PubMed Health⌕ Search

Biomedical subjects

M Varricchio

Publications and source records attributed to M Varricchio.

At least 91 records · Page 5Linked to original sources
PubMed1992

Hyperinsulinemia in patients with hypercholesterolemia.

An independent association between hypercholesterolemia and high insulin levels has not consistently emerged from large-scale epidemiologic observations. We selected 39 patients with elevated low-density (LDL) cholesterol levels but normal body weight, blood pressure, and glucose tolerance, and compared them to 36 normocholesterolemic, healthy control subjects accurately matched to the patients for age, gender, body mass index, and mean arterial blood pressure. Fasting serum total cholesterol concentrations and levels of LDL cholesterol, triglycerides, and apoprotein B were all higher in the patients with hypercholesterolemia than in controls (P < 0.025 or less), whereas high-density lipoprotein cholesterol and apoprotein A levels were significantly lower (P < 0.05 or less). Plasma insulin concentrations were elevated in hypercholesterolemic patients vs. controls both in the fasting state (86 +/- 6 vs. 59 +/- 8 pmol/L) and 2 h after a 75-g oral glucose load (412 +/- 16 vs. 276 +/- 18 pmol/L, P < 0.02 for both). Two-hour plasma glucose concentrations were also significantly raised in the patients (7.8 +/- 0.2 mmol/L) compared to controls (6.4 +/- 0.1 mmol/L, P < 0.025). In a multiple regression model including serum triglyceride concentrations, LDL cholesterol was still significantly related to both fasting and 2-h plasma insulin concentrations, contributing approximately 20% to the overall variability of these measures. Thus, in this group of patients with type IIa familial combined hyperlipoproteinemia hypercholesterolemia was associated with hyperinsulinemia even when controlling for other confounders (age, gender, body mass, glucose tolerance, and blood pressure).

Blood Glucose↗
PubMed1992

Glutathione infusion potentiates glucose-induced insulin secretion in aged patients with impaired glucose tolerance.

OBJECTIVE: To evaluate the effect of glutathione infusion on beta-cell response to glucose in elderly people with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Ten patients with normal glucose tolerance and 10 patients with IGT were matched for age (mean +/- SE, 72.1 +/- 2.8 vs. 71.0 +/- 3.4 yr), body mass index (23.1 +/- 1.1 vs. 22 +/- 2.1 kg/m2), and sex (6/4 vs. 5/5, men/women) underwent glutathione infusion (10 mg/min) under basal conditions and during 75-g oral glucose tolerance tests and intravenous glucose tolerance tests (0.33 g.kg body wt-1.3 min-1). Patients with IGT were also submitted to euglycemic-hyperinsulemic and hyperglycemic glucose clamps. RESULTS: In subjects with normal glucose tolerance, glutathione infusion failed to affect beta-cell response to glucose. In contrast, glutathione significantly potentiated glucose-induced insulin secretion in patients with IGT. Furthermore, in the latter group studied by hyperglycemic clamps, glutathione infusion significantly potentiated the beta-cell response to glucose when plasma glucose levels varied between 10 and 15 mM. This effect disappeared at plasma glucose levels greater than 15 mM. No effect of glutathione on insulin clearance and action was observed. CONCLUSIONS: Glutathione infusion enhances insulin secretion in elderly people with IGT.

Aged↗
PubMed1992

Insulin effects on glucose kinetics in non-insulin-dependent diabetic patients with secondary failure to hypoglycaemic agents: role of different modes and rates of delivery.

OBJECTIVES: This study aimed at investigating the effects of pulsatile and continuous insulin delivery on glucose kinetics in non-insulin-dependent (type 2) diabetic patients with secondary failure to oral hypoglycaemic agents. METHODS: Seven type 2 diabetic patients underwent a 585 minute glucose-controlled glucose intravenous infusion using the Biostator. The endogenous pancreas secretion was inhibited by somatostatin. Three experiments were performed in each patient on different days and in random order. In all cases, glucagon was replaced (58 ng/min). The amounts of insulin infused were: a) 0.15 mU/kg x min continuously; b) 0.20 mU/kg x min continuously and c) 1.0 mU/kg x min in 2 minute pulses every 13 minutes. D-[3-3H]-glucose infusion allowed determination of glucose kinetics. RESULTS: Infusion of identical amounts of insulin (A vs C) demonstrated that pulsatile insulin delivery exerted greater metabolic effects (higher glucose infusion rate and, mainly at the beginning of the experiment, lower endogenous glucose production) than continuous infusion; furthermore pulsatile insulin delivery (C) exerted metabolic effects similar to those of a greater dose of insulin (B) infused continuously. CONCLUSIONS: In type 2 diabetic patients with secondary failure to oral hypoglycaemic agents, pulsatile insulin delivery exerts greater metabolic effects than continuous hormone delivery.

