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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These are the baseline findings of a group of 68 prepubertal children enrolled in a longitudinal study of the development of early diabetes microvascular complications prior to gonadarche. The median age of the children was 9.8 years, the median diabetes duration 3.6 years and the mean HbA1c 8.4%. Mild nonproliferative retinopathy was present in 6 of 67 (9%) children, assessed by 7-field stereoscopic fundus photography. Those with retinopathy had higher total cholesterol (p < 0.05) and lower DHEAS (p < 0.01). Albumin excretion rate (AER) was calculated as the mean of three overnight consecutive urine collections. AER > 7.5 micrograms/min was present in 5 of 64 (8%), and one boy had a mean AER > 15 micrograms/min. Those with AER > 7.5 micrograms/min had higher diastolic blood pressure and diastolic blood pressure percentiles (p < 0.05). Longitudinal study of this cohort will establish which factors in the prepubertal years are important for the development of diabetes microvascular complications.
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PMID:Diabetes microvascular complications in prepubertal children. 946 27

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.
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PMID:[Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)]. 949 4

Albumin modified by Amadori glucose adducts, formed in increased amounts in diabetes, stimulates collagen IV production and gene expression in renal glomerular mesangial cells, and induces mesangial matrix accumulation accompanied by increased mRNA encoding alpha 1 (IV) collagen and fibronectin in diabetic animals. These effects contribute to the pathogenesis of diabetic nephropathy, and resemble biologic activities of the cytokine TGF-beta 1, which also has been causally implicated in diabetic renal disease. We postulated that Amadori-modified glycated albumin modulates TGF-beta 1 expression in mesangial cells, and that TGF-beta 1 participates in mediating the glycated albumin-induced increases in mesangial cell matrix production. To test this hypothesis, we measured mRNA encoding TGF-beta 1, the TGF-beta Type II receptor and fibronectin, a key matrix component of the TGF-beta 1 tissue response, after incubation of mesangial cells with glycated albumin. Steady state levels of the mRNAs encoding for these proteins were stimulated when mesangial cells were cultured in the presence of albumin containing Amadori glucose adducts compared with levels in cells cultured with the nonglycated, glucose-free counterpart. The glycated protein-induced changes in mRNA expression were observed with concentrations of glycated albumin encompassing those found in clinical specimens and in media containing physiologic (5.5 mM) glucose concentrations, indicating that they were due to the glucose-modified protein and not to a hyperglycemic milieu. Further, they were accompanied by increased translated fibronectin protein, which was prevented with TGF-beta neutralizing antibody, as was the glycated albumin-induced increase in fibronectin mRNA. The findings indicate that Amadori-modified glycated albumin stimulates mesangial cell TGF-beta 1 gene expression by mechanisms that are operative under normoglycemic conditions. These data provide the first link between elevated glycated serum albumin concentrations and increased TGF-beta 1 bioactivity in the pathogenesis of mesangial matrix accumulation in diabetes.
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PMID:Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells: involvement of the transforming growth factor-beta system. 950 8

An activated renal endothelin (ET) system is implicated in the pathogenesis of renal fibrosis, as recently shown in ET-1 transgenic mice. Because progressive renal fibrosis is also a major finding in diabetic nephropathy, we analyzed the activity of the renal ET system in rats with streptozotocin-induced diabetes mellitus and the effect of blocking the ETA receptor, using the orally active ETA antagonist LU 135252. The effects of long-term treatment with LU 135252 were compared with those of an ACE inhibitor. Plasma and urinary ET-1 concentrations were measured. Progression of diabetic nephropathy was analyzed by measuring urinary albumin and protein excretion. Urinary ET-1 excretion was significantly elevated as early as 7 days after induction of diabetes and increased further. The daily urine volume was significantly correlated with urine ET-1 excretion. Treatment with LU 135252 significantly decreased the ET-1 excretion by more than 50%, whereas ACE inhibition resulted only in a mild decrease. Albumin excretion was significantly decreased after ACE inhibition, whereas ETA inhibition resulted in a nonsignificant decrease. Urinary ET and albumin excretion probably reflect independent mechanisms of renal damage in diabetes.
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PMID:Renal endothelin system in diabetes: comparison of angiotensin-converting enzyme inhibition and endothelin-A antagonism. 959 22

