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Biomedical subjects

M Varricchio

Publications and source records attributed to M Varricchio.

At least 73 records · Page 4Linked to original sources

Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics.

In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10) subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after vitamin C infusion and the relative increase in plasma vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the increase in plasma vitamin C levels did not affect B cell response to glucose, but it improved Conard's K values and whole body glucose disposal in healthy subjects and in diabetic patients. In both groups of subjects vitamin C-mediated increase in insulin action was mainly due to an improvement in nonoxidative glucose metabolism. After fasting, plasma vitamin C levels correlated with basal whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C infusion, percent change in plasma vitamin C level correlated with the percent decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma vitamin C levels seem to play a role in the modulation of insulin action in aged healthy and diabetic subjects.

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Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients.

The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double blind, and cross-over. Each patient was followed up for a prestudy period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P < 0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P < 0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes.

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Insulin resistance and hypertension in the elderly. Optimal drug therapy.

Numerous trials have demonstrated the negative effects of some antihypertensive drugs upon glucose handling. Such findings seem particularly interesting in aged hypertensive patients who are also insulin resistant and affected by physiological changes in the renal and cardiovascular systems. It appears that calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors are the most appropriate drugs to lower blood pressure in aged insulin-resistant hypertensive patients. All calcium channel blockers studied have displayed similar metabolic effects, while among the ACE inhibitors studied, lisinopril was associated with the best metabolic responses. beta-Blockers and thiazide diuretics have strong negative effects on glucose handling. Further studies are needed in order to investigate the metabolic effects of alpha 1-antagonists in aged patients with insulin resistance and hypertension.

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Different contribution of substrates oxidation to insulin resistance in malnourished elderly patients with cancer.

BACKGROUND: The relative contribution of malnutrition and cancer to insulin resistance in elderly patients is still poorly understood. METHODS: Twenty malnourished and 15 well-nourished patients with cancer matched for age (70 +/- 0.3 versus 69 +/- 0.3 years; P = not significant), mean arterial blood pressure (104 +/- 8 versus 107 +/- 7 mm Hg; P = not significant), gender ratio (10 males/10 females versus 7 males/8 females), and sedentary life style underwent an euglycemic glucose clamp. Simultaneous infusion of 3-D-H-glucose and indirect calorimetry allowed the authors to determine glucose turnover parameters and analyze substrates oxidation. RESULTS: Malnourished patients displayed a reduced total body glucose metabolism (36 +/- 2 versus 31 +/- 3 mumol/kg of lean body mass x min P < 0.04) despite higher glucose oxidation. In the same group of patients, the authors demonstrated a significant increase in lipid oxidation and the lack of the inverse relationship between glucose and lipid oxidation (r = 0.07; P = not significant). Insulin infusion enhanced glucose oxidation and suppressed lipid oxidation, but such changes were at lower extent in malnourished patients. CONCLUSIONS: Our study confirms the presence of insulin resistance in malnourished patients and demonstrates the relative contribution of substrates oxidation to the insulin resistance itself.

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Effects of physiological plasma insulin levels on glucose turnover parameters in familial hypercholesterolemia.

Eight young, non-obese patients with primary familial hypercholesterolemia (FH) and 8 healthy subjects matched for age, body mass index, lean body mass, plasma triglyceride and HDL-levels and arterial blood pressure were selected from a lipid clinic. Patients with FH had higher plasma LDL-cholesterol (8.3 +/- 0.5 vs. 4.1 +/- 0.2 mmol/l, P < 0.001) than controls but similar plasma triglyceride (1.15 +/- 0.04 vs. 1.10 +/- 0.02 mmol/l P = NS) levels. Both study groups were submitted to a euglycaemic hyperinsulinemic glucose clamp combined with simultaneous infusion of [3H]glucose to measure insulin action on whole-body glucose uptake and on hepatic glucose production. Two insulin infusion rates (0.15 mU/kg per min from 0 to 120 min and 0.30 mU/kg per min from 121 to 240 min) were used resulting in similar plasma insulin levels in both groups studied. Our results demonstrate that both whole-body glucose uptake and hepatic glucose output are similar in the fasting state as well as during insulin administration in both groups of subjects. We conclude that, in the absence of other causes of insulin resistance, isolated hypercholesterolemia is associated with normal sensitivity to insulin in both liver and peripheral tissues.

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Evidence for a relationship between free radicals and insulin action in the elderly.

