Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low molecular weight acid phosphatase encoded by the highly polymorphic locus ACP1 is a member of the protein-tyrosin phosphatase family (PTPases) which plays an essential role in the control of receptor signalling through phosphotyrosine pathways. Recent experiments have shown that purified rat liver ACP, corresponding to human ACP1, is able to hydrolyze a phosphotyrosine-containing synthetic peptide corresponding to the 1146-1158 sequence of the human insulin receptor, and shows a high affinity for it. This prompted us to analyze the degree of glycemic control in relation to ACP1 genetic variability in a sample of 214 diabetic pregnant women including IDDM, NIDDM and gestational diabetes. The ACP1 genotype was also determined in 482 non-diabetic pregnant women. In diabetic women glycemic levels in the last trimester of pregnancy appear to be significantly associated with the ACP1 genotype, and correlate positively with ACP1 enzymatic activity. The data suggest that quantitative variations of ACP1 may influence the clinical manifestations of diabetic disorders, and call for further studies on the role of this enzyme in the modulation of insulin-receptor phosphotyrosine pathways.
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PMID:Phosphotyrosine protein phosphatases and diabetic pregnancy: an association between low molecular weight acid phosphatase and degree of glycemic control. 862 Sep 37

IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what beta-cell antigens autoreactive lymphocytes become activated during early disease. We conducted a prospective study from birth, BABY-DIAB, among children of mothers with IDDM or gestational diabetes or fathers with IDDM, and we investigated the temporal sequence of antibody responses to islet cells (ICA), insulin (IAA), GAD (GADA), and the protein tyrosine phosphatase IA-2/ICA512 (IA-2A). Of 1,019 children included at birth, we have currently followed 513 to the age of 9 months, 214 to the age of 2 years, and 37 to the age of 5 years. At birth, all antibody specificities were frequent in newborns of diabetic mothers but not fathers and are suggested to be transplacentally acquired because they are strongly correlated with antibody levels in their diabetic mothers. In early childhood, antibody levels were <99th percentile of control subjects in the majority of children. However, 37 children exhibited elevated antibody levels; these were most frequently detected at the age of 2 years. The antibody prevalence at age 2 years was 2.3% for ICA, 7% for IAA, 4.2% for GADA, and 2.8% for IA-2A (8.9% positive for at least one antibody). Children of diabetic fathers were positive for at least one antibody more frequently than were children of diabetic mothers (9 months of age: 8.5 vs. 3.6%; 2 years of age: 16.7 vs. 7.9%). There was no specific sequence in the appearance of positive autoantibodies, but 13 (35%) antibody-positive cases already had more than one ICA before the age of 2 years and 7 (19%) showed reactivity to three islet cell antigens before age 5 years. The presence of multiple antibodies confers high risk for the future development of diabetes; three of six children who exhibited positive antibody responses to all four antibodies tested and another child with two positive antibodies developed clinical diabetes at the ages of 13, 21, and 27 months and 5 years. We conclude that loss of tolerance to beta-cell autoantigens and appearance of autoimmune phenomena occur very early in life in individuals with genetic susceptibility for IDDM. Screening programs to identify candidates for disease-prevention therapies can therefore be focused on this young age-group, in whom the disease process may be less advanced and who may therefore be best suited to such therapies.
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PMID:Perinatal autoimmunity in offspring of diabetic parents. The German Multicenter BABY-DIAB study: detection of humoral immune responses to islet antigens in early childhood. 866 50

The purpose of our study was to determine the Doppler ultrasound characteristics of fetal breathing-related nasal fluid flow velocity in pregnancies complicated by diabetes mellitus and to examine any changes in the timing parameters of fetal breath cycle relative to maternal blood glucose level. Fetal nasal fluid flow velocity was studied in 67 women at 30-41 weeks of gestation. In 37 cases, the pregnancy was uncomplicated; in 13 cases, the pregnancy was complicated by type I diabetes mellitus; and in 17 cases, the pregnancy was complicated by gestational diabetes. At the examination, subjects with diabetes mellitus were grouped by glucose control (normoglycemic and hyperglycemic) and by gestational age: 30-36 weeks and 37-41 weeks. Maternal hyperglycemia was defined as a plasma glucose value ranging from 140 to 205 mg per 100 ml. A continuous videotape record of the spectral Doppler imaging of fluid flow velocity in the nose was made during each study session. Based on a sample of 25 consecutive fetal breaths, the timing components of breath cycles were determined: time of inspiration (Ti), time of expiration (Te), breath-to-breath interval (Ttotal), and ratio of Ti and Te (Ti/Te). There was a statistically significant difference between the Ttotal (msec) at 30-36 weeks' gestation in the cases of diabetes mellitus with maternal normoglycemia (1,050 +/- 68 SEM) and uncomplicated pregnancy with maternal normal carbohydrate intolerance (1,221 +/- 52). There was a similar difference in the values of Te (552 +/- 37 and 660 +/- 29, respectively) at 30-36 weeks. In cases of maternal hyperglycemia at 30-36 weeks' gestation, the value of Te (689 +/- 84) was significantly higher than in cases of normoglycemia (552 +/- 37). At 37-41 weeks' gestation, only the fetal Ti/Te ratio in normoglycemic diabetic patients was significantly lower than in an uncomplicated pregnancy. No differences were found in the other timing parameters at this gestational age group in cases of diabetes mellitus relative to maternal blood glucose level. No relationship was found between the value of maternal blood glucose and either fetal Ttotal (r2 = 0.003), or Ti/Te ratio (r2 = 0.0001) in cases of diabetes mellitus. Expiratory phase of fetal breath cycle even in well-controlled normoglycemic diabetic women, is significantly shorter than in uncomplicated pregnancies before 37 weeks of gestation. Maternal hyperglycemia in these cases prolonged the duration of expiratory phase of fetal breath cycle and significantly decreased the Ti/Te ratio more than 15% at 30-36 weeks of gestation. It is suggested that blood glucose level is involved in the regulation of fetal respiratory center in pregnancies complicated by diabetes mellitus.
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PMID:Doppler ultrasound characteristics of fetal nasal flow in pregnancies complicated by diabetes mellitus. 879 95

