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

The Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive diabetes treatment delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy in patients with IDDM. A detailed description of the effects of this treatment on diabetic nephropathy is presented here. In the primary prevention cohort, intensive treatment reduced the mean adjusted risk of the cumulative incidence of microalbuminuria (> or = 28 micrograms/min) by 34% (95% CI 2, 56%; P = 0.04). Furthermore, intensive treatment decreased the albumin excretion rate (AER) by 15% after the first year of therapy (6.5 vs. 7.7 micrograms/min, P < 0.001). Thereafter the rates of change for AER within each treatment group were no different from zero, retaining a constant difference in AER between groups in the trial. In the secondary intervention cohort with baseline AER < 28 micrograms/min, intensive therapy reduced the mean adjusted risk of microalbuminuria (> or = 28 micrograms/min) by 43% (95% CI 21, 58%; P < 0.0001); the risk of a more advanced level of microalbuminuria (> or = 70 micrograms/min) by 56% (95% CI 26, 74%; P = 0.002); and the risk of clinical albuminuria (> or = 208 micrograms/min) by 56% (95% CI 18, 76%; P < 0.01). In the secondary intervention cohort, values for AER at year 1 were identical at 9 micrograms/min, but the 6.5% change per year in the conventional group greatly exceeded the rate of change of -0.3% in the intensive group (P < 0.001). Among the 73 secondary cohort subjects with AER levels > or = 28 micrograms/min but < or = 139 micrograms/min at baseline, the reduction of progression to clinical albuminuria with intensive therapy was not statistically significant. The longitudinal treatment effect of conventional versus intensive therapy (11.0% vs. 2.5% per year, respectively, P = 0.087) was similar in magnitude to that among patients with AER < 28 micrograms/min at baseline. For the primary, secondary and combined cohorts, there were no significant differences in the rates of change in creatinine clearance (CCr) between treatment groups during the study. Only seven subjects in the entire study (2 intensive, 5 conventional) developed urinary AER > or = 208 micrograms/min coupled with a CCr < 70 ml/min/1.73 m2. Neither the rate of change of blood pressure nor the appearance of hypertension (BP > 140/90 mm Hg) differed significantly between treatment groups in the primary, secondary or combined cohorts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. 764 40

We applied an open one compartment pharmacokinetic model for the determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on a rapid intravenous loading dose followed by a constant infusion of 125I-iothalamate and 131I-orthoiodohippurate in order to ensure constant plasma levels of the two clearance markers. The loading dose was based on the assumption that the volume of distribution of the two markers equals the extracellular volume (25% of the body weight). The infusion rate as calculated after the clearance of thalamate was estimated from body weight, age, sex and serum creatinine using Cockcrofts formula. The clearance of hippurate was assumed to be four times that of thalamate. We studied the reliability of this model in 212 patients with insulin dependent diabetes mellitus (IDDM; n = 74), nephrotic syndrome (NS; n = 18) and heart (HTX; n = 69) or kidney (KTX; n = 51) transplants. A steady state concentration was obtained in all patient groups, even when GFR was markedly depressed. In patients with diabetes, we observed more variance between plasma and urinary clearances of thalamate, which could be due to inaccuracies in urine sampling. In these patients, GFR should be measured using a method that is not dependent on urine collection. Also, the estimation of GFR by means of Cockcrofts equation seems to underestimate GFR in diabetic subjects.
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PMID:Optimising glomerular filtration rate and effective renal plasma flow measurements using a simple pharmacokinetic model. 769 33

Abnormalities of sodium-lithium countertransport have been extensively implicated in adult primary hypertension and a relationship between sodium-lithium countertransport and family history of hypertension in children has been previously found. More recently it has been suggested that increased sodium-lithium countertransport may play a part in the pathogenesis of nephropathy in insulin dependent diabetes mellitus (IDDM). Children and adolescents with IDDM and their family members were studied. In those with IDDM (n = 36, median age 14.6 years, range 9.5-19.2 years) there was no relationship between sodium-lithium countertransport (range 0.098-0.585 mmol/l red blood cells/hour) and age, blood pressure as expressed by systolic or diastolic SD scores, glycated haemoglobin, serum lipids, or intracellular sodium concentration. A positive relationship (rs = 0.44) was found between sodium-lithium countertransport and early morning urinary albumin to urinary creatinine ratio (UA/UC), expressed as the logarithm of the geometric mean of two consecutive samples, for each individual (range 0.4-22 mg/mmol). Sodium-lithium countertransport was increased in those with IDDM compared with their non-diabetic siblings, in a paired analysis (n = 26). There was no relationship between UA/UC in the children with diabetes and sodium-lithium countertransport in their parents. These studies in this population of diabetic children indicate that increased sodium-lithium countertransport may play a part in the early stages of the development of nephropathy in IDDM.
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PMID:Sodium-lithium countertransport in children with diabetes and their families. 770 75

