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)

Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and 200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all authors. In addition, various methods may influence the results. The significance of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes nephropathy is the most important complication. In adult type 2 diabetics the prognosis concerns mainly cardiovascular death. The excess mortality to be attributed to MA is several fold in type 1 diabetes, less in the adult onset type variety. MA is the expression of an incipient general disease of blood vessels touching as much the kidney as the heart. According to the presence or absence of other vascular damage. MA develops toward nephropathy or cardiovascular complications. The features leading to or worsening MA are elevated blood pressure, poor glucose control, elevated lipoproteins, diminished insulin sensitivity and probably smoking. Retinopathy is an indicator for particularly sensitive patients responding with the development of MA upon only mildly elevated blood pressure or poor metabolic control. The prevalence of MA is close to 20% for both types of diabetes. Non-diabetic persons under 60 years of age exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with hypertension MA is reported to be present in 19%. Over a time span of 5 years, 19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours. In a third of cases albumin excretion normalises. In the remaining half a small progression of MA occurs. For type 2 patients the increased mortality risk is restricted to the first 5 years, thereafter the survival curves return to those of patients without MA. In these patients the excess mortality is already present at albumin excretion rates above 10 micrograms/min. Higher values have, therefore, to be considered pathological. For the treatment of the syndrome ACE-inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine, nifedipine) are recommended. They reduce albumin excretion by 50%. In a single study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would imply that the excess mortality could be halved in patients undergoing this treatment.
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PMID:[Microalbuminuria in diabetes mellitus--illness or symptom?]. 873 41

The influence of diabetic nephropathy on urinary glycosaminoglycan distribution was assessed in 96 patients with insulin-dependent diabetes mellitus (IDDM, 49 female, age: 16 - 64 yrs, median 35; duration of IDDM: 0 - 43 yrs, median 13 yrs) in comparison to 103 healthy controls (57 female, 17 - 82 yrs, median 40 yrs). Glycosaminoglycan concentration of 24 h urine samples was determined by means of precipitation with cethylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (p = 0.0008) in urinary glycosaminoglycan excretion between patients (19.0, 12.4, 35.6 mg/24 h, median, 25th, 75th percentile) and controls (15.8, 10.4, 21.6 mg/24h) could be detected. In patients with insulin-dependent diabetes mellitus of longer duration, glycosaminoglycan excretion was increased (<10 years: 17.3, 10.8, 30.5 mg/24 h; > 10 yrs: 23.3, 16.0, 39.1 mg/24 h; p = 0.03). Furthermore, diabetic patients with manifest nephropathy and retinopathy exhibited a significantly higher glycosaminoglycan excretion compared to patients without nephropathy (40.8, 23.3, 42.2 versus 18.2, 11.4, 31.0 mg/24 h, p = 0.005) or retinopathy (31.9, 16.6, 41.6 versus 17.6, 11.2, 26.7 mg/24 h, p = 0.009). Thus, the results of this study demonstrate a close relationship between diabetic nephropathy and the renal glycosaminoglycan excretion.
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PMID:Insulin-dependent diabetes mellitus and glycosaminoglycans. 875 Jul 85

A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.
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PMID:Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus. 884 Feb 99

Prospective registry of newly diagnosed cases of insulin-dependent diabetes mellitus in subjects under 20 years began in 1988 in Aquitaine, Lorraine, Basse- and Haute-Normandie (population base = 2,288,018 inhabitants under 20). The registry gave a complete coverage of the population as the capture-recapture method gave a 98% yield. The mean annual incidence was 7.6/100,000 for the period 1988-1990. A specific survey aimed at describing clinical and biological presentation at diagnosis. The main symptom was polyuria in 98% of the cases, fatigue in 58% and weight loss in 44%. Abdominal pain was reported in 34% of the cases. Diagnosis was ascertained by measurement of plasma glucose, which was > or = 11 mmol/l in 95% of the cases and associated with ketonuria in 84% of the children. Coma in 13% of the children and acidosis (total CO2 < or = 18 mmol/l) in 48% showed the severity at diagnosis. Ketonuria and acidosis were significantly more frequent in the younger age group (0-4 yr). Diagnosis was made by a general practitioner in the majority of the cases; conversely insulinotherapy was initiated at the hospital in 95% of the cases. Initial insulin treatment was 2 daily injections. Following the French experience the collaborative network EURODIAB ACE has undertaken the same survey among the European Registries. Important geographical variations in incidence rates of IDDM in children has been reported across Europe but it is not known whether this interferes with presentation at diagnosis of the disease.
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PMID:[Diagnosis of insulin-dependent diabetes in children: data from the incidence registry]. 893 70

Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95% CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/- 5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group (P < 0.05). The effect of study medication on albuminuria and GFR was independent of changes in systemic blood pressure and baseline variables in multiple regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic nephropathy during the 1st year of treatment. Longer follow-up is required to clarify whether these drugs have different renoprotective effects.
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PMID:Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment. 903 6

