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Biomedical subjects

I Zavaroni

Publications and source records attributed to I Zavaroni.

At least 19 recordsLinked to original sources
PubMed2006

The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene.

OBJECTIVE: To investigate the contribution of the total antioxidant capacity (TAC) of the diet to plasma concentrations of beta-carotene. DESIGN: Cross-sectional study. SETTING: Department of Public Health and Department of Internal Medicine and Biomedical Sciences, University of Parma. SUBJECTS: A total of 247 apparently healthy adult men (n=140) and women (n=107). METHODS: A medical history, a physical exam including height, weight, waist circumference and blood pressure measurements, a fasting blood draw, an oral glucose tolerance test and a 3-day food record. RESULTS: We observe a negative trend across quartiles of plasma beta-carotene for most biological variables clustering in the insulin resistance syndrome, as well as for traditional and new risk factors for type II diabetes and cardiovascular disease (CVD), including C-reactive protein and gamma-glutamyltranspeptidase (P<0.05). Regarding dietary characteristics, energy-adjusted intake of fat, fiber, fruits, vegetables, beta-carotene, vitamin C, vitamin E and dietary TAC significantly increased with increasing plasma beta-carotene (P<0.05), whereas alcohol intake decreased (P=0.013). Adjusted geometric means (95% confidence interval) of plasma beta-carotene significantly increased across quartiles of dietary TAC, even when single dietary antioxidants were considered in the model (QI=0.087 mg/dl (0.073-0.102); QII=0.087 mg/dl (0.075-0.103); QIII=0.114 mg/dl (0.098-0.132) and QIV=0.110 mg/dl (0.093-0.130); P for linear trend=0.026). When the population was divided on the basis of alcohol consumption, this trend was also observed in subjects drinking <20 g alcohol/day (P=0.034), but not in those with higher alcohol intake (P=0.448). CONCLUSIONS: Dietary TAC is an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.

Alcohol Drinking↗
PubMed2003

What is the contribution of differences in three measures of tumor necrosis factor-alpha activity to insulin resistance in healthy volunteers?

To address the potential role that tumor necrosis factor-alpha (TNF-alpha) might play in modulation of insulin resistance in healthy, nondiabetic individuals, we compared plasma TNF-alpha and soluble TNF-alpha receptor 2 (sTNF-R2) concentrations, as well as TNF-alpha polymorphisms, in 94 healthy individuals, stratified into insulin-resistant (IR) and insulin-sensitive (IS) groups based on their plasma insulin concentrations 120 minutes after oral glucose on 2 occasions (1993 and 2000). The IR group (n = 50; 29 men and 21 women) was in the upper quartile and the IS group (n = 44; 24 men and 20 women) in the lowest quartile of the distribution of post-glucose challenge insulin concentrations in a large unselected population (>50 v <23 microU/mL). The IR group had significantly higher values for body mass index, waist-to-hip girth, fasting and post-glucose challenge insulin concentrations, and fasting triglyceride concentrations, and lower high-density lipoprotein cholesterol concentrations as compared to the IS group. Despite the fact that they were relatively more obese, and insulin-resistant, plasma concentrations of TNF-alpha were similar in the IR (1.6 +/- 0.6 pg/mL) and IS (1.7 +/- 0.6 pg/mL) groups, as were the concentrations (5.4 +/- 1.4 v 5.8 +/- 2.0 pg/mL) of sTNF-R2. Furthermore, TNF-alpha polymorphisms (detected by polymerase chain reaction [PCR]) were similar in the 2 groups, with essentially identical allelic frequencies of the 238 (10.3% v 9.4%) and 308 polymorphisms (17.9% v 18.7%). In conclusion, plasma TNF-alpha and sTNF-R2 concentrations, as well as TNF-alpha gene polymorphisms, were not different in healthy volunteers stratified into IR and IS groups on the basis of their plasma insulin response to an oral glucose challenge. Given these data, it does not appear that differences in TNF-alpha activity contribute to the marked variations in insulin action that occur in healthy individuals.

Aged↗
PubMed2000

Comparison of fasting plasma leptin concentrations in healthy subjects with high and low plasma insulin.