1. Albumin is normally excreted as a mixture of intact protein and fragments that are produced during renal passage. The purpose of this study was to investigate the ratio of intact versus degraded forms of excreted albumin to ascertain whether changes in this ratio could account for the apparent increase in albumin excretion seen in diabetes, as measured by standard radioimmunoassay techniques. 2. Four-week male Sprague-Dawley rats with streptozotocin-induced diabetes and age-matched control rats were intravenously injected with [3H]albumin. Urine collected over 2 h was analysed by size exclusion chromatography and radioimmunoassay. A standard radioimmunoassay found a 7-fold increase in albumin excretion rate in diabetic rats, whereas there was only a 2-fold increase in albumin excretion (intact plus fragments). Urine analysed by size exclusion chromatography showed severe degradation for control rats (% monomer=4+/-2%); in diabetic rats there was a significant amount of monomer albumin excreted, along with moderately degraded and heavily degraded albumin (% monomer=17+/-5%). 3. This study has shown that the radioimmunoassay, which specifically detects intact albumin, considerably underestimates the amount of total urinary albumin which consists of intact and degraded material. The increase in albumin excretion rate observed in diabetes as measured by radioimmunoassay is mainly due to a change in the amount of intact albumin excreted and this is specifically due to the inhibition of albumin degradation at a post-glomerular site and not due to the onset of any type of glomerular 'shunt' pathway.
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PMID:Alterations in renal degradation of albumin in early experimental diabetes in the rat: a new factor in the mechanism of albuminuria. 966 87

Although Type 2 (non-insulin-dependent) diabetes mellitus (Type 2 DM) is more common in South Asians than in Europeans in the UK, very little is known about complications and their risk factors in South Asians. We sought microalbuminuria in a cross-sectional study of 583 European and 889 South Asian Type 2 DM clinic attenders to Ealing Hospital, London, over 1 year. Albumin/creatinine ratios were measured in early morning urines. Prevalence of microalbuminuria was greater in South Asians compared to Europeans (40% versus 33% in men, p = 0.003, and 33% versus 19% in women, p < 0.0001). Glycaemic control was worse and prevalence of hypertension, retinopathy and heart disease was higher in South Asians. Key risk factors for microalbuminuria in both ethnic groups were glycaemic control, diabetes duration, blood pressure, triglyceride and retinopathy, but none accounted for the higher microalbuminuria prevalence in South Asians. Age and sex adjusted odds ratio for microalbuminuria was 1.78 (95% CI 1.02, 2.82, p = 0.02) in South Asians versus Europeans. After adjustment for confounders, this became 2.07, 95% CI 1.13, 3.79, p = 0.02. We conclude that microalbuminuria is more common in South Asians with Type 2 DM than in Europeans and, although risk factor relationships appeared similar in both groups, and some risk factors were more prominent in South Asians, this cannot account for the high prevalence of microalbuminuria observed in South Asians.
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PMID:Comparison of prevalence and risk factors for microalbuminuria in South Asians and Europeans with type 2 diabetes mellitus. 970 71

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.
Diabetes 1998 Sep
PMID:Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM. 972 42

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age < or = 40 years, mean 27.9 +/- 6.5) with a diabetes duration > or = 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 +/- 0.06 mm in control group 1 and 0.50 +/- 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: -0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 +/- 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 +/- 0.17 vs 0.55 +/- 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of < or = 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients.
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PMID:Determinants of carotid artery wall thickening in young patients with Type 1 diabetes mellitus. 979 86

The morbidity and mortality associated with diabetes mellitus are essentially related to the vascular lesions that develop over time in this condition. Both the macrocirculation and microcirculation are involved, and as a consequence, vital organs such as the brain, retina, heart, and kidney and the limbs become damaged. Because microalbuminuria represents the earliest and probably most sensitive indication of endothelial dysfunction in diabetes mellitus, the results of pharmacologic intervention with angiotensin-converting enzyme inhibitors, which treat glomerular hypertension were the first indication of potential beneficial effects in reducing diabetic nephroplasty. The nature of endothelial dysfunction related to diabetes is probably not homogeneous, since microcirculation networks are affected at different periods and with variable intensity. This appears to be the case for the aorta, the heart, segments of the digestive tract, the skin, and the skeletal muscle, the largest consumer of insulin. Although the aorta and large arteries contain a small portion of the total blood volume, their distribution of blood flow (pulse pressure) to peripheral organs may affect endothelial function in the microcirculation. Changes in the structure of conduit arteries, partly responsible for the alteration in compliance characteristics, could well be related to the way these arteries are fed by the vasa vasorum system. This report describes a new in vitro approach to examine capillary permeability in normal and alloxan-induced diabetic rabbits. Preliminary results indicate that the size of terminal arterioles of the vasa vasorum (increased diameter) and the capillary permeability to albumin (markedly enhanced) in this specialized network are profoundly affected in the thoracic aorta obtained from diabetic animals. Albumin extravasation into the interstitial fluid compartment of the aorta is likely to lead to structural and physicochemical changes: in fact, removal of interstitial macromolecules via lymphatic drainage is poor in the blood vessel wall of large arteries. This experimental approach is likely to be useful in the exploration of medications affecting the structure and function of conduit vessels.
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PMID:The blood vessel, linchpin of diabetic lesions. 1009 22

To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER < 20 micrograms/min; n = 50), microalbuminuric (UAER 20-200 micrograms/min; n = 30), and macroalbuminuric (UAER > 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.
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PMID:The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy. 1019 5


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