Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo subendothelial oxidative stress. Increased susceptibility to oxidation has been demonstrated recently in diabetic patients with poorly controlled IDDM. Thus, we conducted studies to determine whether the increased susceptibility of LDL to oxidation was secondary to diabetes per se or to the level of glycemic control. Fifteen IDDM patients with good glycemic control and with no evidence of macrovascular disease or proteinuria were compared with healthy age-, sex-, race-, and BMI-matched nondiabetic subjects. Fasting blood glucose levels averaged 12.1 +/- 1.1 (mean +/- SE) vs. 4.9 +/- 0.1 mmol/l in the diabetic versus the control groups, respectively. HbA1c levels averaged 7.7 +/- 0.5 vs. 4.4 +/- 0.2%, reflecting well-controlled diabetes (P < 0.0001). Total, LDL, VLDL, and HDL cholesterol, triglyceride, and lipoprotein(a) levels did not differ between the groups. The particle size, lipid composition, fatty acid content, antioxidant content, and glycation were similar for LDL isolated from both groups. A rapid LDL preparation technique was used to compare LDL susceptibility to oxidation under the following conditions: final LDL cholesterol concentration of 100 microg/ml, 5 micromol/l of CuCl2 at 25 degrees C. There was no difference in the susceptibility to in vitro oxidation of LDL isolated from IDDM patients compared with control subjects. There was no correlation of glycemic control with any of the parameters of the in vitro oxidation of LDL. LDL from patients with well-controlled IDDM does not differ in composition or in susceptibility to in vitro oxidative stress compared with LDL from nondiabetic subjects.
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PMID:LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation. 863 50

The goal of this study was to compare the structural and biological characteristics of apolipoprotein (apo) B-100-containing particle subfractions isolated from poorly controlled diabetic patients with insulin-dependent diabetes (IDDM), and healthy controls matched for sex, age and body mass index (BMI). Different apo B-containing particles were isolated by sequential immunochromatography and were free of apo A-I, apo A-II, apo A-IV and apo(a). Particles lipoprotein (Lp) B/C-III contained apo B and apo C-III. They were free of apo E. Particles Lp B/E contained apo B and apo E. They were free of apo C-III. Particles Lp B were devoided of apo C-III and apo E. All these particles could contain other known apolipoproteins not cited here, as for example apo C-II and/or apo C-I. The plasma levels of cholesterol, triglycerides, phospholipids, apo A-I, B-100, C-III, E, total Lp B/C-III, total Lp B/E were not different between patients and controls. The physico-chemical properties of Lp B/C-III and Lp B/E were similar in both groups. Only Lp B from patients exhibited some changes, an increase in the size and a decrease in the cholesterol and cholesteryl ester levels. The conformational properties of the lipoproteins were studied through their immunoreactivity against four different anti-apo B-100 monoclonal antibodies (MAb) for which sequential epitopes have been located on the protein, and one MAb for which the epitope is conformationally expressed. Again, minor changes were observed between patients and controls, and only a slight decrease in the immunoreactivity of the epitope encompassing amino-acid residues 405 to 539 of Lp B and of the conformationally expressed epitope of Lp B/C-III were found in patients. Nevertheless, whatever these conformational and/or physico-chemical modifications may be, they were not sufficient to induce functional alterations in the binding of the particles from the patients to the LDL-receptor of HeLa cells. This study shows that IDDM is not associated with any significant abnormalities in the apo-containing lipoprotein particles. The excessive occurrence of coronary heart disease (CHD) and other atherosclerotic vascular disease in patients with IDDM must have other causes.
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PMID:Apo B-containing lipoprotein particles in poorly controlled insulin-dependent diabetes. 864 62

The success with which pancreas transplantation normalizes glucose concentration in patients with Type I diabetes mellitus has made it an important treatment option. Most pancreas transplant operations are performed in combination with a kidney transplant, and neither overall patient survival nor renal graft survival is compromised by the addition of a pancreas graft. Pancreas after kidney transplantation and isolated pancreas transplantation are performed less frequently since the pancreas graft success rate remains lower in these operations compared to combined pancreas-kidney transplantation. Pancreas transplantation improves the quality of life and stabilizes or reverses some diabetic microvascular complications, but its impact on the risk of atherosclerotic vascular disease is still unknown. The relative risks and benefits of pancreas transplantation need to be carefully assessed for each candidate through a thorough screening process, regardless of which type of graft is being considered. However, patient counseling and selection will be greatly aided by further research assessing the long-term risks and benefits of all types of pancreas transplantation. Pancreas transplantation will probably remain an important treatment option for some patients with Type I diabetes mellitus until this disease can either be successfully prevented or alternative treatment strategies are developed that provide equal glycaemic control with less or no associated immunosuppression.
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PMID:Pancreas transplantation: a treatment option for insulin-dependent diabetes mellitus. 879 94

