Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In early type 1 diabetes mellitus, hypertrophy of the kidney is a consistent finding. It is easily diagnosed using current noninvasive methods, especially ultrasonography. Renal functional changes occur in association with hypertrophy, most notably glomerular hyperfiltration. The structural counterpart of this functional change is an early increase in capillary filtration surface area. In most forms of nondiabetic renal hypertrophy, kidney size is closely linked to GFR, but in diabetes, hypertrophy persists after the clinical onset of overt kidney disease (microalbuminuria, hypertension, decreased GFR, etc). The fact that growth factors produced by the kidney can act in both an autocrine and paracrine fashion raises the possibility that the local effects of such substances may act as local mediators of kidney growth, but no such factor has been identified as the initiating or sustaining factor in diabetic hypertrophy. Failure of renal hypertrophy to reverse following strict glycemic control for a few months may turn out to be an important prognostic indicator of future progression of the renal disease, but this remains to be studied in a large group of patients.
 ...
PMID:Renal hypertrophy, growth factors, and nephropathy in diabetes mellitus. 219 Feb 81

Fig. 5 provides a summary of the natural history of diabetic nephropathy in IDDM patients. The figure also includes the possibilities of intervention in the various stages of diabetic nephropathy. GFR values in normals are shown by the hatched area in the upper part of the figure. The lower part shows development of albuminuria. The level 20-200 micrograms/min is the microalbuminuric range. At present it is not possible to predict a malignant course either from the parental history (1), or from the prediabetic course (2). Neither at clinical diagnosis of diabetes, can complications be predicted (3). The figure shows a typical course in a patient developing diabetes at the age of 14 years. The patient showed poor metabolic control as indicated by the high level of GFR (greater than 150 ml/min) (4) and the increasing albumin excretion rate (4). At the age of 22 years the patient developed microalbuminuria (5) and later clinical nephropathy at age 30 years, typically after 16 years of diabetes. Blood pressure rises, and GFR starts to decline during incipient diabetic nephropathy with increasing microalbuminuria (greater than 70 micrograms/min) (5) (6), and end-stage renal failure reached at the age of 40 years,--if intervention is not undertaken. Intervention is possible as follows: A) hyperfiltration may be reduced by non-glycemic intervention such as a moderate reduction of protein intake, treatment with aldose reductase inhibitors (work in progress) or acute administration of a somatostatin analogue.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of blood pressure intervention on renal function in insulin-dependent diabetes. 261 18

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
 ...
PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

Early in the course of type 1 diabetes mellitus, hypertrophy of the kidney is a consistent finding that is easily diagnosed using current noninvasive methods, especially ultrasonography. Renal functional changes occur in association with hypertrophy, most notably glomerular hyperfiltration. The structural counterpart of this functional change is an early increase in capillary filtration surface area. In most forms of nondiabetic renal hypertrophy, kidney size is closely linked to GFR. In contrast, in diabetes, persistence of hypertrophy after the clinical onset of overt kidney disease (microalbuminuria, hypertension, decreased GFR, etc.) suggests that sustained release of one or more growth factors may continue even after kidney function declines. The fact that growth factors can act in both an autocrine and paracrine fashion raises the possibility that the local effects of such substances may act as local mediators of kidney growth. Failure of renal hypertrophy to reverse following strict glycemic control for a few months may turn out to be an important prognostic indicator of future progression of the renal disease, but this remains to be established. Prospective studies of kidney size in patients with newly diagnosed type 1 diabetes, using accurate noninvasive methods, may be helpful in establishing whether irreversible ("autonomous") hypertrophy of the kidney is indeed a useful prognostic indicator. As therapies are developed that target the different microvascular complications of diabetes (retinopathy, nephropathy, neuropathy), a noninvasive estimation of kidney size may be a cost-effective method of predicting ultimate renal involvement. Since microalbuminuria occurs relatively late in the disease process, early and persistent hypertrophy of the kidney may become a useful prognostic test in the earliest stages of the disease.
 ...
PMID:Prognostic implications of renal hypertrophy in diabetes mellitus. 328 9

