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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the impact of metabolic control on renal responses to human atrial natriuretic peptide (hANP) in type 1 diabetes mellitus, 13 patients with HbA1 less than 8.5%, nine patients with HbA1 greater than 8.5% and ten healthy volunteers were studied. According to a randomized, single-blind trial design, 0.5 and 2.0 micrograms/kg hANP-(95-126) (Urodilatin) (Bissendorf Peptide, Hannover) or placebo were given as iv bolus injections at 90-minute intervals. Patients with HbA1 greater than 8.5% differed from those with HbA1 less than 8.5% in longer diabetes duration, more prevalent retinopathy and neuropathy and increased somatomedin C levels and urinary albumin excretion (p less than 0.05). In response to hANP, patients with HbA1 greater than 8.5% had decreased responses of urinary volume and sodium excretion in comparison to patients with HbA1 less than 8.5% (p less than 0.05) in whom renal responses to hANP did not differ from controls. Despite similar hANP levels, hANP-stimulated urinary cGMP excretion in patients was higher than in controls (p less than 0.01). Impaired renal responses to hANP in diabetes patients with insufficient glycemic control apparently contribute to the mechanisms of diabetic sodium retention. Near-normoglycemia may prevent this phenomenon which is intimately involved into the pathogenesis of diabetic nephropathy.
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PMID:[Effect of metabolic control on the renal effects of human atrial natriuretic peptide-(95-126) (urodilatin) in normotensive patients with type I diabetes mellitus]. 131 42

Diabetes mellitus (DM) is frequently associated with hypertension for which an independent pathomechanism has been suggested. We studied 26 patients with insulin-dependent (IDDM) and 18 patients with non-insulin-dependent (NIDDM) uncomplicated DM; all patients were in metabolic balance and none of them had hypertension. Exchangeable body sodium (NaE was estimated by isotope dilution, using appr. 1.1 Mbq 24NA. In a subset of 8 IDDM and 8 NIDDM patients atrial natriuretic peptide (ANP) plasma concentration was determined prior to and after the infusion of 2000 ml physiological saline over 2 hr. NaE was significantly increased both in IDDM and NIDDM patients (104.4 +/- 11.4% and 109.9 +/- 8.0% of the normal value for healthy subjects of identical body surface area; p < 0.05 and < 0.001 resp.). Mean blood pressure (MBP) correlated significantly with NaE in both groups (r = 0.364 and r = 0.520; p < 0.05 and < 0.025, resp.) but not in healthy control subjects (r = 0.112; N.S.). Resting ANP levels were not significantly different in IDDM (34.9 +/- 11.3 pg/ml), NIDDM (42.6 +/- 11.7 pg/ml) or control subjects (40.9 +/- 17.2 pg/ml) however the infusion of saline resulted in a significantly greater increase of plasma ANP in the NIDDM patients (to 82.9 +/- 43.2 pg/ml; P < 0.01) than in the controls (55.6 +/- 23.7 pg/ml; P < 0.01) which was associated with a significantly less increase in sodium excretion (UNAV) in the NIDDM patients (+86% vs. 3170%; P < 0.02) indicating down-regulation of ANP receptors in the kidney of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Body sodium, atrial natriuretic peptide and blood pressure in diabetes mellitus. 134 Jun 60

Insulin-dependent diabetic patients have a large exchangeable body sodium pool, secondary to sodium retention. The pathogenesis of impaired natriuresis in insulin dependent diabetes remains to be elucidated. The present study examines the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance to atrial natriuretic peptide action in determining sodium retention in normotensive and hypertensive insulin-dependent diabetic patients. Eight insulin-dependent diabetic patients had significantly higher daily sodium excretion rate (147 +/- 16 mmol/day; mean +/- SE) during conventional insulin treatment (daily plasma glucose: 11.6 +/- 1.2 mmol/liter; daily plasma insulin: 27 +/- 3 microU/ml) than during intensified insulin treatment (daily sodium excretion rate: 91 +/- 12, P less than 0.01; daily plasma glucose: 6.8 +/- 0.7, P less than 0.01; daily plasma insulin: 44 +/- 4, P less than 0.01). Daily sodium excretion rate was also significantly lower (107 +/- 13, P less than 0.01) in the same diabetic patients during intensified insulin treatment along with hyperglycemic clamp (daily plasma glucose: 12.8 +/- 0.3, NS; plasma insulin 48 +/- 4, P less than 0.01). Seven control subjects had lower extracellular liquid volume than eight insulin-dependent diabetic patients (11.0 +/- 0.8 l/1.73 m2 vs. 14.8 +/- 0.9, P less than 0.05) and also had baseline plasma atrial natriuretic peptide concentrations (18 +/- 5 pg/ml vs. 37 +/- 4, P less than 0.05). Atrial natriuretic peptide response to saline challenge was blunted in insulin-dependent diabetic patients when saline was administered on the basis of body surface area (90 mmol/1.73 m2.90 min) but not when administered on the basis of extracellular liquid volume (ECV) (8.2 mmol/liter ECV.90 min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationships among natriuresis, atrial natriuretic peptide and insulin in insulin-dependent diabetes. 138 32

