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Biomedical subjects

M Varricchio

Publications and source records attributed to M Varricchio.

At least 109 records · Page 6Linked to original sources

Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects.

In eight aged non-insulin-dependent diabetes mellitus (NIDDM) subjects, insulin response and action were studied before and after chronic magnesium supplementation (2 g/day) to diet. Chronic magnesium supplementation to diet versus placebo produced 1) a significant increase in plasma (0.83 +/- 0.05 vs. 0.78 +/- 0.06 mM, P less than .05) and erythrocyte (2.03 +/- 0.06 vs. 1.88 +/- 0.09 mM, P less than .01) magnesium levels, 2) an increase in acute insulin response (AIR) (4.0 +/- 0.6 vs. -1.6 +/- 0.6 mU/L, P less than .05) to glucose pulse, and 3) an increase in glucose infusion rate (GIR) (3.6 +/- 0.6 vs. 2.9 +/- 0.5 mg.kg-1.min-1, P less than .025) calculated in the last 60 min of a euglycemic-hyperinsulinemic (100 mU.m2.min-1 during 180 min) glucose clamp. Net increase in AIR, glucose disappearance rate after glucose pulse, and GIR were significantly and positively correlated to the net increase in erythrocyte magnesium content calculated after chronic magnesium supplementation to diet. In conclusion, our data suggest that NIDDM subjects may benefit from therapeutic chronic administration of magnesium salts.

Aged↗

The long-term efficacy of ibopamine in treating patients with severe heart failure: a multicenter investigation.

This randomized, double-blind, placebo-controlled, multicenter trial compared the effects of treatment with ibopamine with those of placebo in patients with severe heart failure who still showed symptoms although they were receiving standard therapy with digitalis and diuretics. The results showed a significant and sustained improvement in exercise tolerance (+70% about in average), clinical condition, and NYHA functional class and a decrease in cardiothoracic ratio and left ventricular end-systolic wall stress in patients treated with ibopamine, digitalis, and diuretics (group 1) compared with patients treated with digitalis, diuretics, and placebo (group 2).

Adult↗

[Evaluation of cellular immunity in a selected sample of aged subjects].

The immune system in the aging man is known to show age-related defects; the study of the subpopulations in human blood has yielded conflicting results. This mostly seems to be due to the heterogeneity of the subjects admitted to immunogerontological studies. We investigated a group of aged persons fulfilling the admission criteria described in the "SENIEUR" protocol and strictness criteria dietetics. We found a decrease in the number of T cells, while the number of B cells and, above all, the report of the T4/T8 remained constant. There individuals should be considered as optimally healthy and immunologically uncompromised.

Adult↗

Impaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients.

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p less than 0.001) and patients with diabetes (p less than 0.001). However, even in the presence of 100 mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma glucose lowering effect of sparteine sulphate infusion in non-insulin dependent (type 2) diabetic subjects.

Sparteine sulphate, given i.v. as a bolus of 15 mg/ml plus 90 mg in 0.9% NaCl 100 ml over 60 min, increases plasma insulin and decreases plasma glucose and adrenaline in non-insulin dependent (Type II) diabetic subjects. The hypoglycaemic effect was also evident in the presence of a high plasma glucose level produced by Biostator changing glucose infusion from 20.2 +/- 2.8 to 26.4 +/- 4.2 mg.kg-1.min-1 (p less than 0.01), and it was potentiated by simultaneous infusion of arginine. No additional effect of sparteine on the peripheral sensitivity to insulin were detected by the euglycaemic, hyperinsulinaemic glucose clamp technique, as the glucose infusion rate (3.1 +/- 0.8 vs 2.6 +/- 1.2 mg.kg-1.min-1) was not statistically significant different in the last 60 min of the experiment. It is concluded that sparteine sulphate enhances beta-cell secretion, causing a fall in the plasma glucose concentration.

Adult↗

Pharmacological doses of oxytocin affect plasma hormone levels modulating glucose homeostasis in normal man.

Pharmacological doses of oxytocin administered in basal conditions evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin and adrenaline levels. The effects of oxytocin on plasma glucagon and adrenaline levels were potentiated by hypoglycemia. When the endogenous pancreas secretion was suppressed by cyclic somatostatin (150 micrograms/h) and exogenous glucagon (3.5 micrograms/h) and insulin (0.2 mU/kg.min) were both replaced, oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels suppressing the glucose infusion rate (GIR) in the first 60 min. On the contrary at higher insulin infusion rate (0.6 mU/kg.min) plasma glucose levels and GIR remained unaffected throughout the study. Oxytocin seems also to potentiate glucose-induced insulin secretion as evidenced by hyperglycemic glucose clamp. In conclusion, pharmacological doses of oxytocin seem to exert a prevalent hyperglycemic effect by a combined action at the liver site (as glycogenolytic agent) and at the endocrine pancreas (as a stimulatory agent of A cell secretion).

Adult↗

Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes.

