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)

Platelet function (as production of thromboxane B2 by platelets stimulated with collagen, and plasma beta-thromboglobulin) and thrombin activity (as plasma fibrinopeptide A) were investigated in eight young (mean age 27 +/- 3 SE years) male patients in which type 1 diabetes mellitus had been diagnosed 2 to 6 months previously. They were all in excellent stable metabolic control (mean HbA1c 5.6 +/- 0.4 SE %) and free from any complications. The haemostatic variables were assessed at rest and after cycloergometric exercise to exhaustion. When compared to age- and sex-matched healthy controls, patients showed higher beta-thromboglobulin, fibrinopeptide A and thromboxane B2 at rest. After exercise, plasma beta-TG increased only in the controls. Platelet and thrombin activation are present in the very early stages of type 1 diabetes mellitus, in the absence of any complications.
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PMID:Primary platelet activation in recent-onset type 1 diabetes mellitus. 214 55

Abnormalities of platelet aggregation and coagulation have been reported in insulin dependent diabetes mellitus (IDDM), although there is controversy concerning their relationship to microangiopathy. We have studied platelet function and haemostasis in 55 patients with IDDM, 23 without, 14 with mild (background retinopathy) and 18 with severe (proliferative retinopathy, or background retinopathy plus proteinuria) complications. Studies were done on 2 occasions 8 weeks apart and the results compared with 28 control subjects. There was evidence of increased in vivo platelet aggregation in the diabetic group v controls shown by raised values of beta-thromboglobulin (61 +/- 42, mean +/- SD, v 18 +/- 14 micrograms/ml, p less than 0.001), platelet factor 4 (62 +/- 76 v 14 +/- 11 micrograms/ml, p less than 0.01), and platelet micro-aggregates (20 +/- 16 v 12 +/- 11%, p less than 0.01). There was no significant difference in fibrinogen and fibrinopeptide A levels, nor in 'in vitro' tests of platelet aggregation between the groups. Dilute whole blood clot lysis time was increased in the diabetic group v controls (6.4 +/- 2.6 v 4.8 +/- 0.5 hours, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet aggregation and coagulation factors in insulin dependent diabetics with and without microangiopathy. 295 Dec 19

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

Purified fish oil (MaxEpa, 10 g/day) treatment for six weeks increased consistently the content of eicosapentaenoic (20:5, n-3), docosapentaenoic (22:5, n-3) and docosahexaenoic acid (22:6, n-3) and decreased that of arachidonic acid (20:4, n-6) and other n-6 polyunsaturated C-20 fatty acids (PUFA) of platelets both in insulin dependent diabetic (IDDM) (n = 13) and healthy women (n = 7), but it had no effect on the number and aggregation of platelets or on plasma beta-thromboglobulin. Serum TxB2, produced by diabetic platelets was reduced, but the urine 6-keto PGF1 alpha excretion, believed to reflect prostacyclin (PGI2) production was normal in the diabetics. During the MaxEpa treatment the response of thromboxane B2 (TxB2) release to ADP was decreased in platelet-rich plasma in the healthy subjects. However, in diabetics the fish oil treatment resulted in increased TxB2 formation from exogenous arachidonic acid. The results demonstrate the dependence of platelets fatty acid composition on dietary sources and suggest that at least in the diabetic platelets the diminished arachidonic acid content could be compensated by an activation of enzymes of thromboxane B2 pathway.
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PMID:Effects of purified fish oil on platelet lipids and function in diabetic women. 359 18

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16-49 and 101 patients with NIDDM, aged 50-78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P less than 0.05), yet more so in patients with Rd (P less than 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet enzyme activities in diabetes mellitus in relation to endothelial damage. 608 25

The proteins beta-thromboglobulin, platelet factor 4 and thrombospondin are stored in platelet alpha-granules and released from the platelet by the release reaction. The assays of these proteins were studied in patients with type I diabetes mellitus (n = 30) and a healthy control group (n = 15). Platelet factor 4 and beta-thromboglobulin levels were not significantly different in both groups but thrombospondin concentrations in diabetic patients were significantly higher than those of the control group (136.6 +/- 14.2 ng/ml vs 91.2 +/- 14.3 ng/ml, P < 0.05). When the diabetic patients were divided into those with or without complications, the diabetic patients with complications (n = 11) had significantly elevated plasma thrombospondin concentrations compared with the control group (150.4 +/- 23.7 ng/ml vs 91.2 +/- 14.3 ng/ml, P < 0.05), while thrombospondin concentrations in the control group were not statistically different from the diabetic patients without complications. Plasma beta-thromboglobulin and platelet factor 4 levels were not significantly different between the diabetic and the control group. It is suggested that thrombospondin may be a convenient marker of in vivo platelet release reaction.
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PMID:Platelet factor 4, beta-thromboglobulin and thrombospondin levels in type I diabetes mellitus patients. 802 Jun 43

The role of reduced endothelial production of EDRF-NO in the pathogenesis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animal experiments. Limited human experience seems to be available in insulin dependent diabetes, calling attention to decreased EDRF-NO production. Hereby the clinical, as well as laboratory investigation (urinary and serum nitrate/nitrite, lipid peroxidation, glucometabolic parameters, endothelial and in vivo platelet activation markers, etc.) of 35 non-insulin dependent (NIDDM) and 15 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were proven to be reduced in both patients groups. This change was independent of diabetes duration, presence of macroangiopathy, coronary heart disease and the glucometabolic parameters, however, correlation was registered with lipid peroxidation (total antioxidant status). An inverse correlation of nitrate/nitrite excretion with endothelial markers (von Willebrand factor, soluble thrombomodulin) was documented in NIDDM, this correlation was much stronger in IDDM. Moreover, in IDDM patients reduced nitrate/nitrite excretion was strongly associated with elevated plasmatic beta-thromboglobulin levels. The data presented here support to the hypothesis, that EDRF-NO production is reduced in diabetes and this reduction seems to correlate with endothelial damage. In IDDM the decreased nitrate/nitrite excretion may also lead to increased in vivo platelet activation, which suggests that the reduced amount of EDRF-NO might play a role in the pathogenesis of angiopathy in IDDM.
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PMID:The association of reduced endothelium derived relaxing factor-NO production with endothelial damage and increased in vivo platelet activation in patients with diabetes mellitus. 917 38

To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D).Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4).HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.
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PMID:Bioinformatics analysis of gene expression in peripheral blood mononuclear cells from children with type 1 diabetes in 3 periods. 2483 53