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Biomedical subjects

M Sambataro

Publications and source records attributed to M Sambataro.

At least 19 recordsLinked to original sources
PubMed2000

Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate.

Heterogeneity in renal structure has been described in type 2 diabetic patients with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. However, it is currently unknown whether abnormalities in albumin excretion rate (AER) have a different renal prognostic value depending on the underlying renal structure. Aims of this study were: 1) to study the course of renal function in type 2 diabetic patients with altered AER; 2) to evaluate the relationship between the course of glomerular filtration rate (GFR) and renal structure; and 3) to evaluate the relationship between the course of GFR and baseline AER levels, metabolic control, and blood pressure levels during a follow-up period of 4 years. A total of 108 type 2 diabetic patients, 74 with microalbuminuria (MA) and 34 with proteinuria (P), were recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morphometric measurements of glomerular parameters; 2) intensified antihypertensive treatment for an average 4-year period (blood pressure target <140/90 mmHg); and 3) determinations of GFR at baseline and every 6 months. Mean (+/- SD) GFR significantly decreased from baseline in both MA (-1.3+/-9.4 [95% CI -3.51 to +0.86], P < 0.05) and P (-3.0+/-13.0 ml x min(-1) x 1.73 m(-2) per year [-7.71 to +1.61], P < 0.01). However, the changes in GFR were quite heterogeneous. Thus, on the basis of percent GFR change per year from baseline (delta%GFR), both MA and P patients were defined as progressors or nonprogressors when they were below or above the median, respectively. Baseline parameters of glomerular structure had a strong influence on the course of GFR. Indeed, the odds ratios of being progressors significantly increased across the quartiles of baseline glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(mes/glom)], being 2.71 and 2.85 higher, respectively, in the fourth quartile than in the first quartile (P < 0.01 for both). Conversely, nonprogressors outnumbered progressors in the first quartile of GBM width (odds ratio: 2.14, P < 0.05) and in the first quartile of Vv(mes/glom) (odds ratio: 2.28, P < 0.01). Baseline albumin excretion rate (AER) did not influence delta%GFR; in fact, the number of progressors did not increase across quartiles of baseline AER among either MA or P. Similarly, mean blood pressure levels during follow-up (and intensified antihypertensive therapy) did not affect the course of GFR: the number of progressors and nonprogressors did not change across quartiles of mean blood pressure. In contrast, HbA1c during follow-up had an impact on delta%GFR: the odds ratio for being a progressor increased across quartiles of HbA1c, particularly for the highest quartile (HbA1c >9.0%). In conclusion, the course of renal function is heterogeneous in type 2 diabetic patients with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year follow-up period; these patients have more advanced diabetic glomerulopathy and worse metabolic control than the remaining patients, whose GFR remains stable. These two cohorts are otherwise undistinguishable as regards the degree of AER at baseline and tight blood pressure control. Kidney biopsy has an important prognostic role in these patients. Thus, tight blood pressure control, when not associated with satisfactory glycemic control, is unable to prevent rapid GFR decline in type 2 diabetic patients with typical diabetic glomerulopathy.

Adult↗
PubMed1998

Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT.

The minimal model is widely used to evaluate insulin action on glucose disappearance from frequently sampled intravenous glucose tolerance tests (FSIGT). The common protocols are a regular (rFSIGT, single injection of 0.3 g/kg of glucose) and an insulin-modified test (mFSIGT, with an additional insulin administration at 20 min). This study compared the insulin sensitivity index (SI) and glucose effectiveness (SG) obtained in the same individual (16 normal subjects) with the two tests. SI was 7.11 +/- 0.80 10(-4).min-1.microU-1.ml in rFSIGT and 6.96 +/- 0.83 in mFSIGT (P = 0.656), regression r = 0.92, P < 0.0001; SG was 0.0260 +/- 0.0028 min-1 and 0.0357 +/- 0.0052, respectively, statistically different (P = 0.013) but still with a good regression (r = 0.66, P = 0.0051). SG and insulin amount during the early period correlated (r = 0.6, P = 0.015 in rFSIGT and r = 0.76, P = 0.0006 in mFSIGT). In summary, both FSIGTs with minimal model analysis provide the same SI, which is a very robust index. SG was different by 28% due probably to the relationship between SG and the amount of circulating insulin. In studies comparing groups, the simpler rFSIGT can still be used with the advantage of accounting for endogenous insulin, thus offering the possibility of direct inferences on the beta-cell activity.

