Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The kidney changes seen in rats shortly after the induction of experimental diabetes were reviewed: Kidney weight increases by 15 to 20% during the first 4 to 5 days of diabetes and by 70 to 90% after some weeks. GFR increases after a lag-time of some days in parallel to kidney weight. Morphometric analysis shows glomerular hypertrophy to be prominent during the first few days of diabetes. The glomerular filtration surface increases by 40% after 4 days. Diabetic renal hypertrophy is related to the severity of the diabetes, and kidney growth rate relates linearly to blood glucose. Moderate diabetes mellitus and unilateral nephrectomy have approximately the same effect on the kidney (weight increase 20%/4 days). When diabetes mellitus and nephrectomy are combined, renal growth rate almost doubles.
 ...
PMID:Renal hypertrophy in experimental diabetes mellitus. 657 19

Tubuloglomerular feedback activity was evaluated in hydropenic rats, using "borrowed," glucose-free hydropenic late proximal tubular fluid as microperfusion solution, and in rats with modest hyperglycemia using both hyperglycemic (glucose-containing) and hydropenic (glucose-free) late proximal fluid as test solutions. Changes in nephron filtration rate (SNGFR) in the same nephron were evaluated in all states at zero and 24.6 nl/min late proximal tubule microperfusion rates (the observed hyperglycemic late proximal flow rate) using a Hampel microperfusion pump. In hydropenia, increased microperfusion rate decreased SNGFR, but in hyperglycemic rats, increased perfusion rate with glucose-containing fluid failed to change SNGFR. But when glucose-free, hydropenic fluid was used, SNGFR decreased numerically less than it did in hydropenia. Renal interstitial hydrostatic pressure increased in hydropenia during hyperglycemia, which may account for part of the inhibition of feedback response. Abolition of tubuloglomerular feedback activity during modest hyperglycemia is due to (1) the effects of glucose in the tubular fluid beyond the late proximal tubule and (2) the extraluminal effects of hyperglycemia on the renal interstitial pressure. These findings may explain the elevated GFR in early diabetes mellitus and excessive urinary volume losses during modest hyperglycemia.
 ...
PMID:Effect of modest hyperglycemia on tubuloglomerular feedback activity. 695 77

Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m2 (p less than 0.001), serum creatinine remained unchanged: 107 and 112/mumol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p less than 0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p less than 0.001). Glomerular filtration rate decreased linearly with time (slope = -0.75, r = 0.99, p less than 0.001) by a mean of 0.75 ml/min/month (range 0.1 to 1.5 ml/min/month). The decrease in GFR did not correlate wih sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR in each individual was constant, but varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy in young insulin-dependent diabetics.
 ...
PMID:A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. 701 39

GFR and, to a lesser extent, RPF are elevated soon after the onset of human diabetes mellitus. The mechanisms involved in these functional changes are unknown. Since the experimental diabetic rat has renal morphological changes similar to those observed in man, we investigated whole-kidney and superficial-nephron glomerular function in this animal model early during the course of the disease. Alloxan-induced diabetes (50 mg/kg BW) is frequently characterized by severe hyperglycemia and retarded body growth. Supplemental insulin administration (6 U of NPH insulin daily) results in normal body growth, although hyperglycemia persists. As a result, we studied four groups of diabetic rats (1) after 1 month of untreated diabetes, (2) after 3 months of untreated diabetes, (3) after 3 months of untreated diabetes followed by 1 month of insulin supplementation, and (4) after 3 months of insulin-supplemented diabetes. After 1 month of untreated diabetes, GFR and SNGFR each declined by 20% compared to age-matched control rats. RPF and SNGFR were both reduced by 33% as a consequence of a 41% increase in RT. Reduced SNGPF together with a 7 mm Hg reduction in PGC caused the fall in GFR and SNGFR. KWs were not significantly different from those of control rats. The functional changes that occurred after 1 month of untreated diabetes did not significantly deteriorate after 3 months of the disease. Insulin supplementation, when instituted for 1 month after 3 months of untreated diabetes, produced no significant improvement in either whole-kidney or superficial-nephron hemodynamics even though body and kidney growth were stimulated. In contrast, insulin supplementation initiated at the onset of diabetes increased both SNGFR and SNGFR to 23% above control values. GFR and RPF each increased in proportion to the 18% increment in kidney size. RT was reduced in these rats, and the pressures that govern glomerular ultrafiltration were not altered from control values. We conclude that in untreated diabetic rats, an increase in RT is the predominant hemodynamic alteration which produces reduced glomerular hemodynamic function. Once established, this defect may not be reversed with 1 month of insulin supplementation. In contrast, small doses of insulin initiated at the onset of diabetes result in renal hypertrophy and proportionate increases in GFR and RPF with a reduction in RT.
 ...
PMID:Determinants of glomerular filtration and plasma flow in experimental diabetic rats. 703 Nov 54