In forty healthy subjects with normal glucose tolerance divided by age into four groups (group A, subjects with mean age < 25 years [n = 10]; group B, subjects with mean age < 40 years [n = 9]; group C, subjects with mean age < 60 years [n = 11]; group D, subjects with mean age > 75 years [n = 10]) and were matched for body mass index (BMI), lean body mass (LBM), mean arterial blood pressure, and sedentary life style, we determined the plasma O2- production, reduced to oxidized glutathione level ratio (GSH/GSSG), and plasma membrane microviscosity. Euglycemic hyperinsulinemic (1 mU/kg.min-1 for 120 minutes) glucose clamp with simultaneous D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation. In the oldest group of subjects, a significant increase in plasma O2-production and membrane microviscosity associated with a significative reduction in glucose disappearance rate (Rd), total body glucose disposal (TBGD), and nonoxidative glucose metabolism was found. In group D subjects (n = 10), all of these changes were correlated with one another. In a multiple regression analysis of the pooled data from all study subjects (n = 40), only plasma O2- production levels displayed a statistically significant relation with TBGD and nonoxidative glucose metabolism. In conclusion, in aged patients a significant relationship between free radical production and insulin action seems to exist.

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Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients.

Ten control (healthy) subjects and 15 non-insulin-dependent diabetics underwent an oral glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). In control subjects (placebo-treated vs vitamin E-supplemented subjects, respectively) vitamin E reduced the area under the curve for glucose (344 +/- 21 vs 287 +/- 13 mmol.L-1 x min-1; P < 0.05) and increased total body glucose disposal (39.0 +/- 0.3 vs 47.6 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.05) and non-oxidative glucose metabolism (23.4 +/- 0.2 vs 30.8 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.05). In diabetics (placebo-treated vs vitamin E-supplemented subjects, respectively) vitamin E supplementation reduced glucose area under the curve (614 +/- 129 vs 544 +/- 98 mmol.L-1 x min-1; P < 0.03) and increased glucose disappearance (19.4 +/- 0.4 vs 26.4 +/- 0.7 mumol.kg lean body mass-1.min-1; P < 0.03), total glucose disposal (19.0 +/- 0.7 vs 28.1 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.02), and nonoxidative glucose metabolism (8.5 +/- 0.3 vs 13.9 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.02). Therefore we conclude that administration of pharmacologic doses of vitamin E is a useful tool to reduce oxidative stress and improve insulin action.

Blood Chemical Analysis↗

Effects of magnesium and nifedipine infusions on insulin action, substrate oxidation, and blood pressure in aged hypertensive patients.

Eight aged (70.1 +/- 2.1 years), nonobese (body mass index [BMI] = 26.3 +/- 0.4), hypertensive (systolic blood pressure [SBP] = 184 +/- 4.1; diastolic blood pressure [DBP] = 105 +/- 2.4 mm Hg) subjects underwent a euglycemic hyperinsulinemic (7.1 pmol/kg x min during 240 min) glucose clamp with four different infusions: a) 0.9% NaCl; b) 1.0 micrograms/kg x min nifedipine; c) 100 mumol/min magnesium; d) 1.0 micrograms/kg x min nifedipine plus 100 mumol/min magnesium. All tests were performed in random order. Simultaneous D-3-H glucose infusion and indirect calorimetry allowed us to determine glucose turnover parameters and substrate oxidation. Insulin infusion per se stimulated erythrocyte magnesium (1.83 +/- 0.04 v 1.98 +/- 0.03 mmol/L, P < .03) and calcium (4.7 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02) accumulation, and enhanced total body glucose disposal oxidative and nonoxidative glucose metabolisms. Infusion of insulin and nifedipine v insulin alone reduced insulin-mediated increase in intracellular calcium (5.4 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02), but potentiated the insulin effect upon nonoxidative glucose (15.4 +/- 0.4 v 11.1 +/- 0.3 mumol/kg lean body mass [LBM] x min, P < .03) metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

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Metabolic features of patients with and without coronary heart disease but with a superimposable cluster of cardiovascular risk factors.