This study was initiated to evaluate the role of hyperinsulinemia in the regulation of fasting plasma leptin. We measured plasma leptin and insulin concentrations in 404 healthy nondiabetic subjects. For analytical purposes, the population was divided into quartiles on the basis of the lowest (quartile 1) and highest (quartile 4) plasma insulin response to oral glucose, and fasting plasma leptin values in these 2 dichotomous groups were compared. The total plasma integrated insulin response was 4-fold greater in quartile 4, associated with significantly higher (P < .001) fasting plasma leptin (12.60+/-0.85 v8.53+/-0.56 ng/mL). Fasting plasma leptin concentrations remained significantly higher in the hyperinsulinemic quartile when comparisons were made after subdividing the population on the basis of gender, body mass index (BMI), or waist to hip ratio (WHR). These results demonstrate that fasting plasma leptin concentrations are significantly higher in hyperinsulinemic individuals, and this difference is independent of either overall or central obesity.

Administration, Oral↗
PubMed2000

Plasma nitric oxide concentrations are elevated in insulin-resistant healthy subjects.

The goal of this study was to compare plasma nitric oxide (NO) concentrations in healthy subjects, defined as either insulin-resistant or insulin-sensitive on the basis of the plasma insulin response to a 75-g oral glucose challenge. For this purpose, 404 healthy subjects were divided into quartiles on the basis of the plasma insulin response to glucose, and 49 individuals were selected from the quartile with the lowest insulin response and 49 from the quartile with the highest insulin response. The two groups of 49 each were selected to be essentially identical in terms of age, gender distribution, body mass index (BMI), and waist to hip ratio (WHR). The quartile with the greatest insulin response also had a significantly higher plasma glucose response to oral glucose, faster heart rate, higher blood pressure, and the combination of higher triglyceride and lower high-density lipoprotein (HDL) cholesterol concentrations. In addition to the latter changes, previously shown to be associated with hyperinsulinemia, NO concentrations were also higher in the hyperinsulinemic group. It is speculated that this increase in the NO concentration in hyperinsulinemic and presumably insulin-resistant, subjects represents a compensatory effort to overcome the untoward effects of insulin resistance and/or hyperinsulinemia.

Blood Glucose↗
PubMed2000

Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes.

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(-1)/pmol/L) x 10(3)] was significantly greater in those without a family history (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.

Blood Glucose↗
PubMed1999

Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: the Barilla factory revisited.

The study was initiated to evaluate the ability of hyperinsulinemia (as a surrogate measure of insulin resistance) to predict the development in a previously healthy population of three putative outcomes of this abnormality--glucose intolerance, hypertension, and coronary heart disease (CHD). The study involved defining the incidence at which these changes occurred between 1981 and 1993 to 1996 in 647 individuals who were free of any disease when initially studied. The study population consisted of approximately 90% of the subjects evaluated in 1981, divided into quartiles on the basis of the plasma insulin response to a glucose challenge as determined in 1981. The results indicated that the 25% of the population with the highest insulin response in 1981 had significant (P < .001) increases in the incidence of impaired glucose tolerance (IGT) or type 2 diabetes (eightfold), hypertension (twofold), or CHD (threefold). Furthermore, the ability of hyperinsulinemia to predict the three clinical endpoints was independent of differences in age, gender, or body mass index (BMI). Finally, if CHD is considered the clinical endpoint, multiple logistic regression analysis indicates that the values for plasma triglyceride (TG) and mean arterial blood pressure ([MAP] as measured in 1981) also predict the development of CHD. These results indicate that the untoward clinical effects of insulin resistance and/or compensatory hyperinsulinemia, glucose intolerance, hypertension, and CHD clearly can develop in less than 15 years.

Adult↗
PubMed1998

Can weight gain in healthy, nonobese volunteers be predicted by differences in baseline plasma insulin concentration?

In this study, we have evaluated the effect, over approximately 14 yr, of differences in baseline degree of hyperinsulinemia on weight gain in 647 healthy, nonobese factory workers. The subjects were divided into 4 quartiles, on the basis of their plasma insulin response to an oral glucose challenge, in 1981. At that time, the mean (+/-SD) plasma insulin concentration, 2 h after the glucose challenge, varied from 18+/-5 to 106+/-42 microU/mL. Despite this approximate 6-fold difference in plasma insulin response at baseline, the weight gain over the period of observation was similar in all quartiles, with mean (+/-SD) increments (kg) of 1.8+/-5.1, 1.6+/-5.3, 2.3+/-5.2, and 2.3+/-5.7, going from the lowest quartile to the highest quartile, in terms of insulin concentration. Furthermore, when the population was considered as a whole, there was no correlation between baseline degree of hyperinsulinemia and change in either absolute (r = 0.004) or percent (r = 0.003) weight gain. Finally, there was no difference in the number of individuals who gained more than 4.5 kg, as a function of their baseline insulin response. Consequently, we conclude that 6-fold differences in plasma insulin responses to glucose do not predict weight gain in a healthy, nonobese population.

