Biomedical subjects

G De Mattia

Publications and source records attributed to G De Mattia.

At least 19 recordsLinked to original sources

PubMed2002

L-arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in Type II diabetic patients.

AIMS/HYPOTHESIS: Hyperhomocysteinaemia increases cardiovascular risk in Type II (non-insulin-dependent) diabetes mellitus by augmenting oxidative stress and reducing nitric oxide availability. In vitro, nitric oxide decreases homocysteine by its conversion to the vasodilative and antioxidant compound S-nitrosohomocysteine. We investigated whether or not changes in nitric oxide availability decrease homocysteine concentrations in vivo. METHODS: The study group consisted of 20 normotensive, normolipidaemic, non-atherosclerotic Type II diabetic patients in good metabolic control (16 men, 51.2+/-1.4 years) and 15 healthy subjects (12 men, 48.1+/-1.5 years). Circulating concentrations of homocysteine, nitrite+nitrate and sulphydryl groups, a marker of oxidative stress, were assessed at baseline and then 5', 10', 30' and 60' after the intravenous infusion of either L-arginine (3 g in 10 ml saline), the nitric oxide precursor, or vehicle according to a double-blind cross-over randomized protocol. RESULTS: At baseline diabetic patients showed lower plasma sulphydryl group concentrations (491.8+/-16.9 vs 551.3+/-21.0 micro mol/l, p<0.04) and nitrite+nitrate (21.4+/-0.8 vs 29.5+/-0.9 micro mol/l, p<0.0001) and higher total homocysteine concentrations (11.1+/-0.5 vs 8.3+/-0.6 micro mol/l, p<0.002) than the control subjects. After L-arginine infusion, blood pressure levels and total homocysteine concentrations ( p< or =0.05) decreased (peak at 5' and 30', respectively) whereas nitric oxide and sulphydryl group concentrations ( p< or =0.003) increased (peak at 10' and 30', respectively) in the patients and control subjects. CONCLUSION/INTERPRETATION: Acute L-arginine infusion in both Type II diabetic patients and healthy subjects decreases plasma total homocysteine concentrations, counteract oxidative stress and increases the availability of nitric oxide.

Arginine↗

PubMed2002

Gliclazide improves anti-oxidant status and nitric oxide-mediated vasodilation in Type 2 diabetes.

AIMS: To evaluate the effects of gliclazide on oxidative status and vascular response to systemic administration of L-arginine, the natural precursor of nitric oxide (NO), in Type 2 diabetic patients. METHODS: Thirty Type 2 diabetic patients received glibenclamide (n = 15) or gliclazide (n = 15) in a 12-week, randomized, observer-blinded, parallel study. Plasma lipid peroxides, total radical-trapping anti-oxidant parameter (TRAP), and blood pressure responses to an intravenous bolus of L-arginine were measured pre- and post-treatment. RESULTS: At 12 weeks, gliclazide patients had lower plasma lipid peroxides (13.3 +/- 3.8 micro mol/l vs. 19.2 +/- 4.3 micro mol/l; P = 0.0001) and higher plasma TRAP (1155.6 +/- 143.0 micro mol/l vs. 957.7 +/- 104.3 micro mol/l; P = 0.0001) than the glibenclamide patients. Gliclazide but not glibenclamide significantly reduced systolic and diastolic blood pressure (P = 0.0199 and P = 0.00199, respectively, two-way repeated measures analysis of variance) in response to intravenous L-arginine. CONCLUSIONS: Gliclazide reduces oxidative stress in Type 2 diabetic patients by improving plasma anti-oxidant status. This effect is associated with enhanced NO-mediated vasodilation.

Adult↗

PubMed2000

Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality.

