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)

A 62-year-old patient with non-insulin dependent diabetes (NIDDM) was admitted to our hospital for blood pressure control. He had been treated with angiotensin converting enzyme inhibitor (ACEI) for 7 years and showed marked hypokalemia with increased urinary potassium excretion. Hormonal examination revealed a normal plasma aldosterone concentration and increased plasma renin activity (PRA, 13.4 ng/ml/h), so potassium losing nephropathy was suspected. After discontinuation of the ACEI, PRA decreased to normal. An adrenal adenoma was found on abdominal magnetic resonance imaging (MRI) and adrenalectomy was performed to confirm aldosterone producing adenoma (APA). Although ACEIs are said not to alter PRA in APA, this drug was primarily responsible for the increased PRA in this case. This is a rare case of APA, which showed markedly increased PRA during ACEI treatment.
 ...
PMID:A case of aldosterone producing adenoma associated with high PRA after long-term angiotensin converting enzyme inhibitor treatment. 795 96

Lithium is the best available marker of proximal tubular reabsorption of fluid. The first part of the present thesis reviews the background for the use of the lithium clearance (CLi) method. Micropuncture studies on proximal reabsorption of lithium, showed that CLi is a reasonably correct measure of end-proximal fluid delivery rate, even during osmotic diuresis. During severe salt restriction, distal reabsorption of lithium renders the CLi method inappropriate in animals, but this problem does probably not occur in humans. The major current issue is whether a quantitatively significant reabsorption of lithium occurs in the loop of Henle. Available evidence is in accord with the interpretation that it does not occur. The interpretation of results form CLi studies depends to a surprising degree on the investigators beliefs about renal physiology. In the evaluation of proximal tubular function, the relevant parameter is the absolute proximal reabsorption rate of fluid and sodium. In the evaluation of integrated distal tubular reabsorption of sodium, the relevant parameter is the fractional distal reabsorption rate of sodium. The fractional CLi does not give meaningful information, and calculated absolute distal reabsorption rate of sodium is inherently not suited to detect modest changes in distal reabsorption leading to large changes in sodium excretion. Results from the use of the CLi method in relation to diabetes are reviewed in the second section. Even in IDDM patients with early diabetic nephropathy, the proximal reabsorption rate is elevated, resulting in a normal CLi despite glomerular hyperfiltration. Overnight euglycemia did not change GFR in IDDM patients, but during maintained euglycemia, GFR was normalized. A few hours of hyperglycemia prevented the decline in GFR, whereas CLi was unchanged. Thus hyperglycemia produced changes in renal function similar to those observed previously, but the time-course of the effect of euglycemia on kidney function is delayed. Plasma levels of atrial natriuretic peptide, renin and glucagon were not importantly affected by plasma glucose. In NIDDM patients CLi was normal, despite slight hyperfiltration, although this observation must be confirmed in a study with larger sample size. Prompted by the clinical observation of a marked decline in the GFR induced by carbonic anhydrase inhibitors, we studied the renal effects of acetazolamide in a controlled study.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus. 818 64

Enhanced GH secretion and hyperglycemia are suggested to play a role in the pathogenesis of glomerular hyperfiltration in insulin dependent diabetes mellitus. In this study we measured the GH response to GHRH (1 microgram/kg body weight), metabolic control, and renal function in 44 patients in order to explore a possible association between these parameters. Hyperfiltration [glomerular filtration rate (GFR) > 130 ml/min/1.73 m2] was present in 21 patients and normofiltration in 23. The duration of diabetes, plasma concentrations of renin, catecholamines, insulin-like growth factor-1 and blood glucose during renal function measurements were not different. GH response was significantly higher in patients with hyperfiltration. There was a positive relation between GH response and GFR (r = 0.51, P < 0.001) and effective renal plasma flow (r = 0.39, P < 0.01). GFR was correlated with insulin dose (r = 0.48, P < 0.001). There was no difference in glycosylated hemoglobin between the two groups. Patients with hyperfiltration used more insulin, had more frequent blood glucose values below the threshold level for activation of GH secretion, and had greater glycemic excursions than patients with normofiltration. The results suggest that GH hypersecretion and glomerular hyperfiltration are related and they support the possibility of a linkage between GH hypersecretion and glucose variability.
 ...
PMID:Glomerular hyperfiltration in insulin-dependent diabetes mellitus is correlated with enhanced growth hormone secretion. 834 58