We studied 45 IDDM without c-peptide response, duration 7-22 years, without proliferative retinopathy. After 2 months run-in period, they were randomly assigned to: (P) 15 received CSII: (C) 15 received multiple s.c. injections via butterfly 5-6x daily;: (M) 15 received twice daily mixed rapid and long acting insulin. All groups improved blood glucose control in the run-in period (p less than 0.0001). After change of treatment (P) and (M) improved further (p less than 0.01) but (C) was unchanged. GFR was supranormal and decreased in (P) and (M). No regression of retinopathy was shown in any group. One in (P) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment. We conclude that retinal response to strict control is complex. A transient deterioration may been seen.
 ...
PMID:The influence of strict control on diabetic complications. 391 5

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

Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal experiments have shown that noradrenaline (NA) infusion increases the intraglomerular pressure by predominantly efferent arteriolar vasoconstriction. The relationships between ambient plasma NA levels and renal haemodynamics were studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic patients (group D1) (albumin excretion rate (Ualb V) < 20 micrograms min-1), and in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20-200 micrograms min-1), all patients being without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml min-1 1.73 m-2)) and effective renal plasma flow (ERPF (ml min-1 1.73 m-2)) were determined over a 2-h period using constant infusions of 125I-iothalamate and 131I-hippuran, respectively. The subjects were studied in the fasting state. The diabetic patients were investigated during near normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126 +/- 15 and 538 +/- 89, respectively) were elevated as compared with controls (108 +/- 15 and 478 +/- 73; p < 0.01 and p < 0.05, respectively). In group D2, GFR (124 +/- 25, p < 0.05) but not ERPF (515 +/- 104) was higher than in the controls. GFR and ERPF were negatively correlated with venous plasma NA in group C (r = -0.61, p < 0.005 and r = -0.64, p < 0.001, respectively), in group D1 (r = -0.54, p < 0.03 and r = -0.63, p < 0.005, respectively) and in group D2 (r = 0.53, p < 0.03 and r = -0.60, p < 0.01, respectively). Multiple regression analysis disclosed that diabetes per se, independent from plasma NA, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are inversely related to venous plasma NA levels, both in healthy and in diabetic subjects, supporting the hypothesis that plasma NA is a vasoconstrictive substance. The independent positive effect of diabetes as a categorial variable on GFR, suggests that concomitant vasodilating mechanisms play a role in the renal haemodynamic alterations in Type 1 diabetes mellitus.
 ...
PMID:Influence of ambient plasma noradrenaline on renal haemodynamics in type 1 (insulin-dependent) diabetic patients and healthy subjects. 762 32

Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0.35]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged AHT is not known. To elucidate these mechanisms we investigated 42 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured the last day on AHT and one month after withdrawal of AHT. The measured variables were all significantly elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P < 0.0001), BP [mean(SEM)] from 140/82 (2/1) to 151/89 (2/1) (P < 0.0005) and albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P < 0.0001). A correlation between relative rise in systolic blood pressure (delta Sys%) and relative change in GFR (delta GFR%) was found (r = 0.44, P < 0.005). Our results render some support of the hypothesis that the faster initial decline in GFR is due to a functional (hemodynamic) effect of AHT, which does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.
 ...
PMID:Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy. 764 42

The effect was studied of blood pressure lowering treatment on renal failure and albuminuria (UAE) in patients with type I diabetes (IDDM) and imminent nephropathy as well as in patients with over diabetic nephropathy. The group of 24 patients with imminent nephropathy was subdivided: 1. twelve patients with borderline or overt hypertension with mean BP lowered not below 100 mmHg, and 2. twelve patients with BP within the normal limits, taking no hypotensive agents. In the other group of 12 patients with overt diabetic nephropathy hypertension was lowered below 105 mmHg and kept so for at least two years. All patients estimated their glycemia and glycosuria by themselves, ate 0.8 g protein/kg/24 h and about 100 mmol Na/24h. Under hospital conditions the following were estimated: albuminuria, glomerular filtration rate (51Cr EDTA) and effective renal blood flow (131I hippurate). The same examinations were repeated 1 year and 2 years later. The lowering of BP below 100 mmHg in patients with imminent diabetic nephropathy significantly lowered microalbuminuria without changing GFR, ERPF despite good or satisfactory compensation of diabetes. Maintaining BP below 105 mmHg for 2 years did not prevent the patients with overt nephropathy to develop progressive renal failure despite the rate of GFR deterioration and of the increase of albuminuria slowed down.
 ...
PMID:[Effect of treatment of arterial hypertension on renal function in patients with imminent and overt diabetic nephropathy]. 773 1

The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19


<< Previous 1 2 3 4 5 6 Next >>