OBJECTIVE: To determine the isotypes and clonality of antibodies to GAD (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the following consecutive series of patients who attended a diabetes center for antibodies to GADA and IA-2A: 52 newly diagnosed type 1 diabetic patients, 199 type 2 diabetic patients, 200 control patients, and a cohort of 34 nondiabetic identical twins of patients with type 1 diabetes (15 of whom developed diabetes) who were followed prospectively. RESULTS: GADA or IA-2A were detected in 37 (71%) type 1 diabetic patients compared with only 10 (5%) type 2 diabetic patients (P<0.0001). Both GAD and IA-2 antibodies, regardless of the type of diabetes, were usually subclass restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and IA-2A were less prevalent than IgG1 (P<0.017 for either antibody). There was no evidence of spreading or switching of isotypes before the onset of type 1 diabetes. CONCLUSIONS: These observations suggest that the pathogenesis of antigen-specific antibodies in type 1 and type 2 diabetes is similar and probably involves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response.

Adult↗

PubMed1999

Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release.

AIMS/HYPOTHESIS: To evaluate the effects of insulin on vascular cell adhesion molecule-1 expression by cultured human vascular endothelial cells and soluble vascular cell adhesion molecule-1 release in vivo. METHODS: Human vascular endothelial cells derived from umbilical cord veins were incubated with either insulin (from 10(-6) to 10(-9) mol/l) or tumour necrosis factor-alpha (5 ng/ml) for 6 to 24 h. Plasma soluble vascular cell adhesion molecule-1 concentrations were evaluated in 12 non-insulin-dependent diabetic patients (8 men, 4 women, mean age 47.1 +/- 7.7 years) and 12 healthy volunteers matched for age, sex and weight (7 men, 5 women, mean age 42.2 +/- 7.2 years) before and after a 2-h euglycaemic hyperinsulinaemic clamp. RESULTS: Transcriptional activities of nuclear factor-kappaB luciferase and vascular adhesion molecule-1 luciferase statistically significantly increased after incubation with tumour necrosis factor-alpha. By contrast, a slight increment of nuclear factor-kappaB luciferase (mean: 1.8 +/- 0.3 fold) but not of vascular cell adhesion molecule-1 luciferase transcriptional activities were detected in cells stimulated with insulin. Soluble vascular cell adhesion molecule-1 concentrations in cell supernatants increased after tumour necrosis factor-alpha but not insulin stimulation. In vivo, baseline plasma soluble vascular cell adhesion molecule-1 concentrations were higher (p = 0.03) in non-insulin-dependent patients (708.7 +/- 97.4 microg/l) than controls (632.1 +/- 65.2 microg/l) but were not related to fasting insulin concentrations and did not change during insulin infusion. CONCLUSION/INTERPRETATION: The increased concentrations of circulating soluble vascular cell adhesion molecule-1 indicates that the vascular endothelium is activated in non-insulin dependent diabetic patients. Our in vitro and in vivo findings show that vascular cell adhesion molecule-1 activation cannot be due to hyperinsulinaemia. [Diabetologia (1999) 42: 1235-1239]

Adult↗

PubMed1999

Analytical evaluation of virgin olive oil of first and second extraction.

Virgin olive oils from percolation (first extraction) have been compared with the corresponding oils from centrifugation (second extraction). The former were characterized by (i) higher contents of total phenols, o-diphenols, hydroxytyrosol, tyrosol-aglycons, tocopherols, trans-2-hexenal, total volatiles, and waxes; (ii) higher values of resistance to autoxidation and of turbidity; (iii) higher sensory scores; (iv) higher ratios of campesterol/stigmasterol, trans-2-hexenal/hexanal, and trans-2-hexenal/total volatiles; (v) lower contents of chlorophylls, pheophytins, sterols, and aliphatic and triterpene alcohols; (vi) lower alcoholic index and color indices; (vii) similar values of acidity, peroxide index, and UV (ultraviolet) spectrophotometric indices; (viii) similar percentages of saturated and unsaturated fatty acids, triglycerides, and diglycerides; and (ix) similar values of glyceridic indices. Stigmastadienes, trans-oleic, trans-linoleic, and trans-linolenic acid isomers were not detected in the two genuine oil kinds. Hence, the qualitative level of the first extraction oil was superior to the second extraction one.

