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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether variability at the insulin receptor substrate (IRS)-2 locus plays a role in the etiology of early-onset autosomal dominant type 2 diabetes. By means of radiation hybrid mapping, we placed the human IRS-2 gene on 13q at 8.6 cRays from SHGC-37358. Linkage between diabetes and two polymorphic markers located in this region (D13S285 and D13S1295) was then evaluated in 29 families with early-onset autosomal dominant type 2 diabetes. Included were 220 individuals with diabetes, impaired glucose tolerance, or gestational diabetes (mean age at diabetes diagnosis 36 +/- 17 years) and 146 nondiabetic subjects. Overall, strongly negative logarithm of odds (LOD) scores for linkage with diabetes were obtained by multipoint parametric analysis (LOD score -45.4 at D13S285 and -40.9 at D13S1295). No significant evidence of linkage was obtained under the hypothesis of heterogeneity or by nonparametric methods. Fourteen pedigrees for which linkage could not be excluded (LOD score > -2.0) were screened for mutations in the IRS-2 coding region by dideoxy fingerprinting. However, no mutations segregating with diabetes could be detected in these families. These data indicate that IRS-2 is not a major gene for early-onset autosomal dominant type 2 diabetes, although a role of mutations in the promoter region cannot be excluded at this time.
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PMID:Exclusion of insulin receptor substrate 2 (IRS-2) as a major locus for early-onset autosomal dominant type 2 diabetes. 1007 69

Transport of glucose into the cell is catalyzed by glucose transporters (Glut). Glut1 and Glut3 are expressed at various levels in many human tissues, including the placenta. It has been reported that ambient glucose can affect both glucose transport activity and expression of the Glut genes, and protein. To date, very few studies concerning Glut in the placenta have been published, and studies in vivo in human diabetic pregnancy are lacking. We therefore investigated placental Glut1 and Glut3 mRNA by Northern blot analysis in ten diabetic (five insulin dependent diabetes mellitus (IDDM), two non-insulin dependent diabetes mellitus (NIDDM) and three gestational diabetes mellitus (GDM)) and nine non-diabetic women. The quantitative results of specific mRNA/beta-actin ratios were expressed as arbitrary units. The results were evaluated according to metabolic and clinical findings. Glut1 and Glut3 mRNA values in diabetic and non-diabetic pregnant women were similar. The metabolic environment seems to affect the Glut3 mRNA levels in IDDM pregnant women but not the control women. In addition, Glut3 mRNA decreased in late pregnancy in the diabetic but not in the control women. Moreover, Glut1 mRNA levels were correlated with maternal age in the diabetic as well as in the control women (significantly). Finally, an inverse correlation was found between Glut1 mRNA levels and placental weight (in both diabetic and non-diabetic women). These results, although preliminary, shed some light on the function of these glucose transporters in normal as well as in diabetic pregnancies and prompt us to carry out a further investigation to better elucidate fetomaternal metabolic correlation at the placental level.
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PMID:Glucose transporter (Glut1, Glut3) mRNA in human placenta of diabetic and non-diabetic pregnancies. 1008 67

Detailed metabolic studies were carried out to compare major regulatory steps in glucose metabolism in vivo between 25 normal pregnant Latino women without and 150 pregnant Latino women with gestational diabetes mellitus (GDM). The two groups were frequency-matched for age, BMI, and gestational age at testing in the third trimester. After an overnight fast, women with GDM had higher fasting plasma glucose (P = 0.0001) and immunoreactive insulin (P = 0.0003) concentrations and higher glucose production rates (P = 0.01) but lower glucose clearance rates (P = 0.001) compared with normal pregnant women. During steady-state hyperinsulinemia (approximately 600 pmol/l) and euglycemia (approximately 4.9 mmol/l), women with GDM had lower glucose clearance rates (P = 0.0001) but higher glucose production rates (P = 0.0001) and plasma free fatty acid (FFA) concentrations (P = 0.0002) than the normal women. These intergroup differences persisted when a subgroup of 116 women with GDM who were not diabetic < or = 6 months after pregnancy were used in the analysis. When all subjects were considered, there was a very close correlation between glucose production rates and plasma FFA concentrations throughout the glucose clamps in control (r = 0.996) and GDM (r = 0.995) groups. Slopes and intercepts of the relationships were nearly identical, suggesting that blunted suppression of FFA concentrations contributed to blunted suppression of glucose production in the GDM group. In addition to these defects in insulin action, women with GDM had a 67% impairment of pancreatic beta-cell compensation for insulin resistance compared with normal pregnant women. These results demonstrate that women with GDM have multiple defects in insulin action together with impaired compensation for insulin resistance. Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women.
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PMID:Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes. 1010 3