Aged↗
PubMed1992

Effects of mild-to-moderate hyperglycaemia per se on glucose production and uptake in the elderly.

OBJECTIVES: In order to better understand the mechanisms responsible for the diminished glucose tolerance that occurs in the elderly, the present study aimed at investigating the effect of mild hyperglycaemia on glucose production and uptake in a group of aged subjects. For comparison, a group of young subjects was simultaneously investigated. METHODS: Seven aged (71.8 +/- 2.3 yrs) and seven young (25.5 +/- 1.7 yrs) healthy non-obese subjects underwent two hyperglycaemic glucose-clamps having as targets plasma glucose levels 7.5 and 10.0 mmol/L. Contemporary infusion of D-[3-3H]-glucose allowed determination of glucose turnover parameters in basal conditions and during the clamps. Endogenous pancreatic secretion was inhibited by somatostatin (8.3 micrograms/min) while glucagon (67 ng/min) and insulin (0.15 mU/kg/min) were replaced by exogenous infusions. RESULTS: In basal conditions, glucose uptake (12.9 +/- 0.5 vs 14.4 +/- 0.4 mumol/kg/min; p < 0.05) and glucose metabolic clearance rate (2.58 +/- 0.15 vs 3.35 +/- 0.10 ml/kg/min; p < 0.01) were lower in elderly vs young subjects. In the hyperglycaemic glucose-clamps, we observed, in the elderly subjects, the persistence of a greater glucose production during mild (7.5 mmol/L) (11.6 +/- 0.4 vs 9.7 +/- 0.2 mumol/kg/min; p < 0.005) but not moderate (10 mmol/L) (3.5 +/- 0.1 vs 3.4 +/- 0.1 mumol/kg/min; NS) hyperglycaemia. In contrast, glucose-induced glucose uptake and glucose metabolic clearance rate were similarly affected by glucose infusions in both groups of subjects. Moreover, in elderly but not in young subjects, basal glucose disappearance rate was significantly negatively correlated with fasting plasma glucose levels (r = -0.84; p < 0.01). CONCLUSIONS: In the basal state, glucose uptake and glucose metabolic clearance rate are slightly impaired in elderly, compared to young subjects. Furthermore, in the elderly, endogenous glucose production is less suppressed by mild hyperglycaemia i.e. 7.5 mmol/L, than it is in young people. Such impairment in the inhibition of endogenous glucose production is not seen when blood glucose attains 10 mmol/L. We suggest that impairment in glucose tolerance in the elderly results from both reduced glucose uptake (in basal conditions) and excessive glucose production (at mild hyperglycaemic levels).

Adult↗
PubMed1992

ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients.

We have compared the cardiovascular and metabolic responses to five different ACE inhibitors in 86 patients matched for age, body mass index, blood pressure, fasting plasma glucose and insulin levels in a placebo-controlled, double-blind, crossover, randomised trial. In the active drug treatment phase the patients were randomly assigned to one of five ACE inhibitors: captopril (75 mg/day; n = 16); enalapril (20 mg/day; n = 14); quinapril (20 mg/day; n = 17); ramipril (5 mg/day; n = 21) and lisinopril (20 mg/day; n = 18). Placebo and ACE inhibition phases lasted two weeks and were separated by a one week wash-out period. At the end of each treatment period blood pressure and heart rate were recorded and a fasting sample intravenous glucose tolerance test was conducted. Our study demonstrated that ACE inhibition significantly reduces blood pressure and improves insulin sensitivity. All the ACE inhibitors studied had similar cardiovascular responses but lisinopril displayed the larger metabolic response.

Aged↗
PubMed1991

Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus.

