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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the time relationships involved in cyclosporin-induced nephrotoxicity we studied changes in blood pressure, renal haemodynamics and sodium excretion in 22 adult patients with insulin-dependent diabetes mellitus treated with cyclosporin (CsA) for 4 +/- 2 days, compared to 22 insulin-dependent diabetic patients receiving conventional insulin therapy, who were matched for age and duration of diabetes. To further clarify the pathogenic role of the renin-angiotensin system, insulin-dependent diabetic patients receiving CsA were studied before and after sublingual administration of 75 mg captopril. An average of 4 days CsA treatment markedly increased blood pressure and renal vascular resistance, but did not alter glomerular filtration rate, renal plasma flow, sodium urinary excretion, or body-weight. The marked renal vasoconstriction without early changes in GFR suggests that the late decrease in GFR may involve other factors in addition to renal hypoperfusion. Acute inhibition of angiotension II formation was still able to decrease blood pressure and renal vascular resistance, although not to normal control values. These results indicate that a physiological concentration of angiotensin II may potentialise but may not be the sole factor involved in the vasopressor effect of CsA.
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PMID:Renal haemodynamic effects of short term cyclosporin A administration in patients with insulin-dependent diabetes mellitus. 211 42

Elevation of glomerular filtration rate (GFR) is a feature of diabetes mellitus in humans and in animal models. Angiotensin II has been implicated as a mediator of GFR in diabetes. The acute effect of inhibition of angiotensin converting enzyme with captopril on renal haemodynamic and endocrine parameters was therefore studied in 14 normotensive male Type 1 diabetic patients, and the responses compared with those in five normal male control subjects. Following captopril 12.5 mg orally the diabetic patients exhibited an acute fall in GFR from 122 +/- 3.8 to 113 +/- 4.5 ml min-1 1.73-m-2 (p less than 0.02) and a rise in renal plasma flow (RPF) from 670 +/- 57 to 797 +/- 46 ml min-1 1.73-m-2 (p less than 0.01) which resulted in a fall in filtration. This did not occur in normal control subjects. Natriuresis occurred only in normal control subjects. There was no change in urinary excretion of PGE2 or kallikrein in either group but excretion of 6-keto-PGF1 alpha fell in the diabetic patients. There was a significant correlation between glycosylated haemoglobin and baseline RPF (rs = -0.79, p less than 0.001) and filtration fraction (rs = 0.83, p less than 0.001) that persisted when the change in these variables following captopril was analysed. Our results are compatible with the response to ACE inhibition in diabetic patients being secondary to inhibition of angiotensin II and suggest that this response may be related to blood glucose control.
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PMID:Blood glucose control determines the renal haemodynamic response to angiotensin converting enzyme inhibition in type 1 diabetes. 213 98

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201-995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201-995 (8 micrograms h-1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I-iothalamate) and renal plasma flow (131I-hippuran) from 140 +/- 15 (mean +/- SD) and 550 +/- 69 to 131 +/- 14 (2p less than 0.005) and 492 +/- 73 ml min-1 1.73-m-2 (2p less than 0.001), while filtration fraction and total renal resistance rose (both 2p less than 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion. Thus SMS 201-995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.
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PMID:Acute effects of a somatostatin analogue on kidney function in type 1 diabetic patients. 214 82

The effects of streptozotocin-induced experimental diabetes on the morphology and secretory activity of the zona glomerulosa were studied in rats whose hypothalamo-hypophyseal-adrenal axes and renin-angiotensin systems had been pharmacologically interrupted by the simultaneous administration of dexamethasone-captopril and maintenance doses of ACTH-angiotensin II. The animals were examined 7, 14, 21, and 28 days after diabetes induction, which was evidenced by conspicuous hyperglycemia. Experimental diabetes caused notable atrophy of the zona glomerulosa and its cells, along with a significant decrease in both basal and angiotensin II-stimulated plasma aldosterone concentration. There was a positive linear correlation between all these changes and the number of days elapsed after streptozotocin administration. These data indicate that experimental diabetes exerts a profound time-dependent direct inhibition of rat zona glomerulosa. The hypothesis is advanced that the chronic lack of insulin that occurs in rats treated with streptozotocin, may depress de novo synthesis of structural and enzymatic proteins in zona glomerulosa cells and reduce their growth and steroidogenic machinery.
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PMID:Streptozotocin-induced experimental diabetes causes a time-dependent inhibition of growth and steroidogenic capacity of rat adrenal zona glomerulosa. 215 26

Diabetes-associated hypertension is accompanied by high levels of body sodium and cardiovascular hyper-reactivity to noradrenaline. Captopril, a promising drug for the treatment of hypertension in diabetics, may influence sodium metabolism and adrenergic pathways. This possibility was investigated in 11 patients with non-azotaemic diabetes mellitus and hypertension, studied after a 3-week placebo phase and after an 8-week phase of captopril treatment (50-100 mg/day). Blood pressure, exchangeable body sodium, blood volume, plasma renin activity, angiotensin II (Ang II), aldosterone, catecholamine levels and the pressor reactivity to infused Ang II or noradrenaline were measured. Compared with placebo, captopril caused a significant decrease in arterial pressure and stimulation of plasma renin activity. Exchangeable sodium, blood volume, plasma Ang II, aldosterone, noradrenaline and adrenaline levels, the pressor and aldosterone responsiveness to infused Ang II and the pressor response to infused noradrenaline (alone or combined with atropine) were not modified. These findings suggest that in hypertensive diabetics angiotensin converting enzyme inhibition causes a marked decrease in blood pressure. The mechanism of action is unrelated to changes in body sodium or noradrenergic-dependent pressor reactivity. In the stable phase of therapy, Ang II-dependent pathways are left unaltered when captopril is administered twice a day.
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PMID:Cardiovascular regulation during angiotensin converting enzyme inhibition with captopril in diabetes-associated hypertension. 216 58