The aim of the study was to assess the significance of the renin-angiotensin-aldosterone system (R-A-A) in the pathogenesis of arterial hypertension in patients with diabetes type I (IDDM). Testing was accomplished in the hospital conditions in a group of 131 patients with long-term IDDM, who beside of diabetes mellitus and its chronic complications did not show any symptoms of additional diseases. The patients were divided in 5 groups (A-E) depending on the type of coexisting late diabetic complications. The control group was consisted of 20 healthy persons matched for sex and age. In each case the following tests were performed: measurement of blood pressure in succumbent position, daily profile of glycemia and glucosuria, Hb A1 level, ophthalmoscopy, functional assessment of kidney and autonomic system status. Tenin activity in plasma (ARO) and plasma aldosterone (ALD) were determined in basal (after 6 h of succumbent position) and after i.v. administration of 40 mg of furosemide and 3 h of standing position (reactive values). In all groups under study the significant decrease of average, basal and reactive ARO was found in comparison with the control group. This abnormality was the most distinct in subjects with diabetic nephropathy. The autonomic neuropathy was abolishing this tendency. The mean concentration ob basal ALD was in all diabetic subgroups similar as in the controls. The mean reactive ALD was however significantly decreased. In diabetes complicated by retinopathy the negative correlation between ARO and systolic, diastolic and mean blood pressure existed. In diabetes complicated by nephropathy the dependence between blood pressure and ARO and ALD was not found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Basal and reactive renin and aldosterone secretion in arterial hypertension of insulin dependent diabetics]. 836 86

We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.
 ...
PMID:Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats. 839 Feb 68

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
 ...
PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

The objectives of the study were to assess the effects of moderate sodium restriction on blood pressure in insulin-dependent diabetic (IDDM) patients with nephropathy and high normal or mildly hypertensive blood pressure (primary objective), and to document possible associated changes of exchangeable body sodium, body volumes, components of the renin-angiotensin-aldosterone system, atrial natriuretic peptide, and catecholamines (secondary objective). Sixteen patients with untreated systolic blood pressure > or = 140 < 160 mmHg and/or diastolic blood pressure > or = 85 < 100 mmHg were included in a double-blind, randomized, placebo-controlled trial. After a 4-week run-in period on their usual diet and a 2-week dietary training period to reduce sodium intake to about 90 mmol/day, eight patients received 100 mmol/day sodium supplement (group 2) and eight patients a matching placebo (group 1) for 4 weeks while continuing on the reduced-sodium diet. Patients were examined at weekly intervals. Main response variables were mean values of supine and sitting systolic and diastolic blood pressure as measured in the clinic and by the patients at home. The differences in blood pressure between the beginning and the end of the blinded 4-week study period were calculated and the differences in changes between the two patient groups were regarded as the main outcome parameters. During the blinded 4-week study period, average urinary sodium excretion was 92 +/- 33 (mean +/- SD) mmol/day in group 1 and 199 +/- 52 mmol/day in group 2 (p = 0.0002). The differences in blood pressure changes between the two patient groups were 3.9(-1.2 to 9) mmHg [mean (95% confidence intervals)] for systolic home blood pressure, 0.9(-3.7 to 5.5) mmHg for diastolic home blood pressure, 4.9(-3.3 to 13.1) mmHg for clinic systolic blood pressure and 5.3(1 to 9.7 mmHg, p = 0.02) for clinic diastolic blood pressure. Combining all patients, there were relevant associations between changes of urinary sodium excretion and blood volume (Spearman correlation coefficient r = 0.57), blood pressure and angiotensin II (diastolic: r = -0.7; systolic: r = -0.48), and exchangeable body sodium and renin activity (r = -0.5). In conclusion, in this study of IDDM patients with nephropathy and high normal or mildly hypertensive blood pressure, a difference in sodium intake of about 100 mmol/day for a period of 4 weeks led to a slight reduction of clinic diastolic blood pressure. Studies including larger numbers of patients with various stages of nephropathy and hypertension are needed to definitely clarify the effects of sodium restriction in IDDM.
 ...
PMID:Effects of dietary sodium on blood pressure in IDDM patients with nephropathy. 863 74

