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)

Insulin-dependent diabetes mellitus is known to be associated with impaired ability of insulin to enhance tissue glucose uptake. However, no information is available whether or not this insulin resistance extends to insulin-mediated potassium (K+) uptake. Insulin-mediated decrease in serum potassium (K+) and in blood urea nitrogen (BUN) concentration was evaluated in 20 adolescents with IDDM and 10 matched controls during a 3-h hyperinsulinemic (1.7 mU/kg/min)-euglycemic clamp study. Insulin-mediated glucose disposal rate was lower in IDDM compared with controls (37.4 +/- 3.2 vs 63.8 +/- 5.4 mumol/kg/min, P less than 0.001). The decline in serum K+ concentration following hyperinsulinemia was significantly smaller in adolescents with IDDM than controls (0.29 +/- 0.06 vs 0.67 +/- 0.08 meq/liter, P = 0.002). Similarly the decline in BUN concentration was smaller in IDDM compared with control subjects (2.10 +/- 0.40 vs 3.70 +/- 0.56 mg/dl, P = 0.03), suggestive of decreased suppressibility of proteolysis. The changes in serum K+ and BUN concentrations were correlated (r = 0.64, P = 0.02) in controls but not in diabetics. Similarly, the decrement in serum K+ concentration showed a positive correlation with the rate of insulin-mediated glucose disposal (r = 0.68, P = 0.02) in controls but not in diabetics. The correlation of glucose disposal rate with the decline in BUN concentration did not reach a level of significance (r = 0.43, P = 0.1). These results indicate that adolescents with IDDM are resistant to the ability of insulin to stimulate in vivo K+ uptake and to suppress proteolysis.
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PMID:Impaired insulin mediated potassium uptake in adolescents with IDDM. 179 13

Juvenile diabetics have severe loss of beta cell function and require replacement therapy with insulin. Insulin antigenicity can produce anti-insulin antibodies resulting in allergic reactions and insulin resistance. The role of insulin-anti-insulin antibody complexes in the development and progress of chronic diabetic complications like microangiopathy is not very clear. In the present study, there was statistically a significant trend of higher insulin antibody binding levels in IDDM patients who developed retinopathy. Though there was a trend of higher insulin antibody in IDDM patients with retinopathy, there was no association between insulin antibody and HLA antigen which some authors have reported.
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PMID:Anti-insulin antibodies and retinopathy in juvenile onset type-1 diabetes. 181 Aug 80

The present study was conducted on 25 patients with Diabetes Mellitus (DM) having positive indication of diabetic retinopathy on ophthalmoscopic examination. The patients were examined clinically, ophthalmoscopically and with Fluorescein Angiography (FA). It was found that the maximum number of patients with retinopathy were in their 5th and 6th decade and that retinopathy was more common in Non Insulin dependent diabetics (NIDDM) than Insulin dependent Diabetics (IDDM). It was also seen that retinopathy takes longer time to develop in IDDM patients (16.37 years vs 11.7 years). Proliferative diabetic retinopathy was more common with patients having poor glycemic control and in IDDM patients. FA was very helpful in detecting microaneurysms and for exact localization of neovascularization, and other microangiopathic lesions as well as for permanent record.
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PMID:Diabetic retinopathy: a clinical study with special reference to fluorescein angiography. 184 1

Factors associated with diabetes onset were analysed for their predictive value in 708 first-degree relatives of Type 1 (insulin-dependent) diabetic patients including 374 parents and 308 siblings of Type 1 diabetic patients. Relatives were prospectively followed for 2,304 subject years with blood samples for specific autoantibody evaluation. Islet cell cytoplasmic autoantibody titres were quantified in Juvenile Diabetes Foundation units with a threshold of positivity of 5 units. Insulin autoantibodies were determined using Tyr-A14 iodinated human insulin. HLA typing was performed in 92% of the relatives. During the time of study, 17 of 646 (2.6%) relatives showed islet cell antibodies. During follow-up, eight relatives developed diabetes, including six with high islet cell antibody titre. Taking titres above 20 units increased the positive predictive value from 35% to 75% whereas the presence of insulin autoantibodies did not increase the positive predictive value for the disease. Analysis of metabolic profiles months before the onset of diabetes by either oral or intravenous glucose loads, indicated a considerable level of heterogeneity with relatives with a high islet cell antibody titre who rapidly developed insulin-dependent diabetes, whereas other remained insulin-independent during the same observation period despite comparable titres. This study clearly indicates that initial islet cell antibody titre is not sufficient to predict individual outcome. Follow-up samples are clearly needed to monitor progression of the disease. Few relatives with persistent immunologic positivity progress to clinical Type 1 diabetes, suggesting that non-progressive and sub-clinical Beta-cell dysfunction is common.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoantibodies and genetic factors associated with the development of type 1 (insulin-dependent) diabetes mellitus in first degree relatives of diabetic patients. 188 91

Hyperinsulinaemia links non-insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin-resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n = 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican-Americans than non-Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P less than 0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P less than 0.01) more frequent among non-Hispanic whites than Mexican-Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post-glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican-Americans, however, the standardized prevalence of hypertension was significantly (P less than 0.001) lower at any given insulin concentration. Post-glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P less than 0.02) in Mexican-Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL-cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter-ethnic difference.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High blood pressure and insulin resistance: influence of ethnic background. 190 31

