Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We prospectively followed 29 children and adolescents over a 1- to 8-year period who were referred for evaluation of hyperglycemia (in the absence of diabetes) or glycosuria found on routine screening or during acute illness. On initial examination, four subjects had islet cell autoantibodies, 4 of 22 had an abnormal intravenous glucose tolerance test result, 6 of 22 had low first-phase insulin release on intravenous glucose tolerance testing, and 10 of 20 had impaired glucose tolerance on oral glucose tolerance testing. On follow-up, insulin-dependent diabetes had developed in two of the four subjects with islet cell autoantibodies. The other two subjects with islet cell antibodies have had persistently abnormal glucose tolerance on both oral and intravenous glucose tolerance testing and have low first-phase insulin responses. Diabetes has developed in none of 25 subjects without islet cell antibodies, although two have persistently abnormal glucose tolerance or insulinopenia. All five subjects with islet cell antibodies or human leukocyte antigen DR3/DR4 with initial impaired glucose tolerance have either acquired diabetes or have abnormal glucose tolerance. In contrast, only one of five subjects with initial impaired glucose tolerance but lacking these markers has persistent glucose intolerance. We conclude that in the absence of islet cell antibodies or human leukocyte antigen DR3/DR4 heterozygosity, incidental hyperglycemia or glycosuria is unlikely to be associated with progression or diabetes.
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PMID:Natural history of incidental hyperglycemia and glycosuria of childhood. 268 35

The multiplex insulin-dependent diabetes mellitus (IDDM) families have been examined for linkage with the human leukocyte antigen (HLA), Gm, Km, and insulin loci. For the last three, no evidence of linkage (as measured by haplotype sharing in affected siblings) was found. For HLA, strong evidence of linkage was demonstrated, as expected from previous studies of both haplotype sharing and HLA association. The haplotype sharing in affected siblings from this and previous studies would explain a relative risk of about 3.7 in the sibling of an affected individual (95% confidence limits 2.8 to 5.4), considerably less than the values of 10-15 given by epidemiological studies. This discrepancy may be explained by other predisposing genes unlinked to HLA, or be due to common environmental factors. Analysis conditional on the affection status of all individuals, and on the parental HLA haplotypes clearly rejects both a dominant and recessive mode of inheritance in favor of a two-allele model with a reduced risk for heterozygotes, and provides some support for a three-allele model. Some evidence of age effects was found; in particular there was some suggestion of greater haplotype sharing in siblings both affected at a young age, and there was some suggestion that individuals with the predisposing HLA-DR3/DR4, DR3/DRx, and DR4/DRx genotypes were affected at a younger age. These results may be diagnostic artifacts, however, and need investigation in future studies.
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PMID:Linkage analysis and genetic models for IDDM. 273 21

Although triple-drug immunosuppression with cyclosporine, prednisone, and azathioprine has reduced the incidence of acute graft rejection after cardiac transplant, its effect on the development of coronary artery disease is unknown. We have followed up 74 cardiac transplant recipients with yearly coronary angiograms. The probability of acute rejection was 10.8% at 1 year. The incidence of coronary artery disease was 8% at 1 year (six of 74 patients) and 24% at 2 years (11 of 30 patients). In patients who developed posttransplant coronary artery disease, there was a slightly higher, but not statistically significant, incidence of acute graft rejection and pretransplant idiopathic cardiomyopathy. No correlation was found between the incidence of coronary artery disease and recipient age, human leukocyte antigen (HLA) type, hypertension, diabetes, cholesterol level, triglyceride levels, weight gain after transplant, and smoking. These data indicate that triple-drug immunosuppression, despite having produced a significant reduction in the episodes of acute graft rejection, has not decreased the incidence of posttransplant coronary artery disease. Common risk factors for coronary disease and HLA mismatch are probably not important in the pathogenesis of coronary atherosclerosis after cardiac transplantation, whereas the risk for coronary artery disease may be increased by acute graft rejection and pretransplant idiopathic cardiomyopathy.
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PMID:Coronary artery disease in cardiac transplant patients receiving triple-drug immunosuppressive therapy. 280 89

