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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.
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PMID:Diabetes secondary to genetic disorders. 144 74

The goal of the Fourth International Workshop for Standardization of ICA Measurements was to determine the specificity of ICA assays and their ability to distinguish between control sera (n = 57) and sera from IDDM-related individuals--representing relatives of IDDM patients (n = 21), healthy individuals who later developed IDDM (n = 8), or newly diagnosed IDDM patients (n = 23). Results from 28 laboratories were analyzed. The mean specificity (percentage of control sera reported as negative) among 27 laboratories was 91%, including 6 laboratories with 100% specificity. Nevertheless, 78% of laboratories found at least one control sample > 0 JDF U. Among samples from first-degree relatives, the mean concordance was 86%, including three sera found negative (0 JDF U) by all laboratories. Among individuals who later developed diabetes, the mean concordance was 93%, with two sera found positive by 100% of laboratories. In sera from newly diagnosed IDDM patients, the mean concordance was 82%. Three sera were found positive and one serum negative by all laboratories. The JDF U of the sera considered to be positive were significantly greater than each laboratory's average for the controls. In conclusion, the results from laboratories participating in the Fourth International ICA Workshop demonstrated excellent specificity, good concordance, and an ability to separate control sera from defined, IDDM-related subjects.
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PMID:Improved specificity of ICA assays in the Fourth International Immunology of Diabetes Serum Exchange Workshop. 144 98

IDDM patients who maintain strict glycemic control have impaired counterregulatory hormone and symptomatic responses to hypoglycemia. To test the hypothesis that intermittent exposure to hypoglycemia plays an etiological role in these defective responses, we produced 4 consecutive daily episodes of hypoglycemia in 10 healthy, nondiabetic volunteers by using the insulin clamp technique. Fasting (5.3 +/- 0.1 vs. 5.4 +/- 0.1 mM) and nadir (2.3 +/- 0.1 vs. 2.4 +/- 0.1 mM) glucose levels achieved during insulin infusion did not differ on study days 1 and 4. In contrast, the glucose levels required to stimulate an increase in EPI (2.8 vs. 3.1 mM), glucagon (2.8 vs. 3.2 mM), cortisol (2.4 vs. 2.9 mM), GH (2.6 vs. 3.0 mM), and autonomic hypoglycemic symptoms (2.2 vs. 2.5 mM) were all significantly lower on study day 4 versus study day 1 (P < 0.005-0.05). Basal levels of EPI and cortisol, but not glucagon, GH, or NE also were reduced on the final study day. We conclude that intermittent hypoglycemia can result in attenuation of the hormonal and symptomatic responses to insulin-induced hypoglycemia and may contribute to the defective counterregulatory responses in patients with well-controlled IDDM.
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PMID:Intermittent hypoglycemia impairs glucose counterregulation. 144 1

Since their demonstration in 1975, ICSAs have been proposed as serological markers and pathogenic elements in IDDM. ICSAs are detected in the sera of most newly diagnosed IDDM patients by indirect IFL that uses viable preparations of rat islet or insulinoma cells as substrate, but they also can be detected by using human insulinoma or fetal islet cells. We have tried to demonstrate ICSAs in the sera of 31 newly diagnosed diabetic patients, including 6 positive samples on human fetal islet cells, which used their natural target for the first time: normal human islet cells. In spite of using different types of preparations of these cells (i.e., freshly dispersed cell suspensions, monolayer cultures, or dispersed islets after culture), ICSAs could not be detected by IFL under the UV microscope, nor by flow cytometry. In contrast, 9 of 29 of the sera gave a positive staining on the RIN rat insulinoma cells. In an attempt to establish whether the putative ICSA autoantigen is present in the surface of human islet cells in the diabetic pancreas, the insulitis microenvironment was emulated by exposing the islets to three types of stress: 1) cytokines (IFN-gamma and TNF-alpha); 2) heat shock; and 3) hyperglycemia. However, diabetic sera failed again to recognize membrane antigens on the islet cells after either of these treatments. Neither were islet cells from a newly diagnosed diabetic patient stained by its autologous serum (ICA titer > 80 JDF U). These results suggest that ICSA autoantigen is not expressed in the membrane of human islet cells and therefore raises doubts about their proposed pathogenic role.
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PMID:Reevaluation of autoantibodies to islet cell membrane in IDDM. Failure to detect islet cell surface antibodies using human islet cells as substrate. 144 4

Single attempt kidney biopsy was successful in 60 cases of diabetes mellitus out of 83. Histopathological evidence of nephropathy was found in 30 (50%) out of 60 (4 of IDDM and 56 of NIDDM). Microproteinuria was a sensitive indicator of histopathological evidence of nephropathy (by biopsy) and should be used as a non invasive method of evidence of kidney involvement in diabetes mellitus regardless of duration of the disease. Routine renal function tests--commonly used indicators of kidney disease in the presence of hypertension were of no value and should not be relied upon. Duration of diabetes mellitus was important correlation with the evidence of the disease and and its severity but nephropathy was found in newly detected cases of diabetes mellitus (NIDDM). Nephropathy was present in case of DM who had retinopathy and is a better factor of correlation.
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PMID:Correlation of microproteinuria and histopathological changes in kidney in diabetes mellitus. 145 34

