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

Circadian rhythms of insulin needs and action are a frequently discussed issue that is both of considerable physiological interest and of clinical importance in case of insulin substitution in type 1 diabetes. Basally, insulin is released in a pulsatile fashion which seemingly is erratic but at close analysis displays 'free-running' cyclical rhythmicity of 8-30 min duration that possibly guarantees optimal insulin action. This basal mode of insulin secretion is subject to a multitude of endogenous control systems that act on the B-cell both in a stimulatory (e.g., beta-agonists, glucagon as well as glucose and amino acids) and an inhibitory fashion (e.g., alpha-agonists, somatostatin). Since impairment of target cell sensitivity to insulin action and hyperglycemia may be caused by the stress hormones, cortisol, epinephrine and growth hormone included, with in part intrinsic rhythmicity, as well as by dehydration and by prolonged insulin withdrawal, a secondary feed-back signal on insulin release may easily be induced by rising blood glucose levels. In that modulators of insulin release and action are themselves secreted in a circadian fashion they tend to secondarily imprint the mode of insulin release. Therefore, any difference between a daily maximum and minimum in plasma insulin concentration besides its free-running short-term rhythmicity has to be regarded as a composite secondary circadian rhythm. It is in particular due to variable secondary early-morning and late-afternoon insulin resistance.
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PMID:Circadian rhythms of insulin needs and actions. 266 58

The specific genes causing type 1 diabetes susceptibility in any species are unknown. Serological HLA studies have shown susceptibility to type 1 diabetes is linked to HLA DR3 and DR4 allels, whereas DR2 and DR5 alleles contain protective elements. DR4 chromosomes can be divided into diabetes prone or resistant by restriction fragment length polymorphism analyses with cDNA probes for DQ beta-gene. No type 1 diabetes-specific environmental factors have been revealed to be convincingly implicated in human type 1 diabetes. Congenital rubella, by its lasting influence on T cells creates susceptibility to many organ-specific autoimmune diseases. Certain dietary proteins shown in BB rats as well as hyperglycemia during the prenatal period increase the later incidence of type 1 diabetes. Human type 1 diabetes results from a progressive probably autoimmune loss of the pancreatic beta cells. The immunologic hallmarks of type 1 diabetes is the lymphocytic infiltration of pancreatic islets, the hyperexpression of class I MHC on all islet cells and the abarrent class II MHC expression on beta cells within inflamed islets, the increased frequency of activated T cells in islet and circulation. It is generally accepted that cellular immunity plays the major role in the pathogenesis of type 1 diabetes. The heightened autoimmune reactivity being detectable during the preclinical period, lasting months to years, has been proved by antibodies directed against cytoplasmic islet cell antigens (ICA), beta cell surface antigens (ICSA), insulin (IAA), and with a lower frequency against non-islet cell antigens. The presence of IgG insulin autoantibodies and complement fixing ICA confers increased risk for future type 1 diabetes development in genetically predisposed individuals than the presence of either marker alone. For ICSA a more specific and quantitative assay is needed. 90% of children developing type 1 diabetes were detected positive for ICA and/or IAA. By the time of clinical onset if type 1 diabetes some 90% of the insulin secretory beta cell mass has already been destroyed. For this reason, new approaches are needed to address the causes of diabetes and not just the consequences. The development of insulin-dependent diabetes may be reversible, or even preventable by early detection coupled with the judicious use of immunotherapy.
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PMID:Immunological disorders of type 1 diabetes mellitus. 268 94

In a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM. ThS was evaluated as the ability of theophylline to inhibit blastogenic response of peripheral blood lymphocytes (PBL) to Concanavalin A (ConA), after 120 min preincubation of the cells. All patients were connected to an artificial pancreas. Through i.v. continuous insulin infusion (0.02 U/kg/h) and/or i.v. continuous glucose and saline infusion, the following experimental conditions, lasting at least 1h, were obtained: T1: relative euglycemia and normal insulinemia; T2: relative euglycemia and hyperinsulinemia; T3: hyperglycemia and normal insulinemia; T4: hyperglycemia and hyperinsulinemia. ThS was maintained in 6/8 patients at T1 and in 8/8 patients at T4. ThS was lost in 4/8 patients at T2 and T3. These data suggest that the loss of ThS induced by hyperglycemia can be corrected by hyperinsulinemia, and that it is maintained when euglycemia is accompanied by hypoinsulinemia. It is lost when these two parameters lose their interrelationship.
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PMID:Impairment of lymphocyte suppressive system in recent onset insulin-dependent diabetes mellitus. Correlation with blood glucose and serum insulin levels. 269 17

A random sample of 78 IDDM patients were studied retrospectively with regard to longitudinal glycemic control from onset of diabetes in relation to onset of retinopathy from 10-20 years of the disease. During the latter period 40 patients developed retinopathy (retinopathy group) whereas 38 did not (no retinopathy group). Sex ratio as well as age at onset of diabetes was similar between the two groups. Also glycemic control was similar during the first five years of diabetes as assessed from glucose determinations in urine and blood. However, during the period from 5-10 years of diabetes duration glycemic control of the retinopathy group deteriorated significantly in comparison to previous years and in comparison with the non-retinopathy group. The frequency of control visits did not differ between groups; however patients in the retinopathy group more frequently changed from one institution of treatment to another than did the other patients. This study demonstrates that glycemic control deteriorates with time in a sub-group of IDDM subjects and supports the concept that onset of retinopathy depends on cumulative exposure to hyperglycemia.
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PMID:Effect of long term glycemic control on the onset of retinopathy in iddm subjects. A longitudinal and retrospective study. 274 12