The interaction of exogenous, synthetic human atrial natriuretic peptide [(hANP) (ANF 99-126)] and of exogenous insulin was investigated in six healthy men and in seven type I diabetic patients using the euglycemic clamp technique. A primed-continuous (1.0 mU/kg x min) infusion of biosynthetic human insulin was administered to acutely raise and maintain plasma insulin concentrations at approximately 75 to 100 microU/mL during four hours while plasma glucose concentrations were maintained constant at the fasting level by a variable infusion of glucose. In healthy men a decrease in natriuresis (P less than .01) was seen during a euglycemic clamp study without exogenous hANP. No changes in diuresis and natriuresis were seen during a control experiment without exogenous insulin and glucose. Both in healthy men and in the type I diabetics sequential IV bolus doses of hANP of 100, 200, and 400 micrograms induced an increase in urine flow (P less than .01) and in natriuresis (P less than .01). In healthy men these effects were comparable to those achieved by hANP in the absence of induced hyperinsulinemia. It is concluded that the antinatriuretic action of insulin is of no major relevance in counteracting the pharmacologic action of hANP in healthy men. The effects of pharmacologic doses of hANP on diuresis and natriuresis in patients with type I diabetes mellitus is comparable to that in healthy men.
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PMID:The diuretic and natriuretic action of human atrial natriuretic peptide in humans: lack of effect of exogenous insulin. 253 31

We measured plasma- and extracellular fluid volume (125I-albumin, 51Cr-EDTA), plasma concentrations of renin, angiotensin I and II, aldosterone and atrial natriuretic peptide by radio-immunoassays in insulin-dependent diabetic (IDDM) patients with (n=28) and without (n=11) nephropathy and in 14 normal control subjects matched for sex and age. Glomerular filtration rate (GFR) (ml/min/1.73 m2, single intravenous bolus 51Cr-EDTA technique) was within normal range in all nephropathic patients; 107 (range 78-134). Mean arterial blood pressure (mmHg) was elevated 102 +/- 13 (+/- S.D.) compared to the diabetic and normal control group, 92 +/- 8 and 87 +/- 5, respectively (p less than 0.01). Plasma volume was identical in all three groups while extracellular volume (1/1.73 m2) was expanded in nephropathic patients, 14.5 +/- 1.5 vs 13.1 +/- 0.9 and 12.4 +/- 1.3 in the diabetic and non-diabetic control groups, respectively (p less than 0.05). A significant correlation between extracellular fluid volume and mean arterial blood pressure was found (n=53, r=0.49, p less than 0.001). Active renin was significantly increased in patients with diabetic nephropathy compared with the normal control subjects, while all the remaining hormones were about the same in the three groups. Our study suggests that fluid retention plays a dominant role in the initiation and maintenance of arterial blood pressure elevation early in the course of diabetic nephropathy.
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PMID:On the pathogenesis of arterial blood pressure elevation early in the course of diabetic nephropathy. 253 16

