Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration.

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)

Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity.

The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The medium-term effect of natural or extractive dietary fibres on plasma amino acids and lipids in type 1 diabetics.

We evaluated the effect of a diet rich in natural (NF) or extractive fibres (guar gum) on 12 male IDD (insulin-dependent diabetes) out-patients. The treatment lasted for 2 months. During the first month the patients were on an isocaloric diet containing 30 g of fibres and then they were randomly subdivided into two groups. One group followed an isocaloric diet rich in fibres (70 g/day), the second group an isocaloric diet enriched by guar (9 g of guar added to 30 g of natural fibres/day). Reduced serum levels of HbA1c and several amino acids showed that metabolic control significantly improved under each dietary regimen.

Sodium metabolism in insulin dependent diabetic patients. Role of insulin and atrial natriuretic peptide.

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.

Effects of imidazole-2-hydroxibenzoate on glycosaminoglycan and albumin urinary excretion in type 1 diabetic patients.

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Type I insulin-dependent diabetic patients show an impaired renal hemodynamic response to protein intake.

Human kidney responds to a meat meal with an increase in glomerular filtration rate (GFR), but the mechanisms regulating kidney hemodynamics following protein intake are poorly understood in Type I insulin-dependent diabetes. In the present study we investigated GFR response to protein intake (600 gr/1.73 m2 meat meal) in nine normal subjects and 21 Type I insulin-dependent diabetic patients with normal albumin excretion rates as well as proximal tubular sodium reabsorption rates and distal sodium delivery (PRNa and DDNa). The same study was reperformed in normal subjects and diabetic patients, with less than a 5 year diabetes duration, following one week of indomethacin treatment. Normal subjects showed a 38% increase in GFR following protein intake, whereas diabetic patients showed a significantly lower response (18%, p less than 0.01). The response of GFR to protein challenge was negatively related to diabetes duration but not to baseline glomerular filtration rate. Indomethacin treatment completely prevented the protein induced GFR increase in normal subjects but not in diabetic patients. Sodium reabsorption rate was increased following protein challenge both at the proximal and distal tubular level, as was net natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)