Administration, Oral↗
PubMed1996

Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population.

OBJECTIVES: To see if the cluster of metabolic and haemodynamic variables defined as comprising Syndrome X varied as a function of urinary albumin excretion (UAE) rate in a healthy population. DESIGN: A cross-sectional, population-based study. SETTING: A factory in Italy. SUBJECTS: Two hundred and twenty-five healthy volunteers, 115 men and 110 women. OUTCOME MEASURES. Measurements were made of the plasma glucose and insulin responses to oral glucose, fasting triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood pressure, and UAE rates. RESULTS: Only five of the 225 volunteers had micro-albuminuria, defined as a UAE rate > 2 micrograms min-1, and the UAE rate was < 5 micrograms min-1 in 80% of the volunteers. Significant variations in the metabolic and haemodynamic variables measured were not associated with any differences in UAE. Finally, significant relationships were found between various measures of plasma insulin concentration and plasma glucose response to oral glucose, plasma TG and HDL-cholesterol concentrations, and mean arterial blood pressure, independent of variations in age, body mass index, ratio of waist-to-hip girth, and UAE rates. CONCLUSION: The widespread variability in plasma glucose and insulin responses, plasma TG and HDL-cholesterol concentrations, and blood pressure that are seen in the population at large cannot be attributed to variations in UAE rate.

Albuminuria↗
PubMed1996

Renal metabolism of C-peptide in patients with early insulin-dependent diabetes mellitus.

Renal metabolism of C-peptide was studied in 6 patients with early insulin-dependent diabetes mellitus (IDDM) with residual beta cell activity and in 11 nondiabetic subjects by the arterial-venous difference technique both in the postabsorptive state and for 80 min after ingestion of an amino acid mixture (0.8 g/kg). Urinary C-peptide (Cp) excretion, glomerular filtration rate and renal plasma flow were also measured. In the postabsorptive state in IDDM, renal uptake of Cp is reduced, while its urinary excretion and clearance are significantly increased. As a result, net renal extraction is markedly reduced. In contrast to controls, renal uptake and net extraction of C-peptide after amino acid ingestion do not increase in patients; the peritubular uptake evident in normal subjects is not detectable. Urinary excretion and clearance of Cp remain significantly higher in IDDM patients. In both groups, renal uptake of C-peptide is directly related to its renal load: however, in IDDM, the increase in Cp uptake for each increment in renal load is 35% lower than in controls (p < 0.001). Furthermore, as opposed to controls, urinary Cp excretion is not correlated with its arterial levels. Therefore IDDM patients have marked defects in renal handling of endogenous Cp, regarding both the amount metabolized by renal tissue and that reabsorbed by tubular cells. These data indicate an early alteration in the diabetic kidney that also impairs the reliability of urinary Cp evaluation as an index of residual beta cell activity in IDDM patients.

Adult↗
PubMed1995

Comparison of the metabolic changes in rats with hypertension secondary to fructose feeding or renal artery stenosis.

Hypertension was induced in rats by either renal artery stenosis or a fructose-enriched diet, and the consequent changes in plasma glucose, insulin, and triglyceride (TG) concentrations, and the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min continuous infusion of glucose and insulin in these two groups of hypertensive rats, were compared to values in a sham-operated group with normal blood pressure. Mean (+/- SEM) blood pressure was significantly higher than the control values (121 +/- 3 mm Hg) at the end of the study in rats with renal artery stenosis (178 +/- 13 mm Hg) and fructose-fed rats (151 +/- 5 mm Hg), whereas left ventricular weight was only significantly (P < .01) higher in rats with renal artery stenosis. Plasma glucose concentration was the same in all three groups, but fructose-fed rats had significantly higher plasma insulin (59 +/- 7 microU/mL) and TG (317 +/- 48 mg/dL) concentration than either sham-operated rats (30 +/- 4 microU/mL and 121 mg/dL) or rats with renal artery stenosis (34 +/- 5 microU/mL and 124 +/- 14 mg/dL). Although SSPI concentrations were similar (approximately 250 microU/mL) in all three groups of rats, SSPG concentrations were significantly higher (P < .01) in the fructose-fed rats (187 +/- 10 mg/dL) than in either sham-operated normotensive rats (120 +/- 6 mg/dL) or hypertensive rats with renal artery stenosis (133 +/- 4 mg/dL). Thus, insulin resistance, hyperinsulinemia, and hypertriglyceridemia developed in rats with fructose-induced hypertension, whereas none of these changes were seen in rats with renal artery stenosis.