The respective modulating effects of continuous and intermittent insulin delivery on pancreatic islet cell function were studied in seven normal men and nine insulin-dependent (type 1) diabetic patients. In the normal men, saline or continuous (0.8 mU kg-1 min-1) or pulsatile (5.2 mU kg-1 min-1, with a switching on/off length of 2/11 min) human insulin were delivered on different days and in random order. Despite hyperinsulinemia, blood glucose was kept close to its basal value by the glucose clamp technique. The diabetic patients also were infused in random order and on different days with either saline or a smaller amount of insulin delivered continuously (0.15 mU kg-1 min-1) or in a pulsatile manner (0.97 mU kg-1 min-1 for 2 min, followed by 11 min during which no insulin was infused). In all experiments, 5 g arginine were given iv as a bolus dose 30 min before the end of the study, and plasma C-peptide and glucagon levels were determined to assess islet cell function. In the normal men, insulin administration resulted in a significant decline of basal plasma glucagon and C-peptide levels and in a clear-cut decrease in the arginine-induced glucagon response. These effects of insulin were significantly more marked when insulin was delivered in a pulsatile rather than a continuous manner. In the insulin-dependent diabetic patients, the lower dose of insulin infused continuously did not alter the basal or arginine-stimulated glucagon response. In contrast, when the same amount of insulin was delivered intermittently, arginine-induced glucagon release was greatly reduced. Thus, these data support the concept that insulin per se is a potent physiological modulator of islet A- and B-cell function. Furthermore, they suggest that these effects of insulin are reinforced when the hormone is administered in an intermittent manner in an attempt to reproduce the pulsatile physiological release of insulin.

Adult↗

Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients.

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.

Aged↗

Effects of the angiotensin converting enzyme inhibitor enalapril compared with diuretic therapy in elderly hypertensive patients.

The aim of this study was to evaluate the usefulness of the angiotensin converting enzyme (ACE) inhibitor enalapril in a group of 30 patients (mean age 73.3 years) with moderate hypertension and normal haematological and chemical parameters (170 +/- 8.1 mmHg systolic and 104 +/- 5.8 mmHg diastolic blood pressure), who were receiving diuretic therapy with chlorthalidone (12.5 mg/day). This therapy caused a significant decrease in systolic and diastolic blood pressure (to 165 +/- 6.7 and 98 +/- 4.7 mmHg, respectively; P less than 0.001) but it also induced hypokalaemia (3.04 +/- 0.7 mmol/l; P less than 0.001) and multiple (greater than 10/h) and complex premature ventricular depolarizations (2nd, 3rd and 4th Lown grade). Enalapril treatment (5 mg/day for 5 days and 10 mg thereafter) was added to the diuretic therapy and after 2 months a further decrease in blood pressure was observed (to 158 +/- 5.6 mmHg systolic, P less than 0.001; 87.2 +/- 5.0 mmHg diastolic, P less than 0.001). Moreover, there was a significant reduction in the mean heart rate (from 79 to 72 beats/min, P less than 0.005) and an increase in serum potassium (to 4.19 +/- 0.2 mmol/l; P less than 0.001). In 80% of patients a 24-h dynamic electrocardiogram showed a significant reduction in both the number and complexity of premature ventricular depolarizations. Our findings suggest that ACE inhibitors can be useful in patients developing hypokalaemia during therapy. However, we are not yet able to explain the beneficial effects of enalapril in decreasing the frequency of premature ventricular depolarizations.

Aged↗

Diabetes and hypertension in the elderly.

Hypertension combined with diabetes in the elderly is characterized by many important metabolic and cardiovascular changes, among which insulin resistance, hyperinsulinaemia and increased total peripheral resistance appear to be the most relevant. Non-insulin dependent diabetes mellitus is also characterized by insulin resistance and hyperinsulinaemia. Moreover, hyperinsulinaemia itself has been shown to increase total peripheral resistance. Hyperinsulinaemia thus seems to play a key role in the pathophysiology of hypertension in elderly diabetic subjects. Therefore elderly hypertensive diabetic patients should be treated with thiazide diuretics in low doses, calcium channel blockers and alpha-adrenergic blockers.

Age Factors↗

Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance.

We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.

Administration, Oral↗

Effect of sparteine sulphate upon basal and nutrient-induced insulin and glucagon secretion in normal man.

Infusion of a therapeutic dose of sparteine sulphate, increased the basal plasma insulin level and lowered plasma glucose. When an intravenous glucose tolerance test was performed with the infusion, the total insulin AUC was significantly larger than in absence of sparteine (2025 vs 1464 microU/ml X min), plasma glucose levels were lower and improved glucose utilization was observed (kg:1.55 vs 1.39%). In the presence of arginine, sparteine sulphate stimulated both beta and alpha cells, increasing both the total insulin (1907 vs 1516 microU/ml X min p less than 0.02) and total glucagon AUCs (7616 +/- 654 vs 6789 +/- 707 pg/ml X min p less than 0.01). Thus, sparteine sulphate increased both basal and nutrient-induced insulin and glucagon secretion in normal man.

Adult↗

Impaired insulin-mediated erythrocyte magnesium accumulation in essential hypertension.

1. This study was designed to investigate variations in erythrocyte magnesium in the presence of insulin (0.1 unit/l) in hypertensive subjects. 2. Plasma and erythrocyte magnesium levels were found to be significantly lower in hypertensive than in normotensive subjects. 3. The impaired response to insulin (0.1 units/l) of erythrocytes from hypertensive patients was not reversed by elevated extracellular Mg2+ (3.6 mmol/l). 4. Erythrocytes of hypertensive subjects showed an increased membrane microviscosity compared with normotensive subjects. 5. Lidocaine decreased erythrocyte membrane microviscosity and increased erythrocyte magnesium levels in the presence of insulin.

Adult↗