Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Calcium antagonists have become widely used as antihypertensive treatment in diabetic patients, although data concerning a possible influence on glucose tolerance, insulin secretion, and platelet aggregation during long-term, placebo-controlled studies are lacking. Therefore, the effects of isradipine, a new calcium antagonist, on glucose tolerance and insulin secretion during a 75-g oral glucose tolerance test (OGTT) and on ADP- and collagen-induced maximum first-wave platelet aggregation (Tmax%) were studied in 11 type II diabetic patients with borderline hypertension. After a 2-week washout period, patients were treated with placebo or isradipine for 8 weeks in a double-blind, crossover study. Systolic blood pressure was lowered significantly after isradipine therapy compared to placebo (127 +/- 3 vs. 139 +/- 6 mm Hg; p less than 0.05). Fasting blood glucose (153 +/- 14 vs. 157 +/- 16 mg/dl; NS), glucose levels, and basal (17 +/- 4 vs. 17 +/- 2 mU/ml; NS) and stimulated insulin during the OGTT remained unchanged after either treatment. Platelet aggregation after stimulation with different concentrations of ADP and collagen showed no significant differences. These data indicate that calcium antagonists have no adverse effects on glucose tolerance, insulin secretion, and platelet aggregation in type II diabetes mellitus, and are therefore useful in the treatment of hypertension in diabetic patients.
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PMID:Platelet aggregation and metabolic control are not affected by calcium antagonist treatment in type II diabetes mellitus. 169 14

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.
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PMID:Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control. 266 42

Serum levels of type III procollagen peptide (P-III-P) were investigated in 19 patients with type 1 (insulin-dependent) and in 48 (25 orally treated, 23 insulinized) patients with type 2 (non insulin-dependent) diabetes mellitus. Among patients with type 2 diabetes, 16 orally treated and 14 insulin-treated subjects had macrovascular complications. P-III-P levels were not correlated with the duration of diabetes and with glucose control, nor were there any significant sex and age differences in the levels. P-III-P values were significantly higher in the sera of insulin-treated non insulin-dependent diabetic patients with macroangiopathy. These high values (18.5 +/- 10.8 ng/ml) were in contrast with normal values in healthy subjects (8.5 +/- 2.5, P less than 0.001), insulin-dependent diabetics (9.9 +/- 3.4 ng/ml, P less than 0.01), non insulin-dependent diabetics treated with oral agents (8.2 +/- 2.6 ng/ml, P less than 0.001) and insulin-treated non insulin-dependent patients without macroangiopathy (8.2 +/- 4.9 ng/ml, P less than 0.001). Although this study does not demonstrate that an increase in type III collagen synthesis is responsible for the pathogenesis of macroangiopathy, it suggests that insulin-dependent fibroblast sensitization may play a role in the acceleration and progression of macroangiopathy.
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PMID:Serum levels of type III procollagen peptide in diabetes mellitus. 272 32

Platelet aggregate ratios (PAR) were determined, and threshold concentrations (ED50) of epinephrine, adenosine diphosphate (ADP), and collagen were estimated by platelet aggregometry in 88 IDDM and 52 NIDDM patients without hyperlipidaemia or azotaemia, and in 106 healthy volunteers to revise the question of hyperaggregability in diabetes. ED50-s showed a tendency for negative correlation with age, significant in female but not in male controls. Similar trends were obtained in IDDM and NIDDM females, but were not in IDDM and NIDDM males. The ED50-s of different aggregating agents positively correlated with each other. ED50-s were higher in men than in women in both controls and IDDM patients. Similar but minor differences were observed between women and men in NIDDM. IDDM patients had significantly lower PAR and collagen ED50, and a tendency for epinephrine and ADP to be lower as compared to the sex- and age-matched controls. The differences of PAR were the same, while those of ED50-s were diminished in older NIDDM patients compared to the matched controls. It is concluded, that the previously observed general hyperaggregability in diabetic patients may have partly resulted from sex- and age differences. Threshold concentrations should be compared to sex- and age-matched controls.
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PMID:Sex- and age-dependence of platelet aggregation in diabetes mellitus. 341 60

