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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 resistance is a characteristic feature of non-insulin dependent diabetes mellitus (NIDDM) due to target tissue defects in insulin action. Abnormalities of cellular insulin action can be divided into receptor and post-receptor defects. Patients with impaired glucose tolerance are insulin resistant due to decreased insulin receptors resulting in decreased insulin sensitivity and rightward shifted in vivo dose response curves. Patients with NIDDM are insulin resistant due to a combination of receptor and post-receptor defects. The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state. At least one of the abnormalities underlying this post-receptor defect involves a decrease in glucose transport system activity in freshly isolated adipocytes. This defect in glucose transport, is not expressed in cultured fibro-blasts, indicating that the abnormality in glucose disposal seen in vivo and in glucose transport seen in freshly isolated cells is an acquired phenomenon. Consistent with this, the post-receptor defect is partially reversible by insulin therapy, which leads to a 50-70% reversal of the reduced rates of in vivo glucose disposal and in vitro glucose transport. Insulin resistance also exists in poorly controlled IDDM patients, due to a postreceptor defect in insulin action. This insulin resistance is not present in well controlled IDDM patients, and is completely reversible when poorly controlled patients are treated with intensive insulin therapy. Insulin is produced in the pancreatic beta cell as the primary biosynthetic product preproinsulin. This peptide is rapidly converted to proinsulin (MW approximately 9000). Proinsulin is converted to insulin (MW approximately 6000) plus C-peptide in the secretory granule with a small amount (approximately 5 percent) of the proinsulin remaining unconverted. After a brief time in the peripheral circulation (half-life six to 10 minutes), insulin interacts with target tissues to exert its biologic effects. One of insulin's major biologic effects is the promotion of overall glucose metabolism, and abnormalities of this aspect of insulin action can lead to a number of important clinical and pathophysiologic states including Type II diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM). Since insulin travels from the beta cell through the circulation to the target tissues, abnormalities at any of these loci can influence the ultimate action of the hormone. These abnormalities, all
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PMID:Insulin resistance in non-insulin dependent (type II) and insulin dependent (type I) diabetes mellitus. 389 63

Non-insulin dependent diabetes (NIDD) was obtained in adult rats after a neonatal streptozotocin injection. In the fed state 3- to 5-month-old rats with NIDD exhibited modestly elevated plasma glucose levels (controls, 131 +/- 7 mg/dl; diabetics, 159 +/- 4 mg/dl; P less than 0.01), impaired glucose tolerance, and a very low insulin response after glucose injection. In the present study the secretion and biosynthesis of insulin were measured using isolated islets from these rats. The insulin and DNA content of islets freshly isolated from rats with NIDD were significantly lower (60% and 80%, respectively, P less than 0.001) than in the controls. The insulin content per islet cell from diabetic rats was also significantly reduced (75%) (P less than 0.01) as compared to controls. At a low glucose concentration (2.8 mM) the insulin release from islets of diabetic rats was 60% (P less than 0.05) of that the controls. At a glucose concentration of 16.5 mM it was stimulated 5-fold from the islets of NIDD rats and 7-fold from the islets of control rats. (Pro)insulin biosynthesis, assessed in the same islets by measuring the incorporation of [3H]phenylalanine into immunoprecipitable material, was significantly higher (50%) (P less than 0.01) in islets from NIDD rats when measured at 2.8 mM glucose. Although (pro)insulin biosynthesis in these islets was significantly stimulated by 16.5 mM glucose (5-fold), it was less (P less than 0.05) than in the control islet (9-fold). To determine whether the derangements described above in the islets of the rats with NIDD could be modified by changing the environmental conditions of the B cells, corresponding experiments were performed after a 5-day culture of the islets at 5.5 mM glucose or at 11 mM glucose. The insulin release and the (pro)insulin biosynthesis, either measured in basal or stimulated states, were then found to be similar in the islets of diabetic and control islets after the 5.5 mM glucose culture period. By contrast, after the 11 mM glucose culture period the insulin release and the proinsulin biosynthesis in the islets of diabetic rats were found significantly less stimulated by 16.5 mM glucose than in the control islets. This suggests that islets of rats with NIDD, once removed from the chronic in vivo exposure to diabetic metabolic disorders, can behave as isolated islets of normal rats, at least as far as insulin handling is concerned.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Decreased glucose-induced insulin release and biosynthesis by islets of rats with non-insulin-dependent diabetes: effect of tissue culture. 389 13

Recent epidemiologic studies of the determinants and natural history of IDDM using HLA typing and detecting islet cell antibodies have shown that HLA-identical siblings of probands with IDDM are at extremely high risk of developing IDDM, and that islet cell antibodies and glucose intolerance usually appear long before clinical manifestations. Thus, the disease often has a long latent period. The epidemiologic characteristics of the disease, in particular relating to variation in age of onset and seasonal variation, must now be reinterpreted in the light of these observations. It appears that the variation in seasonal onset and the age distribution probably reflect the effects of factors that precipitate clinical manifestations of the disease rather than those that are directly responsible for initiating pancreatic beta-cell destruction. The ability to identify individuals at high risk of developing IDDM now allows investigations designed to identify factors responsible for initiating pancreatic beta-cell destruction, and many ultimately result in the application of preventive measures for the disease.
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PMID:Changing concepts of the epidemiology of insulin-dependent diabetes. 390 26

