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Query: UMLS:C0029713 (immaturity)
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The aim of this study was to demonstrate what factors influence preterm termination of pregnancy complicated by diabetes, in dependence of diabetes progression. The following factors have been analysed: rate and causes of preterm labours according to White classification, mean duration of pregnancy, mode of delivery, birth weight, Apgar score and diabetes control in the preterm delivered women with different progression of disease. As a result we observed, that in G/A and G/B classes and in short lasting class B, the most common cause of preterm labour was spontaneous delivery and prematurity rate was low, oscillated between 1.7 and 15.8 percent. In those classes we also observed that diabetes control was very good or adequate. In D, R, F, and RF classes the most common cause of preterm labour is intrauterine fetal distress, that causes preterm termination of pregnancy, despite immaturity, and prematurity rate is 30-50 percent. We observed bad diabetes control in above mentioned classes.
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PMID:[Causes of premature labor in pregnancy complicated by diabetes depend on diabetes progression]. 1139 96

Insulin-dependent neonatal diabetes (ND) mellitus is uncommon with a frequency of 1/500,000 neonates in Europe. ND is characterised by hyperglycaemia, very low or undetectable insulin levels associated with intrauterine growth retardation and malformations. HLA haplotypes of juvenile diabetes or autoimmunity are not present in ND patients. Sporadic and familial forms are observed. ND could be persistent (PND) or transient (TND). Diabetes relapses occur in approximately 40% of TND patients. Hypothesis for ND aetiology such as pancreatic or beta pancreatic islets of Langerhans immaturity or abnormalities of pancreas organogenesis are postulated. Different genetic basis underlie transient or permanent forms though their clinical features do not allow to distinguish them. TND may in about 20-30% of the cases be associated with chromosome 6 paternal uniparental disomy. A candidate locus for an imprinted gene is mapped to 6q24. The permanent forms are less understood. Homozygous mutations of the IPF1/PDX1 (MODY4) and of the Glucokinase (GK, MODY2) genes have been reported. The association of a ND with a macroglossia should be a strong indicator for genetic testing. The genetic findings of a paternal disomy uniparental allows the prediction of a transient rather than a permanent form. Mutation in the Glucokinase gene should be sought in an infant with ND whose first degree relatives have glucose intolerance.
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PMID:[Insulin-dependent neonatal and infant diabetes: genetics and physiopathology]. 1208 68

The NADH shuttle system, which transports the substrate for oxidative metabolism directly from the cytosol to the mitochondrial electron transport chain, has been shown to be essential for glucose-induced activation of mitochondrial metabolism and insulin secretion in adult beta-cells. We examined the role of these shuttles in the fetal beta-cell, which is immature in being unable to secrete insulin in response to glucose. The activity and concentration of the two key enzymes of the NADH shuttles, mitochondrial glycerol phosphate dehydrogenase (mGPDH) and mitochondrial malate dehydrogenase (mMDH), were eight- and threefold lower, respectively, in fetal compared with adult rat islets. Likewise, mGPDH and mMDH activity was fivefold lower in islet-like cell clusters (ICCs) and sevenfold lower in purified beta-cells compared with adult islets in the pig. The low level of enzyme activity was a result of low gene expression of the mitochondrial enzymes in the fetal beta-cells. Increasing NADH shuttle activity by transduction of fetal rat islets with mGPDH cDNA enabled the fetal islets to secrete insulin when stimulated with glucose. We concluded that the immaturity of the NADH shuttles contributes to the inability of fetal beta-cells to secrete insulin in response to glucose.
Diabetes 2002 Oct
PMID:Role of NADH shuttles in glucose-induced insulin secretion from fetal beta-cells. 1235 38

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.
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PMID:Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants. 1312 78

