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Biomedical subjects

A Quatraro

Publications and source records attributed to A Quatraro.

At least 19 recordsLinked to original sources
PubMed1992

New insights on non-enzymatic glycosylation may lead to therapeutic approaches for the prevention of diabetic complications.

It is generally accepted that chronic hyperglycaemia is responsible for most of the long-term complications of diabetes. Several studies suggest that accelerated non-enzymatic glycosylation may be the underlying mechanism by which hyperglycaemia causes complications. More recently, glucose auto-oxidation has been linked to non-enzymatic glycosylation, and glycosylated proteins have been shown to be a source of free radicals. These findings suggest the possibility that oxidative stress may be related to the development of diabetic complications. Anti-oxidants such as vitamins C and E have recently been demonstrated to reduce protein glycosylation both in vivo and in vitro. In addition they also act as scavengers of free radicals generated by non-enzymatic glycosylation of protein. These findings may lead to new therapeutic approaches for the prevention of complications by limiting the damage caused by non-enzymatic glycosylation and oxidant stress. Such therapies may also be useful in complementing existing treatment in those with the long-term complications of diabetes.

Antioxidants↗
PubMed1991

Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported. 2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol. 3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.

Adult↗
PubMed1991

Metabolic control may influence the increased superoxide generation in diabetic serum.

Superoxide anion (O2-) generation in serum from 10 Type 1 diabetic patients and 10 normal subjects was measured ex vivo. The amount of O2- production was significantly increased in diabetic serum 0.41 +/- 0.04 (+/- SD) vs 0.14 +/- 0.04 mumol l-1 min-1, p less than 0.001) and correlated with fasting plasma glucose and glycosylated protein levels in both diabetic (r = 0.72, p less than 0.01, and r = 0.62, p less than 0.05) and normal r = 0.75, p less than 0.01 and r = 0.64, p less than 0.05) subjects. Improved metabolic control in the diabetic patients was associated with a reduction of serum O2- production (0.28 +/- 0.06 mumol l-1 min-1, p less than 0.01), but the correlation between O2- levels and fasting plasma glucose and glycosylated protein concentrations was retained (r = 0.86 and r = 0.72, respectively, both p less than 0.01).

Adolescent↗
PubMed1991

Vitamin E reduction of protein glycosylation in diabetes. New prospect for prevention of diabetic complications?

OBJECTIVE: This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. RESEARCH DESIGN AND METHODS: Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA1, and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients. RESULTS: Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA1 levels, stable HbA1, and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration. CONCLUSIONS: These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.

Blood Proteins↗
PubMed1990

Protein C deficiency in insulin-dependent diabetes: a hyperglycemia-related phenomenon.

In 30 insulin-dependent diabetic patients protein C (PC) antigen and PC activity were significantly lower than those of matched control healthy subjects. An inverse correlation between fasting plasma glucose and both PC concentration and activity was present in diabetics, while a direct correlation between PC concentration and PC activity was observed. Induced hyperglycemia in diabetic and normal subjects was able to decrease both PC antigen levels and PC activity, and heparin reversed in part this effect. In diabetic patients euglycemia obtained by insulin infusion restored to normal the depressed PC levels. Heparin did not alter both the basal PC concentration and activity in healthy controls. These data stress the major role of hyperglycemia in determining PC decrease in diabetics, and suggest that PC reduction is probably associated to hyperglycemia-enhanced thrombin formation.

Adult↗
PubMed1990

Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug?