In a study of prevention of spontaneous diabetes in BB rats by therapeutic doses of cyclosporine (10 mg/kg/day), the male control non-diabetes-prone rats showed glucose intolerance after a 0.25 g/kg glucose load by gavage, at 90 and 130 days of treatment. Non-BB male Wistar rats treated similarly showed glucose intolerance at 1 wk of treatment, with progressive worsening for 5 wk, then sustained up to 12 wk of treatment. Fasting euglycemia was maintained, but both pre- and postchallenge plasma insulin levels were significantly lower with cyclosporine at several time points. Total pancreatic insulin was decreased to one-third that of control after 5 wk. After withdrawal of cyclosporine, glucose tolerance returned to normal in 2 wk. Sprague-Dawley rats responded similarly and in both strains, an increase in the cyclosporine dose to 15 mg/kg/day augmented the glucose intolerance. These results demonstrate that therapeutic doses of this agent induce reversible glucose intolerance due, in part, to inhibition of insulin secretion and also possibly inhibition of synthesis, though a peripheral effect is not excluded. This hyperglycemic effect of cyclosporine has implications for its potential use in type I diabetes mellitus, transplantation, and other autoimmune disease.
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PMID:Effects of cyclosporine on glucose tolerance in the rat. 390 64

Since mumps virus seems to be one of the most likely candidates in viral etiology of insulin-dependent diabetes (IDDM) we studied the possible relationship of glucose tolerance (75 g oGTT), beta cell function, diabetes associated HLA antigens, haptoglobin phenotype, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) in 125 subjects with antecedent mumps infection. Impaired glucose tolerance (IGT) was diagnosed in 3.2% (n = 4) but onset of diabetes did not appear within 14 months after mumps infection. There was no relationship between glucose tolerance and complications of antecedent mumps infection (e.g. pancreatitis, meningitis, orchitis). The prevalence rate of ICA was 76%. ICSA were detectable in about 36% of children and 62% of the adults tested (p less than 0.01). There was no relationship between ICA/ICSA and diabetes-associated HLA antigens, haptoglobin phenotype or beta cell function (fasting C-peptide and insulin response to 75 g oGTT). However, adults with circulating ICA were characterized by a significantly lower insulin response to glucose. Fifty two "risk" subjects characterized by IGT, diabetes associated HLA antigen(s), ICA or ICSA either alone or combined were studied again 26 months after mumps infection. No symptomatic diabetes appeared and IGT was diagnosed in one case only. ICA and ICSA persisted in more than 50% of subjects in whom ICA or ICSA were present 14 months after mumps infection. Since the used immunological techniques do not clearly distinguish organ-specific from non-organ-specific antibodies the results must be interpreted with caution. To summarize, the preliminary results do not support a close temporal relationship between mumps infection and the onset of IDDM. The pathogenetic role of mumps virus and ICA/ICSA and their possible relation to a slow progressive beta cell destruction has still to be determined.
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PMID:Metabolic, hormonal, and immunological alterations in subjects with antecedent mumps infection. 391 1

There are residual ambiguities between the two main current glycaemic definitions of the categories of DM, IGT and normal GT which should be resolved. IGT is clearly a highly heterogeneous category and could with advantage be resolved into its identifiable subsets though adequate data for this is not yet available. The concept of insulin dependency requires clearer definition for operational purposes. Biochemical parameters (e.g. C-peptide responses) may help. Attempts to combine clinical manifestations and pathogenic mechanisms in a single classification (e.g. IDDM/NIDD versus Type I/Type II) should be handled with care. If the term Type I is to be retained, it should be applied to a defined pathogenic process, not to a clinical type of DM. The term Type II is inadequately defined at present. IDDM and NIDDM, clinical descriptive terms, may be provoked by a variety of pathogenic mechanisms (i.e. they are 'heterogeneous'). They could be subclassified by mechanism (when known). More visibility should be given in classification to non-Europid forms of DM (e.g. 'Tropical or 'Nutritional' DM). A staging dimension should be recognised in classifications of DM. Future classifications will benefit from the incorporation of the presence or absence of susceptibility/resistance factors to diabetes itself or to its severe long term sequelae. There remain uncertainties about the definitions and clinical implications of gestational DM (and gestational IGT) not discussed above. It should be accepted that different user groups may need different subclassification of diabetes and glucose intolerance to meet their specific requirements and so long as this is made clear and definitions are adequate this should not be a problem. However, for the present, all groups should accept the proposed glycaemic definitions of DM or IGT for the purposes of comparability.
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PMID:Limitations and problems of diabetes classification from an epidemiological point of view. 403 18