We examined renal responses to a pharmacological dosage of human atrial natriuretic peptide (hANP) and the potential interference of nifedipine administration with the effects of hANP on kidney function in healthy subjects and normoglycemic patients with type 1 diabetes mellitus. Ten healthy volunteers (age, 28 +/- 1 years) and ten patients (age, 33 +/- 2 years; diabetes duration; 14 +/- 3 years; HbAI 7.2% +/- 0.2%) were studied. According to a double-blind, randomized, placebo-controlled trial design, three experiments were performed in each subject using the double-dummy technique: placebo only, hANP only, and nifedipine + hANP. As i.v. bolus injection 100 micrograms hANP was given; nifedipine was applied buccally, at a dose of 10 mg 90 min before and at a dose of 5 mg together with hANP injection. At base-line and in the placebo only experiment, patients did not differ from controls. In the hANP only experiment, in both groups hANP resulted in increased urinary volume and both sodium and chloride excretion (P less than 0.05 vs placebo only experiment). In patients, hANP-induced increase in electrolyte excretion was greater than in controls (P less than 0.05). In the nifedipine + hANP experiment, hANP-induced changes in renal indexes were enhanced in controls (P less than 0.05 vs hANP only experiment) but not in patients. Thus, diuretic response to nifedipine + hANP in patients was decreased in comparison with controls (P less than 0.05). In patients, however, nifedipine administration decreased the hANP-induced increase in urinary albumin excretion (P less than 0.05 vs hANP only experiment). Creatinine clearance was uninfluenced throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nifedipine on renal responses to human atrial natriuretic peptide in healthy subjects and normoglycemic patients with type 1 diabetes mellitus. 253 91

Acute insulin administration shows an antinatriuretic effect in normal man. Thus it can be postulated that insulin therapy resulting in circulating hyperinsulinemia can lead to sodium retention and in turn to hypertension in insulin dependent diabetes. Moreover it has been proved that atrial natriuretic peptide (ANP) plays a major role in modulating natriuresis in man. The aim of the present study was to investigate the relationship between insulin and ANP in modulating sodium metabolism in seven insulin dependent diabetic patients in comparison with eight normal control subjects at baseline and during a saline infusion (2 mmol/kg/90 min) at euglycemic blood levels. Diabetics received a subcutaneous insulin infusion (0.015 U/kg/hr) resulting in a two fold higher plasma free insulin levels (16 +/- 2 microU/ml) than in control subjects (7 +/- 2 microU/ml). During saline challenge sodium excretion rate increased by 29 +/- 6% in control patients and only by 6 +/- 0.7% in diabetic patients (p less than 0.01). At baseline ANP plasma concentrations were significantly higher in diabetic patients than in control subjects (diabetics = 37 +/- 8 pg/ml and controls = 21 +/- 3 (p less than 0.01). After saline challenge ANP concentration rose to 71 +/- 9 pg/ml in control subjects, whereas no significant change above baseline values was shown by diabetic patients.
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PMID:Sodium metabolism in insulin dependent diabetic patients. Role of insulin and atrial natriuretic peptide. 253 10

Potential impairment of the efficacy of human atrial natriuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22-37 years). After giving informed consent, patients and eight male control subjects (aged 22-28 years) received in a random double-blind study design i.v. bolus injections of 100 micrograms hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P less than 0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P less than 0.01); hANP resulted in increased plasma protein concentrations only in controls (P less than 0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P less than 0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.
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PMID:Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus. 297 Nov 31

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)
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PMID:Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus. 818 64

There is controversy as to whether increased plasma levels of human atrial natriuretic peptide (hANP) in patients with type 1 diabetes mellitus may contribute to the development of diabetic nephropathy. Therefore, we decided to conduct two studies to examine the relationship of hANP levels to urinary albumin excretion and blood pressure. In a cross-sectional study, 83 randomly selected type 1 diabetic patients were investigated. 19 of the patients had increased urinary albumin excretion. 45 healthy volunteers served as controls. In a longitudinal study, 19 type 1 diabetic patients were examined for one year at monthly intervals. An increased risk of eventually developing diabetic nephropathy was identified in 7 out of these patients by repeatedly revealing increased urinary albumin excretion. On the average, hANP levels were increased in type 1 diabetic patients in comparison to controls (P < 0.001). In both studies, hANP levels were positively related (P < 0.05) to mean arterial blood pressure. There was no correlation between hANP levels and metabolic control. hANP levels lay within normal range irrespective of normal or elevated urinary albumin excretion provided that mean arterial blood pressure was normal. In the longitudinal study, increased urinary albumin and alpha-1-microglobulin excretion preceded the increase in both hANP levels and mean arterial blood pressure. Although hANP levels were evidently not related to the disease mechanisms of early diabetic nephropathy, it is tempting to speculate that hANP may contribute to the vicious circle connecting diabetic kidney disease to hypertension once that its levels are increased by elevated blood pressure.
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PMID:Human atrial natriuretic peptide in patients with type 1 diabetes mellitus: is it related to the development of diabetic nephropathy? 821 53


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