Adult↗
PubMed1997

Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria.

We have recently described heterogeneity in renal structure in non-insulin-dependent diabetic patients (NIDDM) with microalbuminuria (MA; defined as albumin excretion rate from 20 to 200 micrograms/min). Thus, at variance with IDDM patients, "typical" diabetic glomerulopathy by light microscopy is observed only in a third of NIDDM with MA (Category II, CII). Further, despite persistent MA, 30% of NIDDM have normal or near normal renal structure (Category I, CI). Another one-third shows "atypical" patterns of renal injury with absent or mild diabetic glomerular changes, associated with disproportionately severe tubulointerstitial lesions and/or arteriolar hyalinosis and global glomerular sclerosis (Category III, CIII). The aims of this study were to evaluate whether similar patterns of renal lesions could be confirmed in a larger group of NIDDM with MA and to investigate tubular function in order to understand the mechanisms underlying MA in NIDDM patients. Renal biopsies were performed in 53 NIDDM with MA. Categories I, II and III were found in 41%, 26% and 33% of NIDDM with MA, respectively. All 8 patients with proliferative diabetic retinopathy were in CII. We also studied the urinary daily excretion rate of alpha 1-microglobulin (alpha 1 m), a low molecular weight protein, which is a useful indicator of tubular function. alpha 1 m was markedly increased only in CII patients (CI vs. CII vs. CIII: 6.2 +/- 1.2 vs. 13.7 +/- 2.1 vs. 7.3 +/- 0.9 mg/day, ANOVA, P < 0.01). In conclusion, we confirm that there is heterogeneity in renal structure in NIDDM patients with MA. This heterogeneity is not due to renal diseases other than diabetes. Increased alpha 1 m and proliferative retinopathy are useful indicators of the subgroup of MA NIDDM patients with typical diabetic glomerulopathy. It is suggested that diabetic microangiopathy explains the simultaneous occurrence of typical diabetic glomerulopathy, proliferative retinopathy and tubular dysfunction in a subgroup of NIDDM patients with MA.

Albuminuria↗
PubMed1996

Patterns of renal injury in NIDDM patients with microalbuminuria.

Microalbuminuria predicts overt nephropathy in non-insulin-dependent diabetic (NIDDM) patients; however, the structural basis for this functional abnormality is unknown. In this study we evaluated renal structure and function in a cohort of 34 unselected microalbuminuric NIDDM patients (26 male/8 female, age: 58 +/- 7 years, known diabetes duration: 11 +/- 6 years, HbA1c: 8.5 +/- 1.6%). Systemic hypertension was present in all but 3. Glomerular filtration rate (GFR) was 101 +/- 27 ml.min-1.1.73 m-2 and albumin excretion rate (AER) 44 (20-199) micrograms/ min. Light microscopic slides were categorized as: C I) normal or near normal renal structure; C II) changes "typical" of diabetic nephropathology in insulin-dependent diabetes (IDDM) (glomerular, tubulo-interstitial and arteriolar changes occurring in parallel); C III) "atypical" patterns of injury, with absent or only mild diabetic glomerular changes associated with disproportionately severe renal structural changes including: important tubulo-interstitial with or without arteriolar hyalinosis with or without global glomerular sclerosis. Ten patients (29.4%) were classified as C I, 10 as C II (29.4%) and 14 as C III (41.2%); none of these patients had any definable non-diabetic renal disease. GFR, AER and blood pressure were similar in the three groups, while HbA1c was higher in C II and C III than in C I patients. Diabetic retinopathy was present in all C II patients (background in 50% and proliferative in 50%). None of the patients in C I and C III had proliferative retinopathy, while background retinopathy was observed in 50% of C I and 57% of C III patients. In summary, microalbuminuric NIDDM patients are structurally heterogeneous with less than one third having "typical" diabetic nephropathology. The presence of both "typical" and "atypical" patterns of renal pathology was associated with worse metabolic control, suggesting that hyperglycaemia may cause different patterns of renal injury in older NIDDM compared to younger IDDM patients.