Glibenclamide, a hypoglycemic sulfonylurea, is a blocker of the adenosine triphosphatase-modulated potassium ion channels. The opening of these channels in the myocardial cells, induced by acute myocardial hypoxia, can be responsible for ischemic ventricular arrhythmias. To evaluate the antiarrhythmic effects of this drug 19 non-insulin-dependent diabetic patients were selected. They had coronary artery disease and evidence on Holter monitoring of ventricular premature complexes or nonsustained ventricular tachycardia, or both, induced by transient myocardial ischemia. In all patients, 24-hour electrocardiographic monitoring was performed to evaluate the number and duration of myocardial ischemic events, the frequency of ventricular premature complexes and nonsustained ventricular tachycardia per minute of ischemia and the percentage of ventricular premature complexes versus total ischemic beats. Selected patients were classified in 2 groups: group A (9 patients) received metformin (placebo) and group B (10 patients) was treated with glibenclamide. On the fourteenth day patients underwent 24-hour control monitoring. Then a crossover between the 2 groups was made and a new Holter monitoring sequence was performed at the end of the second phase. Results indicate that glibenclamide significantly (p less than 0.001) reduced both the frequency of ventricular premature complexes and the episodes of nonsustained ventricular tachycardia during transient myocardial ischemia, but did not change the number and duration of acute myocardial ischemic attacks and did not reduce the spontaneous ventricular arrhythmias. Thus, glibenclamide appears to have an antiarrhythmic effect in preventing ventricular arrhythmias induced by transient myocardial ischemia.

Adult↗
PubMed1991

Simvastatin reduces plasma lipid levels and improves insulin action in elderly, non-insulin dependent diabetics.

Twelve elderly non-insulin dependent diabetic patients took part in a double-blind, cross-over, randomized study comparing simvastatin 30 mg/day and placebo. Each treatment period lasted 3 weeks and was separated by a 3 week wash-out period. At the end of each treatment period all subjects underwent in randomized order an oral glucose tolerance test (OGTT; 75 g) and an euglycaemic hyperinsulinaemic (50 mU/kg.h) glucose clamp. Simvastatin compared to placebo significantly reduced plasma total cholesterol (7.9 vs 5.3 mmol.l-1), LDL-cholesterol (7.2 vs 4.3 mmol.l-1), triglycerides (2.9 vs 2.1 mmol.l-1), free fatty acids (1106 vs 818 mmol-1) and glucose (7.4 vs 6.6 mmol.l-1) levels. After simvastatin, and in the last 60 min of the glucose clamp, there was an improvement in the action of insulin as demonstrated by stronger inhibition of hepatic glucose output (2.7 vs 5.2 mumol.kg-1.min-1) and stimulation both of the glucose disappearance rate (26.3 vs 19.5 mumol.kg-1.min-1) and glucose metabolic clearance rate (4.3 vs 3.6 ml.kg-1.min-1). The changes in glucose turnover parameters were significantly correlated with basal plasma free fatty acids and were independent of plasma glucoregulatory hormones. In conclusion, simvastatin seems to exert beneficial effects both on lipid and glucose metabolism.

Aged↗
PubMed1991

Evidence for peripheral impaired glucose handling in patients with connective tissue diseases.

Sixteen patients suffering from rheumatoid arthritis (RA) (n = 8), systemic lupus erythematosus (SLE) (n = 5), and systemic sclerosis (SSc) (n = 3), and 10 healthy subjects matched for age, sex, and body mass index, were submitted to an intravenous (IV) glucose tolerance test (GTT) (0.33 g/kg of body weight in 3 minutes) and to a euglycemic hyperinsulinemic glucose clamp to study insulin response and action. In the euglycemic clamp, along with the two insulin infusion rates (0.5 mU/kg.min from 0 to 120 minutes and 1 mU/kg.min from 121 to 240 minutes), a primed (20 microCi) continuous (0.2 microCi/min) infusion of 3H-glucose allowed determination of glucose kinetics. Our data show that patients versus controls have (1) a significant increase in basal plasma insulin levels (87.2 +/- 14.8 v 41.3 +/- 6.0 pmol/L, P less than .05); (2) similar glucose-induced acute insulin response; and (3) a lower glucose disappearance rate (Rd), glucose metabolic clearance rate (gMCR), and glucose infusion rate (GIR) when the lowest insulin infusion rate was delivered. These differences disappeared when the insulin infusion rate was doubled. Furthermore, basal plasma insulin levels and glucose disappearance rate significantly correlated with the main inflammatory indices of each disease studied. We conclude that in our patients impaired glucose handling is mainly due to peripheral insulin resistance.