Endocrine epithelial cells do not normally express human leukocyte antigen (HLA) class II molecules, but do so in a variety of autoimmune diseases. This finding suggests the hypothesis that such inappropriate class II-positive expression may enable these cells to present autoantigens and thus contribute to autoimmune pathogenesis. Indeed, class II-positive thyrocytes can present both exogenous antigenic peptides and intrinsic autoantigens to the appropriate T cells. Class II expression by thyrocytes can be induced by interferon-gamma, and is positively and negatively regulated by thyroid-stimulating hormone and epidermal growth factor, respectively. Furthermore, heterogeneity of thyrocyte class II subregion expression appears to be related to the nature of the inducing stimulus. The complexity of regulatory signals is underlined by findings in type I diabetes: islet beta cells aberrantly express class II in this disease, but class II cannot be induced in normal beta cells by interferon-gamma.
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PMID:New ideas in thyroid autoimmunity. 329 60

'Secondary failure' of oral hypoglycemics, in non-insulin dependent diabetics, has been attributed to dietary non-compliance, inadequate drug dosage, metabolic stress, or true drug failure. Progressive loss of beta cell function is a suggested mechanism for true drug failure but on the basis of little documented evidence. In view of this, we have measured basal and glucagon-stimulated C-peptide levels, human leukocyte antigen (HLA) types, and islet cell antibodies in 20 non-insulin dependent diabetics with 'secondary failure' of oral agents. There were 16 females and four males with a mean ideal body weight of 1.30 units and mean duration of diabetes of 9.5 years. Fasting insulin (mean +/- SD: 15.1 +/- 10.6 mU/l) and fasting C-peptide (2.3 +/- 1.2 micrograms/l) were normal or slightly elevated in all but one patient. Mean C-peptide increased from 2.3 +/- 1.2 micrograms/l to 3.5 +/- 2.2 micrograms/l (152% over basal) 6 minutes after 1 mg i.v. glucagon. In 15 patients the C-peptide response was greater than 130% of basal. Islet cell cytoplasmic antibodies were detected in only two patients. The distribution of HLA types was not significantly different from a control population, with no increase in DR3 or DR4. Thus, absolute insulin deficiency is uncommon in non-insulin dependent diabetics with 'secondary failure' of oral hypoglycemic agents and such patients do not exhibit the immuno-genetic markers of insulin-dependent diabetes.
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PMID:Insulin secretion and immuno-genetic markers in diabetics with 'secondary failure' of oral hypoglycemic agents. 389 15

The University of Minnesota has the largest experience with pancreas transplantation of any institution, with 130 cases since 1966, including 116 in 98 patients between July 1978 and June 1985. Currently, 30 patients are insulin-independent, 19 for greater than one year, the longest for seven years. One-year patient and graft survival rates overall are 87% and 30%, respectively. Of 98 recipients, 49 had had previous kidney transplants, while 49 had not, and currently most of the pancreas recipients do not have uremia and have not had a kidney transplant but have early complications of diabetes. A total of 44 of the grafts were procured from related and 72 from cadaver donors. Although 32 of the 116 grafts (28%) failed for technical reasons, the most common cause of graft failure has been rejection. Various immunosuppressive regimens have been used in attempts to reduce the rejection rate, and one combination, low-dose cyclosporine-azathioprine-prednisone (triple therapy), has been particularly effective, with a one-year functional survival rate of 73% in recipients of technically successful grafts from human leukocyte antigen-mismatched cadaver or related donors (N = 20). The pancreas graft survival rates have improved gradually (43% for 1984 to 1985, N = 30; versus 27% for 1978 to 1983, N = 86) for transplants from both related and cadaver donors. Metabolic studies from most recipients with functioning grafts (insulin-independent) show normal or nearly normal results. Preliminary observations on secondary complications suggest a more favorable course in recipients whose grafts have functioned long term than in those whose grafts failed early.
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PMID:One institution's experience with pancreas transplantation. 391 96