Aged↗
PubMed1996

Plasma clearance rate of 51Cr-EDTA provides a precise and convenient technique for measurement of glomerular filtration rate in diabetic humans.

It has not yet been fully clarified whether the plasma or renal clearance approach is the most reliable to investigate GFR in humans. The study presented here aimed to compare plasma decay with renal clearance of 51Cr-EDTA in 27 diabetic patients with patterns of renal function broadly dispersed in a wide range of values. Moreover, the comparison was also performed with renal clearance of nonlabeled iothalamate in a subgroup of 17 patients. A biexponential function was found to fulfill statistical and heuristic criteria for the modeling analysis of plasma 51Cr-EDTA decay with 19 samples after bolus intravenous 51Cr-EDTA injection. Individual GFR values from 51Cr-EDTA plasma clearance highly correlated with those from renal clearance (r2 = 0.977, P < 0.0001), but resulted on average about 2.5 mL.min-1.1.73 m-2 higher (66.8 +/- 6.5 mL.min-1.1.73 m-2 (mean +/- SE) versus 64.3 +/- 6.4, P < 0.02). This difference remained relatively constant from patients with normal renal function to those with impaired renal function, suggesting that the plasma clearance is slightly less accurate than renal clearance approach because of a constant extrarenal clearance rate. In the subgroup studied, a similar difference was found between GFR values from 51Cr-EDTA plasma clearance (84.7 +/- 7.3) and renal clearance of iothalamate (82.8 +/- 7.3), although not statistically significant (P = 0.4). Individual GFR values well correlated (r2 = 0.913, P < 0.0001). The precision and reproducibility of the experimental approaches were assessed by comparing three coefficients of variation: (1) CVb of the bolus injection, because of measurement errors; (2) CVc of the continuous infusion, which additionally includes errors of urine volume measurement and physiological variability in the same day; and (3) CVr of repeated measurements by using bolus injection, which also accounts for physiological variability in different days. CVc of iothalamate and 51Cr-EDTA infusions were 7.5 +/- 1.9% and 7.4 +/- 1.2% respectively. CVb and CVr of bolus injection of 51Cr-EDTA were 2.6 +/- 0.3% and 3.5 +/- 0.8% respectively. CVb and CVr of bolus injection of 51Cr-EDTA, but not CVc of iothalamate and 51Cr-EDTA infusions were twofold to tenfold lower than the percent yearly change reported in IDDM and NIDDM patients. More particularly, CVr was significantly less than CVc. In order to make the test less cumbersome, a reduced sampling schedule with seven samples was designed and validated. GFR measured with seven samples was 66.1 +/- 6.4 (P = 0.1 when compared with the full 19-sample schedule) with a CVb of 3.5 +/- 0.5%. This seven-sample protocol was not different from that obtained with the previously described simplified method of Brøchner-Mortensen (63.9 +/- 6.8, P = 0.16), yet yielding a statistically more accurate estimate (coefficient of variation for Brøchner-Mortensen method = 12.1 +/- 2.9, P = 0.004). Moreover, only bolus injection, along with modeling analysis of plasma clearance rate, allows the accurate measurement of the extracellular fluid volume, an important parameter in diabetic patients. It was concluded that the reduced seven-plasma sample protocol is able to detect as small as 4 to 5% changes per year in a single patient. Moreover, it provides precise and accurate estimate of GFR in diabetic patients with hyperfiltration, who are postulated to be at higher risk to develop renal damage.

Chromium Radioisotopes↗
PubMed1994

Peripheral, rather than hepatic, insulin resistance and atherogenic lipoprotein phenotype predict cardiovascular complications in NIDDM.