Arthritis, Rheumatoid↗
PubMed1991

Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure.

Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while D-3H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 +/- 0.1 v 4.9 +/- 0.2 mmol/L,P = NS), but higher plasma insulin (125.7 +/- 9.2 v 35.7 +/- 3.3 pmol/L,P less than .01), norepinephrine (5.39 +/- 0.13 v 1.47 +/- 0.22 nmol/L,P less than .001), and free fatty acid (FFA) (927 +/- 79 v 792 +/- 88 mumol/L,P less than .05) levels. In patients, basal plasma norepinephrine correlated with FFA levels (r = .65, P less than .025). After loading glucose, plasma glucose and insulin levels were still significantly higher in patients than controls. Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates (25 and 50 mU/kg/h). By contrast, these differences disappeared during the highest insulin infusion rate (100 mU/kg/h). Insulin-mediated decrease in plasma FFA levels was also lower in patients than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Hemodynamic changes in left ventricular function during acute coronary insufficiency: a Doppler echocardiographic study.

To define the availability of Doppler echocardiography in evaluating left ventricular hemodynamic changes induced by some clinical findings of acute coronary insufficiency, we selected 12 patients with angina and 32 affected by acute myocardial infarction. Doppler echocardiography was performed at hospital admittance and during recovery time. Left ventricular contractility was defined on the systolic aortic flow spectrum by measuring the aortic velocity maximum, the time to peak/left ventricular ejection time ratio, and the cardiac output. During the first examination, left ventricular contractility significantly decreased in patients with angina and in those with acute myocardial infarction. After the acute phase, these parameters slightly improved. Left ventricular diastolic filling was evaluated in the transmitral flow. A decreased E-wave velocity and an increased late component (A wave) with inversion of the E/A wave ratio were found in patients with acute myocardial infarction during the first examination. This morphology inverts when the patients stabilize. On the contrary, this ratio stayed above one during and after angina. In this study, we also defined the usefulness of the color Doppler method in setting up criteria to identify some early morphological complications of acute myocardial infarction in 12 patients with acute infarction and a new systolic murmur. This technique showed an ischemic rupture of the ventricular septum in five cases and mitral regurgitation in seven. The color Doppler method has allowed us to obtain a semi-quantitative assessment of the mitral regurgitation and the location of the ventricular septal defect.

Adult↗
PubMed1991

Pulsatile insulin delivery has greater metabolic effects than continuous hormone administration in man: importance of pulse frequency.

The aim of this study was to see if the greater effect of insulin on hepatic glucose output when insulin is given using 13-min pulses in man remains when the same amount of insulin is delivered using 26-min pulses. The study was performed on nine male healthy volunteers submitted to a 325 min glucose-controlled glucose iv infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin. Three experiments were performed in each subject on different days and in random order. In all cases glucagon was replaced (58 ng min-1). The amounts of insulin infused were identical in all instances and were 0.2 mU kg-1 min-1 (continuous), 1.3 mU kg-1 min-1, 2 min on and 11 min off (13-min pulses) or 2.6 mU kg-1 min-1, 2 min on and 24 min off (26-min pulses). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using D-[3-3H] glucose infusion allowed to study glucose turnover. When compared with continuous insulin, 13-min insulin pulses induced a significantly greater inhibition of endogenous glucose production. This effect disappeared when insulin was delivered in 26-min pulses. We conclude that, in man, an adequate pulse frequency is required to allow the appearance of the greater inhibition of pulsatile insulin on endogenous glucose production.

Adult↗
PubMed1990

Pulsatile glucagon has greater hyperglycaemic, lipolytic and ketogenic effects than continuous hormone delivery in man: effect of age.

The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2 +/- 1.2 years) and in eight healthy aged subjects (69.4 +/- 2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non-esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma beta-hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and beta-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced.

3-Hydroxybutyric Acid↗
PubMed1990

Metabolic effects of pulsatile insulin infusion in the elderly.