Japan Diabetes Society organized a committee for the revision of diagnostic criteria of diabetes mellitus in 1995. Like ADA and WHO reports, this committee adopts a classification based on etiologies, and presents a two-dimensional figure with etiologies and the state of insulin deficiency on different axis. The words IDDM and NIDDM will be retained as terms representing the different degree of insulin deficiency. On the basis of glycemia, diabetic type is defined when fasting plasma glucose exceeded 126 mg/dl and/or 2-hour plasma glucose by 75 g GTT exceeded 200 mg/dl. The diagnosis of diabetes in an individual can be made by confirming sustained diabetic type on repeated tests or co-existance of characteristic clinical features of diabetes. Normal type is defined by FPG < 110 mg/dl and 2hPG < 140 mg/dl. The borderline type, defined as neither normal nor diabetic types, corresponds to IFG plus IGT according to ADA and WHO reports. The application of HbA1c for diagnosis of diabetes and the criteria for gestational diabetes mellitus are also discussed.
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PMID:[Outline of revision of classification and diagnostic criteria of diabetes mellitus in Japan]. 1019 34

Secondary diabetes can be defined as a diabetic condition that develops after the destruction of the beta-cells in the pancreatic islets and/or the induction of insulin resistance by an acquired disease (e.g. endocrinopathies) or others. Recently, diabetes mellitus has divided into four distinct types (type 1 diabetes, type 2 diabetes, other specific types of diabetes and gestational diabetes) in the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus in USA. The categories between secondary diabetes and the other specific types of diabetes might be different a little, some of the latter being described here. The details of the genetic defects in insulin action has been presented elsewhere (see Chapter V-3).
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PMID:[Secondary diabetes]. 1019 47

A missense mutation of the beta3-adrenergic receptor gene (Trp64Arg) has been associated with obesity and increased capacity to gain weight in nonpregnant populations. Furthermore, the mutation is a potential modifying factor in the etiology of impaired glucose tolerance and type 2 diabetes. We studied the relation of the beta3-adrenergic receptor genotype to glucose tolerance during pregnancy, a state of physiological insulin resistance. In 179 pregnant women (mean age, 28.5 +/- 0.4 yr), a 2-h oral glucose tolerance test was performed between gestational weeks 20 and 31. The beta3-adrenergic receptor genotype was assessed using restriction fragment length polymorphism. The frequency of the Arg64 allele was 9.15%. In women with mild gestational diabetes (n = 70), as defined by 60 min postload glucose values, the Trp64Arg genotype was more frequent than in women with normal glucose tolerance (n = 109; 26% vs. 11%; P = 0.01). Furthermore, the Trp64Arg polymorphism was associated with increased weight gain during pregnancy (baseline to gestational weeks 20-31) and increased postload glucose, insulin, and C peptide values during the oral glucose tolerance test. The results of the present study extend current knowledge about the association of the Trp64Arg beta3-adrenergic receptor polymorphism with glucose tolerance to a pregnant population. The association with mild gestational diabetes suggests that the impact of the polymorphism may be clinically important during pregnancy, a state of physiological insulin resistance.
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PMID:Trp64Arg polymorphism of the beta3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus. 1032 2

Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.
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PMID:The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks. 1035 18

As currently defined (5), gestational diabetes is associated with important perinatal and long-term health risks. Many of the risks increase, in relation to the severity of maternal hyperglycemia. For perinatal risks to infants, the relationship seems to be continuous. Maternal fasting glucose levels can be used to identify subsets of patients with very low and very high risks. The majority of pregnancies lie between these two extremes; and nonglucose measures, such as fetal ultrasound, can be used to enhance risk assessment, thereby minimizing over- and undertreatment of patients. The major long-term maternal risk is development of type 1 or type 2 diabetes, predominantly the latter. The risk increases continuously, in relation to maternal glycemia during and, especially, after pregnancy. Patients seem to have a B-cell defect that is characterized by maladaptation to insulin resistance. The B-cell defect is predictive of future diabetes, supporting the testing and clinical application of interventions that minimize insulin resistance to delay or prevent diabetes. Women with impaired glucose tolerance in the first few months postpartum are at particularly high risk for diabetes and should receive the most intensive education, intervention, and follow-up. Offspring of women with GDM are at increased risk for obesity and have an unexpectedly high prevalence of elevated glucose levels during childhood and adolescence. Both genetic and intrauterine environmental influences are likely to contribute to these abnormalities. Optimal strategies to detect and prevent the long-term risks to offspring remain to be established.
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PMID:Gestational diabetes: risk or myth? 1037 74

Pregnancy is associated with important changes in mother metabolism, especially in late gestation, among which a decreased glucose tolerance caused by insulin resistance. In some of these women, glucose intolerance is increased by a defect in B-cell function and diabetes mellitus occurs. These women who develop a gestational diabetes need a close follow-up because they are at high risk for further development of diabetes, especially type 2 diabetes.
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PMID:[Gestational diabetes: physiopathology and prognostic significance for the mother]. 1039 43

Gestational diabetes, even if it seems to induce far less foetal complications than classical type 1 or type 2 diabetes mellitus, may be deleterious for the child. We will successively consider the complications that could affect the child during gestation, during the neonatal period and during adult life. These consequences for the offspring require optimal screening and management of gestational diabetes mellitus.
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PMID:[Gestational diabetes: prognostic significance for the infant]. 1044 20


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