Animals↗
PubMed1995

Association between salt sensitivity and insulin concentrations in patients with hypertension.

This study was performed in 28 patients with mild to moderate hypertension, classified as being either salt sensitive or salt resistant on the basis of the percent decrement in mean arterial blood pressure (MAP) seen 7 days after daily salt intake was decreased from 220 to 30 mmol/L. Ten patients had a percent decrease of MAP > 10% and were defined as being salt sensitive. Salt resistance was defined as a percent decrease in MAP of < 3% and eight patients satisfied this criterion. Both plasma glucose and insulin concentrations following a 75-g oral glucose challenge were significantly higher after the high-salt diet in the salt-sensitive patients. Furthermore, there were correlations of marginal statistical significance between the decrease in MAP after the low-salt diet and the plasma glucose (r = 0.32, P < .10) and insulin (r = 0.38, P < .06) responses to oral glucose. These data are consistent with the view that there is an association between resistance to insulin-mediated glucose disposal and salt sensitivity in patients with high blood pressure.

Adult↗
PubMed1994

Hyperinsulinaemia, obesity, and syndrome X.

OBJECTIVE: The major aim of this study was to compare various aspects of carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration, and blood pressure in normal subjects stratified on the basis of both plasma insulin concentration and degree of obesity. The hypothesis to be tested was that hyperinsulinaemia, per se, was associated with relative glucose intolerance, higher triglyceride and uric acid concentrations, lower high-density lipoprotein cholesterol concentration and higher blood pressure, irrespective of degree of obesity. DESIGN: This represents a case-control study, in which normal volunteers were subdivided into four equal groups based upon degree of obesity and plasma insulin response to a 74 g oral glucose challenge. SETTING: The study was performed in the out-patient clinic of a university hospital. SUBJECTS: Sixty-four individuals were recruited for this study, subdivided into four groups based upon their plasma insulin concentration and body mass index. Subjects were classified as hyperinsulinaemic if their plasma insulin concentrations in response to an oral glucose challenge were more than two standard deviations above the mean of 732 volunteers previously studied [1]. Obesity was defined as a body mass index of > 30 kg m-2, and individuals were classified as non-obese if their body mass index was < 27.0 kg m-2. Based upon these criteria, four experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper); (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normoinsulinaemic (NOB normo); and (iv) obese normoinsulinaemic (OB normo). MAIN OUTCOME MEASURES: Subject groups were compared on the basis of the integrated plasma glucose response to a 75 g oral glucose challenge, fasting plasma triglyceride, cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations, and blood pressure. RESULTS: Mean (+/- standard error of the mean) integrated plasma glucose response area for 2 h following a 75 g oral glucose load was significantly higher (13.4 +/- 0.4 vs. 11.0 +/- 0.4 mmol l-1, P < 0.001) in the hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 +/- 0.2 vs. 1.4 +/- 0.1 mmol l-1, P < 0.001) and uric acid (5.3 +/- 0.2 vs. 4.4 +/- 0.2 mmol l-1, P < 0.05) concentrations. In contrast, high-density lipoprotein concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 +/- 0.05 mmol l-1, P < 0.001). In addition, blood pressure was higher in the hyperinsulinaemic group (136 +/- 5/87 +/- 2 vs. 123 +/- 2/82 +/- 1 mmHg, P < 0.05). Furthermore, when each of the two groups were divided into obese (n = 16) and non-obese (n = 16) groups, all of the differences outlined above persisted. These changes were independent of age, gender distribution, generalized and abdominal obesity, cigarette smoking, and estimated physical activity. CONCLUSIONS: The cluster of changes subsumed under the heading of syndrome X are closely associated with hyperinsulinaemia (and presumably insulin resistance), and can be discerned irrespective of degree of obesity.

Adult↗
PubMed1993

Changes in insulin and lipid metabolism in males with asymptomatic hyperuricaemia.

