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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 results from destruction of pancreatic beta cells. Viruses and autoimmunity have been implicated as possible causes of beta cell destruction in genetically predisposed individuals. The evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as triggers in the pathogenesis of diabetes in some cases. In animal models, at least 4 different possible mechanisms for virus-induced diabetes have been proposed. The first mechanism is direct cytolytic infection of pancreatic beta cells. One group of viruses, including encephalomyocarditis virus, Mengovirus 2T, and Coxsackie B viruses, can directly infect and destroy pancreatic beta cells independent of autoimmune processes. The second mechanism is triggering of autoimmune responses. In contrast to the encephalomyocarditis virus-induced diabetes, reovirus type 1 and rubella virus seem to be somehow associated with autoimmunity in the genesis of a diabetes-like syndrome in a certain strain of suckling mice and hamsters, respectively. The third mechanism is cumulative environmental insults. The cumulative environmental insults with viruses and beta cell toxic chemicals can result in diabetes in genetically predisposed non-human primates and certain inbred strains of mice. The fourth mechanism is persistent infection. A certain virus, such as lymphocytic choriomeningitis virus, persistently infects murine pancreatic beta cells and produces hyperglycemia. The evidence that viruses cause diabetes in humans is more circumstantial.(ABSTRACT TRUNCATED AT 250 WORDS)
Clin Invest Med 1987 Sep
PMID:Possible mechanisms in the pathogenesis of virus-induced diabetes mellitus. 282 13

To evaluate the role of Coxsackie B viruses in the pathogenesis of insulin-dependent (juvenile-onset, type 1) diabetes mellitus (IDDM), attempts were made to correlate virus-specific IgM responses with HLA genes, autoimmune responses, and C-peptide secretion. HLA DR3, DR4, or both were present in 73 of 90 (81%) diabetic patients; 22 of 23 (96%) with Coxsackie-B-virus-specific IgM had at least one of these HLA types, compared with 51 of 67 (76%) without virus-specific IgM. There was no correlation between HLA A, B, or C types or immunoglobulin allotypes and virus-specific IgM responses. 16 of 22 (64%) patients with Coxsackie-B-virus-specific IgM compared with 26 of 72 (36%) without had complement-fixing islet-cell antibodies; no relation was found between virus-specific IgM and antibodies against thyroid or adrenal tissue or parietal cells. C-peptide secretion was significantly lower in patients with Coxsackie-B-virus-specific IgM.
Lancet 1985 Sep 21
PMID:Coxsackie-B-virus-specific IgM responses, complement-fixing islet-cell antibodies, HLA DR antigens, and C-peptide secretion in insulin-dependent diabetes mellitus. 286 32

Human genomic DNA samples from Caucasoids, Chinese, and Koreans of known serological DR antigen specificity were studied for IDDM-associated variation in HLA-DR and -DQ RFLPs (restriction fragment length polymorphisms). Genotyping allowed for accurate assignment of HLA-DR types and in Caucasoids DRw6 as well as DR2 was unequivocally decreased in IDDM. Further, the universality of certain DR2-associated DQ beta subtypes in protection against IDDM was established. HLA-DR3 was found to be increased in IDDM irrespective of whether carried on the B8. DR3 or B18. DR3 haplotype in Caucasoids or on the Bw58. DR3 haplotype in Chinese. These haplotypes have different DR alpha and DX alpha arrangements, so the region of susceptibility is confined to DQ alpha, DQ beta. For HLA-DR4, a 12kb/DQ beta/Bam HI fragment was increased in Caucasoid IDDM, but since this fragment is haplotype specific in Caucasoids and occurs in most healthy DR4- and w9-positive Asians, the 12 kb fragment may be a marker for a DR beta subtype of DR4 associated with IDDM in Caucasoids only. This study has shown the value of ethnic comparisons of HLA-associated diseases, where different linkage disequilibrium relationships have permitted identification of common susceptibility determinants and have provided evidence for some heterogeneity between Caucasoid and Asian populations, in the genetics of IDDM.
Dis Markers 1987 Sep
PMID:Insulin-dependent diabetes mellitus: HLA-DR and -DQ genotyping in three ethnic groups. 290 33