Major determinants of susceptibility to Type 1 (insulin-dependent) diabetes (IDDM) have been mapped to the HLA complex, near to or identical with genes encoding class II molecules. The association of IDDM with HLA-DR3 and/or DR4 antigens and the highest risk for DR3/4 heterozygotes suggest a synergistic effect of the two haplotypes. The characterization at the molecular level of the class II region has provided evidence that DQ rather than DR determinants may primarily influence the disease. In caucasians the susceptibility strongly correlates with the absence of aspartic acid at position 57 on the DQ beta chain and/or the presence of arginine at position 52 on the DQ alpha chain. The formation of a putative DQ susceptibility molecule (DQ alpha Arg52+, DQ beta Asp57-) accounts best for the disease associations when trans-complementation between alpha and beta chains encoded by different haplotypes is postulated to explain the excess of heterozygotes. Observations in other populations and in animal models indicate, however, that other residues on DQ alpha and beta chains, other class II (DR beta) molecules and non-HLA linked genes also contribute to the susceptibility. The mechanism(s) by which susceptibility determinants influence IDDM is not known. It is probably in relation with the role of class II molecules in the antigen presentation to T lymphocytes.
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PMID:[The role of the HLA system in the genetics of Type I diabetes mellitus]. 145 12

A major goal of research into IDDM has been the identification of the 'causative antigen'. As described in this article by Len Harrison, this reductionist aim is confounded by the fact that numerous candidate islet cell antigens have been described. He scrutinizes the credentials of these candidates and discusses the problem of using autoantibodies to identify causative antigens in a T-cell-mediated disease.
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PMID:Islet cell antigens in insulin-dependent diabetes: Pandora's box revisited. 850 37

OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.
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PMID:Renal hemodynamics and albumin excretion rate in patients with diabetes secondary to acquired pancreatic disease. 146 90

The prevalence of nonadherence in IDDM and NIDDM populations and conceptual and methodological issues relevant to measuring diabetes regimen adherence are reviewed. The prevalence of nonadherence varies across the different components of the diabetes regimen, during the course of the disease, and across the patient's life span. Although prevalence rates might be expected to differ between IDDM and NIDDM populations, this rarely has been evaluated. Conceptual problems in defining and measuring adherence include: the absence of explicit adherence standards against which the patient's behavior can be compared; inadvertent noncompliance attributable to patient-provider miscommunication and patient knowledge/skill deficits; the behavioral complexity of the diabetes regimen; and the confounding of compliance with diabetes control. Methods for measuring adherence include: health status indicators, provider ratings, behavioral observations, permanent products, and patient self-reports, including behavior ratings, diaries, and 24-h recall interviews. A measurement method should be selected on the basis of reliability, validity, nonreactivity, sensitivity to the complexity of diabetes regimen behaviors, and measurement independence from the patient's health status. The timing of measurements should be based on the stability of adherence behaviors and temporal congruity with other measures of interest (e.g., indexes of metabolic control). Directions for future research and suggestions for clinical practice are provided.
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PMID:Methodological issues in diabetes research. Measuring adherence. 146 98

In this study, 52 nonproteinuric Japanese patients with non-insulin-dependent diabetes (NIDDM) were followed from 1985 to 1990 to investigate the rate of development and progression of microalbuminuria and the factors which influence it. In 1985, 34 patients were normoalbuminuric, and 18 patients were microalbuminuric. Five years later, 11 of 34 initially normoalbuminuric patients (32.4%) developed microalbuminuria, and 6 of 18 initially microalbuminuric patients (33.3%) developed overt proteinuria. At the beginning of the study, hypertension existed more frequently in the patients who later developed microalbuminuria (8 of 11, 72.7%) than in the patients who stayed normoalbuminuric (4 of 23, 17.4%). Age-adjusted values of mean blood pressure (+/- SEM) at the beginning of the study in the patients who developed microalbuminuria (98.2 +/- 3.4 mm Hg, n = 11) were significantly higher than those in the patients who stayed normoalbuminuric (87.3 +/- 2.4 mm Hg, n = 23). In six patients who developed overt proteinuria, initial urinary albumin excretion rates (AER) were higher than those in the patients who stayed microalbuminuric, and four patients who presented with initial AER greater than 100 micrograms/min all developed overt proteinuria. These results indicate that, in Japanese patients with NIDDM, the rate of development of microalbuminuria is faster than that reported in Caucasian IDDM, and preexisting hypertension with relatively poor control of blood pressure may be a risk factor for the development of microalbuminuria.
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PMID:High blood pressure is a risk factor for the development of microalbuminuria in Japanese subjects with non-insulin-dependent diabetes mellitus. 147 44


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