UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 78 Chinese patients with clinically uncomplicated non-insulin-dependent diabetes (NIDDM) who had plasma creatinine concentrations of < 150 mumol/l were studied. Antihypertensive treatment was discontinued for at least six weeks prior to measurements of routine biochemistry, proteinuria, plasma atrial natriuretic peptide (ANP) concentrations and components of the renin-angiotensin-aldosterone system (RAAS). BP was measured on three occasions during the six weeks period prior to these measurements. At the end of the six week period, a total of 33 patients had definite hypertension (supine BP > or = 160/95 mmHg). The hypertensive patients had significantly higher plasma sodium (mean +/- SD): 140.3 +/- 1.9 vs. 138.5 +/- 2.0 mmol/l, P < 0.001) and lower plasma potassium (3.8 +/- 0.5 vs. 4.2 +/- 0.5 mmol/l, P < 0.01) concentrations. These were associated with reduced plasma aldosterone (median (range): 297 (98-1145) vs. 448.5 (93-1330) pmol/l, P < 0.01) and renin concentrations (16.8 (7.4-71.8) vs. 23.5 (7.4-83.7) ng/l, P = 0.06). The hypertensive patients also had significantly higher plasma ANP concentrations (36.5 (20.5-125.1) vs. 23.2 (11.7-63.0) pg/ml, P < 0.001), serum angiotensin converting enzyme (ACE) activity (65 (26-140.9) vs. 47 (22-106) units/l, P < 0.001) and urinary albumin excretion (UAE) (35.4 (1.6-4800) vs. 7.8 (1.8-310.4) mg/day, P < 0.001). Glycaemic control and renal function were similar between the two groups. Mean arterial pressure (MAP) correlated positively with plasma ANP concentration (r = 0.53, P < 0.001) and serum ACE activity (r = 0.37, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide and renin-angiotensin-aldosterone system in non-insulin-dependent diabetes mellitus. 808 30

Acute effects of 20 mg oral enalapril (E), and angiotensin-converting enzyme inhibitor, on renal function and the renin-angiotensin-aldosterone system were investigated in 13 patients with type II diabetes mellitus (8 female, 5 male) and 10 hypertensive controls using a radionuclide method. Plasma glucose control was evaluated with fructosamine (F) determinations. After intravenous administration of 370 MBq 99mTc-DTPA, sequential images were recorded. Glomerular filtration rate (GFR), perfusion index (PI), time to maximum activity and reno index values of the kidneys were calculated. Two days later, renal scintigraphy was repeated after oral administration of E. Plasma levels of renin, angiotensin II and aldosterone were analyzed using RIA. Basal GFR values (mean: 92.6 ml/min) correlated with F (r = 0.364; p < 0.05). In the diabetic group, 5 patients had a decrease in GFR and an increase in PI after oral E. The mean percent change of GFR was 12 +/- 32 for patients and 20 +/- 12 for controls, respectively. Percent change of GFR had a slightly negative correlation with F values (r = -0.51; p < 0.05) and with PI (r = -0.65; p < 0.001). The patients with good metabolic control had an increase in GFR and a decrease in PI indicating an increase in renal blood flow and glomerular filtration. In patients with proteinuria and poorly controlled diabetes, in response to E-induced efferent arteriolar dilation, there is a decrease in GFR and an increase in PI which indicates a fall in filtration and renal blood flow. This glomerular hemodynamic pathology precedes morphological changes due to diabetes.
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PMID:Scintigraphic evaluation of functional renal reserve using angiotensin-converting enzyme inhibition in patients with type II diabetes mellitus. 821 32