The present study investigated the metabolic effects of pulsatile insulin delivery at a pulse rate of 2 + 11 and 2 + 18 min in 7 healthy, elderly subjects (71.4 +/- 2.1 years), submitted to 260 min controlled iv glucose infusion via the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostain (3 micrograms/min) and glucagon was replaced (67 ng/min) to basal levels. The same total insulin dose was delivered on both occasions. Insulin infusion rate was 1.3 and 2.0 mIU. kg-1. min-1 during switching on/off of 2 + 11 and 2 + 18 min, respectively. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator; [D-3-3H]glucose infusion allowed determination of glucose turnover. During the last 60 min of the experiment, pulsatile insulin at a pulse rate of 2 + 11 vs 2 + 18 min produced a stronger inhibition of endogenous glucose production, whereas glucose disappearance rate and glucose metabolic clearance rate were similarly affected. Plasma triglycerides, apolipoprotein B, and free fatty acids levels were also more suppressed during insulin delivery at pulse rate of 2 + 11 than at 2 + 18 min.

Aged↗
PubMed1990

Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in normal man.

In normal man oxytocin infusion under basal conditions and at pharmacological doses evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion indicated that oxytocin also produced a prompt and significant increase in hepatic glucose output with a secondary increase in glucose disappearance rate. Eight healthy volunteers were studied during euglycemic glucose clamp and simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic secretion by cyclic somatostatin (250 micrograms/h) and during exogenous glucagon (67 ng/min) and insulin (0.15 mU.kg-1.min-1 from 0 to 120 min and 0.40 mU.kg-1.min-1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels and hepatic glucose output with a simultaneous suppression of the glucose infusion rate. No difference in glucose disappearance and metabolic clearance rates were recorded throughout the clamp irrespective of whether oxytocin was infused or not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell stimulation and a glycogenolytic action.

Adult↗
PubMed1989

Effects of oxytocin delivery on counter-regulatory hormone response in insulin-dependent (type 1) diabetic subjects.

In insulin-dependent (type 1) diabetic subjects (n = 7) with intact hormone response to hypoglycaemia, oxytocin infusion (0.2 mU/min over 60 min) produced significant rises in basal plasma glucagon and adrenaline levels, while it reduced basal plasma cortisol levels. During insulin-induced hypoglycaemia, oxytocin potentiated the increases in plasma glucagon and adrenaline, while an inhibitory effect on plasma cortisol levels was still present. In insulin-dependent (type 1) diabetic subjects (n = 7) with blunted counter-regulatory hormone response to hypoglycaemia, the same dose of oxytocin (0.2 mU/min over 60 min) increased basal plasma glucose and glucagon concentrations and lowered basal plasma cortisol concentration. In the same group of patients, oxytocin delivery (0.2 mU/min), simultaneously to an insulin-induced hypoglycaemia, produced a significant elevation of plasma glucagon and adrenaline concentrations thus enhancing glucose recovery from hypoglycaemia. In conclusion, in insulin-dependent (type 1) diabetic patients, oxytocin delivery enhances plasma glucagon and adrenaline levels in basal conditions and during insulin-induced hypoglycaemia.

Adult↗
PubMed1989

Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects.

Hypomagnesemia and low erythrocyte magnesium content are both common findings in non-insulin-dependent diabetic subjects. Moreover, intracellular magnesium may play a crucial role in modulating B-cell response to glucose by interfering with potassium permeability. Eight elderly, moderately obese, non-insulin-dependent diabetic subjects were treated with either magnesium supplementation (3 g/day) to the diet or placebo. Both treatment schemes lasted 4-weeks and were separated by a 'wash-out' of 3 weeks. At the end of each treatment period, in glucose test (0.33 g/kg for 3 min) and an iv arginine (5 g) test were performed to determine the B-and A-cell responses. Dietary magnesium supplementation vs placebo produced a slight but significant decrease in basal plasma glucose (8.6 +/- 0.3 vs 8.0 +/- 0.1 mmol/l, p less than 0.05) and an increase in acute insulin response after iv glucose (3.7 +/- 2.3 vs - 14.7 +/- 0.9 pmol.l 1. (10 min)-1, p less than 0.01) and after iv arginine (151 +/- vs 81 +/- 15 pmol.l-1. (10 min)-1, p less than 0.01), respectively. Plasma glucagon levels were unaffected by chronic dietary magnesium supplementation as well under basal conditions as in response to arginine. Net increase in acute insulin response after iv glucose and after iv arginine was significantly correlated to the net increase in erythrocyte magnesium content after dietary magnesium supplementation. We conclude that magnesium administration may be a useful adjuvant to the classic hypoglycemic agents in the treatment of non-insulin-dependent diabetic subjects.

Aged↗