The aim of the study was to evaluate the frequency of islet cell (ICA) and insulin (IAA) antibodies and of HLA antigen typing in a group of subjects diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic program during pregnancy. ICA, complement-fixing (CF) ICA and other autoantibodies, absolute number and percentage of lymphocyte subpopulations, and HLA antigens were evaluated in 68 women with GDM and compared with those of matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA-positive women had CF-ICA; one of them was receiving insulin therapy. while the other was on a special diet. No correlations were found between ICA and IAA, nor between IAA and insulin treatment. As far as lymphocyte subsets were concerned, we found a significant increase in the absolute number of total and activated (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57) in GDM patients compared with normal pregnant controls. Concerning frequency for HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be significantly increased and A10 significantly decreased in comparison with controls. Our study suggests that GDM is a heterogeneous disorder in which few patients present with the immunologic and genetic markers of type 1 diabetes.
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PMID:An immunological and genetic study of patients with gestational diabetes mellitus. 887 Aug 16

Presymptomatic autoantibody markers of insulin-dependent (Type 1) diabetes mellitus (IDDM) are less well characterized in adults than in children. We quantitated anti-GAD, anti-ICA512 and ICA by titration to endpoint and compared frequencies and levels in 139 Finnish women from whom 390 serum samples had been archived during antecedent pregnancies for 10 years before and up to 1 year after diagnosis of diabetes. Also, we compared the autoantibody status in adults with IDDM with that of children with newly diagnosed IDDM. Of the 35 women seropositive for 1 or more autoantibodies, 77% developed IDDM, 11% non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), 9% gestational diabetes mellitus requiring insulin (GDM-ins) and 3% GDM controlled by diet. The frequency of antibodies during the 10-year presymptomatic period was 83% for anti-glutamic acid decarboxylase (GAD), 52% for anti-ICA512 and 41% for islet cell antibodies (ICA) for those who developed IDDM, 25%, 17%, and 0% for NIDDM, 12%, 4%, and 8% for GDM-ins and 1%, 0%, and 1% for GDM-diet. Anti-GAD was found most consistently in early samples; 13 of 15 with a single autoantibody at their first test had anti-GAD. Among those who developed IDDM, the frequency of anti-GAD was constant, anti-ICA512 increased threefold, and ICA increased slightly before diagnosis. Levels of the autoantibodies varied between subjects, but were relatively stable in individual subjects. Comparison of tests on the women, and children after diagnosis of IDDM, showed the frequencies and levels to be the same for anti-GAD but lower for anti-ICA512 and ICA in adults. Our observations show in women the long latency of seropositivity before overt IDDM, the predominance of anti-GAD among these three serological markers, and the presence of these markers in NIDDM presumably representing a NIDDM phase of autoimmune insulitis.
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PMID:Autoantibodies associated with presymptomatic insulin-dependent diabetes mellitus in women. 927 95