STUDY OBJECTIVE: To evaluate the usefulness and safety of hydroxychloroquine in patients with decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. DESIGN: Prospective, randomized, placebo, double-blind 6-month trial. PATIENTS: Thirty-eight patients with noninsulin-dependent diabetes resistant to commonly used therapies (oral drugs, insulin, combination of insulin and oral drugs). INTERVENTIONS: Two study groups: one received insulin (n = 22) and the other, glibenclamide (n = 16). In each group, half of the patients were randomly allocated into two subgroups who continued the previous treatment but took either placebo tablets or hydroxychloroquine, 200 mg three times a day. The four subgroups were as follows: insulin and placebo (n = 11); insulin and hydroxychloroquine (n = 11); glibenclamide and placebo (n = 8); and glibenclamide and hydroxychloroquine (n = 8). MEASUREMENTS AND MAIN RESULTS: At 6 months, relevant and statistically significant improvement occurred in the 11 patients who received the insulin and hydroxychloroquine (glucose profile decrease, -11.7 mmol/L; 95% CI, -13.9 to -9.5, P = 0.001; glycated hemoglobin A1c decrease, -3.3%; 95% CI, -3.9 to -2.7, P = 0.001). No significant changes were seen in patients on placebo. The daily insulin dose in patients treated with the combined insulin and hydroxychloroquine therapy had to be reduced an average of 30%. No important side effects were detected. CONCLUSIONS: Combining antidiabetic therapy with hydroxychloroquine in decompensated, treatment-refractory patients with noninsulin-dependent diabetes may help to break the vicious circle of hyperglycemia and lead to better management of the disease.

Adult↗
PubMed1990

Evidence for a hyperglycaemia-dependent decrease of antithrombin III-thrombin complex formation in humans.

In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus.

Adult↗
PubMed1990

Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.

Antithrombins↗
PubMed1990

The role of hyperglycaemia-induced alterations of antithrombin III and factor X activation in the thrombin hyperactivity of diabetes mellitus.

Factor X concentration and factor X activation, antithrombin III anti-Xa activity and plasma concentration, and fibrinopeptide A were measured in 20 diabetic patients and 20 normal subjects. Although factor X activation (81.3 +/- 2.2 vs 97.3 +/- 2.1%, p less than 0.01; mean +/- SE) and antithrombin III activity (76.5 +/- 2.2 vs 96.3 +/- 1.8%, p less than 0.01) were reduced in the diabetic patients, fibrinopeptide A concentration was increased (3.7 +/- 0.4 vs 1.7 +/- 0.2 ng ml-1, p less than 0.01). The ratio of factor X activation to antithrombin III anti-factor Xa activity was increased in the diabetic patients (1.10 +/- 0.01 vs 1.01 +/- 0.02, p less than 0.01). Induced hyperglycaemia was able to mimic all these abnormalities, without changing factor X or antithrombin III concentration. The results suggest that in vivo hyperglycaemia produces a decrease of factor X activation, but at the same time increases fibrinopeptide A formation due to a greater decrease of antithrombin III anti-Xa activity.

Adult↗
PubMed1990

Evidence for a reduced heparin cofactor II biological activity in diabetes.

A reduction of heparin cofactor II (HCII) biological activity, despite its normal plasma concentration, is reported in insulin-dependent diabetic patients. A good linear correlation between HCII activity and concentration is present in normal controls but not in diabetics. In these subjects HCII activity correlates inversely with fasting blood glucose and glycated proteins but not with Hb A1. These data demonstrate the presence of a depressed HCII activity in the presence of its normal plasma concentration in insulin-dependent diabetics and suggest a role for short-term metabolic control in conditioning this phenomenon.

Adult↗
PubMed1990

Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

Adult↗
PubMed1989

Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

Adult↗
PubMed1989

Hyperglycemia-conditioned increase in alpha-2-macroglobulin in healthy normal subjects: a phenomenon correlated with deficient antithrombin III activity.

Induced hyperglycemia in normal subjects increases alpha 2-macroglobulin (alpha 2M) activity and alpha 2M concentration and reduces antithrombin III (ATIII) activity, while it does not affect ATIII plasma concentration. Hyperglycemia-determined variations in ATIII activity and alpha 2M molecules are correlated in an inverse and parallel fashion. A compensatory role for the increase in alpha 2M in the regulation of the coagulation system may be hypothesized. Moreover, these data provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may influence the levels of some risk factors for the development of complications in diabetes.

Adult↗