Food Handling↗

PubMed1999

Treatment of nonproliferative diabetic retinopathy with Defibrotide in noninsulin-dependent diabetes mellitus: a pilot study.

PURPOSE: Microvascular alterations, impairment of coagulation, ischemia and diffuse endothelial damage are related to the progression of diabetic retinopathy. Defibrotide has been demonstrated to produce profibrinolytic, cytoprotective and vasofacilatory activities. The aim of the present study was to evaluate the therapeutic effect of Defibrotide in the treatment of nonproliferative diabetic retinopathy. METHODS: Two randomized age- and sex-matched groups (cases and controls) of 35 NIDDM patients presenting non-proliferative diabetic retinopathy were included in this study: cases were treated with Defibrotide (800-1600 mg daily) for two years. RESULTS: All tested parameters (ETDRS visual acuity; computerized perimetry; retinography; fluorescein angiography), improved significantly (p<0.001) in Defibrotide-treated patients compared to controls. In our opinion, Defibrotide's manifold effects on vascular endothelia may account for this improvement by stimulation of tPA, PGI2, PGE2, thrombomodulin and modulation of endothelin-1 release. CONCLUSIONS: Our preliminary data seem to suggest that Defibrotide could be proposed for medical treatment of nonproliferative diabetic retinopathy.

Aged↗

PubMed1999

High plasma renin activity is combined with elevated urinary albumin excretion in essential hypertensive patients.

BACKGROUND: Several studies suggest that the hyperactivity of the circulating renin-angiotensin system might favor the progression of renal disease in essential hypertension. To elucidate this aspect, we investigated the relationship between plasma renin activity (PRA) and the urinary albumin excretion rate (UAER), an early marker of hypertension-related renal changes, in human essential hypertension. METHODS: Ninety nonobese, nondiabetic, nonhyperlipidemic patients with mild-to-moderate essential hypertension (67 males, 23 females; mean age 51.4 +/- 6.2 years) were divided into low renin (LR), normal renin (NR), and high renin (HR) subgroups according to individual PRA while they were on a constant NaCl intake (120 mmol NaCl/day). The UAER was assessed during the same NaCl intake. RESULTS: Data showed significantly higher UAER (31.3 +/- 12.9 microg/min) in HR (N = 30) than NR (N = 30, 22.7 +/- 14.4 microg/min, P < 0.02) and LR patients (N = 30, 21.7 +/- 10.8 microg/min, P < 0. 01). CONCLUSIONS: Our study demonstrates that the UAER is elevated in HR essential hypertensive patients, suggesting that high PRA accelerates the onset of early renal changes in human essential hypertension.

Adult↗

PubMed1999

Early upregulation of endothelial adhesion molecules in obese hypertensive men.

Upregulation of endothelial adhesion molecules is the earliest step of atherogenesis. Whether obesity induces endothelial adhesin upregulation is unknown. To address this topic, circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor (vWF) concentrations were evaluated in 22 obese hypertensive (51.4+/-4.6 years [mean+/-SD age]), 19 obese normotensive (50.6+/-3.8 years), 18 nonobese hypertensive (52.3+/-3.9 years), and 16 nonobese normotensive (52. 4+/-3.5 years) men without other risk factors or overt atherosclerosis. All measurements were repeated in the obese subgroups after weight loss induced by 12 weeks of caloric restriction. Basal circulating VCAM-1 levels were similar between the 2 obese groups but were higher (P<0.0001) than in the 2 nonobese groups. No differences were found between nonobese hypertensives and normotensives. Serum low density lipoprotein cholesterol was weakly correlated with plasma soluble VCAM-1 levels in pooled, obese subjects (r=0.362, P=0.02). Plasma soluble adhesin and vWF concentrations decreased significantly after weight loss in obese hypertensives (VCAM-1 P=0.03, ICAM-1 P=0.004, E-selectin P<0.0001, and vWF P=0.003) and normotensives (VCAM-1 P=0.04, ICAM-1 P=0.003, E-selectin P<0.0001, and vWF P<0.0001). Body mass index was correlated with plasma E-selectin concentrations at baseline and after weight loss in obese hypertensives (r=0.501, P=0.018 and r=0. 466, P=0.03, respectively) and obese normotensives (r=0.523, P=0.021 and r=0.460, P=0.05, respectively). In conclusion, our data show that obesity per se induces early endothelial activation in hypertensive and normotensive men. Weight loss counteracted endothelial activation in both obese hypertensive and normotensive men.