Women with gestational diabetes mellitus (GDM) have a considerable risk of developing diabetes later in life. To determine the predictive value of autoantibody markers in gestational diabetic pregnancy for the development of type 1 diabetes postpartum, we tested 437 patients with GDM (289 women treated with diet only [GDM-A] and 148 requiring insulin treatment during pregnancy [GDM-B]) for antibodies to islet cells (ICAs), GAD (GADAs), and tyrosine phosphatase ICA512/IA-2 (IA2As). We prospectively followed them with repeated oral glucose tolerance tests and antibody determinations for up to 7 years postpartum (mean, 1.6 years; range, 0-7.2 years). The cumulative risk of diabetes up to 5 years postpartum was 17% (95% CI 12-22%). The risk of type 1 diabetes was 3% (2-5%) by 9 months and 7% (4-9%) 2 years after delivery. At delivery, 8.5% of all patients were ICA+, 9.5% were GADA+, 6.2% were IA2A+, and 18.1% were positive for at least one antibody (12.6% for GDM-A vs. 30.4% for GDM-B, P < 0.0001). During follow-up, GADAs persisted in 75%, ICAs in 35%, and IA2As in 30% of the subjects positive for the respective marker at delivery. By 2 years postpartum, 29% (19-39%) of patients positive for at least one antibody developed type 1 diabetes, compared with 2% (1-4%) of antibody-negative patients (P < 0.0001). Thereby, the risk for type 1 diabetes 2 years postpartum increased with the number of antibodies present at delivery from 17% (6-28%) for one antibody, to 61% (30-91%) for two antibodies, and to 84% (55-100%) for 3 antibodies. Risk of progression to type 1 diabetes postpartum was also associated with the status of parity. Women with one or more pregnancies before the index pregnancy had a higher risk for type 1 diabetes 2 years after delivery (14.7% [4.9.-24.5%]) than women having their first (i.e., index) pregnancy (5% [2.9-7.1%]) (P < 0.006). A comparison of different prediction strategies showed that single antibody screening with GADA yielded the highest sensitivity of 63% (45-75%), compared with ICA (48% [31-65%]) and IA2A (34% [13-47%]). Combined screening with two autoantibodies increased sensitivity to 74% (58-90%) and 75% (60-92%) when using GADA plus ICA or GADA plus IA2A, respectively. Screening with all three markers improved sensitivity further to 82% (67-100%). Beta-cell autoantibodies determined at delivery in women with GDM are highly predictive for the development of type 1 diabetes postpartum. Autoantibody screening in pregnant women with GDM from populations at high risk for type 1 diabetes should therefore be considered to allow early diagnosis and appropriate therapy.
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PMID:Prediction of type 1 diabetes postpartum in patients with gestational diabetes mellitus by combined islet cell autoantibody screening: a prospective multicenter study. 928 47

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.
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PMID:Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked immunosorbent assay (ELISA) with radioimmunoassay methods: a multicenter study. 928 79

The impaired glucose tolerance in pregnancy (IGT) represents an important fact in aetiopathogenesis of insulin dependent diabetes mellitus (IDDM) and non insulin dependent diabetes (NIDDM) as well as obesitas and cardiovascular diseases in context with fetal hyperinsulinism. Prospective studies of diabetic mothers newborns are difficult by reason of health controls in different outpatient departments. The aim of this review is to claim a general glucose screening in pregnancy looking on the development of newborns in later life. In present preventive prospects were not used to decrease the morbidity in diabetes, obesitas and cardiovascular diseases without gestational diabetes screening in pregnancy. The neonatal onset and late morbidity is dependent on the quality of maternal glycemia in pregnancy measured by means of glycosylated hemoglobin and insulin the amniotic fluid.
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PMID:[Gestational diabetes--perinatal hyperinsulinism and postnatal developmental disorders]. 934 Sep 71

Aims of the study were: evaluation of HbA1c levels in the peripheral blood of pregnant women with insulin dependent diabetes, gestational diabetes, glucose intolerance, and healthy pregnant controls; implications of HbA1c concentration on detection and the control of women with impaired carbohydrate metabolism in pregnancy; comparison of HbA1c levels with appearance of miscarriages, and premature deliveries; comparison of weight gain during pregnancy to HbA1c levels; comparison of difference from ideal body weight with HbA1c in diabetic pregnant women; comparison of neonatal birth weight and HbA1c levels. 290 pregnant women were enrolled to the study. The highest value of HbA1c was in the group IDDM pregnant women (7.7% +/- 1.8%), and the lowest value of HbA1c was in the control group (4.1% +/- 0.5%). Statistically significant coefficients were found between HbA1c and weight gain during pregnancy, between weight deviation from ideal body weight and HbA1c (r = 0.54 and r = 0.48 respectively); and between newborns weight and HbA1c (r = 0.51). Well regulated glycemia and intensive pregnancy follow-up of diabetic women reduces stillbirths, neonatal complications and neonatal macrosomia incidence.
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PMID:Glycosylated hemoglobin and fetal growth in normal, gestational and insulin dependent diabetes mellitus pregnancies. 943 79

The study compares an occurrence rate of congenital malformations in newborn infants of mothers with insulin dependent diabetes (IDDM) and newborns of healthy mothers and mothers with pregnancy diabetes (GDM). This paper evaluates the influence of stage of advancement (a class) of diabetes in the mother and its control during early pregnancy on a rate of congenital malformations in the fetus. We have taken a group of 170 neonates of mothers with IDDM. The control group was 56 newborn infants of mothers with GDM and 26,368 newborn infants of healthy women. We found 11.2% of congenital malformations in newborn infants of mothers with IDDM, compared to 1.8% of ones in the newborn infant population of mothers with GDM and 2.2% in the population of healthy mothers. The occurrence rate of congenital malformations in offspring of diabetic mothers with IDDM was 5-times higher than in the general population of newborn infants of healthy and also mothers with GDM. A risk of major birth defect occurrence in the fetus was directly proportional to the grade of the blood glucose level control in mothers during the I trimester of pregnancy, but the presence of diabetic angiopathy (classes D-H) had a significant influence on the occurrence rate of major birth defects in the fetus only in metabolic imbalance cases.
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PMID:A class of diabetes in mother, glycemic control in early pregnancy and occurrence of congenital malformations in newborn infants. 947 16


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