Doppler parameters enable noninvasive and direct detection of placental insufficiency and brain sparing effect, which occurs as an adaptive mechanism to chronic hypoxemia. It is of great interest if further changes of Doppler parameters, which occur after the detection of the first pathologic value, can anticipate a moment of fetal distress. We investigated growth-restricted fetuses with the brain sparing effect in the time interval between the detection of blood flow redistribution until the distress. The aim of our study was to evaluate longitudinally Doppler parameters in umbilical (Aum), medial cerebral (MCA), renal (AR) and femoral (AF) artery, and find: 1) if there are significant changes in their value; 2) the character and time interval of these changes; and 3) if they differ from changes in biophysical profile (BFP). Prospective clinical study evaluated 35 pregnancies with fetal growth restriction. Fetuses were selected for the study if: 1) there were pathologic cerebral/umbilical (C/U) ratio, 2) at least four Doppler examinations in 3-4 days interval were performed and 3) prepartal fetal distress, defined as silent fetal heart rate pattern with spontaneous and late decelerations, was present. In 28 neonates after delivery umbilical artery gas and acid-base status was determined. Blood flow velocity waveforms were evaluated in Aum, MCA, AR, and AF. Arterial blood flow was estimated by pulsatility index (Pi), while in Aum we also used: present end-diastolic velocity (PEDV), absent end-diastolic velocity (AEDV) and reverse end-diastolic velocity (REDV). All of the fetuses were monitored by cardiotocogram (CTG) once to twice a day and by BFP twice a week. Elective Cesarean section was done in the presence of distress, except if severe immaturity or extreme malnutrition occurred. Etiological factors of placental insufficiency were: 1) hypertensive syndrome (n = 26), 2) chronic renal disease (n = 3), 3) primary antiphospholipid syndrome (n = 2), 4) diabetes mellitus (n = 1), 5) cardiac disease (n = 1) and 6) unknown (n = 2). Initial Doppler examination, with the detection of pathological C/U, was done in time interval between 26. to 32. weeks of gestation (wg) (29.4 +/- 2.5); delivery was between 29. to 34. wg (32.2 +/- 1.9); and average body weight was 1327 +/- 245 g. Pathological BFP was registered in 91.4% of fetuses. Cesarian section has not been done, in spite of distress, in two fetuses (5.7%) due to their extreme immaturity and/or malnutrition, so they died "in utero". Hypoxemia was registered in 96.4% (27/28) neonates, while acidosis in 71.4% (20/28). Neonatal morbidity was 93.9% (31/33), neonatal mortality 8.6%, while perinatal mortality was 14.3%. We found high significant difference (P < 0.001) in Pi Aum, Pi ACM and Pi AR in the time interval between the detection of pathological C/U ratio and fetal distress, while the difference was insignificant for the values of Pi AF (table). The value changes are characterized by: continuing increase of Pi Aum, with a maximum in the last week before the distress; biphasic character of PI MCA--tendency to decrease in the first two and significant increase in the last week; and significant increase of Pi AR one and a half week before the distress (table, graphic). Three weeks before the distress in 7 (53.8%) cases we registered PEDV, in 6 (46.2%) AEDV, while we didn't register REDV in any case. In the last week there were 3 (8.6%) PEDV, 23 (65.7%) AEDV and 9 (25.7%) REDV. Significant changes in Doppler parameters suggest that even after the blood redistribution in growth restricted hypoxemic fetuses further haemodynamic changes occur. Preterminal increase in Pi Aum can be due to: 1) release of leucotrien, tromboxan and free oxygen radicals and consecutive vasoconstriction in villous arteries; 2) increase of diastolic arterial pressure as a result of hypoxic-ischemic central nervous system (CNS) insult; 3) decreased combined heart minute volume in preterminal phase of hypoxemia. The increase of Pi MCA values is a result of hypoxic-ischemic CNS insult. As a consequence of hypoxia ischemia occurs by two mechanisms: local vasodilatatory agents production decrease, or due to the brain edema. The increase of Pi AR values can be explained by severe hypoxemia with the failure of local autoregulation of renal blood flow. The greatest changes in BFP values were registered in the first half, while in Doppler parameters in the second half of the studied interval suggesting that Doppler parameters more accurately announce fetal distress. We can conclude the following: 1) fetal distress appears after the presence hypoxic-ischemic CNS insult, and therefore late when sequels are concerned; 2) if the fetus is mature, elective delivery should be planed after the appearance of pathological C/U ratio, or with the pathological BFP at the latest, in order to avoid post-hypoxic sequels; 3) if the fetus is immature, pregnancy can be prolonged safely, in spite of pathological C/U ratio and BFP, with intensive monitoring of Doppler parameters until the detection of their increased values.
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PMID:[Longitudinal analysis of arterial Doppler parameters in growth retarded fetuses]. 1460 57