Increased free radical-mediated lipoprotein oxidation may contribute to the increased prevalence of atherosclerosis in non-insulin dependent diabetes. We have determined levels of malondialdehyde (MDA) and 7-ketocholesterol, a specific indicator of free radical-mediated oxidation of lipoprotein cholesterol, in serum in very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein (LDL) and high density lipoprotein fractions of serum separated by sequential flotation ultracentrifugation. Four groups of male subjects were studied: normal controls, diabetic patients with no evidence of microvascular complications or macrovascular disease, diabetic and non-diabetic patients with peripheral vascular disease (PVD). MDA was increased in vascular disease patients (diabetic 4.5 (3.7-5.8), non-diabetic 4.4 (3.2-5.7) mumol/l, median (2.5-97.5 percentiles)) than controls (3.6 (2.9-5.0) mumol/l) (P < 0.01), but was not increased in uncomplicated diabetic patients (3.8 (3.0-4.8) mumol/l). There were no significant differences in 7-ketocholesterol concentration in LDL, but calculated total 17-ketocholesterol was lower in non-diabetic vascular patients than controls (P < 0.01). Vitamin C concentration was reduced in diabetic and non-diabetic patients with vascular disease. No significant difference in concentration of vitamin E or A was found. In six normal subjects the concentration of MDA was low in lipoproteins separated by ultracentrifugation but high in the residue following lipoprotein fractionation (70-80% total serum MDA). In conclusion, the concentration of MDA by the thiobarbituric acid assay in untreated serum may not reflect free radical damage to lipoproteins. There was no evidence of increased lipoprotein oxidation using 7-ketocholesterol in NIDDM or PVD.
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PMID:7-ketocholesterol, a specific indicator of lipoprotein oxidation, and malondialdehyde in non-insulin dependent diabetes and peripheral vascular disease. 910 Oct 96

Anti-single-stranded(ss)DNA antibodies were searched for by enzyme-linked immunosorbent assay (ELISA) in the serum of 202 outpatients with non-insulin-dependent diabetes mellitus and 135 healthy subjects to investigate their prevalence in the serum of patients with type 2 diabetes and their relationship with the presence of vascular complications. Of the 202 patients 128 had vascular complications. Anti-ssDNA antibodies were observed to be significantly more frequent in the serum of patients with vascular complications (33.6%) and in particular in patients with overt nephropathy (50%) than in patients without complications (6.7%) or controls (6.7%). Anti-ssDNA antibodies have been previously described in patients with type 1 diabetes before clinical evidence of vascular disease and their cross-reactivity with a variety of anionic biological molecules or cells, i.e. platelets and endothelial cells, assessed. It seems not unreasonable that these auto-antibodies detected in patients with type 2 diabetes could be of importance in the pathogenesis or progression of angiopathy.
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PMID:Anti-single-stranded DNA antibody in the sera of patients with type 2 diabetes mellitus. Relation to vascular complications. 913 56

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

The aim of this follow-up study was to assess whether slightly elevated urinary albumin excretion, i.e., microalbuminuria, precedes development of atherosclerotic vascular disease in IDDM. Out of 259 IDDM-patients 30 developed vascular disease during 2,457 person-years. Microalbuminuria was significantly predictive of vascular disease (hazard ratio (95% confidence interval) 1.06 (1.02-1.18) per 5 mg/24 hours increase in urinary albumin excretion; p = 0.002). The predictive effect was independent of age, sex, blood pressure, tobacco smoking, serum concentrations of total-cholesterol, HDL-cholesterol, sialic acid, and von Willebrand factor, and of haemoglobin A1c, insulin dose, diabetes duration, and diabetic nephropathy (hazard ratio (95% confidence interval) 1.04 (1.01-1.08) per 5 mg/24 hours increase in urinary albumin excretion; p = 0.03). It is concluded that slightly elevated urinary albumin excretion is an independent predictor of atherosclerotic vascular disease in insulin-dependent diabetes mellitus.
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PMID:[Microalbuminuria as predictor of atherosclerotic cardiovascular disease in IDDM]. 919 Jul 30