Streptozotocin-induced diabetes significantly decreased plasma aldosterone concentration in rats whose renin-angiotensin system had been pharmacologically interrupted. Isolated zona glomerulosa cells showed a marked atrophy, coupled with a reduced basal secretion of aldosterone and corticosterone. The secretory response to the three main physiological stimuli (ACTH, angiotensin II and potassium) was also notably impaired. The hypothesis is advanced that the chronic lack of insulin may directly impair the growth and steroidogenic capacity of rat adrenal zona glomerulosa.
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PMID:Morphology and functional responses of isolated zona glomerulosa cells of streptozotocin-induced diabetic rats. 216 30

To evaluate the renin-angiotensin-aldosterone system in relation to circulatory catecholamines, we determined renin activity, angiotensin II, aldosterone, adrenaline, and noradrenaline in plasma before and during a submaximal bicycle exercise test in 23 Type 1 (insulin-dependent) diabetic patients (aged 19-57 years, mean 37; duration of diabetes 2-32 years, mean 16), 17 with signs of cardiac autonomic neuropathy, and in 18 healthy non-diabetic subjects (aged 24-41 years, mean 29). At rest, Type 1 diabetic patients showed significantly lower aldosterone values than control subjects (0.14 +/- 0.02 nmol/l and 0.22 +/- 0.02 nmol/l; p less than 0.01) while renin activity (1.0 +/- 0.1 nmol.l-1.h-1 and 0.9 +/- 0.1 nmol.l-1.h-1) and angiotensin II (14 +/- 1 nmol/l and 18 +/- 2 nmol/l) did not differ significantly between patients and control subjects. During exercise, increments (increase from the resting value to the value at 80% of maximal working capacity) in renin (1.5 +/- 0.4 nmol.l-1.h-1 and 3.7 +/- 0.5 nmol.l-1.h-1; p less than 0.001), angiotensin II (28 +/- 8 nmol/l and 60 +/- 8 nmol/l; p less than 0.001), aldosterone (0.16 +/- 0.04 nmol/l and 0.25 +/- 0.05 nmol/l; p less than 0.05), adrenaline (1.96 +/- 0.49 nmol/l and 2.92 +/- 0.51 nmol/l; p less than 0.05), and noradrenaline (12.01 +/- 1.25 nmol/l and 18.74 +/- 1.45 nmol/l; p less than 0.01) were significantly lower in the patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The activity of the renin-angiotensin-aldosterone system before and during submaximal bicycle exercise in relation to circulatory catecholamines in patients with type 1 (insulin-dependent) diabetes mellitus. 207 87

Angiotensin (Ang) II and prostaglandins, especially prostaglandins E2 and I2, regulate the glomerular filtration of albumin. Albuminuria can be induced by angiotensin II and possibly by prostaglandins. Angiotensin converting enzyme inhibition with captopril, enalapril or lisinopril reduces albuminuria and glomerular injury in experimental and clinical renal diseases, especially diabetes mellitus. Inhibition of prostaglandin synthesis with non-steroidal anti-inflammatory drugs reduces albuminuria in nephrotic patients regardless of the aetiology of the nephrosis. Judicious clinical use of either class of therapy can result in sustained reductions (50-75%) in proteinuria and possible attenuation of the rate of decline of glomerular function.
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PMID:The roles of angiotensin II and prostaglandins in the regulation of the glomerular filtration of albumin. 218 53

The purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one-fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone.
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PMID:The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study. 219 80

We here report a case of Bartter's syndrome occurring in association with diabetes mellitus. The patient, an insulin-dependent diabetic, presented with hypokalaemia, inappropriate kaliuresis and metabolic alkalosis. He had high plasma renin activity, relatively low plasma aldosterone, and resistance to infused angiotensin II. A high potassium diet raised total body potassium and serum potassium, did not affect plasma renin activity, but raised plasma aldosterone significantly and did not alter the resistance to angiotensin II. Indomethacin administered acutely reduced urinary potassium and kallikrein excretion and, on chronic administration, lowered plasma renin activity, urinary chloride excretion, and raised serum potassium. Salt restriction resulted in a prompt and significant reduction in urinary sodium and chloride excretion. Urinary kallikrein excretion was very high throughout, increased with sodium restriction, and decreased with sodium loading. Oral potassium supplementation partially corrected the hypokalaemia, but did not affect blood sugar control. In this patient the primary defect appears to have been primary urinary potassium wasting, rather than sodium or chloride wasting. The striking effects of indomethacin suggest that prostaglandins may play a fundamental role in the genesis of the syndrome.
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PMID:Bartter's syndrome and diabetes mellitus. 225 25


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