Diabetes mellitus not infrequently coexists with hypo- and hyperthyroidism. Hyperthyroidism aggravates glucose intolerance. A review of this phenomenon reveals multiple mechanisms, which include increased hexose intestinal absorption, decreased responsiveness to insulin, and increased glucose production. Conflicting results are obtained when circulating insulin level is measured in thyrotoxicosis. The role of glucagon and alpha-cell sensitivity is unclear. Diabetes mellitus influences the assessment of thyrotoxicosis by falsely decreasing the blood levels of thyroxine (T4) and triiodothyronine (T3) during severely uncontrolled hyperglycemia. Hypothyroidism is found in about 3% of patients with insulin-dependent diabetes mellitus (IDDM). Moreover, 13-20% of IDDM patients have elevated blood thyrotropin levels and anti-thyroid antibodies. Hypothyroidism per se seems to ameliorate hyperglycemia. A subtype of IDDM shares similar immunogenetic features with familial autoimmune thyroiditis. Studies of IDDM probands who show a high prevalence of circulating thyroid antibodies reveal the presence of such antibodies in their first-degree relatives. Circulating islet-cell antibodies, detected in a majority of IDDM patients at the onset of their disease, tend to persist only in those patients with coexistent polyendocrine autoimmune disease, including thyroiditis. Similar human leukocyte antigen (HLA) locus types are associated with thyroiditis and IDDM, namely HLA-Dr3 and -Dr4.
Diabetes Care
PMID:Diabetes mellitus and thyroid disease. 640 Jul 13

A teenage boy with both secretory component deficiency and selective serum immunoglobulin A deficiency also developed pernicious anemia, insulin-dependent diabetes mellitus, pancreatic insufficiency, lymphopenia, intestinal candidiasis, and anti-intestinal antibody. The patient's father had pernicious anemia and diabetes mellitus while the paternal grandfather also had pernicious anemia. Because the patient had inherited the paternal grandmother's human leukocyte antigen complex, there was no direct association between pernicious anemia and the genetic markers. The presence of multiple immunologic abnormalities in a single patient supports the concept of an underlying defect in immune regulation as a central factor in the pathogenesis of these disorders.
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PMID:Secretory component and serum immunoglobulin A deficiencies with intestinal autoantibody formation and autoimmune disease: a family study. 676 5

Antipancreas autoimmunity is one of several immunity problems in diabetes. Such of its features as are revealed by inhibition of leukocyte migration, lymphocyte transformation in response to insulin antigens, relation between cell autoimmunity and later complications, and the behaviour of peripheral T and B lymphocyte membrane markers are explained. The aetiological role of viral infections is discussed, and the pathogenetic hypothesis deducible from the histological findings. Lastly, the modalities underlying a combination between the HLA (human leukocyte antigen) system and diabetes are considered.
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PMID:[Diabetes and autoimmune diseases. II]. 704 54

In 5 patients (2 women and 3 men, aged 16-36 years), diabetic ketoacidosis developed without precipitating illness. Pancreatic islet cell antibody was negative, and the duration of insulin dependency was shorter than 4 weeks. Hemoglobin A1c was < or = 6.3% for the mean period of 2.8 years thereafter, with diet therapy alone in 4 and with 5 mg glyburide in 1. Four were overweight before the development of diabetes, and 3 of them positive for family history of adult-onset, non-ketotic diabetes. Frequency of human leukocyte antigen B61 was increased significantly in the patients. In a patient not previously overweight, family history of diabetes was negative, and human leukocyte antigen haplotypes common in insulin-dependent diabetes mellitus were accumulated. Serum immunoreactive insulin was within normal range or supranormal with normal glucose tolerance after recovery. The patients closely resemble black Americans with ketoacidosis-onset non-insulin dependent diabetes.
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PMID:Ketoacidosis-onset noninsulin dependent diabetes in Japanese subjects. 748 23


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