Adult↗

PubMed1999

Relationship between insulin resistance and nonmodulating hypertension: linkage of metabolic abnormalities and cardiovascular risk.

Insulin resistance is a feature common to patients with diabetes and to some with hypertension. It is assumed that this feature confers the increased metabolic risk in hypertension. However, the state of the renin-angiotensin system might contribute to cardiovascular risk, although there is no clear mechanistic explanation. Our recent observation that insulin levels are increased in a specific subset of patients with normal/high-renin hypertension, the nonmodulators, provided the background for the current hypothesis: to ascertain whether abnormalities in lipid and carbohydrate metabolism are observed in the same patients in whom alterations in sodium transport, sodium homeostasis, and the renin-aniotensin system response have been identified. Exploration of a family history of cardiovascular risk was a secondary goal. Insulin sensitivity (assessed by a 75-g oral glucose load), lipid levels, and two defects in the renin-angiotensin system were assessed in 62 hypertensive and 14 normotensive subjects placed on a high (210 mmol/l) and a low (10 mmol/l) sodium intake for 2 weeks, to classify them as low-renin, nonmodulator, or modulating hypertensive subjects. Only in nonmodulators were the following cardiovascular risk factors significantly increased: fasting insulin (P < 0.01); increment in post-glucose load insulin (P < 0.01); total, LDL, and VLDL cholesterol and triglyceride levels (P < 0.05); and erythrocyte Na+/Li+ countertransport activity (P < 0.001). Both nonmodulators and low-renin hypertensive subjects had a significantly (P < 0.01) increased frequency of a family history of hypertension by questionnaire compared with subjects with intact modulation. However, only nonmodulators had a significantly (P < 0.02) higher frequency of a family history of myocardial infarction. Thus, there is a clustering of metabolic abnormalities in a discrete subset of the essential hypertensive population with a specific dysregulation of the renin-angiotensin system--nonmodulation. The absence of this cluster in low-renin hypertensive subjects may explain their relatively diminished cardiovascular risk. Its presence in nonmodulators likely contributes to the increased cardiovascular risk observed in normal/high-renin hypertension.

Adult↗

PubMed1999

Angiotensin II increases the release of endothelin-1 from human cultured endothelial cells but does not regulate its circulating levels.

We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 30 min each; Study B, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 120 min each; Study C, 3.0 ng x min-1 x kg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ng x min-1 x kg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ng x min-1 x kg-1 followed by 3.0 ng x min-1 x kg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10(-9), 10(-8), 10(-7) mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.

Adult↗

PubMed1998

Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes.

To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 +/- 6 years old) before and after 1 month of either oral N-acetyl-L-cysteine (1.200 mg/day) or placebo treatments, given in randomized, cross-over, double-blind fashion. Ten healthy subjects (7 men, 3 women, 52 +/- 4 years old) served as control subjects. Baseline plasma VCAM-1 concentrations were higher (p = 0.007) in non-insulin-dependent diabetic patients (707.9 +/- 52.5 ng/ml) than in control subjects (627.3 +/- 84.6 ng/ml). Intraerythrocytic GSSG content was higher (non-insulin dependent diabetic patients: 0.618 +/- 0.185 micromol/g Hb; control subjects: 0.352 +/- 0.04 micromol/g Hb, p = 0.0002), whereas intraerythrocytic GSH concentrations were lower (p = 0.001) in non-insulin dependent diabetic patients (6.0 +/- 0.7 micromol/g Hb) than in control subjects (7.1 +/- 0.5 micromol/g Hb). The mean GSH:GSSG ratio was also lower (p = 0.0001) in the first (10.9 +/- 4.5) than in the second group (20.2 +/- 1.4). Circulating VCAM-1 and intraerythrocytic GSH concentrations were negatively correlated in non-insulin diabetic patients (r = 0.605, p = 0.01). Treatment with N-acetyl-L-cysteine decreased plasma VCAM-1 (p = 0.01) and intraerythrocytic GSSG (p = 0.006) but increased GSH concentrations (p = 0.04) and the GSH:GSSG ratio (p = 0.004) in non-insulin dependent diabetic patients. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes.