Diabetic nephropathy affects a subset of about 40% patients with Insulin-Dependent Diabetes Mellitus (IDDM); it also develops in a less defined percentage (30-50%) of patients with non Insulin-Dependent Diabetes Mellitus (NIDDM), after a period of 15-20 years. It is usually divided in 5 stages: the first 3 are characterized by renal hypertrophy and increased glomerular filtration surface area (I stage) followed by glomerular histological lesions (II stage) and early nephropathy with microalbuminuria (III stage). At these stages nephropathy is still reversible by medical treatment (ACE inhibitors) and good metabolic control. Aim of this study was to assess the usefulness of duplex sonography with Doppler wave form analysis in the evaluation of early diabetic nephropathy, in order to detected patients at risk for irreversible renal disease. Fifteen patients (10 males and 5 females) aged 28-46 years, affected by IDDM were studied; 15 healthy subjects (7 males and 8 females) aged 20-45 years composed the control group. All of them underwent duplex Doppler sonography of kidney; a scanner with a 3.5 MHz transducer (Toshiba 270 SSA) was used. All patients had renal function tests within normal range. Pulsatily Index (P.I.) and Resistive Index (R.I. of Doppler waveform were obtained at the interlobar arteries; the average value of 3 bilateral measurements was taken. Doppler sonography was done by the same authors without knowledge of the patient group (case or control). Both indexes (P.I. and R.I.) resulted to have higher values in patients with IDDM compared to controls: P.I. = 1.46 +/- 0.30 vs. 1.07 +/- 0.06, p < 0.05; R.I. = 0.77 +/- 0.09 vs 0.60 +/- 0.03, p < 0.05. Even if our data have to be confirmed by further studies, they suggest that duplex Doppler sonography may be a useful complementary test in the evaluation of diabetic nephropathy, even in the early stages.
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PMID:[Pulsed-wave color Doppler echography of the intrarenal vessels in patients with insulin-dependent diabetes mellitus and incipient nephropathy]. 916 57

Diabetic nephropathy accounts for almost a third of all causes of ESRD. Microalbuminuria screening among diabetics can offer early detection of incipient nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of overt renal failure or delay its progression. Furthermore, intensive control of blood glucose has also been proven to prevent the microvascular complications of diabetes and should be pursued in both IDDM and NIDDM. The high association of diabetes mellitus with hypertension presents another problem to the clinician. It is necessary to control blood pressure to prevent further progression of renal failure. The choice of antihypertensive medications, however, becomes a therapeutic dilemma because of the metabolic and lipid disturbances that some drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics, alone or in combination, may be tried to normalize blood pressures. Although beta-blockers are widely used and effective in nondiabetics, these agents should be considered the drugs of last resort because of their adverse effects, which are particularly troublesome for diabetics. Moderate protein restriction should also be advocated as a helpful adjunct to therapy.
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PMID:Diabetic nephropathy. 916 51

Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data supporting an additional place in managing normotensive patients with microalbuminuria and IDDM. These findings, together with some evidence for an effect of lisinopril in delaying progression of retinopathy and in reducing mortality, suggest a broader role for the drug in managing diabetic vascular complications.
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PMID:Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus. 917 32

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.
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PMID:Diabetic microangiopathy and urinary glycosaminoglycans. 922 10

High resolution 1H nuclear magnetic resonance (NMR) spectroscopic analysis of biofluids is a recently established tool for evaluating inherited and acquired errors in metabolic control. In the present study 1H NMR analysis of urine was used to monitor efficacy of BRL 49653, a potent and selective antihyperglycaemic agent, following oral administration for up to 36 weeks to the genetically diabetic C57BL/KsJ db/db mouse. The effects of BRL 49653 on carbohydrate and fatty acid metabolism were monitored by determination of changes in concentrations of low molecular weight urinary metabolites. A qualitative comparison of the NMR spectra of urine from untreated diabetic mice with those of lean littermates and literature examples revealed several abnormalities, the majority of which could be explained in terms of the non-insulin dependent diabetes syndrome exhibited by these animals. Quantitatively the most prominent was the extreme glycosuria of both young (8-12 weeks; 0.9 g glucose kg-1 h-1) and older (42 weeks; 2 g glucose kg-1 h-1) diabetic mice. This was accompanied by the excretion of a number of unassigned sugar derivatives and by ketone bodies. Administration of BRL 49653 (3 mumol kg-1) to db/db mice for 24 days reduced blood glucose concentrations to values comparable with non-diabetic lean littermates and reduced glycosuria by > 90%. BRL 49653 significantly reduced excretion of unassigned sugars, acetate, lactate, and the ketone bodies, acetoacetate, 3-D-hydroxybutyrate and acetone. The anti-diabetic efficacy of BRL 49653, assessed from the pattern of urinary metabolites, was maintained over a 36-week treatment period. These results demonstrate the value of 1H NMR to evaluate non-invasively the efficacy of novel therapeutic agents.
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PMID:Antidiabetic efficacy of BRL 49653, a potent orally active insulin sensitizing agent, assessed in the C57BL/KsJ db/db diabetic mouse by non-invasive 1H NMR studies of urine. 923 58


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