A rate of albumin excretion rate above 20 micrograms/min is a predicting factor of overt nephropathy in Type I diabetes. It has not yet been established whether this is the case also for Type II diabetes, where microalbuminuria is antecedent to general and cardiovascular mortality but not to end-stage renal disease. The reasons accounting for this discrepancy between Type I and Type II diabetes have not been fully elucidated. In principle two different hypotheses can be postulated to explain these findings. Firstly it can be suggested that overt proteinuria is not detected with similar incidence rates in microalbuminuric patients with the two types of diseases because Type II diabetics are older and more prone to develop cardiovascular events. Therefore these patients would die frequently before developing overt proteinuria not because microalbuminuria is not a predicting factor of End-stage Renal Disease, but rather because the follow-up period is not long enough to monitor the patients till the very moment they develop renal complications. Alternatively it is possible that microalbuminuria reflect a systemic, endothelial and vascular disorder rather than glomerular structural abnormalities in these patients. We have recently described a clustering of clinical features encompassing microalbuminuria, hypertension, peripheral extrahepatic insulin resistance, renal and cardiac hypertrophy and altered cation membrane transport systems, not in the overall Type II diabetic population, but only in a cohort of these patients. Evidences in keeping with a strict association between insulin resistance, hypertension and microalbuminuria in a subgroup of Type II diabetic patients have been recently reported by several authors both in cross-sectional and longitudinal studies. However the hypothesis that microalbuminuria reflects a systemic endothelial and vascular disorder in Type II diabetic patients, does not rule out the possibility that these systemic disturbances are also associated with histologic abnormalities of the kidney. With regard to the characteristics of renal histology in Type II diabetic patients with and without microalbuminuria, preliminary data from our laboratory demonstrate that there is no evidence of any renal disorder other than diabetes in microalbuminuric Type II diabetic patients. More particularly in this subset of patients we observed typical features of diabetic nephropathology (glomerular, tubulo-interstitial and arteriolar changes), while a substantial number of patients with increased albumin excretion rate exhibited either marked tubulo-interstitial lesions or arteriolar hyalinosis or both, in absence of significant glomerular changes. These findings suggest that it is not true that Type II diabetic patients with microalbuminuria show quite often normal renal histology, but rather than hyperglycemia may cause different patterns of renal injury as compared to Type I Diabetes. Furthermore always with regard to renal histology, it has been pointed out that in Type I diabetes glomerulopathy (especially mesangial) is the crucial change, whereas recent studies found considerable structural heterogeneity amongst proteinuric Type II diabetic patients with relatively high incidence of renal diseases other than diabetes. However parallel studies in a small group of micromacroalbuminuric Type II diabetic patients reported the typical glomerular changes, usually shown by Type I diabetic patients with similar patterns of renal damage. The issue of the relationships between microalbuminuria, hypertension and the development of overt nephropathy in Type II diabetes has been also examined in Pima Indians. The clinical scenario found in these patients does closely resemble that of Caucasian Type I diabetic patients.
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PMID:Relationships among microalbuminuria, insulin resistance and renal-cardiac complications in insulin dependent and non insulin dependent diabetes. 928 31

We investigated 24-hour ambulatory blood pressure and arterial distensibility, a marker of biophysical vessel wall properties, in 32 normoalbuminuric type I diabetic patients and 32 healthy control subjects on diets containing 50 mmol and 200 mmol sodium per day. The increase in daytime diastolic blood pressure from 50 to 200 mmol sodium was significantly higher in the diabetic patients than in the control subjects (2.3+/-4.9 versus 0.2+/-3.7 mm Hg, P<.05). On a high sodium regimen, femoral artery distensibility was decreased in the diabetic patients compared with the control subjects (19.2+/-7.6 versus 24.1+/-9.3 10[-3]/kPa, P<.05). Angiotensin-converting enzyme inhibition in the diabetic patients on a high sodium diet decreased daytime diastolic blood pressure and increased femoral artery distensibility. The blood pressure decrease in response to angiotensin-converting enzyme inhibition correlated significantly with the blood pressure increase to sodium (for 24-hour systolic and diastolic blood pressure, r=.72, P<.001 and r=.76, P<.001). In addition, we found that in the diabetic patients on a high sodium diet, the renal blood flow response to exogenous angiotensin II was not bimodally distributed, as is the case in essential hypertension, in which a subgroup of the patients are characterized by sodium sensitivity of the blood pressure and an abnormal renal blood flow response to exogenous angiotensin II ("nonmodulator phenotype"). These results show that blood pressure in insulindependent diabetes mellitus is sodium sensitive, but that this is not related to the nonmodulator phenotype, and suggest that in IDDM a relatively high sodium intake may be a factor that predisposes to the development of diabetic vascular disease.
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PMID:Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus. 936 71

Abnormalities in cutaneous blood flow (CBF) in otherwise healthy subjects with Type 1 diabetes mellitus (DM) have been demonstrated in response to local insults to the skin. To investigate whether defects also occurred in response to a regular daily activity, CBF was measured with laser Doppler flowmetry (LDF), before and 20 min after starting a mixed meal in 13 male Type 1 DM subjects with no clinical evidence of neuropathy, nephropathy or macroangiopathy and compared to 7 non-diabetic controls. Diabetic subjects and controls were of similar age and body mass index (mean +/- SD, 33.7 +/- 7.4 vs 37.1 +/- 9.2 years and 25.2 +/- 2.9 vs 24.5 +/- 2.9 kg m(-2), respectively). In subjects with DM, HbA1c was 8.3 +/- 0.6% (normal range 4-5.5%) and duration of diabetes was 18 (8-38) years, median (range). Following a mixed meal the CBF fell in the controls by 36% (24 to 56), median (range), compared to 3% (-5 to 18) in Type 1 DM subjects, P < 0.0005. These results show there is a normal physiological fall in CBF following food ingestion which is attenuated in Type 1 DM. These abnormalities of vasoconstriction in the peripheral microcirculation are present after 8 years of diabetes and precede the development of clinically apparent neuropathy or vascular disease.
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PMID:Impaired vasoconstriction of peripheral cutaneous blood flow in Type 1 diabetic patients following food ingestion. 963 19


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