Acetylcysteine↗

PubMed1998

Influence of reduced glutathione infusion on glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

To evaluate the relationship between oxidative stress and glucose metabolism, insulin sensitivity and intraerythrocytic reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio were measured in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients and 10 healthy subjects before and after the intravenous administration of GSH. In particular, after baseline insulin sensitivity was assessed by a 2-hour euglycemic hyperinsulinemic clamp, either glutathione (1.35 g x m2 x min(-1)) or placebo (saline) were infused over a period of 1 hour. The same protocol was repeated at a 1-week interval, in cross-over, according to a randomized, single-blind design. In healthy subjects, baseline intraerythrocytic GSH/GSSG ratio (P < .0005) and total glucose uptake (P < .005) were significantly higher than in NIDDM patients. In the same subjects, GSH infusion significantly increased total glucose uptake (from 37.1 +/- 6.7 micromol kg(-1) x min(-1) to 39.5 +/- 7.7 micromol x kg(-1) x min(-1), P < .05), whereas saline infusion was completely ineffective. In addition, the mean intraerythrocytic GSH/GSSG ratio significantly increased after GSH infusion (from 21.0 +/- 0.9 to 24.7 +/- 1.3, P < .05). Similar findings were found in diabetic patients, in whom GSH infusion significantly increased both total glucose uptake (from 25.3 +/- 9.0 micromol x kg(-1) x min(-1) to 31.4 +/- 10.0 micromol x kg(-1) x min(-1), P < .001) and intraerythrocytic GSH/GSSG ratio (from 14.8 +/- 4.1 to 21.7 +/- 6.7, P < .01). Pooling diabetic patients and controls, significant correlations were found between intraerythrocytic GSH/GSSG ratio and total glucose uptake (r = .425, P < .05), as well as between increments of the same variables after GSH infusion (r = .518, P < .05). In conclusion, our data support the hypothesis that abnormal intracellular GSH redox status plays an important role in reducing insulin sensitivity in NIDDM patients. Accordingly, intravenous GSH infusion significantly increased both intraerythrocytic GSH/GSSG ratio and total glucose uptake in the same patients.

Adult↗

PubMed1998

Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy.

To evaluate the role of circulating and renal endothelin-1 (ET-1) in early diabetic nephropathy, plasma ET-1 levels and urinary ET-1 excretion were evaluated in lean, normotensive patients affected by non-insulin-dependent diabetes (NIDDM) either with (n = 9, NIDDM+) or without microalbuminuria (n = 18, NIDDM-); in never-treated, lean, essential hypertensive patients with (n = 12, EH+) or without microalbuminuria (n = 10, EH-); and in healthy volunteers (n = 12). Results showed higher plasma ET-1 levels in NIDDM+ (1.97 +/- 0.58 pg/mL) than in NIDDM- (1.59 +/- 0.14 pg/mL, P = .013), EH+ (1.40 +/- 0.21 pg/mL, P = .005), EH- (0.91 +/- 0.19 pg/mL, P < .0001), and controls (0.60 +/- 0.10 pg/mL, P < .0001). The circulating ET-1 concentration was also higher in EH+ than EH- and controls (P < .0001). Urinary ET-1 excretion did not differ (P = .387, NS) between NIDDM+ (48.5 +/- 20.1 pg/min) and NIDDM- (40.9 +/- 21.6 pg/min), but was significantly reduced (P < .0001) in both groups compared with controls (70.0 +/- 15.5 pg/min). Similar findings were observed in hypertensive subgroups. No correlations were found between urinary ET-1 and other variables, including plasma ET-1 levels, in all groups. In conclusion, NIDDM+ is accompanied by a significant increase in plasma ET-1 levels. A significant elevation of circulating ET-1 concentration was evident also in NIDDM-, suggesting that early abnormalities of ET-1 production might precede the microalbuminuric phase of diabetes-related renal damage.

