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

In adult diabetic patients microalbuminuria is a marker of early vascular damage in the micro- and macrocirculation. Microalbuminuria is a powerful predictor of renal and cardiovascular disease outcome and is associated with other, potentially modifiable, risk factors of vascular damage. Studies of secondary prevention have shown that blood pressure lowering drugs effectively reduce albumin excretion rate. Angiotensin converting enzyme (ACE) inhibitors seem particularly effective in reducing the risk of progression to clinical albuminuria in both insulin dependent and non-insulin dependent diabetic patients and this beneficial effect appears to be long-lasting. Whether this postpones the onset of end-stage renal failure and/or reduces early mortality in these patients remains to be established. Recent studies of primary prevention in insulin-dependent diabetic patients predominantly with normoalbuminuria demonstrate that ACE inhibition reduces significantly the rate of progression of albumin excretion rate and, of great interest, seems to affect beneficially the progression of retinopathy. These results compare favorably with the beneficial effect of intensified insulin therapy and strict blood glucose control in this same group of patients. Thus, ACE inhibitors are a powerful tool to prevent progression of microalbuminuria in diabetes and may prove useful as an adjunct therapy to intensified insulin therapy in the prevention of development of microalbuminuria and of retinopathy progression in insulin dependent diabetes.
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PMID:Angiotensin converting enzyme inhibitors in diabetic patients with microalbuminuria or normoalbuminuria. 940 17

Non insulin dependent diabetes mellitus (NIDDM) and obesity are defined as classical insulin resistant states. Essential hypertension is now also considered to be an insulin resistant state, even in absence of NIDDM or obesity, as shown in epidemiological, clinical and experimental studies. Neither the underlying mechanism nor a direct causality between the two phenomena has been detected as yet, but different hypotheses have been postulated where, on the one hand, insulin resistance and hypertension are considered to be causally related and, on the other hand, they are considered to be parallel phenomena due to genetic and acquired factors. The clarification of the connection between hypertension and insulin resistance seems to be of great clinical importance, since they are both independent risk factors for cardiovascular disease and mortality from cardiovascular complications. This paper gives an overview of the results of recent research on the possible underlying pathogenetic mechanisms linking hypertension and insulin resistance.
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PMID:[Hypertension and insulin resistance]. 944 22

The polycystic ovary syndrome (PCOS) is diagnosed by the simultaneous presence of polycystic ovaries by ultrasound together with clinical and biochemical signs of hyperandrogenaemia. Recently, it has been shown that a majority of PCO patients exhibit metabolic abnormalities, i.e. android obesity, insulin resistance and dyslipidaemia, all of which dispose to "civilized" life-style diseases such as cardiovascular disease and non-insulin dependent diabetes. PCOS is therefore not merely a gynaecological curiosity, but an endocrinopathy with multisystem sequelae. The endocrinological and metabolic aspects of the disease are discussed.
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PMID:[Polycystic ovary syndrome II. Endocrinology and metabolism]. 945 94

Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195+/-49% and C III: 161+/-46%) than in category A (C I: 119+/-42%), (chi-square, p < 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p < 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies.
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PMID:Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. 949 59

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.
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PMID:Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. 950 84

In diabetic nephropathy and hypertension, a major cause of mortality is from cardiovascular disease. Since low levels of antioxidants such as vitamin C have been associated with such complications, we have examined the uptake mechanisms for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM) patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive patients (HT) using mass assays of uptake and measuring AA using high-performance liquid chromatography. Precautions were taken to prevent oxidation of AA and to take into account the instability of DHA in buffers. DHA uptake was the major mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/- 2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1) h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON group (p < 0.001). There were no significant differences in the Km or passive membrane permeability for DHA or the AA uptake. DHA uptake showed a negative correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings suggest that impaired DHA uptake may be one component of the phenotype expressed by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially in the presence of hyperglycaemia, leads to impaired regeneration of AA and depletion of anti-oxidant defences, exposing such individuals to increased risk of cardiovascular disease.
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PMID:Uptake mechanisms for ascorbate and dehydroascorbate in lymphoblasts from diabetic nephropathy and hypertensive patients. 956 48

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.
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PMID:Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients. 964 37

Serum paraoxonase is a glycoprotein which binds to high-density lipoproteins (HDL) and may prevent oxidation of LDL by hydrolyzing lipid peroxides. Two polymorphisms identified in the paraoxonase gene (Met-Leu 54 and Gln-Arg 192) have been associated with cardiovascular disease. Oxidative low-density lipoprotein (LDL) is also toxic to retinal capillary endothelial cells and pericytes, so that mildly modified LDL may contribute to the development of diabetic retinopathy. To investigate the potential significance of these polymorphisms in the pathogenesis of diabetic retinopathy in IDDM, 80 patients with diabetic retinopathy and 119 controls without diabetic retinopathy were investigated in the current project. The allelic frequency of leucine 54 (L) was significantly higher in the group with retinopathy than without retinopathy (73% vs. 57%, p < 0.001). The genotype L/L was strongly associated with the development of diabetic retinopathy (p < 0.001), but a similar association was not found with Gln-Arg 192. Leucine 54 is a risk factor for diabetic retinopathy.
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PMID:A variant of paraoxonase (PON1) gene is associated with diabetic retinopathy in IDDM. 966 50

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.
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PMID:Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease? 1009 95

This study evaluates the impact of diabetic nephropathy on the incidence of coronary heart disease, stroke and any cardiovascular disease in the Finnish population, which has a high risk of Type 1 (insulin-dependent) diabetes mellitus and cardiovascular disease. We performed a prospective analysis of the incidence of coronary heart disease, stroke and cardiovascular disease in all Type 1 subjects in the Finnish Type I diabetes mellitus register diagnosed before the age of 18 years between 1 January 1965 and 31 December 1979 nationwide. The effect of age at onset of diabetes, attained age at the end of follow-up, sex, diabetes duration and of the presence of diabetic nephropathy on the risk for cardiovascular disease was evaluated. Cases of nephropathy, coronary heart disease, stroke and all cardiovascular diseases were ascertained from the nationwide Finnish Hospital Discharge Register and National Death Register using computer linkage with the Type I diabetes mellitus register. Of the 5148 Type 1 diabetic patients followed up, 159 had a cardiovascular event of which 58 were coronary heart diseases, 57 stroke events and 44 other heart diseases. There were virtually no cases of cardiovascular disease before 12 years diabetes duration. The cumulative incidence of cardiovascular disease by the age of 40 years was 43% in Type 1 diabetic patients with diabetic nephropathy, compared with 7% in patients without diabetic nephropathy, similarly in men and women. The relative risk for Type 1 diabetic patients with diabetic nephropathy compared with patients without diabetic nephropathy was 10.3 for coronary heart disease, 10.9 for stroke and 10.0 for any cardiovascular disease, similarly in men and women. The presence of nephropathy in Type I diabetic subjects increases not only the risk of coronary heart disease, but also of stroke by tenfold.
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PMID:Incidence of cardiovascular disease in Type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland. 968 19

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