Alfredo Gironi

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10 mmol taurine/L did not modify aggregation in healthy subjects.

TAURINE LEVELS IN PLASMA AND PLATELETS IN INSULIN-DEPENDENT AND NON-INSULIN-DEPENDENT DIABETES MELLITUS: CORRELATION WITH PLATELET AGGREGATION

In human volunteers it has been shown that taurine supplementation decreases collagen-induced thromboxane release and platelet aggregation (6). In addition, we found that, while in vitro taurine did not modify platelet aggregation per se, it potentiated the effect of anti-aggregating agents such as aspirin, papaverine, or sodium nitroprusside (13). These observations seem to indicate a possible role for taurine in the modulation of platelet function.

Raised plasma fibronectin concentration is related to the presence of diabetic retinopathy

SummaryPlasma concentrations of fibronectin were studied in 152 diabetics (77 males, 75 females), divided according to their hypoglycemic treatment, and in 60 normal subjects (30 males, 30 females) closely matched for age. In both sexes no significant difference of plasma fibronectin (PF) levels was observed between controls and treated groups. In the whole group of diabetics PF levels were weakly correlated with age (r=0.16; p<0.05) and not associated with HbA1 or duration of illness. Both male and female diabetics, either on sulfonylureas or insulin, with retinopathy (background, except for 2 proliferative in the group of insulin-requiring females) were characterized by significantly higher PF concentrations than either controls or patients without retinopathy.

Raised erythrocyte polyamine levels in non-insulin-dependent diabetes mellitus with great vessel disease and albuminuria.

Erythrocyte content of polyamines has been previously found increased in insulin-dependent diabetes mellitus with microalbuminuria. Since increased urinary albumin excretion (AER) is associated with the presence of vascular diseases in non-insulin-dependent diabetes mellitus (NIDDM) the aim of this study was to verify the hypothesis that the presence of increased urinary albumin excretion (AER), and of macroangiopathy in NIDDM would be related to a significant modification in polyamine erythrocyte levels. The erythrocyte content of spermine and spermidine was measured by a HPLC method in 39 patients affected with NIDDM and in 24 age- and sex-matched healthy control subjects, evaluating the relationship between erythrocyte polyamines of NIDDM patients with the presence of macroangiopathy as well as with retinopathy or increased AER (> or = 20 micrograms/ml). Both spermidine and spermine were not modified in the group of NIDDM patients while the presence of raised urinary AER was characterised by an increase in erythrocyte spermine (11 +/- 1.7 vs. 7.7 +/- 1.7 nmol/ml packed erythrocytes; P = 0.04) and spermidine (18.9 +/- 1.7 vs. 12.6 +/- 1.5 nmol/ml packed erythrocytes; P = 0.02), being both polyamines significantly related to AER and to metabolic control. Erythrocyte spermidine and spermine were moreover significantly higher in the group of patients with macroangiopathy (22.8 +/- 1.5 vs. 12.3 +/- 1.5 nmol/ml; P = 0.0001 and 11.5 +/- 1.7 vs. 7.8 +/- 1.7 nmol/l packed erythrocytes; P = 0.04) and being, moreover, erythrocyte spermidine augmented in patients with retinopathy (24.2 +/- 1.5 vs. 12.2 +/- 1.5 nmol/ml packed erythrocytes; P = 0.009). In conclusion the levels of erythrocyte spermine and spermidine are both associated with the presence of albuminuria and macroangiopathy in NIDDM, while spermidine is on the average increased in the group of diabetic patients with retinopathy.

Increased Plasma Fibronectin Concentration in Diabetic Patients With Microalbuminuria

Raised levels of plasma fibronectin (PF), an α2- glycoprotein produced by vascular endothelia, have been previously described in diabetic patients with retinopathy and overt nephropathy. The aim of this study was to investigate whether the presence of microalbuminuria is associated with increased PF concentrations. Twenty Albustix-negative diabetic outpatients with microalbuminuria [ median albumin excretion rate (AER): 30.2 μg/ min; range 12.1-194 (μ g/ min[ were compared with 58 sex- and agematched patients without microalbuminuria (median AER 3.1 μg/ min; range 0.8-12 μg/ min) and 34 control subjects (median AER 2.8 (μg/ min; range 0.8-12.1 μg/ min). Mean PF was significantly higher in the group with microalbuminuria (406.7 ± 85.5 μg/ml) than in the group without it (325.3 ± 76.5 μg/ml) or in control subjects (334.5 ± 76 μg/ml; P >.05). PF increase associated with microalbuminuria was independent of the presence of retinopathy. Futhermore, in the whole group of diabetic patients, PF was significantly correlated with AER (r = .33; P = .003). Such correlation also remained significant (P = .0002) after covariance analysis by a stepwise discriminant procedure taking into account age, duration of disease, sex, blood pressure, body weight, therapy, and HbA,. In conclusion, PF increase is associated with microalbuminuria independent of the other considered variables; its role as a possible marker for early diabetic nephropathy remains to be fully clarified.