Evidence that an increase in plasma atrial natriuretic peptide (ANP) concentrations mediates, at least in part, glomerular hyperfiltration in diabetic rats prompted us to study the relationship between ANP and renal haemodynamics in hyperfiltering type 2 diabetic patients in association with other hormones implicated in the control of glomerular filtration rate (GFR) (catecholamines, vasopressin, renin) and in sodium tubular transport (aldosterone, ouabain-displacing factor, ODF). Since hyperglycaemia is also associated to hyperfiltration, diabetic patients who presented with secondary drug failure were studied both in hyperglycaemic and in normoglycaemic condition. For this purpose, 11 normotensive non-macroproteinuric hyperfiltering patients with type 2 diabetes were treated with an 8-day continuous insulin infusion (days 0-7). Dehydration was prevented or corrected and natriuresis was on day 0 above 100 mmol/day. The following parameters were determined on days 0 and 7: GFR and renal plasma flow (RPF) by 99mTc-DTPA and 131I-hippuran clearances; the extracellular volume, assimilated to the DTPA diffusion volume; urinary ODF by receptor-binding assay and urinary as well as plasma catecholamines by HPLC after extraction on alumin. Plasma ANP and antidiuretic hormone (ADH) were measured by radioimmunoassay after extraction on phenyl-silylsilica (ANP) and with ether (ADH). Unextracted plasma was used for radioimmunological measurement of plasma renin activity and aldosterone. When correcting hyperglycaemia to normoglycaemia GFR decreased from high to normal mean value (138 +/- 27 and 115 +/- 6 ml/min, p < 0.001), RPF followed the same trend, and the DTPA diffusion volume did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natriuretic and vasoactive hormones and glomerular hyperfiltration in hyperglycaemic type 2 diabetic patients: effect of insulin treatment. 844 67

We examined the effect of an orally effective, nonpeptide AVP.V1-receptor antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non-insulin dependent diabetes mellitus (NIDDM) patients (seven patients with microalbuminuria, four with overt nephropathy, and three with normoalbuminuria) and in three normal subjects. The oral administration of 100 mg of OPC21268, which is sufficient to suppress the vasoconstriction induced by exogenously infused AVP, caused a significant decrease in urinary albumin excretion only in NIDDM with microalbuminuria concomitantly with a slight decrease in filtration fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2 microglobulin excretion did not change at all during the study. Neither change in systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In conclusion, in NIDDM patients with microalbuminuria, an increase in the sensitivity of contraction of glomerular efferent arterioles via an activation of AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a decrease in urinary albumin excretion due partly to decrease the intraglomerular capillary pressure. This compound may be useful for the treatment of NIDDM microalbuminuria.
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PMID:Effect of AVP.V1-receptor antagonist on urinary albumin excretion and renal hemodynamics in NIDDM nephropathy: role of AVP.V1-receptor. 857 58

During long-term treatment of arterial hypertension with calcium antagonists of the dihydropyridine type activation of the sympathetic nervous system and subsequently also of the renin-angiotensin-aldosterone system persists, while the haemodynamic reaction to vasodilatation, manifested by an elevated pulse rate and minute volume from the initial stage of therapy, recedes. In type II diabetics the basal and stimulated response of the renin-angiotensin-aldosterone system is reduced. The administration of calcium antagonists of the dihydropyridine type does not stimulate significantly the renin-angiotensin-aldosterone system as the starting function of the sympathetic nervous system is impaired within the framework of vegetative neuropathy. In almost 20% NIDDM plasma renin activity and aldosterone do not respond to furosemide administration and the vertical posture. In others the response is found but takes place at reduced levels. Hyporeninaemic hypoaldosteronism is thus manifested not so much by a drop of plasma renin and aldosterone beneath the lower range of reference values as by a reduced response to stimulation. Functional hyporeninaemic hypoaldosteronism is another, frequent late complication of diabetes. In advanced forms a further block of the renin-angiotensin-aldosterone system by ACE inhibitors can then produce, even in the absence of diabetic nephropathy, in the stage of chronic renal failure dangerous hyperkaliaemia which may threaten the patient. Dynamic examination of the sympathetic nerve and the renin-angiotensin-aldosterone system makes it possible to predict this condition. In practice it is necessary in diabetics with arterial hypertension after starting with ACE inhibitors during the first days to monitor repeatedly plasma potassium and creatinine. ACE inhibitors and calcium antagonists are otherwise for diabetics drugs of first choice which can arrest the progression of nephropathy, effectively reduced the blood pressure without causing deterioration of insulin resistance and hyperlipoproteinaemia and lead even to regression of hypertrophy of the vascular wall and left ventricle.
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PMID:[The effect of long-term treatment of arterial hypertension with Ca antagonists on the renin-angiotensin-aldosterone system in diabetics. Hyporeninemic hypoaldosteronism]. 857 95