Adult↗

PubMed1997

Polyol pathway activation and glutathione redox status in non-insulin-dependent diabetic patients.

The current study aimed to evaluate whether nicotinamide adenine dinucleotide phosphate (NADPH) alteration in erythrocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) is responsible for the impaired glutathione (GSH) redox status, and to assess if short-term inhibition of the polyol pathway normalizes NADPH levels and GSH redox status via an amelioration of the NADPH/total NADP (tNADP) ratio. For this purpose, erythrocyte NADPH and GSH levels were measured in 18 NIDDM patients at baseline and then after 1 week of random double-blind assignment to treatment with either tolrestat (an aldose reductase inhibitor, 200 mg daily) (n = 12) or placebo (n = 6). A group of 16 healthy volunteers served as the control. In the basal condition, mean GSH (P < .0001) and NADPH (P < .0001) levels and NADPH/tNADP (P < .0001) and GSH/ glutathione disulfide (GSSG) (P < .005) ratios were lower in NIDDM patients than in control subjects. Tolrestat treatment increased GSH levels (P < .05 v placebo and baseline) and the NADPH/tNADP ratio (P < .05 v placebo and baseline). Interestingly, tolrestat-induced changes in GSH and NADPH levels and in GSH/GSSG and NADPH/tNADP ratios were significant only in patients who showed a decreased NADPH/tNADP ratio at baseline (n = 8). In these latter patients, we also found a direct correlation between percentage increments in GSH levels and NADPH/tNADP ratios after tolrestat treatment (r = .71, P < .05). In conclusion, our findings support the hypothesis that polyol pathway activation decreases NADPH and GSH levels. Accordingly, short-term inhibition of this enzymatic route increased both the GSH level and the NADPH/tNADP ratio. These changes were observable only in the subgroup of patients with an abnormal NADPH/tNADP ratio at baseline. Polyol pathway inhibition could be useful for decreasing oxidative stress in NIDDM.

Adult↗

PubMed1997

Circulating endothelin-1 levels in obese patients with the metabolic syndrome.

We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome.

Adult↗

PubMed1997

Increased levels of plasma endothelin-1 in non-insulin dependent diabetic patients with retinopathy but without other diabetes-related organ damage.

Increased levels of endothelin (ET-1), a potent endothelium-derived vasoconstrictive peptide, have been found in plasma from non-insulin dependent diabetic (NIDDM) patients, suggesting that ET-1 might represent a new marker of diabetes-related vascular damage. To elucidate this topic, circulating ET-1 levels were evaluated in 16 NIDDM patients in good metabolic control without either cardiovascular risk factors (obesity, hypertension, smoking, hyperdislipidaemia, etc.) or diabetes-related damage of other districts and in 12 healthy subjects. Retinopathy was assessed by ophthalmological evaluation and its severity determined by Klein criteria. Resulting data showed higher levels of plasma ET-1 in NIDDM patients than in control subjects (0.80 +/- 0.13 vs 0.60 +/- 0.12 pg/mL, p < 0.001). Plasma ET-1 levels were directly correlated with retinopathy degrees in NIDDM patients affected by retinopathy (n = 10; r = 0.368; p = 0.02), and were significantly higher in these latter (n = 10) than in those without retinopathy (n = 6) (0.89 +/- 0.13 vs 0.71 +/- 0.19 pg/mL, p < 0.05). The increased levels of ET-1 could contribute to retinopathy development or, more probably, represent a marker of this diabetes-related complication.