Serum prorenin is increased in patients with insulin dependent diabetes mellitus (IDDM) with microvascular complications. The present longitudinal study investigated whether increases in serum total renin concentration (TRC, active+prorenin) can predict the development of microalbuminuria in IDDM patients over a 10 year period. TRC and albumin excretion rates (AER) were determined in 78 IDDM patients who were followed longitudinally for 10.4 +/- 0.2 (mean +/- SE) years. Twelve patients had progressively increasing albuminuria (progressors), and these were compared to 66 patients in whom albuminuria did not rise (non-progressors). The two groups had similar duration of diabetes, age, follow-up, glycemic control and blood pressure at the start of the study. Serum TRC was increased in progressors [350 (1.1) mIU/liter, geometric mean (tolerance factor)] compared to non-progressors [189 (1.2)] after 5 to 10 years duration of diabetes, and continued to rise in this group, reaching a mean of 923 mIU/liter (normal range 131 to 170) after 20 years of diabetes. When serial measurements of TRC and AER were compared in individual progressors, a significant increase in TRC was apparent up to five years before the onset of microalbuminuria. Microalbuminuria in patients with IDDM is preceded by a substantial increase in serum TRC, suggesting that serum TRC may predict the subsequent development of incipient nephropathy.
 ...
PMID:Serum total renin is increased before microalbuminuria in diabetes. 887 65

Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.
 ...
PMID:Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM. 887 96

Hypertension is seen in approximately 85% of IDDM patients with diabetic nephropathy and blood pressure elevation is an early event in the development of this complication. In IDDM patients with clinical nephropathy, a positive correlation has been demonstrated between the blood pressure and the urinary albumin excretion and reduction of blood pressure reduces albuminuria as well as the rate of decline in glomerular filtration rate. Also extrarenal abnormalities such as retinopathy, cardiovascular diseases and signs of endothelial dysfunction, sometimes seen in non-diabetics with severe and/or prolonged hypertension, are frequently demonstrated in IDDM patients with clinical nephropathy. The aim of the present study was to provide circumstantial evidence for the thesis that hypertension in IDDM patients with nephropathy is secondary to the kidney involvement and not the cause of the kidney disease. Furthermore, by familial and physiological studies the review also aimed to contribute to the understanding of the pathogenesis of hypertension in patients with clinical nephropathy. Finally the question of optimal pharmacological antihypertensive treatment was discussed. It was demonstrated that in IDDM patients with elevated urinary albumin excretion above normal level the prevalence of hypertension is 60%, whereas in patients without signs of renal impairment hypertension is not more prevalent as in the age and sex-matched background population (about 4% in both groups). Based upon the observation, that some of these IDDM patients with hypertension but normal UAE were hypertensive for many years, we designated this group as IDDM patients with essential hypertension for further studies. In this group, we had the opportunity to study the association between blood pressure and the development of extrarenal complications in patients with IDDM. The group with essential hypertension and IDDM showed to have less retinopathy compared with diabetics with similar blood pressure but elevated UAE. In contrast to the hypertensive patients with nephropathy, a normal transcapillary escape rate of albumin and normal plasma levels of von Willebrand factor, of angiotensin-converting-enzyme and of inactive renin were demonstrated in the former group of patients. Thus, the extrarenal abnormalities found in IDDM patients with hypertension are more closely associated to the presence of albuminuria than to the elevation of blood pressure, indirectly supporting the hypothesis that hypertension per se is not the cause of these abnormalities in the IDDM patients with nephropathy. Furthermore, the present study does not disclose a genetic disposition to hypertension in IDDM patients with elevated UAE.
 ...
PMID:Hypertension in insulin-dependent diabetes. 890 79


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