Insulin dependent diabetes (IDDM) has an autoimmune pathogenesis. Included is the presence of antibodies to pancreatic islet cells. The first identified were islet cell antibodies (ICA), detected by indirect immunofluorescence, and which react with all cells within islets. Importantly, the autoantibodies are found several years prior to disease and although a pathogenic role for the autoantibodies is unclear, they have become useful markers of prediabetes. A number of studies of twins discordant for IDDM and of first degree relatives of IDDM patients have established that there is an increased risk for disease in individuals who have ICA, especially when ICA levels are high. This high predictive value of ICA decreases in the general population where the incidence of IDDM is lower than in first degree relatives, and both ICA and the disease risk associated with ICA, appear to be influenced by a genetic susceptibility. This has been sustained in a study of patients with endocrine autoimmunity and ICA (Polyendocrine Study) where the predictive value of very high levels of ICA is less than 50% in patients without a first degree relative with IDDM. Hence, there remain a substantial number of patients with ICA who do not develop disease. From these patients, it was demonstrated that ICA include at least two distinct specificities, one of which is beta cell specific and is not associated with a high risk for IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel considerations on the antibody/autoantigen system in type I (insulin-dependent) diabetes mellitus. 193 Sep 42

We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.
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PMID:Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report. 195 84

Insulin deficiency is a prominent feature of non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus that could result from defects in the insulin gene. Cloning of this gene has permitted molecular-genetic studies including the definition of multiple-DNA-sequence polymorphisms detected with restriction endonucleases, or restriction-fragment-length polymorphisms (RFLPs), and the mapping of the insulin gene to the short arm of chromosome 11 adjacent to the insulinlike growth factor II (IGF-II) and tyrosine hydroxylase genes. The combined RFLPs for the insulin, IGF-II, and tyrosine hydroxylase genes make this a highly informative locus for genetic studies of the insulin gene in diabetes. Early studies of an RFLP consisting of variable-number tandem repeats (VNTR) of DNA near the insulin gene suggested an association of certain alleles with approximately 170 copies of the repeat unit with NIDDM. Although subsequent studies in NIDDM did not confirm this association, an association of different alleles defined by approximately 40 copies of the repeat unit in this VNTR region with IDDM has been demonstrated in multiple studies. This VNTR region and the multiple other RFLPs for this region have been used in linkage analysis to study the segregation of insulin genes in families. These studies have failed to demonstrate a major significant role for insulin-gene defects in NIDDM, maturity-onset diabetes of the young, or IDDM in American Blacks and Whites and under various models of inheritance. Several pedigrees with diabetes and defects of the insulin gene have been described, however, and a minor role for this gene in NIDDM cannot be eliminated from available studies. Similarly, the association studies of the insulin gene and IDDM suggest a minor modifying role undetectable in pedigree studies. The role of defects in or near the insulin gene in a small subset of NIDDM or in IDDM must await direct investigation of the insulin gene in diabetic individuals with the most recent methods for gene amplification and sequence analysis.
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PMID:Insulin gene in diabetes. Analysis through RFLP. 196 74

To increase knowledge on the predictability of the onset of insulin-dependent diabetes mellitus (IDDM; type I), we followed 38 subjects less than 18 years of age who had positive results on two or more islet-cell antibody tests and one identical twin who had positive results on one islet-cell antibody test. All 39 patients had longitudinal intravenous glucose tolerance tests to determine the first-phase insulin response (FPIR). Insulin dependence has developed in 10 untreated subjects less than 18 years of age. Of the 10 subjects, insulin dependence developed in eight a mean of 4.6 months after their FPIR fell to less than 30 microU/ml and a mean of 14 months after it fell to less than 46 microU/ml. Nine of the untreated subjects had an FPIR less than 67 microU/ml on at least two occasions and became insulin dependent a mean of 19 months after the value first fell below this level (95% confidence limit = 66.4% to 100%). All but one of the 10 subjects in whom IDDM developed initially had islet-cell antibody levels of greater than 80 JDF units. Insulin autoantibody values at onset were available for 9 of the 10 subjects and were positive (greater than 39 nU/ml) in six. We conclude that the combination of positive results on two islet-cell antibody tests and two diminished FPIRs (less than 67 microU/ml) in subjects less than 18 years of age reliably predicts the onset of IDDM. These data should permit intervention studies to be planned.
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PMID:Prediction of the course of pre-type I diabetes. 204 Sep 17

Insulin-like growth factor binding proteins interfere in the IGF-I and -II radioimmunoassays. In an attempt to overcome this problem, we have compared the use of truncated IGF-I, with reduced IGFBP affinity, and IGF-I as radioligands for IGF-I RIA measurements in serum separated by acid gel filtration or acid ethanol extraction followed by cryo-precipitation. With truncated IGF-I as radioligand the IGF-I measurements in acid gel filtrates and acid ethanol extracts were significantly correlated in healthy subjects (N = 42, r = 0.91, p less than 0.001) and in patients with acromegaly (N = 10, r = 0.85, p less than 0.01), GH deficiency (N = 10, r = 0.88, p less than 0.001) or Type I diabetes mellitus (N = 10, r = 0.90, p less than 0.001). In contrast, the IGF-I concentrations in acid ethanol extracts determined with IGF-I as radioligand did not correlate with those in acid gel filtrates using truncated IGF-I radioligand in patients with acromegaly (r = 0.61, NS) or GH deficiency (r = 0.46, NS). In the latter group the mean IGF-I concentrations measured in acid ethanol extracts were erroneously elevated by 112%. Low-affinity antibodies used for IGF-II RIA determinations failed to give reliable results in acid ethanol extracts from patients with Type I diabetes mellitus or GH deficiency. In conclusion, erroneously high IGF-I concentrations owing to binding of the radioligand to IGFBPs not completely removed by acid ethanol extraction can be avoided by the use of truncated IGF-I as radioligand.
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PMID:Comparison of acid ethanol extraction and acid gel filtration prior to IGF-I and IGF-II radioimmunoassays: improvement of determinations in acid ethanol extracts by the use of truncated IGF-I as radioligand. 206 92


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