Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (+/- SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5 < or = fpg < 7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m2. The parents were aged 62 (6) years and had BMI 29 (6) kg/m2 and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level > 2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We conclude that the study of women who have had gestational diabetes allows detection of probands with diabetes or impared glucose tolerance, who have both parents available for study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes. 767 91

Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated.
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PMID:Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology. 778 40

Gestational diabetes encompasses a variable spectrum of decompensated glucose tolerance, with a substantial risk for developing future NIDDM. Several easily identifiable risk factors for subsequent diabetes have been identified, notably elevated fasting glucose levels during pregnancy, early diagnosis of gestational diabetes, and obesity. By continuing to identify independent risk factors during pregnancy and in the puerperium, we can develop better intervention programs and medical therapy to prevent or delay the onset of diabetes. Glucose tolerance testing in the postpartum period followed up by annual glucose surveillance for diabetes should be performed in all women with prior GDM. They should be actively educated about their high risk of diabetes and strongly encouraged to continue their diabetes and strongly encouraged to continue their diabetic diet, achieve an ideal body weight, and implement an exercise program. Combining such a program of preventive care with contraceptive visits contributes to a complete health care program for women with prior GDM during their reproductive years.
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PMID:Maternal implications of gestational diabetes. 782 73

The purpose of these experiments was to test the hypothesis that impaired glucose-stimulated insulin secretion in NIDDM is due to mutations in the islet beta cell/liver glucose transporter (GLUT 2) gene. Using oligonucleotide primers flanking each of the 11 exons, the structural portion of the gene was studied by PCR-SSCP analysis. DNA from African-American females (n = 48), who had gestational diabetes but developed overt NIDDM after delivery, was studied. Each SSCP variant was sequenced directly from genomic DNA. Two amino acid substitutions from the previously reported sequence were found, one in exon 3 and the other in exon 4B. Four additional silent mutations in the coding region, and six intron mutations outside the splice junction consensus sequences, were also identified. The mutation GTC x ATC in exon 4B substituted Val197 to Ile197. This amino acid substitution was found in only one NIDDM patient in a single allele, and was not found in 52 control subjects. This residue exists in the fifth membrane spanning domain, and Val at this position is conserved in mouse and rat GLUT 2, and human GLUT 1 to GLUT 4. The other codon change in exon 3, ACT x ATT, substituted Thr110 to Ile110 in the second membrane spanning domain. To determine the frequency of this non-conservative amino acid substitution, a PCR-LCR assay was developed. This assay was simple and highly specific for detection of this single nucleotide substitution. The allelic frequency of the ATT (Ile110) in NIDDM patients (39.6%, n = 48) and that in controls (47.1%, n = 52) did not differ (p = 0.32, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Variability of the pancreatic islet beta cell/liver (GLUT 2) glucose transporter gene in NIDDM patients. 806 45

The WHO has defined standardized diagnostic criteria for manifest diabetes mellitus and disorders of glucose tolerance. Owing to a low level of sensitivity and only moderate specificity, coupled with an unfavorable cost-benefit rating, glucosuria screening is not suitable for large-scale use at population level and, as recommended by the WHO, should be replaced by plasma glucose screening. The method of choice for the latter is the determination of the fasting plasma glucose level. Its use should be restricted to target groups with a high risk of contracting diabetes. In the doctor's office, a health check is of particular importance for the diagnosis of type 2 diabetes, which is usually asymptomatic. Screening for diabetes with the aid of a 50 g oral dose of glucose to detect gestational diabetes is a must during pregnancy.
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PMID:[Screening studies in diagnosis of diabetes. Do they still have practical value?]. 820 May 97