The prevalence of limited joint mobility (LJM) was studied in 110 insulin-dependent (IDDM) and 190 non-insulin-dependent (NIDDM) consecutive Ethiopian African diabetics and 300 age- and sex-matched controls at the Tikur Anbassa Teaching Hospital in Addis Ababa over a period of 18 months. Mean ages +/- S.D. of the IDDM, NIDDM, and controls were 35 +/- 9.9, 49.4 +/- 12.0, and 43.3 +/- 14.0 years, respectively. LJM was found in 44.5% of IDDM, 25.3% of NIDDM, and 6.7% of controls, being significantly commoner in IDDM than NIDDM (p less than 0.001) and in the diabetics than in controls (p less than 0.001). In IDDM those with LJM were significantly younger (p less than 0.05), had a higher prevalence of median fasting blood glucose (FBG) levels of 15 mmol/l and above (p less than 0.01), and retinopathy (p less than 0.05), but did not differ from those without LJM in duration of diabetes, or prevalence of neuropathy and nephropathy. In NIDDM those with LJM had a significantly longer duration of diabetes (p less than 0.005) and a higher prevalence of nephropathy (p less than 0.005), but did not differ from those without LJM in age at onset of diabetes, prevalence of neuropathy, and retinopathy or median FBG level.
Diabet Med 1985 Sep
PMID:Limited finger joint mobility in insulin-dependent and non-insulin-dependent Ethiopian diabetics. 295 Oct 96

Recent evidence indicates that immunoglobulin light chain variable region genes are genetic determinants for Graves' disease, which is caused by autoantibodies which stimulate the thyroid gland. We have tested whether germline immunoglobulin kappa light chain variable region (V kappa) genes contribute to the genetic predisposition for IDDM. Status for the kappa light chain constant region (C kappa) allotype, Km(1), was determined in members of suitable multiplex IDDM families. Such families had two or more siblings with IDDM, together with one parent negative for Km(1) and the other heterozygous, so that each sibling had a 50% chance of receiving the kappa light chain marker. Twenty-one families of this type were found. Of the siblings, disregarding disease status, 31 were concordant with the diabetic proband for Km(1) and 29 were discordant, this close approximation to equality confirming the validity of the methodology. Of the diabetic siblings of the probands, 14 were concordant and 15 discordant. Of the non-diabetic siblings, 17 were concordant and 14 discordant. This similarity shows that V kappa genes, which are closely linked to C kappa genes, are not genetic determinants for IDDM. The contrast with Graves' disease favours the possibility that the islet beta cell destruction of IDDM is mediated by forbidden clones of cytotoxic T cells, rather than of B cells.
Diabetes Res 1988 Sep
PMID:Genetic evidence favouring cytotoxic T cell forbidden clones as the cause of insulin-dependent diabetes mellitus. 297 6

Physical properties of food may account for differences in glycemic and other metabolic responses to food with similar amounts of carbohydrate, fat and protein. Blending of cooked beans made no difference to plasma glucose, insulin, or GIP (gastric inhibitory polypeptide) responses in nondiabetics, NIDD (noninsulin-dependent diabetics), and IDD (insulin-dependent diabetics). The cooked blended beans gave a greater plasma glucose response and a lesser hormonal response than a cooked flummery (containing cornstarch, protein and fat) in nondiabetics. In NIDD and IDD, however, the reverse applied for plasma glucose. In nondiabetics, cooked flummery gave a lesser glycemic response at some time points than uncooked flummery. In NIDD the opposite occurred. Cooking led to no significant change in insulin response in nondiabetics, but to a lesser insulin response in NIDD. The effect of some physical properties of food on diabetic control cannot be inferred from findings in nondiabetics.
Am J Clin Nutr 1985 Sep
PMID:Food physical factors have different metabolic effects in nondiabetics and diabetics. 299 52