GFR, RPF, and kidney size were measured in nine young recently diagnosed insulin-dependent diabetics before (days 0) and 3 and 8 days after the beginning of the initial insulin treatment and in comparable control subjects. Kidney function was measured by a constant infusion technique using I-125-iothalamate and 131-I-hippuran. Kidney size was determined by means of ultrasound. Before insulin treatment elevated values for GFR (+44%, P less than 0.01), RPF (+18%, P less than 0.05), and kidney size (+29%, P less than 0.01) were found. Near-normal metabolic control was achieved in all patients using either multiple subcutaneous injections of insulin or an artificial betacell. GFR decreased from 160 +/- 9 SEM to 141 +/- 6 ml/min X 1.73 m2 (P less than 0.01) and further to 133 +/- 5 ml/min X 1.73 m2 (P less than 0.01, compared to day 0). Renal plasma flow was 601 +/- 33 and 588 +/- 44 ml x 1.73 m2 at days 0 and 3, respectively (NS) and decreased to 558 +/- 35 ml/min x 1.73 m2 at day 0 (P less than 0.01). By contrast no statistically significant changes in kidney volume were observed; the results on day 0, 3 and 8 were 145 +/- 7, 162 +/- 11 and 143 +/- 9 ml/1.73 m2, respectively. The present study demonstrates that kidney size and function are elevated at the onset of insulin-dependent diabetes. Near-normal metabolic control; for 8 days induces a reduction but not a complete normalization in kidney function. From the present observations it is suggested that the rapidly reversible part of the elevation in GFR cannot be explained by concomitant changes in kidney and glomerular size (morphological origin) but is probably due to a reduction in renal plasma flow and to a decreased transglomerular pressure (functional origin).
 ...
PMID:Kidney function and size in diabetics before and during initial insulin treatment. 705 May 6

The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.
 ...
PMID:Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia. 705 May 9

The relationship between exercise albuminuria and changes in renal haemodynamics during exercise in diabetes was investigated. In thirteen male, juvenile diabetic patients and seven comparable normal subjects GFR (125 I-iothalamate clearance) and RPF (131 I-hippuran clearance) as well as urinary albumin excretion were measured during the exercise test (450 kpm/min followed by 600 kpm/ min each for 20 min). All examined persons had normal baseline albumin excretion. The diabetics with a diabetes duration of 3-17 years exhibited increased albumin excretion during exercise, whereas there was no difference between the normals and the diabetics with less than 2 years of diabetes duration. The percentage changes during exercise in GFR, RPF and filtration fraction (FF) were at the same level in diabetics and normals. The FF was higher both in baseline values and during exercise for the two groups of diabetics when compared to the normals but no correlation between FF and albumin excretion could be demonstrated. Thus, elevated FF alone per se does not induce increase in albumin excretion. Systemic haemodynamics, heart rater and blood pressure, showed no difference between any of the groups. Concerning the abnormal albumin response in diabetics, it is concluded that the most likely explanation is that the glomerular membrane in these patients is unable to retain albumin when increased filtration pressure is operating during exercise. Altered renal haemodynamics during exercise may play a contributory role.
 ...
PMID:Albumin excretion and renal haemodynamic response to physical exercise in normal and diabetic man. 733 64