Current methods for the screening and diagnosis of glucose intolerance first discovered in pregnancy are reviewed and innovative approaches to the detection of metabolic disturbances in pregnancy are presented. Glucose intolerance first detected in pregnancy, termed gestational diabetes mellitus (GDM), is amongst the most significant risks of adverse fetal and maternal outcome. Normal pregnancy is characterized by both insulin resistance and pancreatic B cell compensation. In those pregnancies complicated by glucose intolerance reflected in hyperglycemia, insulin resistance appears to be heightened, both blood flow and transcapillary transport of insulin are compromised and insulin receptor and post receptor defects are exacerbated. The resulting hyperinsulinemia and hyperglycemia have, in turn, been associated with accumulated maternal fat deposition and fetal macrosomia. This cascade of events constitutes GDM or impaired glucose tolerance. The discovery of GDM is made through a process of screening and diagnosis, employing standardized oral glucose challenge tests. These tests were designed to identify those women at risk for subsequent development of non-insulin dependent diabetes mellitus. The current efficacy of glucose challenge tests has been questioned in light of increasing concern over their usefulness in detecting those women at risk for maternal and fetal complications of pregnancy. Alternative methods, including both the modification of the standardized tests, as well as the introduction of newer methodologies, such as capillary blood glucose monitoring, have been proposed. The implementation of newer approaches may result in improved detection of those women whose infants are at high risk for both metabolic and morphologic complications of persistent hyperglycemia in pregnancy.
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PMID:Detection of glucose intolerance in pregnancy. 822 93

Mechanisms causing cellular insulin resistance in gestational diabetes mellitus are not known. We, therefore, studied isolated omental adipocytes obtained during elective cesarean sections in nondiabetic (control) and GDM gravidas. Cellular insulin resistance was attributed to impaired stimulation of glucose transport; compared with control subjects, basal and maximally insulin-stimulated transport rates (per surface area) were reduced 38 and 60% in GDM patients, respectively. To determine underlying mechanisms, we assessed the number, subcellular distribution, and translocation of GLUT4, the predominant insulin-responsive glucose transporter isoform. The cellular content of GLUT4 was decreased by 44% in GDM patients as assessed by immunoblot analysis of total postnuclear membranes. However, GDM patients segregated into two subgroups; half expected profound (76%) cellular depletion of GLUT4 and half had GLUT4 levels in the normal range. Cellular GLUT4 was negatively correlated with adipocyte size in the control subjects and GDM patients with normal GLUT4 (r = 0.60), but fell way below this continuum in GDM patients with low GLUT4, indicating that heterogeneity was not caused by differences in obesity. All GDM. distribution. In basal cells, increased amounts of GLUT4 were detected in membranes fractionating with (such that the plasma membrane GLUT4 level in GDM (such that the plasma membrane GLUT4 level in GDM patients was equal to that observed in insulin-stimulated cells from control subjects). Furthermore, insulin stimulation induced translocation of GLUT4 from low-density microsomes to plasma membranes in control subjects but did not alter subcellular distribution in GDM patients. In other experiments, cellular content of GLUT1 was normal in GDM patients, and GLUT1 did not undergo insulin-mediated recruitment to plasma membranes in either control subjects or GDM patients. A faint signal was detected for GLUT3 only in low-density microsomes and only with one of two different antibodies. In GDM, we conclude that insulin resistance in adipocytes involves impaired stimulation of glucose transport and arises from a heterogeneity of defects intrinsic to the glucose transport effector system. GLUT4 content in adipocytes is profoundly depleted in approximately 50% of GDM patients, whereas all patients are found to exhibit a novel abnormality in GLUT4 subcellular distribution. This latter defect is characterized by accumulation of GLUT4 in membranes cofractionating with plasma membranes and high-density microsomes in basal cells and absence of translocation in response to insulin. The data suggest that abnormalities in cellular traffic or targeting relegate GLUT4 to a membrane compartment from which insulin cannot recruit transporters to the cell surface and have important implications regarding skeletal muscle insulin resistance in GDM and NIDDM.
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PMID:Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. Heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters. 824 23