Type 1 diabetes mellitus is thought to derive from organ-specific autoimmune reactions, probably triggered by environmental factors. In view of the possible involvement of mumps virus and reoviruses in the pathogenesis of autoimmune endocrine disease, serum antibody levels to these viruses were measured in newly-diagnosed diabetic patients aged 5 to 25 years and in matched control subjects. Diabetic patients showed a significantly lower prevalence and reduced titers of antibodies to mumps and reoviruses. By contrast, the antibody response to measles virus (a non-diabetogenic agent) was remarkably similar in the two groups. It is suggested that individuals with an impaired humoral response to some viral agents are at increased risk of developing diabetes when exposed to pancreotropic viruses.
Eur J Epidemiol 1985 Sep
PMID:Role of antecedent mumps and reovirus infections on the development of type 1 (insulin-dependent) diabetes. 302 16

The beta-adrenergic receptors were investigated in partially purified mononucleal leukocytes (MNL) plasma membranes from 18 patients with IDDM in pediatric period, 9 healthy children and 8 normal adults. The decreased beta-adrenergic receptor number was seen in patients with IDDM (Bmax = 27.6 +/- 8.3 fM (125I) IHYP/mg protein) compared with normal children (Bmax = 40.4 +/- 10.4 fM (125I) IHYP/mg protein) and normal adults (Bmax = 36.9 +/- 6 fM (125I) IHYP/mg protein). MNL beta-receptor binding affinities (apparent Kd = 109.8 +/- 26.1 pM in IDDM, 102.8 +/- 46.6 pM in normal children, 130.0 +/- 43.1 pM in normal adults) did not differ. We divided the patients with IDDM into two groups based on their level of blood glycosylated hemoglobin (HbA1) when samples were taken. Group A IDDM (consisted of 9 diabetic patients with below 10% of HbA1) had markedly decreased beta-receptor numbers compared with group B IDDM (consisted of 9 diabetic patients with more than 10% of HbA1), whereas Kd was not significantly different. Also, there was negative correlation between Bmax and level of blood sugar or HbA1 in IDDM. This is the first report concerning the beta-adrenergic receptor in IDDM in pediatric period. We suggest that decreased Bmax in group B is a homeostatic response to restore the poorly-controlled hyperglycemic state to normoglycemia because the group B patients had high level of HbA1 and blood sugar.
Horm Metab Res 1986 Sep
PMID:Adaptive regulation of beta-adrenergic receptors in children with insulin dependent diabetes mellitus. 302 24

The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.
J Clin Endocrinol Metab 1988 Sep
PMID:Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach. 304 44

This study tests the hypothesis that improved glycemic control decreases the postprandial plasma triglyceride (TG) response to ingestion of a saturated fat load. Fifteen normotriglyceridemic subjects with insulin-dependent diabetes mellitus (IDDM, group I) and six hypertriglyceridemic subjects with non-insulin-dependent diabetes mellitus (NIDDM, group II) were studied. Each subject was studied before and after 12 days of continuous subcutaneous insulin infusion (CSII). Each subject ingested identical meals on both study days. Plasma glucose was determined in all patients before and two hours after each meal and at 3 AM, and a mean value was calculated for each patient. CSII reduced mean plasma glucose from 252 to 140 mg/dL in group I, and from 209 to 120 mg/dL in group II (P less than .001 in both groups, paired t test). Plasma TG levels were measured before and 1.5, 3, 4.5, 6, and 7.5 hours after a breakfast which contained 50 g of mostly saturated fat. A repeated-measures ANOVA was performed to assess the effects of glycemic control (factor A) and TG response (factor B) to fat ingestion. In both groups plasma TG levels increased significantly after fat ingestion (P less than .001), and were significantly reduced during improved glycemic control (P less than .001). The reduction was observed in 14 of 15 patients in group I and in all patients in group II. In group I the lowering of the postprandial plasma TG levels after CSII was secondary to a decrease in the fasting plasma TG levels, as shown by the unchanged mean percent TG elevation over the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism 1988 Sep
PMID:Effect of improved glycemic control on the response of plasma triglycerides to ingestion of a saturated fat load in normotriglyceridemic and hypertriglyceridemic diabetic subjects. 304 21


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