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 is an autoimmune disease that may be becoming more prevalent. It has a polygenic mode of inheritance with a major gene being present in the HLA DQ locus on chromosome 6. Inferential data suggest that environmental factors may be important to genetic penetrance albeit we still lack proof for involvement of often maligned viruses. Patients with IDD and their families are predisposed to organ-specific autoimmunities which should be routinely screened for. Autoantibodies to insulin, to a beta cell cytoplasmic lipid containing moiety and to a beta cell protein of 64KDa, which is believed to be the GABA forming enzyme GAD, can be used to predict IDD among relatives and probably the general population as well. Immunosuppressive therapy can modify the course of IDD after diagnosis and should be able to delay the clinical onset if given before diagnosis. Rigorous insulin therapy should also be given as needed to control hyperglycemia and avoid glucose toxicity to the islets. Such trials are now underway.
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PMID:Immunology of diabetes mellitus. 832 19

One of the earliest histopathological signs of diabetic retinopathy is a selective loss of intramural pericytes from retinal capillaries. In the present study, the retinal vessels of rats with streptozotocin-induced diabetes (STZ Wistar) and rats with genetically-induced insulin dependent diabetes mellitus (BB Wistar) and non-insulin dependent diabetes mellitus (SHR/N-corpulent) were examined after 6 to 8 months duration for diabetes-related retinal microangiopathies. The SHR/N-corpulent (cp) rats were fed a 54% sucrose diet, whereas the STZ Wistar and BB Wistar rats were fed laboratory chow for 32 to 36 weeks. In all the diabetic rats, the retinal capillaries in enzyme-digested flat mounts exhibited an increase in periodic-acid-Schiff (PAS) staining and loss of pericytes compared to their respective euglycemic controls. Pericyte "ghosts", like those defined in human diabetes as intramural pockets lacking normal cell contents, were documented by high resolution micrographs in all the diabetic rats. Endothelial cell proliferation, capillary dilation, and varicose loop formation were noted in some of the diabetic rats. Hence, similar capillary lesions were found in very different groups of diabetic rats. The findings suggest that a chronic high tissue concentration of glucose is the underlying factor which triggers pathogenesis in the pericyte. Hyperglycemia-induced activation of endogenous aldose reductase of the polyol pathway is probably the initial insult, but other factors such as advanced glycosylation products may affect the final outcome.
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PMID:Degenerated intramural pericytes ('ghost cells') in the retinal capillaries of diabetic rats. 182 96

We screened 1,000 individuals for pre-type I diabetes mellitus: 927 were first degree relatives of patients treated at our institution, 31 other had related autoimmune diseases, 42 had fortuitously discovered slight hyperglycemia. Islet cell antibodies were present in 31 subjects, 13 adults and 18 children. Among these 18 children, 7 also had complement-fixing islet cell antibodies, and 5 anti-insulin antibodies. All but one initially had a normal insulin response to intravenous glucose. The child with the abolished response, as well as another whose insulin secretion fell down during the study period, became diabetic. Based on these preliminary data, we are developing large scale family screening of pre-type I diabetes.
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PMID:[Result of 3 years of screening for preclinical phase of juvenile insulin-dependent diabetes mellitus]. 208 43

Despite many advances in the overall treatment of type I diabetes mellitus during the last few years, no major advance has been made in decreasing the mortality rate of diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic coma. A major concern in both of these disease states is the development of cerebral edema during treatment. The guiding principles of therapy in both disease states are rehydration, electrolyte replacement, insulin therapy, and treatment of any underlying illnesses. If the patient is hypotensive, therapy begins with colloid or normal saline administration to support blood pressure. Fluid and electrolyte deficits should be calculated and replaced during 48 hours. Low-dose insulin therapy is employed for treatment of hyperglycemia. Neurologic function should be carefully monitored and mannitol administered if a change in neurologic function occurs.
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PMID:Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma. 210 50

The urinary excretion of kappa light chains, beta 2-microglobulin and albumin was examined in patients with newly diagnosed and long-standing insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus, and compared to age-matched control subjects. Patients with IDDM diagnosed within two months, presented with normal albumin excretion, whereas the concentrations of beta 2-microglobulin and kappa light chain in urine were higher than in control subjects. The initiation of insulin therapy reduced, but did not completely normalize, the elevated rate of kappa light chain excretion. Patients with IDDM of long duration showed increased urine excretion of kappa light chains and albumin. In keeping with the findings in IDDM, patients with newly diagnosed NIDDM (within one year) showed increased urinary excretion of kappa light chains compared with control subjects. There was, however, no further increase in light chain excretion with longer duration of NIDDM. To study the effect of short-term hyperglycemia on urinary protein excretion, 12 normal subjects participated in a three-step hyperglycemic clamp study, during which their plasma glucose concentration was raised by +50, +125 and +300 mg/dl. The urine excretion of albumin and beta 2-microglobulin rose progressively with each hyperglycemic clamp step, whereas that of kappa light chain excretion was unaffected by hyperglycemia. We conclude that increased urinary excretion of kappa light chain is a consistent finding in all types of diabetes mellitus, and can be observed even when the albumin excretion is normal. Since the serum concentration of kappa light chain is normal in diabetes, the increased urinary excretion of kappa light chains must be of renal origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary excretion of kappa light chains in patients with diabetes mellitus. 211 17