Isolated hypoaldosteronism is found in 75% diabetics where the disease has persisted for 10 or more years. Sporadically it is found in congenital autonomous neuropathy, in acute glomerulonephritis, in gouty kidney, tubulointerstitial nephritis, after transplantation of the kidney, on mytomycin etc. During dynamic testing of the response of plasma renin activity and aldosterone to the administration of furosemide and a vertical position in diabetics a significantly reduced response was recorded as compared with non-diabetic hypertonic subjects. In 18.3% no response was observed (decompensated form of IHH). Diabetic hypertonics behaved like control hypertonics on long-term beta-blocker treatment. In the decompensated form of IHH after administration of drugs interfering with the activity of SNS-RAAS activity (ACEI, spirolactone etc.) a hyperkalaemic crisis may develop which threatens the patient with acidosis, dehydration, myoplegia, muscular spasms, however, in particular with fatal disorders of the cardiac rhythm. A similar effect may be exerted also by blockers of prostaglandin synthetase (non-steroid antirheumatics) and other drugs. The cause of IHH in diabetics is the coincidence of several pathogenic factors: 1. hypersecretion of ANF with hyperosmolar hyperglycaemic hypervolaemia and hyperfiltration already at the onset of DN, 2. early development of autonomous neuropathy of the sympathetic nerve, 3. reduced renin and prostaglandin formation already in the early stages of DN, 4. reduced extrarenal isorenin formation, 5. reduced conversion of prorenin into active renin, 6. reduced reactivity of the zona glomerulosa to AII, hyperkalaemia and ACTH for its functional reconstruction as a result of periodic activation of contraregulative hormones by fluctuations of the blood sugar level in diabetic patients, 7. reduced response of the distal renal tubule to aldosterone because of tubulointerstitial changes. IHH is thus another serious but rarely diagnosed late complication of diabetes which depends only partly on the stage of DN. It must be, however, diagnosed and respected with regard to the selection of drugs for the treatment of arterial hypertension and the syndrome of insulin resistance and the 5H syndrome resp., i.e. the association of hyperinsulinism which compensates insulin resistance with hyperglycaemia (NIDDM), hypertension, hyperlipoproteinaemia and hirsutism in women (so-called Stein-Leventhal syndrome).
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PMID:[Diabetic nephropathy and isolated hyporeninemic hypoaldosteronism]. 892 9

Base on their own experience with isradipine and results of a multicentric study with amplodipine in the Slovak Republic, as well as based on data in the literature the authors conclude that: 1. In the treatment of arterial hypertension associated in the syndrome of insulin resistance (syndrome X and 5H resp.) with type 2 diabetes, hyperlipiproteinaemia and hyperinsulinism drugs of first choice include ACE-inhibitors and Ca antagonist of the second generation, dihydropiridine type, such as amplodipine, isradipine, fellodipine, nirtendipine etc. ACE inhibitors and Ca antagonist of the dihydropyridine type with prolonged effect have a good tolerance, few undesirable effect, a favourable effect on the decline of BP, regression of hypertrophy of the left ventricle and vascular wall; they do not cause deterioration of insulin resistance and thus do not interfere with compensation of diabetes and associated hyperlipoproteinaemia. 2. ACE inhibitors moreover reduce glomerular filtration and albuminuria and thus retard along with the effect on BP the progression of diabetic nephropathy. 3. In pre-existing hyporeninemic hypoaldosteronism (cca in 18% diabetic subjects) they can however cause dangerous hyperkalinaemia by further inhibition of the damaged renin-angiotensin-aldosterone system. In instances Ca inhibitors are indicated. The latter activate RAAS and do not have an impact on albuminuria. By their effect on the vas deferens they can increase glomerular filtration. 4. Diuretics are not suitable for the treatment of hypertension in X syndrome and the use of beta-blocking agents even with ISA and beta-1-selective preparations in restricted in particular when insulin is administered or other numerous contraindications are present (cardiac failure, bradyarrythmias, bronchitis etc.). Perhaps a combination of ACE-inhibitors and Ca antagonists of the 2nd generation with an alpha-blocking agent or hybrid alpha-beta-blocking agent is a suitable solution.
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PMID:[The role of calcium inhibitors in the treatment of arterial hypertension]. 924 72

Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.
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PMID:Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? 1115 22

11beta-hydroxysteroid dehydrogenases (11beta-HSDs) catalyze the interconversion of active glucocorticoids (cortisol, corticosterone) and inert 11-keto forms (cortisone, 11-dehydrocorticosterone). 11beta-HSD type 2 has a well recognized function as a potent dehydrogenase that rapidly inactivates glucocorticoids, thus allowing aldosterone selective access to otherwise nonselective mineralocorticoid receptors in the distal nephron. In contrast, the function of 11beta-HSD type 1 has, until recently, been little understood. 11beta-HSD1 is an ostensibly reversible oxidoreductase in vitro, which is expressed in liver, adipose tissue, brain, lung, and other glucocorticoid target tissues. However, increasing data suggest that 11beta-HSD1 acts as a predominant 11beta-reductase in many intact cells, whole organs, and in vivo. This reaction direction locally regenerates active glucocorticoids within expressing cells, exploiting the substantial circulating levels of inert 11-keto steroids. While the biochemical determinants of the reaction direction are not fully understood, insights to its biological importance have been afforded by use of inhibitors in vivo, including in humans, and the generation of knockout mice. Such studies suggest 11beta-HSD1 effectively amplifies glucocorticoid action at least in the liver, adipose tissue, and the brain. Inhibition of 11beta-HSD1 represents a potential target for therapy of disorders that might be ameliorated by local reduction of glucocorticoid action, including type 2 diabetes, obesity, and age-related cognitive dysfunction.
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PMID:Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action. 1125 Sep 14

We have documented, contrary to expectation, that the renin-angiotensin-aldosterone system (RAAS) is stimulated normally by restriction of sodium intake inpatients with Type 2 diabetes mellitus (DM) and hypertension. Conversely, plasma renin activity (PRA)is suppressed less than in normal subjects by a high-salt diet in these patients. Increasing plasma angiotensin II (Ang II) concentration through intravenous Ang II infusion also suppresses renin release, via the short feedback loop. In this study, we sought to ascertain whether the limited renin suppression in Type 2 diabetes mellitus via high-salt intake is a unique defect or part of a more generalised abnormality of PRA suppression. We studied 38 patients with Type 2 DM and hypertension, 158 hypertensive control patients, and 61 normotensive controls. All patients were studied while in metabolic balance on a 10 mEq sodium (Na) diet. The response to the Ang II infusion at 3 ng/kg/min for 45 minutes was measured. We found that PRA fell significantly in normal subjects, from 4.0 +/- 0.33 to 2.5 +/- 0.23 ngAngI/ml/hr (p=0.0056). In patients with essential hypertension, the Ang II infusion also led to a fall in PRA from 3.51 +/- 0.23 to 2.76 +/- 0.17 ng Angl/ml/hr(p=0.014). In patients with DM, despite a similar basal PRA (3.7 +/- 0.40 ng AngI/ml/hr), the infusion of Ang II did nor influence PRA significantly (3.43 +/- 0.42ng AngI/ml/hr; p > 0.77), though these patients had the most robust mean arterial pressure response. Our data are in complete accord with the concept of high intrarenal Ang II in DM and suggest lower systemic Ang II despite comparable PRA.
J Renin Angiotensin Aldosterone Syst 2000 Sep
PMID:Blunted suppression of plasma renin activity in diabetes. 1188 Oct 33

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