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

Due to the recent knowledge that the distribution of fat deposits would be a better predictor of cardiovascular disease than the degree of obesity, some risk factors for atherosclerosis were evaluated in middle age type II male diabetics and in obese subjects with and without glucose intolerance. In non-insulin dependent diabetes, abdominal adiposity reflected by the waist/hip-circumference (WHR) was related to parameters of metabolic control, lipid parameters, blood rheology, insulin status, hypertension and known vascular complications in three different groups. In the groups with abdominal obesity, the mean annual HbA1 is significantly (p less than 0.01) higher than the group without an abdominal fat mass distribution. Atherogenic index is significantly increased in the group with the highest WHR. HDL-cholesterol levels are significantly decreased in both groups with upper body fat distribution. A highly significant (p less than 0.001) correlation was present between WHR and HDL-cholesterol and WHR and total/HDL-cholesterol ratio; this significant correlation remains after correction for body mass index. Whole blood and plasma viscosity and fibrinogen levels are significantly (p less than 0.05) increased in diabetics with upper body fat accumulation and could be compared to patients with proven coronary ischemic heart disease. The frequency of peripheral vascular disease, coronary ischemic heart disease and hypertension is most prominent in diabetics with an abdominal fat mass distribution. Systolic blood pressure even seems to be increased in non-obese diabetics with the highest WHR. A correlation could be found between WHR and both systolic and diastolic blood pressure. When corrected for body mass index the same significant correlation between WHR and blood pressure remained. Both fasting and postprandial insulin and C-peptide values may be the link between abdominal fat deposits and all metabolic disturbances. These results confirm the negative effect of an excess of abdominally located fat cells, even without manifest obesity, on diabetes metabolic control, lipid fractions, hypertension, insulin behaviour, blood rheology and cardiovascular complications. In obese patients with upper body fat accumulation a higher prevalence of glucose intolerance and diabetes is present, in contrast to their counterparts with lower body fat deposit. Both fasting glycemia, insulin and insulin area are significantly (p less than 0.005) increased in the group with the greatest WHR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Body fat mass distribution. Influence on metabolic and atherosclerotic parameters in non-insulin dependent diabetics and obese subjects with and without impaired glucose tolerance. Influence of weight reduction. 280 Jun 85

The chronically hyperinsulinemic Zucker fatty rat, with peripheral insulin resistance and glucose intolerance, represents a model of noninsulin dependent diabetes mellitus (NIDDM). These animals have elevated hepatic glycogen levels. Hepatic levels of synthase phosphatase and phosphorylase phosphatase, which are diminished in the IDDM rat, were markedly increased in the obese rats. Glyburide, a sulfonylurea used in treatment of NIDDM, resulted in reduced levels of glycemia and increased insulin levels in Zucker rats. Hepatic glycogen levels were increased, as was the activation of glycogen synthase, although there were no effects of drug administration on synthase phosphatase or phosphorylase phosphatase activities. G6P levels were increased by glyburide in lean rats but not in obese animals. These effects of glyburide on liver glycogen metabolism are accounted for via potentiation of the glycogenic effects of insulin.
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PMID:Hepatic glycogen synthase phosphatase and phosphorylase phosphatase activities are increased in obese (fa/fa) hyperinsulinemic Zucker rats: effects of glyburide administration. 282 45

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.
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PMID:Platelet and clotting activities after cold stress in diabetic patients. 297 Jun 90

Insulin-dependent diabetes mellitus (IDDM) results from the destruction of pancreatic beta cells. Viruses have been suggested as one of the possible causes. The evidence for viruses comes largely from experiments in animals, but several studies in humans also point to viruses as a trigger of this disease in some cases. Encephalomyocarditis (EMC) virus, Mengovirus (2T), and Coxsackie B4 virus infect and destroy pancreatic beta cells when inoculated into mice. This results in hypoinsulinemia and hyperglycemia. The development of EMC virus-induced diabetes is dependent on the genetic background of the host and genetic makeup of the virus. Animals with diabetes for several months show some long-term complications, including glomerulosclerosis, ocular changes, and decreased bone formation and mineralization in addition to acute metabolic changes. EMC virus-induced diabetes can be prevented by a live-attenuated vaccine. The capacity of Coxsackie B4 virus to induce diabetes is also influenced by the genetic background of the host. However, Mengovirus-induced diabetes is not dependent on the genetic background of the host. In contrast to the EMC, Mengo, and Coxsackie B4 viruses, reovirus type 1 seems to be somehow associated with an autoimmune response producing a diabetes-like syndrome in suckling mice. This virus produces an autoimmune polyendocrinopathy that results in very mild and transient glucose intolerance. Several common human viruses including mumps, Coxsackie B3 and B4 viruses, and reovirus type 3 can infect human beta cells in culture and destroy them. A variant of Coxsackie B4 virus has been isolated from the pancreas of a child who died of acute-onset IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perspectives on the role of viruses in insulin-dependent diabetes. 299 65