Little is known of the natural history of nephropathy in type 2 (non-insulin-dependent) diabetes, yet type 2 diabetes is a major cause of end-stage renal disease in the United States. The incidence rate of heavy proteinuria was determined in Pima Indians participating in a longitudinal population study of diabetes and its complications. Heavy proteinuria was defined by a urine protein (g/liter) to urine creatinine (g/liter) ratio greater than or equal to 1.0 (greater than or equal to 113 mg protein/nmol creatinine), a level which corresponds to a urine protein excretion rate of about 1 g/day. The incidence rates of proteinuria in diabetic Pimas were 4, 12, 37, and 106 cases/1,000 person-years at risk in the periods 0 to 5, 5 to 10, 10 to 15, and 15 to 20 years after the diagnosis of diabetes. The cumulative incidence rates were 2%, 8%, 23%, and 50% at 5, 10, 15, and 20 years, respectively. The duration of diabetes, severity of diabetes as determined by the degree of hyperglycemia and type of treatment, and blood pressure were risk factors for proteinuria. The presence of heavy proteinuria was strongly associated with the development of renal insufficiency, defined by serum creatinine greater than or equal to 2.0 mg/dl (greater than or equal to 177 mumol/liter). The incidence of proteinuria in type 2 diabetes in Pima Indians was as high as that reported in type 1 diabetes in other populations and represents a frequent, serious complication of the disease.
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PMID:Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians. 278 25

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)
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PMID:Possible mechanisms in the pathogenesis of virus-induced diabetes mellitus. 282 13

Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life.
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PMID:Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients. 284 45

Altogether 54 male patients with insulin-dependent diabetes mellitus participated in the studies. The impact of insulin-induced hypoglycemia on posthypoglycemic insulin sensitivity was evaluated for up to 12 hours following nadir hypoglycemia. The effect on glucose homeostasis following transient elevation of counterregulatory hormones was studied by exogenous administration of adrenaline, adreno-corticotropic hormone and growth hormone and by suppression of the endogenous release of growth hormone in connection with hypoglycemia. The studies were performed in the fasting state preceded by a 24 hour intravenous insulin infusion in order to avoid interference of subcutaneous insulin. Insulin resistance was determined by a constant rate intravenous infusion of somatostatin, insulin and glucose. This test seemed appropriate for the evaluation of total insulin resistance, and its reproducibility was acceptable. By using this method it was demonstrated that insulin resistance occurred for at least 12 hours after a hypoglycemic event in patients with IDDM, and that adrenaline caused immediate insulin resistance which, however, faded out within four to six hours, while GH exerted no immediate effect on insulin sensitivity but caused marked and sustained insulin resistance after a lag period of about four hours. Cortisol had no apparent effect within six hours but enhanced the effect of GH. The magnitude of these diabetogenic effects of hypoglycemia and GH was less pronounced in patients who already were more insulin resistant. These results are compatible with the idea that adrenaline is of major importance for the counterregulation and restoration of blood glucose during the first few hours following hypoglycemia, while GH is responsible for the induction of a long-lasting state of insulin resistance. It is possible that such prolonged insulin resistance may cause posthypoglycemic hyperglycemia in patients with IDDM. These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin-dependent diabetes mellitus and labile blood glucose control.
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PMID:Studies on posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus. 290 16

Potential impairment of the efficacy of human atrial natriuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22-37 years). After giving informed consent, patients and eight male control subjects (aged 22-28 years) received in a random double-blind study design i.v. bolus injections of 100 micrograms hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P less than 0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P less than 0.01); hANP resulted in increased plasma protein concentrations only in controls (P less than 0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P less than 0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.
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PMID:Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus. 297 Nov 31

The paper is concerned with some data on the effect of the diabetic gene (db) on mouse sensitivity to streptozotocin (SC). Male mice aged 2-3 mos. of mutant C57BL/KsJ strain (genotypes: m+/+m, db+/+m, db+/+db) were used for investigation. Insulin-dependent diabetes mellitus was induced by intraperitoneal injections of streptozotocin at a daily dose of 40 mg/kg for 5 days. The structure and function of the insular apparatus were histologically assessed as well as by the blood level of insulin and glucose within 15 days after the start of the experiment. The earliest hyperglycemic reaction to SC was typical of mice, homozygous by the diabetic gene; they had normoglycemia at the time of treatment. In mice, heterozygous by the diabetic gene, a hyperglycemic reaction developed later after treatment. However by the end of the investigation it reached values which were typical of mice, homozygous by the diabetic gene, with basal normoglycemia. Mice, not carrying the diabetic gene, as well as homozygotes by this gene with basal hyperglycemia, possessed lesser sensitivity to SC. The expression of hyperglycemic reactions showed correlation with a degree of dystrophic changes and the development of lymphocellular infiltration in the pancreatic islets of mice with basal normoglycemia in low dose streptozotocin diabetes. The development of spontaneous hyperglycemia in homozygotes by the diabetic gene lowered their sensitivity to SC diabetogenic effects.
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PMID:[Importance of db gene for the development of low dose streptozotocin diabetes in C57BL/KsJ mice]. 297 80


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