Phenotypically "immature" dendritic cells (DCs), defined by low cell surface CD40, CD80, and CD86 can elicit host immune suppression in allotransplantation and autoimmunity. Herein, we report the most direct means of achieving phenotypic immaturity in NOD bone marrow-derived DCs aiming at preventing diabetes in syngeneic recipients. CD40, CD80, and CD86 cell surface molecules were specifically down-regulated by treating NOD DCs ex vivo with a mixture of antisense oligonucleotides targeting the CD40, CD80, and CD86 primary transcripts. The incidence of diabetes was significantly delayed by a single injection of the engineered NOD DCs into syngeneic recipients. Insulitis was absent in diabetes-free recipients and their splenic T cells proliferated in response to alloantigen. Engineered DC promoted an increased prevalence of CD4(+)CD25(+) T cells in NOD recipients at all ages examined and diabetes-free recipients exhibited significantly greater numbers of CD4(+)CD25(+) T cells compared with untreated NOD mice. In NOD-scid recipients, antisense-treated NOD DC promoted an increased prevalence of these putative regulatory T cells. Collectively, these data demonstrate that direct interference of cell surface expression of the major costimulatory molecules at the transcriptional level confers diabetes protection by promoting, in part, the proliferation and/or survival of regulatory T cells. This approach is a useful tool by which DC-mediated activation of regulatory T cells can be studied as well as a potential therapeutic option for type 1 diabetes.
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PMID:Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. 1538 62

Apparent increase of the incidence of childhood diabetes mellitus has been observed in many countries over the last decades. Data of seasonality are not consistent, especially in younger group. The triggering of the autoimmune process in genetically susceptible individuals may be the result of a variety of environmental factors including viral infections, specific nutrients, early introduction of cow's milk proteins and ingestion of nitrosamines, stress-inducing events, early perinatal lesions. Clinical studies of the last decade have confirmed that diabetes mellitus in young children is specific type of type 1 diabetes. At presentation, children in preschool age group, who have type 1 diabetes, have higher incidence of ketoacidosis with coma because of immaturity of the central nervous system. Delays in diagnosis in small children often lead to more severe dehydration and ketoacidosis. Chi dren in the young age group who have type 1 diabetes represent unique set of problems for their families and health care team.
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PMID:[New aspects of etiopathogenesis and clinical characteristics of diabetes mellitus type 1 in children]. 1561 86