Fifty-five renal allografts (44 from living-related and 11 from cadaver donors) that have functioned for at least 20 years (mean 22.9 +/- 2.3, range 20.1 to 30.7 years) were evaluated in three groups based on renal function: group I (n = 26), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl and no proteinuria; group II (n = 9), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl but > 150 mg proteinuria/24 hr; and group III (n = 20), with a GFR < 60 ml/min/1.73 m2 and/or serum creatinine > 1.4 mg/dL with or without proteinuria. Allograft factors, including acute rejection (AR) in 62% (34/55) and delayed function (DF) in 55% (6/11) of the cadaver grafts, did not preclude 20-year success and the prospect of continued survival since they were not significantly more frequent in group I, II, or III. However, AR was confined to a limited period within the first three months posttransplant in 18/18 recipients in groups I and II but only in 7/16 of group III (P = 0.0002). In groups I and II AR was treated with IVMP in 14/18 cases and only 6/16 in group III (P = 0.035). Donor age < or = 50 years and recipient age < or = 40 years each occurred in 87% (48/55) of these transplants. One- or two-HLA haplotype matching was present in 98% (43/44) of living related transplants. Major risks to the recipient were coronary artery disease (11 cases and 3 deaths), malignancy (18 cases and 1 death), and severe infection and hepatitis (35 cases and 3 deaths, 2 of whom also had coronary artery disease). Hypertension occurred in 25 recipients and diabetes mellitus in 12. Potential open-end success was compromised by renal dysfunction in groups II and III, but appeared possible in 12 of the 26 patients in group I. There is no apparent "safe-haven" point of time for immunosuppressed renal allograft recipients, who remain at increased risk for eventual renal allograft dysfunction, as well as cardiovascular, neoplastic, infectious, and metabolic diseases. In order to clarify and standardize the words "long-term," a simple classification of long-term allograft survivals is proposed.
 ...
PMID:The fate of renal allografts functioning for a minimum of 20 years (level 5A)--indefinite success or beginning of the end? A proposed classification of long-term allograft survivals. 748 35

Diabetic nephropathy is a progressive renal disease and represents a serious late complication of diabetes. There are familial clustering and huge ethnic differences in the occurrence of diabetic nephropathy, which point to a genetic predisposition. Diabetic nephropathy is defined by persistent albuminuria (albumin excretion rate [AER] > 300 mg/day), declining glomerular filtration rate and rising blood pressure. Several years of incipient nephropathy, characterized by worsening microalbuminuria (AER 30 to 300 mg/day or 20 to 200 micrograms/min), which is Albustix-negative and detectable by special assays only, are followed by established nephropathy. The natural history of nephropathy differs between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In IDDM, nephropathy develops in 30 to 40% of cases. The incidence peaks after 15 to 16 years of diabetes. In NIDDM, estimates of prevalence range from 15 to 20%, and nephropathy often supervenes after a shorter known duration of diabetes than in IDDM. GFR is often increased above normal (hyperfiltration) from the onset of IDDM due to increased renal blood flow, glomerular capillary hypertension and increased filtration surface. The glomeruli are hypertrophied and the kidneys enlarged. In both IDDM and NIDDM, GFR begins to decline irreversibly, when AER has risen to 100 to 300 mg/day at an average rate of 10 ml/min. per year. This is due to progressive reduction of the filtration surface area through mesangial expansion. Serum creatinine levels begin to rise when GFR falls below 50 ml/min, and then end-stage renal failure follows after an average of five years.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Diabetic nephropathy: significance of microalbuminuria and proteinuria in Type I and Type II diabetes mellitus]. 749 50

The renin-aldosterone axis was evaluated by captopril test in 22 normotensive normoalbuminuric insulin-dependent diabetes mellitus (IDDM) patients with and without glomerular hyperfiltration. Patients were divided into those with glomerular hyperfiltration (Hf-IDDM) and with normal glomerular filtration rate (GFR; Nf-IDDM) according to the upper limit of GFR (134.7 ml/min per 1.73 m2). Sixteen normal individuals were also studied. GFR was measured by the 51Cr-EDTA single injection method, extracellular fluid volume as the distribution volume of 51Cr-EDTA, and blood volume using 51Cr-sodium chromate-labelled red blood cells. Twenty-five mg of captopril were administered per os and plasma renin activity (PRA; RIA), plasma aldosterone (RIA) and blood pressure were measured at 0 and 120 min post-captopril. PRA at time zero (Hf-IDDM = 2.4 +/- 1.7; Nf-IDDM = 2.5 +/- 1.9; controls = 1.0 +/- 0.6 ng/ml/h) and at 120 min (Hf-IDDM = 9.9 +/- 8.3; Nf-IDDM = 11.2 +/- 8.9; controls = 5.4 +/- 5.7 ng/ml/h) was higher in IDDM patients than in controls (P = 0.01). The increase of PRA was similar in patients (Hf-IDDM = 7.5 +/- 7.3, and Nf-IDDM = 8.7 +/- 7.2 ng/ml/h) and controls (4.4 +/- 5.3 ng/ml/h). There was no difference in PRA levels between Hf-IDDM and Nf-IDDM patients. PRA did not correlate with GFR, aldosterone, blood pressure, blood volume, duration of diabetes, 24-h urinary sodium and metabolic control indexes. Plasma aldosterone and the magnitude of its decrease after captopril was similar among patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1995 Mar
PMID:Renin-aldosterone axis in normoalbuminuric insulin-dependent diabetes mellitus patients with glomerular hyperfiltration. 755 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>