Epidemiologic studies have suggested that the severity of periodontitis is greater in juvenile and adult onset diabetes. In juvenile diabetic patients, the periodontal disease seems to be initiated around puberty and progresses by age. Reviewing the medical literature indicates a similar age of onset for known systemic complications resulting from diabetes. Angiopathy, abnormal collagen metabolism, abnormal PMN function, and altered sulcular microbial flora have been found to be closely associated with the severity of periodontitis in diabetic patients. The association between abnormal neutrophil function and severity of periodontal disease in diabetic patients provides an opportunity for examining the role of neutrophil in periodontal disease. Future investigation in the function of sulcular PMN may shed light on the complex mechanism of periodontal disease.
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PMID:Periodontal disease in juvenile and adult diabetic patients: a review of the literature. 635 23

Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of human diabetic nephropathy. Renal tissues from 15 patients with type II (non-insulin-dependent) diabetes (NIDDM) were studied by immunofluorescence (IF) and immunogold electron microscopy (IEM) for the distribution of 2 type IV collagen peptides [alpha 3(IV) noncollagenous (NC) domain and alpha 4(IV) NC domain] and 2 classical type IV collagen chains [alpha 1(IV) NC domain and alpha 2(IV) domain]. There was intense staining for alpha 3(IV) NC and alpha 4(IV) NC domain in the GBM but not in the mesangial matrix of patients with overt diabetic nephropathy. In contrast, staining with antibodies to alpha 1(IV) NC and alpha 2(IV) NC domain reacted with mesangial matrix but was significantly decreased in the GBM in the patients with overt diabetic nephropathy. IEM confirmed the IF findings. These data suggest that expansion of the mesangial matrix and thickening of GBM in NIDDM involves separate and distinct type IV collagen components and that the site-specific matrix alterations in NIDDM and type I (insulin-dependent) diabetes are parallel.
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PMID:Differential distribution of type IV collagen chains in patients with diabetic nephropathy in non-insulin-dependent diabetes mellitus. 761 16

The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n = 10) and diabetic patients (type II diabetes mellitus n = 12). Platelet aggregation in the whole blood induced by collagen (2 micrograms/ml), ADP (10 microM), arachidonic acid (0.5 mM) and epinephrine (10 microM), and in PRP induced by collagen (2 micrograms/ml), ADP (5 microM), arachidonic acid (250 microM), epinephrine (10 microM) and serotonin-5-HT (1 microM) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5-HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT2 receptor blockers may be of value in DM patients.
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PMID:Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes. 799 57

The aim of the present study was to characterize the eventual presence and molecular forms of gelatinase/type IV collagenase activities in gingival crevicular fluid (GCF) and saliva in different forms of periodontitis; patients with clinically healthy periodontium served as controls. Enzyme activities were monitored electrophoretically by zymography using gelatin and type IV collagen as substrates and analyzed visually and/or densitometrically. Both saliva and GCF collected from adult periodontitis, localized juvenile periodontitis and type II diabetes mellitus periodontitis patients contained species moving identically with gelatinase isolated from human neutrophils or MMP-9 (mean 98 kD), and species with mobility similar to gelatinase in fibroblast cell culture supernatants or MMP-2 (mean 76 kD). Hitherto, undescribed high molecular weight forms (mean 128 kD), were found, possibly representing polymerized or complexed enzyme active/activated in situ in the gel matrix. Small molecular forms of gelatinases (mean 51 kD and 46 kD), unable to cleave type IV collagen, were also found, most likely representing in vivo proteolytically activated, truncated enzymes. Although multiple forms of gelatinases/type IV collagenases in saliva and GCF may take part in the tissue destruction in periodontitis, their profile judged according to molecular weights does not differentiate between different forms of periodontitis.
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PMID:Multiple forms of gelatinases/type IV collagenases in saliva and gingival crevicular fluid of periodontitis patients. 812 40

MCI-9042, a potent inhibitor of 5HT2 receptor, was used to examine its effects on serotonin induced-aggregation of platelets obtained from patients with type 2 diabetes mellitus (DM). The extent of platelet aggregation induced by serotonin increased in DM patients without retinopathy, but the increase was further significant in DM patients with retinopathy. MCI-9042 as well as ketanserin, inhibited significantly serotonin induced-aggregation of platelets obtained from DM patients with retinopathy. MCI-9042 dose dependently inhibited platelet aggregation induced by serotonin and collagen. These results suggest that serotonin which may be released from platelets of DM patients may activate platelets together with collagen exposed on atherosclerotic endothelium and that MCI-9042 may be inhibitory to enhanced platelet aggregability under these conditions.
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PMID:The effect of MCI-9042 on serotonin-induced platelet aggregation in type 2 diabetes mellitus. 832 84


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