs, and HbA1c were assayed before gestation; during the first, second, and third trimester of pregnancy; and 3 months postpartum., Results: HbA1c was significantly higher in TPO-Ab+ women than in those who were TPO-Ab- during the second (P < 0.01) and third (P < 0.05) trimesters. HbA1c levels significantly decreased in TPO-Ab- patients when the second (P < 0.01) and third (P < 0.05) trimesters were compared with before the pregnancy and the first trimester. There was a significant increase in the dosage of insulin for TPO-Ab+ versus TPO-Ab- patients during the second (P < 0.05) and third (P < 0.01) trimesters and 3 months postpartum (P < 0.05). TSH was significantly increased in the second (P < 0.001) and third (P < 0.05) trimesters and 3 months postpartum (P < 0.01) when compared with TPO-Ab- patients; 7.6% of the TPO-Ab- group and 29% in the TPO-Ab+ group presented postpartum thyroid dysfunction, and 42% of the TPO-Ab+ women required thyroid treatment., Conclusions: Pregnant women with IDDM who have a positive test for TPO-Abs before gestation have poorer glucose control and a high prevalence of hypothyroidism. Therefore we recommend that prepregnant IDDM patients be screened for anti-TPO-Abs. Those with a positive result should be followed with serial monitoring of free T4 and TSH levels during each trimester as well as the postpartum period.

Several methods are available for the measurement of antibodies to glutamic acid decarboxylase (anti GAD). These antibodies are valuable tools for the immunodiagnosis of insulin-dependent (type 1) diabetes mellitus (IDDM) and for the assessment of risk for the future development of IDDM. We here describe a new enzyme-linked immunosorbent assay (ELISA) for the detection of anti-GAD which was tested in a multicenter study. The results of the new anti-GAD ELISA correlate well with those obtained by radioimmunoassays (RIA) and they have a higher sensitivity (69%) and specificity (98%) compared to other anti-GAD enzyme immunoassays as determined in the IDW Proficiency Test Program for the detection of GAD antibodies. The new ELISA is simple and easy to perform, with convenient handling of the reagents. Quantitative and reproducible test results are available within approximately four hours. The new anti-GAD ELISA can be used for large scale population screening to indicate a prediabetic state as well as to diagnose autoimmune diabetes in adults (LADA) and the risk for IDDM in pregnant women with gestational diabetes.

For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n = 113) and gestational diabetes (n = 55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies > or = 20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies > 49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies > or = 20 JDF-U, 76% insulin antibodies > 49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies > or = 20 JDF-U, 18% insulin antibodies > 49 nU/ml; neonates: 13% islet cell antibodies > or = 20 JDF-U, 55% insulin antibodies > 49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive).(ABSTRACT TRUNCATED AT 250 WORDS)

No marker except repeated fasting glucose determinations has proven useful to ascertain prospectively which women with gestational diabetes mellitus will remain euglycemic by diet modification or will require insulin therapy. We screened 183 black women with gestational diabetes mellitus to determine if the presence of islet cell, mitochondrial, nuclear, DNA, parietal cell, smooth muscle, thyroid microsomal, thyroid thyroglobulin autoantibodies, or rheumatoid factor predicted the need for insulin therapy to maintain euglycemia in women with gestational diabetes mellitus. One hundred forty-two women maintained normal fasting plasma glucose levels with dietary modifications and 41 required institution of split-dose insulin therapy. We found no significant differences in the prevalence of these autoantibodies in black women with Class GB versus Class A1 diabetes mellitus. We conclude that screening for autoantibodies in women with gestational diabetes mellitus is not useful in determining which patients will subsequently require insulin therapy during their pregnancies.

Islet cell antibodies (ICAs) are markers for patients at risk for insulin-dependent diabetes and are associated with progressive beta-cell destruction. This prospective study was performed to estimate the incidence of these antibodies in 187 women with previous gestational diabetes. With a specific protein A monoclonal antibody (MoAb) assay, the incidence of ICAs was only 1.6% (3 of 187). Oral and intravenous glucose tolerance tests were performed in these 3 women and compared with 6 women with previous gestational diabetes without ICAs and 5 control women. Glucose tolerance was impaired only in the 3 women with ICAs, who also had an increase (P less than 0.03) in fasting plasma glucose and a decrease (P less than 0.03) in early first-phase insulin response. We conclude that the more specific MoAb method indicates a lower incidence of ICA in women with a history of gestational diabetes than previously reported and that a decreased first-phase insulin response is associated with the presence of ICAs, suggesting progressive islet cell damage.

Antibodies to islet cells and thyroid gland were examined in a mother with insulin-dependent diabetes mellitus and Graves' disease and in her infant. Islet cell antibodies (ICA), complement-fixing ICA, islet cell surface antibodies (ICSA) and anti-microsomal antibodies (MAb) persisted in the mother during pregnancy. At birth, ICA, ICSA and MAb could be detected in the infant. ICSA and ICA in the infant disappeared by the 3rd and 7th months, respectively. There was no clinical or laboratory evidence of diabetes in the infant. These data suggest that anti-islet cell antibodies themselves may have no significant effect on islet cells.

Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post--partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls. Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14 +/- SE 0.03 x 10(9)/l; 7.1 +/- 1.1%) when compared with normal parous controls (0.09 +/- 0.01 x 10(9)/l; 4.2 +/- 0.6%), p less than 0.01 x 10(9)/l; showed significant increases when compared with nulliparous controls (0.04 +/- 0.01 x 10(9)/l; 2.1 +/- 0.2%), p less than 0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4), suppressor cytotoxic T-lymphocytes (CD8), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes. Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin-dependent) diabetes. No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type 1 diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon.

The presence of islet cell antibodies (ICA), complement fixing islet cell antibodies (CF-ICA), other organ-specific autoantibodies, insulin antibodies and two different types of immune complexes (AgAb) in diabetic pregnant women treated with insulin during pregnancy was investigated and compared with maternal metabolic control and with the course and outcome of pregnancy. One hundred and eighteen pregnant diabetic women were grouped according to type of diabetes: 56 were insulin-dependent diabetic patients who had been previously treated with insulin (Group 1); 23 were non-insulin-dependent diabetic patients who had previously received diet or oral treatment (Group 2); 39 had gestational diabetes (Group 3). 94 patients were subjected to regular check-ups during pregnancy and blood samples were taken during the last month of pregnancy (phase A); some were treated with standard preparations of insulin, the remainder with purified insulins. 24 patients were treated with purified insulins (a bovine and porcine mixture) on entering the study and blood samples were taken at regular intervals during pregnancy (phase B). ICA were detected in 12% of the patients in Group 1 and in 5% of those in Group 3. There was no significant variation in the titre during the gestational period. ICA were not detected in the patients in Group 2. No CF-ICA were found in any of the patients. The positivity of the other organ-specific autoantibodies was similar to that the normal control group. Insulin antibodies were found in concentrations of 67%, 73% and 25% in Groups 1,2 and 3 respectively during the last month of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)