Microalbuminuria, hypertension and hyperinsulinaemia are three independent risk factors for cardiac disease in non insulin-dependent diabetes (NIDDM). However, it is unknown to what extent hyperinsulinaemia reflects resistance to insulin action at hepatic, extrahepatic or at both sites. A cross-sectional study from our Department showed that peripheral insulin resistance, hypertension, microalbuminuria and lipid abnormalities are associated in NIDDM. Non diabetic individuals with the so-called 'atherogenic lipoprotein phenotype', characterized by small dense low density lipoproteins (LDL subclass pattern B) have up to 3-fold higher risk of myocardial infarction. The aim of the present study was to investigate whether impaired peripheral insulin sensitivity, during euglycaemic-hyperinsulinaemic clamp, as well as abnormalities in lipid concentrations and LDL size, predict abnormalities in albumin excretion rate, blood pressure and cardiac function in 73 consecutive normotensive (< 85 mmHg diastolic level) and normoalbuminuric (< 15 micrograms min-1 daily albumin excretion rate) NIDDM patients. These patients showed a bimodal distribution of whole body glucose utilization rate, a parameter of peripheral insulin sensitivity. The cut-off point between the two modes of distribution was located close to the mean value minus one standard deviation in a population of 24 control subjects. Therefore, this latter value was used to identify two subgroups inside the overall population of NIDDM patients, i.e. 28 patients (group 1), with whole body glucose utilization rate, above, and 45 patients (group 2), below, the mean value minus 1 SD in the 24 controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Lipoprotein abnormalities in non-insulin-dependent diabetic patients with impaired extrahepatic insulin sensitivity, hypertension, and microalbuminuria.

We investigated whether specific lipoprotein abnormalities are present in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension and/or microalbuminuria. Fifteen normotensive normoalbuminuric (H-M-), 32 hypertensive normoalbuminuric (H+M-), and 22 hypertensive microalbuminuric (H+M+) NIDDM patients and 20 sex-, age-, and weight-matched nondiabetic control subjects were studied. Lipoprotein size was measured by nondenaturing polyacrylamide gradient gel electrophoresis; insulin sensitivity was assessed by using a euglycemic hyperinsulinemic clamp and [6,6(2)H]glucose tracer infusion for simultaneous measurement of hepatic glucose output and whole-body glucose utilization. Total plasma and very-low-density lipoprotein cholesterol were higher in H+M+ than in control subjects (5.84 +/- 0.98 versus 4.97 +/- 0.98 and 0.57 +/- 0.54 versus 0.26 +/- 0.21 mmol/L, mean +/- SD, P < .05). Plasma triglycerides were higher in H+M+ than in either control or H-M- subjects (2.17 +/- 1.32 versus 1.18 +/- 0.67 and 1.30 +/- 0.59 mmol/L, respectively; P < .05). The mean low-density lipoprotein diameter was 27.2 +/- 0.8 in control, 26.7 +/- 0.8 in H-M-, 26.5 +/- 0.8 nm in H+M- (P < .05 versus control subjects), and 26.0 +/- 0.8 nm in H+M+ subjects (P < .05 versus control subjects). The mean cholesterol level of the large high-density lipoprotein particles was lower in H+M- and H+M+ (0.37 +/- 0.14 and 0.36 +/- 0.16 mmol/L) than in control and H-M- (0.54 +/- 0.41 and 0.54 +/- 0.27 mmol/L, P < .05) subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1994

Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles.