Captopril given in dosages of 25 mg reduced the doubling of serum creatinine levels by 48% in patients with insulin-dependent diabetes mellitus. Intensive insulin therapy in patients with IDDM delays the onset and slows the progression of diabetic nephropathy, retinopathy, and neuropathy.
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PMID:Nephrology. 775 21

We compared urinary albumin excretion during and after pregnancy in 30 insulin-dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with microalbuminuria (> 15 micrograms.min-1) prior to conception. There was a 6.7-fold increase in the urinary albumin excretion up until the third trimester in the women with pre-existing microalbuminuria, compared with a 3.8-fold increase in the normoalbuminuric women. In both groups of patients the urinary albumin excretion reached a peak during the third trimester with 492 +/- 404 micrograms.min-1 in the microalbuminuric women vs 43 +/- 36 micrograms.min-1 in the normoalbuminuric women (p < 0.0005). Two women from each of the groups developed eclampsia with diastolic blood pressure over 90 mm Hg, mild or moderate oedema and macroproteinuria. Four of the pregnant women with pre-existing microalbuminuria showed a transient nephrotic syndrome (33.3%) with protein excretion over 3 g in 24-h urine samples during the third trimester. In contrast, this was not observed in any of the normoalbuminuric women (p < 0.05). Within 12 weeks after delivery the urinary albumin excretion rates dropped to the pre-conception values in both patient groups. Renal function remained normal during pregnancy in both of the groups, with a physiological increase in creatinine clearance up until the third trimester (26% increase in the normoalbuminuric women vs 22% in the microalbuminuric women). In conclusion, the effect of pregnancy on the urinary albumin excretion in diabetic women with pre-existing microalbuminuria is an exaggeration of the increase of albuminuria in diabetic women with normoalbuminuria; normalization occurs within 12 weeks after delivery in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal increases in urinary albumin excretion during pregnancy in IDDM women with pre-existing microalbuminuria. 780 20

Tubular damage is a recognized feature of both overt diabetic nephropathy and glomerulonephritis. However, the pattern and mechanism of tubular damage in the two clinical settings remain unclear. Two groups of patients with macroalbuminuria (albuminuria > 300 mg/day) were studied. Group 1 comprised 41 patients with biopsy proven primary glomerulonephritis and group 2 comprised 28 patients with clinical diabetic nephropathy due to insulin dependent diabetes mellitus. Serum creatinine, creatinine clearance, glomerular proteinuria (albuminuria and transferrinuria), markers of tubular damage such as urinary excretion of lysosomal enzyme (N-acetyl glucosaminidase), brush border enzymes (leucine aminopeptidase and gamma-glutamyl transferase) and retinol binding protein (tubular protein) were measured. Both groups were comparable in serum creatinine, creatinine clearance, glomerular proteinuria and excretion of N-acetyl-glucosaminidase. However, a significantly higher degree of tubular brush border enzymuria and a lower level of tubular proteinuria were seen in group 1 than in group 2. In group 1, albuminuria correlated to tubular enzymuria and tubular proteinuria. However, there was no correlation in diabetic patients between parameters of glomerular and tubular damage or dysfunction. The data presented suggested that the pattern of tubulopathy is different in patients with comparable degree of macroalbuminuria due to diabetic nephropathy and glomerulonephritis. Moreover, in diabetic nephropathy contrary to glomerulonephritis, markers of tubular damage are unrelated to glomerular proteinuria. This may suggest different mechanisms of tubular damage in the two clinical settings. We recommended that in all patients with proteinuria, particularly those with diabetic nephropathy, markers of renal tubular damage may be useful in monitoring the course of their disease.
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PMID:Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis. 786 56