Erythrocyte Spermidine Levels in IDDM Patients

Objectives To evaluate whether erythrocyte levels of polyamines spermidine and spermine (expressed in nmol/ml packed erythrocytes [PRBCs]) are modified in insulin-dependent diabetes mellitus (IDDM) and are associated with the presence of retinopathy or nephropathy. Research Design and Methods We studied erythrocyte spermidine and spermine levels in 38 IDDM patients with or without persistent microalbuminuria (urinary albumin excretion rate [AER] between 20 and 200 μg/min), macroalbuminuria (AER >200 μg/min), or retinopathy compared with 60 sex- and age-matched control subjects. Results Mean ± SD erythrocyte spermine content was similar in both diabetic (9.7 ± 5.5 nmol/ml PRBCs) and control (8.8 ± 3.5 nmol/ml PRBCs) subjects, whereas spermidine was higher in diabetic (19.1 ± 7.2 nmol/ml PRBCs) than in control (14.5 ± 4 nmol/ml PRBCs, P = 0.0007) subjects. Moreover, spermidine was significantly higher in the groups with microalbuminuria (n = 11, 22.5 ± 9.2 nmol/ml PRBCs) and macroalbuminuria (n = 4, 22.2 ± 5.7 nmol/ml PRBCs) than in both normoalbuminuric (n = 23, 16.9 ± 5.6 nmol/ml PRBCs) and control (F = 9.78, P = 0.0001) subjects, and correlated with log AER (r = 0.41, P = 0.009). Similarly, proliferative retinopathy was associated with a significant increase in spermidine (n = 5, 20 ± 7 nmol/ml PRBCs compared with control subjects [P = 0.0009]). Conclusions Our data suggest that erythrocyte spermidine content is increased in IDDM patients associated with both diabetic nephropathy and advanced retinopathy.

Serum digoxin and Beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables

SummarySerum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age >60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD.The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI > the median value, were characterized by a lower daily dose and dosage frequency.Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.

Serum spermidine oxidase activity in patients with insulin-dependent diabetes mellitus and microvascular complications

SummaryMetabolism of polyamines (spermidine and spermine) is known to be strictly related to the growth processes of eukaryotic cells. Since cell replication processes appear altered in insulin-dependent diabetes mellitus (IDDM), especially when associated with its microvascular complications, the aim of this study was measuring serum spermidine oxidase activity (SOA), a key enzyme in the metabolic pathway of polyamines, in 47 patients with IDDM as compared with 63 healthy control subjects matched for age and sex. Mean SOA levels±SD were significantly lower in IDDM patients (177.4±57.2 µkat/l) than in controls (247.6±68.1 µkat/l; p<0.001), being SOA inversely related with daily insulin dose. SOA was moreover significantly higher (but similar to controls) in the group with increased urinary albumin excretion rate (AER persistently >20 µg/min); (n=17; 213.1±62.6 µkat/l) in comparison with normoalbuminuric subjects (n=30; 156.6±43.5 µkat/l; F=21.78; p=0.0001). SOA was correlated with AER (r=0.45; p=0.001), independently of age, duration of disease, serum creatinine, body weight, blood pressure and metabolic control, as shown by a multiple regression analysis model (p=0.003). Presence of background retinopathy was not associated with modified levels of SOA, which was conversely higher, although not significantly, in the patients with proliferative retinal lesions. In conclusion serum SOA is deeply altered in IDDM patients, being markedly reduced in the whole group of patients and conversely independently increased up to the mean values of controls in presence of increased AER or advanced retinopathy.

Plasma fibronectin in normolipidaemic and hyperlipidaemic uraemic patients treated with haemodialysis

Plasma fibronectin (PF) concentrations, were investigated in normolipidaemic and hyperlipidaemic (type IV) patients with chronic renal failure treated with hemodialysis (n = 29) and in controls (n = 34). Mean PF was significantly reduced in both subsets of dialysed patients. Among the hemodialysed patients the presence of hyperlipidaemia did not modify PF levels, which resulted, on the contrary, significantly higher in hyperlipidaemic controls as compared with the normolipidaemic group. In controls, according to a multivariate analysis model, PF was directly related with age and inversely with HDL-cholesterol. In the hemodialysed patients total cholesterol was the unique significant PF related variate, being this group, therefore, characterized by the lack of any inverse relation between PF and HDL-cholesterol. Finally, no PF modifications were observed in hemodialyzed patients affected by arterial hypertension or clinically evident atherosclerotic lesions.