The insulin response to a glucose load has been investigated in twenty-five patients with small-vessel disease (ischaemic lesions of toes or feet in the presence of foot pulses). The clinical presentation was similar to that of juvenile diabetic microangiopathy, but in small-vessel disease there was no glucose intolerance. Unexpectedly in the patients with small-vessel disease there was no striking insulin secretion response to the stimulus of a glucose load. Controls increased their circulating insulin levels on average sixfold over fasting levels after 50 g. oral glucose: all the small-vessel-disease patients had increases of less than three times their fasting levels, and nine of them had completely flat curves throughout the test. Tolbutamide also did not stimulate insulin secretion. The refractory state of these patients' responses to the normal stimulus of insulin output has similarities to the picture in juvenile diabetes mellitus and may be important in the aetiology of the small-vessel lesions.
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PMID:Abnormal insulin response in patients with small-vessel disease. 414 92

To study the role of somatostatin in the pathophysiology of glucose intolerance in man, plasma somatostatin-like immunoreactivity (SLI) was measured in 8 normal subjects, 6 patients with insulin dependent diabetes mellitus (IDDM), 13 with non-insulin dependent diabetes mellitus (NIDDM), and 9 with hyperthyroidism, by extraction of plasma SLI and radioimmunoassay. The extraction method gave a recovery rate for synthetic somatostatin-14 and somatostatin-28 of 72 +/- 6 and 55 +/- 7%, respectively. No SLI corresponding to somatostatin-28 in human peripheral blood was observed. Incubation of somatostatin-28 in plasma gave a rapid decrease of immunoreactivity, and no conversion to somatostatin-14 was observed. It is speculated that SLI extracted with acid-acetone mainly represents a molecular weight similar to somatostatin-14. After oral administration of glucose (75 g), a clear and sustained rise in plasma SLI was seen in normal subjects from an initial value (+/- SEM) of 29.9 +/- 5.4 pg/ml to a peak value, at 60 min of 93.4 +/- 15.5 pg/ml. The increase of plasma SLI after 75 g glucose was also observed in IDDM and NIDDM. The peak level of SLI was significantly less than that for normal subjects. The extraction of plasma SLI with acetic acid and acetone gave reproducible results and showed a fluctuation of SLI with glucose concentration.
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PMID:Response of plasma somatostatin-like immunoreactivity (SLI) to a 75 g oral glucose tolerance test in normal subjects and patients with impaired glucose tolerance. 614 Aug 6

Genetic, immunological and viral factors have been implicated in pathogenesis of Type 1 diabetes mellitus. The development of Type 1 diabetes in two siblings of patients with Type 1 diabetes studied as part of a large epidemiological study, is described. One case, a 13-year-old male not sharing either HLA haplotype with his diabetic sister, had virtually normal glucose tolerance 80 days before symptomatic presentation. He showed serological evidence of infection by Coxsackie CB4 (at diagnosis) and influenza A virus (soon after diagnosis). The other case, a 15-year-old male, had impaired glucose tolerance for over 500 days (i.e., since the diagnosis of diabetes in his HLA-identical brother) before symptomatic presentation which was not associated with serological evidence of acute viral infection. The former case was negative for islet cell antibody (cytoplasmic) when first seen though positive at diagnosis, while the latter was positive throughout. These two cases suggest contrasting interactions of the main pathogenetic factors associated with Type 1 diabetes.
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PMID:The development of Type 1 (insulin-dependent) diabetes mellitus: two contrasting presentations. 631 59

The BB rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) or an insulin-dependent diabetic (IDDM) syndrome. Passive transfer of insulitis from newly detected diabetic BB rats to nude mice has been achieved by intraperitoneal or intravenous injection(s) of blood and spleen lymphocytes. After a single injection of cells, 37% of the mice (n = 72) showed insulitis with a mean intensity of 1.9 +/- 0.3 (on a scale of 0 to 3). After three successive injections, 58% of the recipient mice (n = 12) showed insulitis with a mean intensity of 2.5 +/- 0.3. Only one of the control mice (n = 45) demonstrated mild insulitis. The small number of affected islets (13% after a single injection, 17% after three injections) probably explains the absence of random or post IP glucose hyperglycemia in the recipient mice. During this study the yield of lymphocytes in diabetic BB rats was found to be consistently lower than in control normal Wistar rats. This lymphopenia was found not only in the blood and the spleen but also in the thymus and the lymph nodes. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis alone or with IGT or IDDM were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed a marked decrease in the proportions of T+ lymphocytes in all tissues whereas the proportion of B(Ia+) lymphocytes was normal in blood, spleen, and thymus but increased in lymph nodes. However, in absolute terms both T+ and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues, except in the thymus was the one that includes helper T lymphocytes. This lymphopenia could be related to the presence of circulating antilymphocyte antibodies. These results strongly support a role for altered immunity in the etiology of the syndrome. If the observed anomalies of lymphocyte numbers and subsets are responsible, then a novel mechanism different from most other "autoimmune" disorders must be implicated.
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PMID:Passive transfer of insulitis and lymphopenia in the BB rat. 634 96


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