Transient hyperglycemia may represent the earliest manifestation of IDDM. In a series of 30 children referred for transient hyperglycemia, 8/30 (27%) developed IDDM within 10 months of their initial evaluation. Three children with detectable cytoplasmic islet cell antibodies (ICA) and/or positive insulin autoantibodies (CIAA) all developed IDDM, compared to 21% of ICA negative children and 13% who were CIAA negative. Of those with impaired glucose tolerance, 6/11 (55%) developed IDDM, as did 1/14 with normal OGTT. Of the children with a low "K rate" on IVGTT, 75% developed IDDM, compared to 1/13 with a normal "K rate". All four children (100%) whose first phase (1' + 3') insulin secretion never exceeded the first percentile developed IDDM within nine months, while no child with first phase insulin secretion above the first percentile (0/16) developed IDDM during 19 +/- 9 months (mean +/- SD) of follow-up. Thus, in our experience the oral glucose tolerance test is a less accurate predictor of impending IDDM; immunological abnormalities have the highest positive predictive value, while the first phase insulin secretion during an intravenous glucose tolerance test has the highest negative predictive value and the greatest overall accuracy of prediction.
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PMID:Transient hyperglycemia in childhood: identification of a subgroup with imminent diabetes mellitus. 307 2

Activation of T lymphocytes and islet cell antibodies were studied in two groups of insulin dependent diabetics and their non-diabetic identical cotwins. Group 1 comprised 12 "short term" twin pairs (diabetic twin diagnosed less than five years previously) in whom only a third of the cotwins were likely to develop diabetes; 10 of the 12 non-diabetic cotwins showed increased values of activated T lymphocytes, islet cell antibodies, or both. Group 2 comprised 10 "long term" twin pairs (diabetic twin diagnosed more than 11 years previously) in whom none of the non-diabetic cotwins was likely to develop diabetes; these pairs were selected because all the non-diabetic cotwins had shown islet cell antibodies at some time in the past, but only two still did so (one with an increased value of activated T cells). There was relative glucose intolerance in the cotwins of the short term group but not in those of the long term group. Non-diabetic cotwins of diabetics may show the immune changes associated with insulin dependent diabetes and relative glucose intolerance, but these changes may remit without leading to diabetes.
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PMID:Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins. 308 44

Non-insulin dependent diabetes appears to be an inherited condition. A study of young offspring of non-insulin dependent diabetics was conducted to determine whether metabolic abnormalities could be found at a young age before clinical diabetes developed. Thirteen patients with non-insulin dependent diabetes were selected who fulfilled the following criteria: they had a sibling who also had non-insulin dependent diabetes, their spouse was non-diabetic, and the offspring were aged between 12 and 45 years, not diabetic, and available for study. All 32 offspring had a 75 g oral glucose tolerance test, and results in 13 of them, one randomly selected from each family, were compared with 13 controls of similar age, sex, and weight. The offspring had significantly higher fasting concentrations of glucose, higher proportions of haemoglobin A1, and higher concentrations of insulin, C peptide, and glucagon. After glucose challenge the increases in both glucose and C peptide concentrations were significantly greater in the offspring. These differences were maintained in all 32 offspring when compared with 18 controls of similar age, sex, and weight; seven of the 32 offspring had impaired glucose tolerance. These results indicate that young offspring of selected non-insulin dependent diabetics can show extensive metabolic changes including impaired glucose tolerance. These changes are associated with hyperinsulinaemia and hyperglucagonaemia.
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PMID:Metabolic abnormalities in children of non-insulin dependent diabetics. 309 81

As part of a continuing epidemiological study of non-insulin dependent diabetes among Pima Indians 154 subjects who had had a transient impairment of glucose tolerance were followed up for 1.2-16.9 (median 5.8) years after their glucose tolerance had returned to normal. Of these, 49 subsequently developed diabetes; 26 subsequently developed impaired glucose tolerance; and 79 had normal glucose tolerance at the last examination. The cumulative incidence of diabetes was 16% and 48% at five and 10 years of follow up respectively, compared with 3% and 8% for a control group of 1245 members of the same population. After adjustment for age, sex, body mass index, and plasma glucose concentration two hours after glucose loading the incidence of diabetes among the subjects who had had transient impaired glucose tolerance was 3.0 times that among the controls (95% confidence interval 2.1 to 4.3). Proportional hazards function analysis indicated that obesity was the most important predictor of subsequent development of diabetes. The results suggest that transient impairment of glucose tolerance indicates, at least in some subjects, a predisposition to diabetes and should not be considered clinically unimportant.
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PMID:Transient impaired glucose tolerance in Pima Indians: is it important? 314 6