Serum ascorbic acid (AA) is reduced in diabetic patients. Aim of this study was 1) to verify whether such a decrease might be due to an altered urinary excretion of AA, and 2) whether this latter was modified in presence of early diabetic nephropathy with microalbuminuria (albumin excretion rate [AER] > 20 micrograms/min) in a group of 21 patients affected by insulin-dependent (type 1) diabetes mellitus (IDDM) as compared with 13 healthy controls matched for sex, age, dietary AA intake, and creatinine clearance per 1.73 m2 (CCl). Mean serum AA (+/- SD) was lower in diabetics (40.3 +/- 14 microM/l) than in controls (85.1 +/- 23.5 microM/l; p = 0.0001) and there was no difference between serum AA of patients with or without microalbuminuria. Urinary excretion of AA to creatinine x 100 (UAA/Cr) was higher in micro- (n = 6; 4.6 +/- 1.7) as compared to normoalbuminurics (n = 15; 1.6 +/- 0.9) or controls (1.5 +/- 1.2; p = 0.0001). For values exceeding renal threshold of tubular AA reabsorption (39 microM) the regression line of serum AA to UAA/Cr was significantly (p = 0.001) steeper in diabetics than in controls, suggesting an impaired tubular reabsorption of filtered AA in IDDM. The ratio of AA clearance to CCl was moreover related to AER (r = 0.48; p = 0.03) and to blood glucose (r = 0.51; p = 0.01), being unrelated to uric acid clearance, glycosuria and to urinary excretion of both alanine aminopeptidase and N-acetyl-beta-glucosaminidase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal excretion of ascorbic acid in insulin dependent diabetes mellitus. 796 Apr 90

Urinary enzymes were determined in a controlled study including 28 type I diabetes mellitus patients. Fifteen patients had persistent microalbuminuria and were compared to 13 normoalbuminuric patients with comparable age and sex distribution. All patients had normal renal function as measured by serum creatinine. Human intestinal alkaline phosphatase (hIAP), a specific marker of the proximal tubular S3 segment, was elevated in the urine of microalbuminuric patients while human tissue non-specific alkaline phosphatase (hTNAP), indicating effects mainly at the S1-S2 segments, was not. Urinary hIAP was correlated with serum glycated haemoglobin. These results suggest that tubular alterations are present at an early stage of diabetic nephropathy, especially at the S3 segment, and that hIAP may have promise as an early marker.
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PMID:Human urinary intestinal alkaline phosphatase as an indicator of S3-segment-specific alterations in incipient diabetic nephropathy. 808 50

Measurement of bone density and turnover was assessed in 20 premenopausal females with Type 1 diabetes mellitus and 27 age-sex-matched controls. Measurement was made of spinal (L2-4) and neck of femur bone density by dual-energy X-ray absorptiometry. L2-4 density was significantly higher in the diabetic patients compared with controls (1.224 +/- 0.021 g cm-2 vs. 1.161 +/- 0.020 g cm-2: p = 0.016). No significant difference was noted between the groups in neck of femur density. Measurement of bone formation was assessed by serum alkaline phosphatase and bone resorption by fasting urinary hydroxyproline/creatinine ratio. Alkaline phosphatase was significantly higher in the diabetic patients (185 +/- 16 Ul-1 vs 135 +/- 10 Ul-1: p < 0.01) as was hydroxyproline/creatinine ratio (0.028 +/- 0.003 vs 0.017 +/- 0.002: p = 0.002). No significant correlation was found between L2-4 density and glycated haemoglobin, duration of diabetes or daily dose of insulin taken. These data suggest that osteopenia is not associated with Type 1 diabetes mellitus; however these patients do have evidence of increased bone turnover and may therefore be at risk of osteoporosis in later life, particularly after the menopause.
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PMID:An evaluation of bone density and turnover in premenopausal women with type 1 diabetes mellitus. 809 68

The development of kidney disease in diabetes mellitus can be viewed as a two-stage process: (1) the development of proteinuria, and (2) its progression to chronic renal failure. Determinants of the latter were examined in 439 IDDM patients who had nephropathy and participated in the Diabetic Retinopathy Study. Using serum creatinine levels obtained during the follow-up period to assess the rate of loss of renal function, we found that only one-third of these patients experienced a rapid loss of function, while the others had slowly declining or unchanging renal function despite the presence of proteinuria and severe diabetic retinopathy. Among the many baseline variables examined, only elevated cholesterol and elevated systemic blood pressure were predictors of a rapid loss of renal function. Patients with this rapid loss of renal function also had the highest risk of death due to cardiovascular causes, as well as all causes. Once again, hypercholesterolemia was the major predictor of these deaths. In conclusion, efforts should be undertaken early to identify patients who are rapidly losing renal function so that interventions to modify systemic blood pressure and hypercholesterolemia may prevent or postpone the development of renal failure and death in patients with IDDM.
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PMID:Hypercholesterolemia--a determinant of renal function loss and deaths in IDDM patients with nephropathy. 815 81


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