The authors studied the correlations between electroretinographic, ophthalmologic, and clinical parameters in 30 pregnant women (20 with diabetes and 10 control subjects). Diabetic patients were divided into two groups: group 1 included 11 cases of insulin-dependent diabetes (IDDM); and group 2 included 6 cases of noninsulin-dependent diabetes (NIDDM) and 3 cases of gestational diabetes (GDM). Adapto-electroretinography (AERG) was used as the main monitoring parameter, and in particular, the relationship between the cone-mediated (b1) and rod-mediated (b2) components of the b wave (b2/b1 ratio) 7 minutes after photobleaching was studied. The results indicate that the b2/b1 ratio can detect functional modifications before the onset of ophthalmoscopically detectable retinopathy. Significant statistical correlations were demonstrated both between the type of diabetes and AERG responses, and between metabolic control (HbA1c values) and AERG alterations. A higher maternofetal complication rate in those patients with severe and frequent AERG alterations during pregnancy also was found.
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PMID:Electrophysiologic monitoring of diabetic retinopathy in pregnancy. 833 8

Mutations in the glucokinase gene are a major cause of maturity-onset diabetes of the young. To evaluate the contribution of this gene to the development of late-onset NIDDM, linkage analyses between DNA polymorphisms at the glucokinase locus and NIDDM were performed in 79 multigenerational French families. In addition, all exons and the islet promoter region of glucokinase gene from 1 affected member from each family as well as from 17 unrelated women with previous gestational diabetes were amplified by polymerase chain reaction and screened for mutations by single-strand conformational polymorphism and DNA sequencing. Linkage of glucokinase and NIDDM was significantly rejected under all models tested. However, in 1 family, the lod score was 2.30, and we found a nucleotide substitution at the position -30 in the islet promoter region that cosegregated with diabetes. The proband of this family was a gestational diabetic individual. No other mutation in glucokinase was found in the 79 NIDDM families. We identified a missense mutation (TGG257-->CGG257) in exon 7 of glucokinase gene from 1 of 17 women with gestational diabetes, which was present in all diabetic members of her family. This family is likely to be a cryptic maturity-onset diabetes of the young, as 4 younger members, carrying this mutation, were subsequently found to be hyperglycemic. In conclusion, no evidence was obtained to incriminate glucokinase as a major gene for late age of onset NIDDM. Diabetic families with mutations in glucokinase must be carefully investigated, to differentiate cryptic maturity-onset diabetes of the young from late-onset NIDDM. Furthermore, pregnancy reveals diabetes in women carrying a glucokinase defect.
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PMID:Linkage analysis and molecular scanning of glucokinase gene in NIDDM families. 834 34

Recent work in healthy subjects, the aged, and subjects with gestational diabetes or drug-induced insulin resistance using minimal model analysis of the tolbutamide-modified frequently sampled intravenous glucose tolerance test suggested that a reduced sampling regimen of 12 time points produced unbiased and generally acceptable estimates of insulin sensitivity (SI) and glucose effectiveness (SG) compared with a full sampling schedule of 30 time points. We have used data from 26 insulin-modified frequently sampled intravenous glucose tolerance tests in 21 subjects with NIDDM to derive and compare estimates of SI and SG from the full sampling schedule (SI(30), SG(30)) with those estimated from the suggested 12 time points (SI(12), SG(12)) and those estimated with the addition of a 25-min time point (SI(13), SG(13)). Percentage relative errors were calculated relative to the corresponding 30 time-point values. A statistically significant bias of 15% (97% confidence interval from 7.4 to 25.6%, interquartile range 25%) was introduced by the estimation of SI(12) but not SI(13) (1%, 97% confidence interval from -9.4 to 9.3%, interquartile range 21%). Results for SG(12) (-12%, 97% confidence interval from -46.7 to 1.2%, interquartile range 49%) and SG(13) (-5%, 97% confidence interval from -27.8 to 6.8%, interquartile range 37%) were statistically equivocal. The precision of estimation of SI(12), SG(12), and SG(13) measured by the interquartile range of the percentage relative errors was poor. The precision of determination measured by the median minimal model coefficient of variation was 18, 29, and 27% for SI(30), SI(12), and SI(13) and 9, 11, and 11% for SG(30), SG(12), and SG(13), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced sampling protocols in estimation of insulin sensitivity and glucose effectiveness using the minimal model in NIDDM. 840 6


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