Adult↗

PubMed1997

Vitamin E and nicotinamide have similar effects in maintaining residual beta cell function in recent onset insulin-dependent diabetes (the IMDIAB IV study)

OBJECTIVE: Protection of residual beta cell function at the time of diagnosis of insulin-dependent diabetes mellitus (IDDM) by intensive insulin therapy and the addition of nicotinamide (NA) has been established. The objective of this study was to evaluate the effect of a free oxygen radical scavenger such as vitamin E (Vit E) on residual beta cell function and parameters of metabolic control in patients with recent onset IDDM undergoing intensive insulin therapy. DESIGN: The effect of Vit E was compared with that of NA (control group) in a randomized multicentre trial. METHODS: Eighty-four IDDM patients between 5 and 35 years of age (mean age 15.8 +/- 8.4 (s.d.) years) entered a one year prospective study. One group of patients (n = 42) was treated with Vit E (15 mg/kg body weight/day) for one year; the other group (n = 42) received NA for one year (25 mg/kg body weight/day). All patients were under intensive insulin therapy with three to four injections a day. Basal and stimulated (1 mg i.v. glucagon) C-peptide secretion, glycosylated haemoglobin and insulin dose were evaluated at diagnosis and at three-monthly intervals up to one year. RESULTS: Preservation and slight increase of C-peptide levels at one year compared with diagnosis were obtained in the two treated patient groups. No statistically significant differences were observed in basal or stimulated C-peptide levels between the two groups of patients for up to one year after diagnosis. Glycosylated haemoglobin and insulin dose were also similar between the two groups; however patients receiving Vit E under the age of 15 years required significantly more insulin than NA-treated patients one year after diagnosis (P < 0.04). CONCLUSIONS: Our data indicate that Vit E and NA possess similar effects in protecting residual beta cell function in patients with recent onset IDDM. Since their putative mechanism of protection on beta cell cytotoxicity is different, combination of these two vitamins may be envisaged for future trials of intervention at IDDM onset.

Adolescent↗

PubMed1997

Effects of ACE inhibition on spontaneous and insulin-stimulated endothelin-1 secretion: in vitro and in vivo studies.

To evaluate the effect of angiotensin-converting enzyme inhibition on spontaneous and insulin-stimulated endothelin-1 (ET-1) secretion in vitro and in vivo, human endothelial cells derived from umbilical cord veins were cultured onto acellular collagen-coated permeable membrane, thus mimicking in vivo conditions with a luminal and abluminal side. Insulin (10(-6,-8,-9) mol/l) significantly stimulated ET-1 secretion by cultured cells (P < 0.05 starting from 2-h incubation). Captopril (10(-7,-8,-9) mol/l) significantly reduced both spontaneous and insulin-stimulated ET-1 secretion, while increasing nitric oxide production. Considering each cell side, captopril significantly inhibited the apical secretion of ET-1, while its effect on the basolateral compartment was modest. In the presence of D-Arg,[Hyp3,Thi5,8,D-Phe7]-bradykinin (10(-6) mol/l), a bradykinin B2 receptor antagonist, captopril had no effects on ET-1 and nitric oxide production and also when insulin was added to the culture media. With regard to in vivo experiments, oral captopril therapy (25 mg twice daily for 1 week) was given to normotensive (n = 5) and hypertensive (n = 6) subjects and significantly decreased plasma ET-1 concentration (normotensive subjects, before: 0.98 +/- 0.09 pg/ml; after: 0.55 +/- 0.08 pg/ml, P < 0.0001; hypertensive subjects, before: 1.05 +/- 0.03 pg/ml; after: 0.56 +/- 0.05 pg/ml, P < 0.0001). Transient hyperinsulinemia was accompanied by a significant rise in plasma ET-1 concentrations in both groups (P < 0.0001 at 180 and 210 min) before but not after captopril treatment. In conclusion, captopril inhibits both spontaneous and insulin-stimulated ET-1 secretion by endothelial cells, acting on angiotensin-converting enzyme bound to the luminal cell side. In vivo, captopril significantly reduces plasma ET-1 levels in both basal and insulin-stimulated conditions.

Adult↗