The aim of the present study was to investigate the possible role of the thymus-dependent immune system in the disease mechanisms underlying type 1 (insulin-dependent) diabetes mellitus. Both animal experiments and human studies were carried out. Firstly, a brief historical review is given of the scientific progress within the aetiology and pathogenesis of diabetes mellitus during the last few decades. Mention is made summarily of some elements of the thymus-dependent immune system, and the athymic nude mouse is presented. Three diabetic animal models are reported, viz. two exogenously provoked diabetes models in mice, virus-induced diabetes and diabetes induced by streptozotocin, besides the spontaneously diabetic BB rat. Insofar as the mouse models are concerned, experiments were carried out on both nude mice and normal thymus-intact mice. Encephalomyocarditis virus was used in the virus model and could after inoculation be isolated in large quantities from nude mice as well as normal thymus-intact mice. Only the latter developed diabetes; the C57 mice in the form of glucose intolerance and the BALB/c/BOM mice in the form of elevation of the mean blood glucose values to about threefold normal level. The nude mice exhibited only a very short-lasting virus antibody formation, while in the thymus-intact mice it was possible, as might be expected, to demonstrate high titres of neutralizing virus antibodies for months after the virus inoculation. In the streptozotocin model, where the streptozotocin was administered by repeated small injections, the nude mice developed considerably milder diabetes than the thymus-intact mice. This survey includes other experiments using various forms of immunosuppression (thymectomy, irradiation, treatment with antilymphocyte serum), which together supply evidence that the thymus-dependent immune system is involved in the pathogenesis of diabetes in the two mouse models mentioned as well as in the spontaneously diabetic BB rat, regardless of the different aetiologies in the models. On this background, clinical immunological studies in patients with type 1 diabetes were carried out. Firstly, studies are reported of subpopulations of the peripheral lymphocytes which, after labelling with monoclonal antibodies, were investigated by means of flow-cytometry. The number of cytotoxic/suppressor T-lymphocytes was found to be reduced at the time of diagnosis of type 1 diabetes, but increasing towards normal levels five months later. The helper T-cells were found to be slightly increased at diagnosis as compared with the values in controls, whereas there were no differences in the total T-lymphocyte counts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The thymus-dependent immune system in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. Animal model and human studies. 316 May 50

The metabolic and cellular immune changes during adoptive transfer of type I diabetes mellitus in the BB rat were examined. Concanavalin A (Sigma Chemical Co, St Louis) stimulation of acutely diabetic BB rat splenocytes increased the Ia-positive cells, but no other lymphocyte subset. Each spleen cell preparation was divided into two and injected into two separate recipients. Thirty-day-old diabetes-prone BB rats received these splenocytes intravenously (62 +/- 5 x 10(6) cells, n = 30) or buffer alone (controls, n = 14). Seventy-seven percent of the cell-injected rats became diabetic before 60 days of age, 15 +/- 1 days after injection. They were glucose intolerant two to three days before onset, with normal fasting glucose. All controls maintained normal glucose tolerance. The morphology revealed intense insulitis in all the rats that became diabetic, and its absence in all the controls. Eighty-three percent of the spleen cell preparations produced the same outcome in both recipients. The cell-injected rats had an increase in lymphocyte counts eight days after injection compared with the controls. The most affected subsets were the pan T cells (OX19+) and helper T cells (W3/25+). While the rats that ultimately became diabetic had a decrease of their lymphocyte subsets to control levels between eight and 14 days, the injected rats that maintained normal glucose tolerance maintained elevated T cells. We conclude that (1) adoptive transfer of diabetes occurs in the presence of an increase of the helper T (W3/25+) lymphocytes after spleen cell injections; (2) glucose intolerance precedes by two to three days fasting hyperglycemia; and (3) while the lymphocyte counts are increased in all recipients of splenocyte preparations, these counts decrease rapidly only in the rats that develop diabetes, possibly by entrapment of lymphocytes in the insulitis.
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PMID:Metabolic time course and immunologic concomitants of adoptive transfer of type I diabetes in the BB rat. 326 60


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