Pulsatile GnRH (pGnRH) was administered to 292 anovulatory patients in 600 consecutive cycles between February 1984 and February 1993. This represents the largest single pGnRH series ever reported. Patients were divided into the following groups: primary hypogonadotropic amenorrhea (PHA), 73 patients, 161 cycles; other hypogonadotropic hypogonadisms (OHH), 57 patients 107 cycles; multifollicular ovary (MFO), 39 patients 75 cycles; polycystic ovary (PCO), 85 patients 172 cycles; and other hyperandrogenic anovulations (OHA), 38 patients 85 cycles. GnRH was administered iv at a dose of 1.25-20.0 micrograms every 30-120 min; most cycles (505) were performed with a regimen of 2.5-5.0 micrograms GnRH every 60-90 min. In 228 cycles of MFO, PCO, and OHA patients, pGnRH was preceded by GnRH agonist (GnRH-A) suppression. Ovulatory rates were 75%, and pregnancy occurred in 105 cycles (pregnancy rate of 18%/treatment cycle and 23%/ovulatory cycle). Ovulatory and pregnancy rates were higher in PHA, OHH, and MFO and lower in PCO and OHA. Only 4 multiple pregnancies occurred (3.8%), none after GnRH-A suppression. The abortion rate was 30% and was highest in PCO (45%). GnRH-A pretreatment improved ovulatory rates only in PCO (from 49% to 71%; P < 0.001), whereas it had no significant effect on pregnancy and abortion rates in any group. Higher weight and insulin were associated with lower ovulatory and pregnancy rates; higher LH and testosterone were associated with lower ovulatory rates only. We conclude that 1) pGnRH is a highly effective ovulation induction method; 2) pGnRH does not cause ovarian hyperstimulation; 3) low dose pGnRH is associated with a remarkably low incidence of multiple pregnancy; 4) GnRH-A pretreatment improves pGnRH outcome in PCO and further lowers the incidence of multiple pregnancy; 5) pGnRH is associated with relatively elevated abortion rates, particularly in PCO; and 6) pGnRH is less successful in overweight patients and when high baseline LH, testosterone, and insulin levels are present.

Adult↗
PubMed1994

Impaired insulin-induced glucose uptake by extrahepatic tissue is hallmark of NIDDM patients who have or will develop hypertension and microalbuminuria.

Insulin resistance may be a mechanism linking non-insulin-dependent diabetes mellitus (NIDDM) to hypertension and cardiovascular mortality. Microalbuminuria also is an independent risk factor of cardiovascular mortality and of hypertension. Little information is available in the literature on the relationship between microalbuminuria and insulin action. This study investigated the relationships between blood pressure (BP) levels, microalbuminuria, and insulin resistance in NIDDM patients. Seventy-five NIDDM patients attending the outpatient clinic of the Department of Internal Medicine of the University Hospital in Padua, Italy participated in the cross-sectional part of our study. These subjects were divided into four groups on the basis of BP levels and albumin excretion rate (AER): 28 normotensive normoalbuminuric (NIDDM1), 19 hypertensive normoalbuminuric (NIDDM2), 15 normotensive microalbuminuric (NIDDM3), and 13 hypertensive microalbuminuric patients (NIDDM4). We defined microalbuminuria as an AER > 20 micrograms/min. Patients with BP levels > 145/90 mmHg were considered hypertensive. A group of 20 normal subjects served as control subjects. The results from the cross-sectional study indicate that the mean of insulin-induced whole-body glucose utilization, primarily an index of extrahepatic insulin action, was lower at all insulin infusion steps in the group of hypertensive and/or microalbuminuric patients than in the group of normotensive normoalbuminuric patients and control subjects. Hepatic glucose output, an index of insulin action in the liver, was on average less efficiently inhibited in all of the patients than in the control subjects, regardless of the BP levels or the AER.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes.

Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic-hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)--nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 +/- 13 vs. 185 +/- 15 mg/dl, mean +/- SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 +/- 3 vs. 18 +/- 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 +/- 4 mg/dl and 6 +/- 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Role of gonadotrophin releasing hormone secretory dynamics in the control of the human menstrual cycle.

The pattern of episodic gonadotrophin releasing hormone (GnRH)-driven luteinizing hormone (LH) secretion changes dynamically across the human menstrual cycle. Adherence to a specific regimen of pulse amplitude and frequency is critical for normal ovulation, menstrual cyclicity and reproductive function. Derangements of episodic LH secretion are associated with anovulation. We have shown that in the human slowing of GnRH-induced LH pulses results in lower ovulatory rates and dysfunctions of the mid-cycle LH surge. This information is relevant for the understanding of the endocrine dynamics of the menstrual cycle both in normal and anovulatory subjects.

Anovulation↗
PubMed1992

Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus.

The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1992

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)

Adolescent↗