The development of islet cell transplantation as a cure for diabetes is limited by the shortage of human donor organs. Moreover, currently used grafts exhibit a marginal beta-cell mass with an apparently low capacity for beta-cell renewal and growth. Although duct-associated nonendocrine cells have often been suggested as a potential source for beta-cell production, recent work in mice has demonstrated the role of beta-cells in postnatal growth of the pancreatic beta-cell mass. The present study investigated whether the beta-cell mass can grow in implants that are virtually devoid of nonendocrine cells. Endocrine islet cells were purified from prenatal porcine pancreases (gestation >110 days) and implanted under the kidney capsule of nude mice. beta-Cells initially presented with signs of immaturity: small size, low insulin content, undetectable C-peptide release, and an inability to correct hyperglycemia. They exhibited a proliferative activity that was highest during posttransplant week 1 (2.6 and 5% bromodeoxyuridine [BrdU]-positive beta-cells 4 and 72 h posttransplant) and then decreased over 20 weeks to rates measured in the pancreas (0.2% BrdU-positive cells). beta-Cell proliferation in implants first compensated for beta-cell loss during posttransplant week 1 and then increased the beta-cell number fourfold between posttransplant weeks 1 and 20. Rates of alpha-cell proliferation were only shortly and moderately increased, which explained the shift in cellular composition of the implant (beta-cell 40 vs. 90% and alpha-cell 40 vs. 7% at the start and posttransplant week 20, respectively). beta-Cells progressively matured during the 20 weeks after transplantation, with a twofold increase in cell volume, a sixfold increase in cellular insulin content, plasma C-peptide levels of 1-2 ng/ml, and an ability to correct diabetes. They became structurally organized as homogenous clusters with their secretory vesicles polarized toward fenestrated capillaries. We concluded that the immature beta-cell phenotype provides grafts with a marked potential for beta-cell growth and differentiation and hence may have a potential role in curing diabetes. Cells with this phenotype can be isolated from prenatal organs; their presence in postnatal organs needs to be investigated.
Diabetes 2005 Dec
PMID:Growth and functional maturation of beta-cells in implants of endocrine cells purified from prenatal porcine pancreas. 1630 53

Mortality from cancer of the prostate is increasing in the Asia-Pacific, when much of this region is undergoing a transition to a Western lifestyle. The role that lifestyle factors play in prostate cancer appears limited, but existing data mainly are from the West. We conducted an individual participant data analysis of 24 cohort studies involving 320,852 men (83% in Asia). Cox proportional hazard models were used to quantify associations between risk factors and mortality from prostate cancer. There were 308 deaths from prostate cancer (14% in Asia) during 2.1 million person-years of follow-up. The age-adjusted hazard ratio (95% confidence interval; CI) for men with body mass index (BMI) 28 kg/m2 or more, compared with below 25, was 1.55 (1.12 - 2.16); no such significant relationship was found for height or waist circumference. The BMI result was unchanged after adjustment for other variables, was consistent between Asia and Australia/New Zealand (ANZ) and did not differ with age. There was no significant relationship with diabetes, glucose or total cholesterol (p > or = 0.18). Smoking, alone, showed different effects in the two regions, possibly due to the relative immaturity of the smoking epidemic in Asia. In ANZ, the multiple-adjusted hazard ratio for an extra 5 cigarettes per day was 1.12 (95%CI: 1.03 - 1.22), whereas in Asia it was 0.77 (0.56 - 1.05). Body size is an apparently important determinant of prostate cancer in the Asia-Pacific. Evidence of an adverse effect of smoking is conclusive only in the predominantly Caucasian parts of the region.
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PMID:The impact of modifiable risk factors on mortality from prostate cancer in populations of the Asia-Pacific region. 1769 31

Normal human pregnancy is considered a state of enhanced oxidative stress. In pregnancy, it plays important roles in embryo development, implantation, placental development and function, fetal development, and labor. However, pathologic pregnancies, including gestational diabetes mellitus (GDM), are associated with a heightened level of oxidative stress, owing to both overproduction of free radicals and/or a defect in the antioxidant defenses. This has important implications on the mother, placental function, and fetal well-being. Animal models of diabetes have confirmed the important role of oxidative stress in the etiology of congenital malformations; the relative immaturity of the antioxidant system facilitates the exposure of embryos and fetuses to the damaging effects of oxidative stress. Of note, there are only a few clinical studies evaluating the potential beneficial effects of antioxidants in GDM. Thus, whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus needs to be explored. This review provides an overview and updated data on our current understanding of the complications associated with oxidative changes in GDM.
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PMID:The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. 2167 77


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