Human type I diabetes mellitus has been shown to be an autoimmune disease. The BioBreeding/Worcester (BB/W) rat is an excellent model of insulin dependent diabetes mellitus (IDDM). Using the spontaneous diabetic BB/W rats, autoimmune recurrence of diabetes mellitus was evaluated. To prevent allorejection of islets, a combination of ultraviolet B (UVB) donor islet pretreatment and brief peritransplant host immunosuppression with cyclosporine was utilized. Such combination led frequently to indefinite survival of MHC mismatched islets in the chronically diabetic BB/W recipients more than 15 days after onset of hyperglycemia, while MHC matched islets survived only briefly. The most likely reason for the relatively rapid loss of graft function of MHC matched islets is the autoimmune destruction by previously primed cells. The result of this study, together with the previous report of CHABOT et al that both MHC matched and MHC mismatched islets are destroyed in acutely diabetic BB/W rats (less than 15 days after onset) despite the use of UVB irradiation and cyclosporine, demonstrates that the initiation of autoimmune response toward islets is most likely MHC restricted. These results led to the conclusion that MHC matching may be contraindicated in future human pancreatic islet transplantation to avoid reactivation of the original autoimmune disease.
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PMID:The role of MHC compatibility in recurrence of autoimmune type I diabetes mellitus: comparison of the immune response of BB/W rats to pancreatic islet and heart allografts. 213 45

Insulin-dependent diabetes mellitus results from the autoimmune destruction of the insulin-producing beta cells of the pancreatic islets. The target antigen(s) involved in this immunopathological process has not been identified. Our strategy was to determine whether expression of a novel surface antigen by murine pancreatic beta cells would result in insulin-dependent diabetes mellitus. We have generated lines of transgenic mice (RIP-HA) that express the hemagglutinin of the A/Japan/305/57 strain of influenza virus on their insulin-producing beta cells. Hyperglycemia developed in mice derived from all three founders at a frequency varying from 13% to 27%, and was associated with lymphocytic infiltration of the islets and a humoral response against beta cell antigens, including hemagglutinin. These results suggest that the RIP-HA mice should provide a useful system in which to study the cellular interactions involved in the induction of self-tolerance and autoimmunity.
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PMID:The expression of influenza virus hemagglutinin in the pancreatic beta cells of transgenic mice results in autoimmune diabetes. 218 89

Our objective was to define glomerular filtration rate (GFR) and renal plasma flow (RPF) in Black Americans with non-insulin-dependent diabetes mellitus (NIDDM). This was a cross-sectional study of 71 Black NIDDM patients with diagnosed diabetes duration from 1 mo to 21 yr. Hyperglycemia was regulated and stabilized before patients were entered into the study. GFR and RPF were determined by the clearance of [125I]iothalamate and 131I-labeled hippuran, respectively, with a constant-infusion technique and four urine collection periods. Hyperfiltration, as defined by a GFR of greater than 140 ml.min-1.1.73 m-2, was found in 7 of 20 patients (35%) with newly diagnosed (less than 2 yr duration) NIDDM. The percentage of patients with hyperfiltration decreased with increasing duration of diagnosed diabetes. Decreasing GFR and RPF occurred with increasing duration of diagnosed diabetes. In conclusion, renal hemodynamic changes in Black Americans with NIDDM are similar to those known to occur in White populations with IDDM.
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PMID:Cross-sectional analysis of renal function in black Americans with NIDDM. 226 40

Diabetes mellitus is characterized by recurrent metabolic abnormalities which postmortem studies suggest might be associated with degenerative changes in the central nervous system. Acute hypoglycemia does indeed lead to cognitive impairment, whereas acute hyperglycemia in the absence of ketoacidosis or hyperosmolarity does not. Insulin-dependent diabetes mellitus is associated with cognitive deficits that tend to be relatively slight, inconsistent between different studies, and unrelated to clinical indicators; they can be ascribed as plausibly to psychogenic factors as to degenerative disease. In contrast, cognitive impairment in noninsulin-dependent diabetes mellitus is more conspicuous in tests of learning and memory, consistently associated with a patient's level of glycemic control, and more plausibly to be ascribed to structural neuropathology. Nevertheless, in both cases the deficits in question are unlikely to interfere significantly with patients' everyday functioning.
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PMID:Cognitive function in diabetes mellitus. 228 78

Insulin-dependent diabetes mellitus (IDDM) is associated with several complications, including painful diabetic neuropathy. Both animal and human investigations suggest an altered pain response in IDDM. Furthermore, it has been suggested that glucose may be an important mediating factor in these painful symptoms. In the present study, pain threshold was assessed via tail flick latency in alloxan-diabetic and control rats. In addition, tail flick latency was determined under conditions of both hyperglycemia and euglycemia in diabetic rats. Conditions of hyperglycemia resulted in a significant decrease in the tail flick latency of alloxan-diabetic rats. In contrast, tail flick latency was significantly increased in diabetic rats following normalization of blood glucose levels. It is concluded that elevated blood glucose levels contribute to a decrease in pain threshold in alloxan-diabetic rats.
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PMID:Effect of hyperglycemia on pain threshold in alloxan-diabetic rats. 229 48


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