OBJECTIVES: To define the effect of asymptomatic hyperuricaemia on various facets of glucose, insulin, and lipoprotein metabolism. DESIGN: Case control study in health volunteers. SETTING: The volunteers for this study were selected on the basis of their laboratory results from a larger population participating in a general survey in one large factory. SUBJECTS: The study population consisted of 40 healthy males: 20 with asymptomatic hyperuricaemia (serum uric acid concentration equal to or greater than 420 mmol l-1) and 20 with normal serum uric acid concentrations (180-320 mmol l-1). The two groups were similar in terms of age, general obesity (estimated by body mass index), smoking and alcohol intake, and estimate of work and leisure time activity. INTERVENTIONS: All subjects received a 75 g oral glucose challenge, with blood taken before and at frequent intervals thereafter. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, and lipid concentrations and plasma glucose and insulin responses to the oral glucose challenge. RESULTS: By selection, mean (+/- SEM) serum uric acid concentration was higher in the hyperuricaemic individuals (454 +/- 7 vs. 274 +/- 12 mmol l-1). In addition, the plasma insulin response to oral glucose was increased in individuals with asymptomatic hyperuricaemia (P < 0.005) as were both systolic (136 +/- 3 vs. 126 +/- 3 mmHg, P < 0.05) and diastolic (91 +/- 1 vs. 82 +/- 1, P < 0.01) blood pressure. Furthermore, subjects with asymptomatic hyperuricaemia were dyslipidaemic (higher plasma TG and cholesterol and lower HDL-cholesterol concentrations) as compared to the normouricaemic control group (P < 0.07-0.005). CONCLUSIONS: These results provide a possible explanation for the well-known association of hyperuricaemia with coronary heart disease, as well as suggesting that hyperuricaemia be added to the cluster of metabolic and haemodynamic abnormalities associated with insulin resistance and/or hyperinsulinaemia and designated as Syndrome X.

Adult↗
PubMed1992

Prevalence of hyperinsulinaemia in patients with high blood pressure.

A total of 41 patients with hypertension were identified in a survey of 732 healthy factory workers. Twenty-three of these individuals were receiving antihypertensive medication, whereas 18 cases were newly discovered. Plasma glucose and insulin responses to oral glucose and fasting plasma triglyceride (TG), cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations of these 41 individuals were compared with those of 41 other factor workers, with normal blood pressure, matched with the hypertensive group in terms of gender, age, degree of obesity, job in the factory, and leisure-time activity. Patients with hypertension had significantly higher plasma glucose (P less than 0.05) and insulin (P less than 0.05) concentrations in response to oral glucose, as well as a higher plasma TG concentration (P less than 0.05). Similar findings were obtained when the treated and untreated hypertensive groups were analysed separately and compared with their respective control groups. However, there were no differences between the treated and untreated hypertensive groups. Ninety per cent of the normotensive group had a plasma insulin concentration of less than 500 pmol l-1 2 h after the glucose load. Using this value as the criterion for definition of hyperinsulinaemia, 41% of the patients with high blood pressure were hyperinsulinaemic. In addition to meeting this cut-off point, the patients with hypertension and hyperinsulinaemia were also glucose intolerant and dyslipidaemic. In conclusion, approximately 50% of an unselected group of patients with hypertension were hyperinsulinaemic. Insulin levels were comparable in treated and untreated patients with high blood pressure, and hyperinsulinaemic patients also tended to be glucose intolerant and dyslipidaemic.

Blood Glucose↗
PubMed1991

Changes in blood pressure, plasma triglyceride and aldosterone concentration, and red cell cation concentration in patients with hyperinsulinemia.

Blood pressure, plasma concentration of triglyceride, aldosterone, renin activity (PRA), and atrial naturietic peptide (ANP), and red blood cell, urine, and plasma sodium and potassium concentration were determined in 24 healthy individuals divided into two groups defined as being either hyperinsulinemic or normoinsulinemic. The results demonstrated that the hyperinsulinemic group had significantly higher values for both systolic (P less than .01) and diastolic (P less than .05) blood pressure. In addition, plasma concentrations of triglyceride (P less than .02), aldosterone (P less than .05) and potassium (P less than .05) were higher in hyperinsulinemic individuals as compared to those who were normoinsulinemic. Furthermore, red cell potassium was lower (P less than .01) and red cell sodium higher (P less than .01) in the hyperinsulinemic group. Finally, the magnitude of hyperinsulinemia correlated directly with systolic (r = 0.50, P less than .01) and diastolic (r = 0.44, P less than .05) blood pressure, concentration of plasma triglyceride (r = 0.55, P less than .01) and aldosterone (r = 0.46, p less than .05), and erythrocyte sodium concentration (r = 0.57, p less than .01). In contrast, plasma insulin response was negatively correlated with erythrocyte potassium concentration (r = 0.40, P less than 0.05). These observations provide further support for the view that hyperinsulinemia, presumably secondary to resistance to insulin-stimulated glucose uptake, is associated with a cluster of variables that may play important roles in the etiology and clinical course of hypertension.

Aldosterone↗