BACKGROUND: Many studies have shown a significant association between the magnitude of insulin resistance and the plasma insulin levels in non-diabetic patients. It has also been shown that all major cardiovascular risk factors are associated with the presence of hyperinsulinemia or insulin resistance. However, studies have not addressed the possible metabolic differences in insulin action that can occur in patients with and without coronary heart disease (CHD) but with a superimposable cluster of risk factors. METHODS: Three groups of patients matched for age, sex, and lean body mass, but different in their absence of risk factors (group A; n = 8), presence of risk factors but no clinical and electrocardiographic signs of CHD (group B; n = 12), and the presence of risk factors, family history of CHD, and clinical and electrocardiographic signs of CHD (group C; n = 14) volunteered for the study. Patients in groups B and C were also matched for main risk factors. All patients were submitted to a euglycemic hyperinsulinemic glucose clamp during which a an infusion of 3H-glucose and indirect calorimetry facilitated the determination of glucose turnover parameters and substrate oxidation. RESULTS: Patients with CHD (group C) had the highest fasting plasma insulin levels (98 +/- 13 pmol/l) compared with patients in group B (86 +/- 4 pmol/l; P < 0.05) and in group A (63 +/- 4 pmol/l; P < 0.05) and the lowest insulin-mediated stimulation in non-oxidative glucose metabolism. Fasting lipid oxidation was similar in the three groups, but a stronger insulin-mediated inhibition in the control patients (group A) was found. Multiple regression analysis of the pooled data from the patients in groups B and C (n = 26) demonstrated that all risk factors considered correlated (t = 1.58, P < 0.04) with total body glucose disposal (TBGD) and accounted for 77% of the variability in TBGD. Furthermore, a separate analysis for groups B and C demonstrated a different contribution of all risk factors (89% and 65% for groups B and C, respectively) to the variability in TBGD. In group C patients, a multiple logistic regression analysis encompassing all risk factors studied, but also the family history of CHD, explained 92% of the variability in TBGD. CONCLUSION: In patients with and without CHD but with similar risk factors, a significant reduction in non-oxidative glucose metabolism occurs; nevertheless, such impaired glucose handling seems to be worsened in the presence of CHD. Further studies will be needed to determine the cause of such differences.

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Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients.

OBJECTIVE: To investigate the potential metabolic benefits deriving from daily vitamin E administration in type II diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-five type II diabetic patients were invited to randomly take placebo or vitamin E (d-alpha-tocopherol; 900 mg/day) along a similar 3-mo period in a double-blind, crossover procedure. A wash-out period of 30 days separated the two treatment periods. At the end of each treatment period blood samples were drawn for plasma metabolites determination, and an intravenous glucose tolerance test (25 g of glucose as bolus in 3 min) was performed. During this study oral hypoglycemic agents were not discontinued or changed in their dosage. RESULTS: Chronic vitamin E administration reduced plasma glucose (8.3 +/- 0.3 vs. 7.5 +/- 0.2 mM, P > 0.05), triglycerides (2.27 +/- 0.08 vs. 1.67 +/- 0.09 mM, P < 0.02), free fatty acids (786 +/- 116 vs. 483 +/- 64 mM), total cholesterol (6.74 +/- 0.09 vs. 5.50 +/- 0.10 mM, P < 0.05), low-density lipoprotein cholesterol (4.73 +/- 0.11 vs. 3.67 +/- 0.07 mM, P < 0.04), and apoprotein B (1.7 +/- 0.3 vs. 1.0 +/- 0.1 g/L) levels but did not affect beta-cell response to glucose. HbA1 levels (7.8 +/- 0.3 vs. 7.1 +/- 0.5%, P < 0.05) were also significantly lowered after chronic vitamin E administration. CONCLUSIONS: Daily vitamin E supplements seem to produce a minimal but significant improvement in the metabolic control in type II diabetic patients. More studies are necessary before conclusions can be drawn about the safety of vitamin E during long-term administration.

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Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus.

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.

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Metabolic and cardiovascular benefits deriving from beta-adrenergic blockade in chronic congestive heart failure.

Ten patients with congestive heart failure were given metoprolol (50 mg/day) or placebo during a double-blind, crossover, randomized study. After a run-in period of 4 weeks, metoprolol and placebo were administered over a period of 3 months, which was separated by a washout period of 4 weeks. At the end of the run-in, metoprolol, and placebo periods, all patients underwent metabolic (oral glucose tolerance and hyperinsulinemic glucose clamp tests) and noninvasive cardiologic (New York Heart Association classification, bimodal echocardiographic left ventricular end-diastolic determination, maximal oxygen consumption, left ventricular radionuclide ejection fraction) tests. Our results show that beta-adrenergic blockade significantly enhances insulin-mediated suppression of hepatic glucose output (p less than 0.005) and increase in glucose uptake (p less than 0.01) with a concurrent improvement in New York Heart Association functional class (p less than 0.05) and the multistage exercise treadmill test score (p less than 0.05). After administration of metoprolol all changes in glucose turnover parameters were found to correlate with the decrease in basal plasma free fatty acid levels. In conclusion, our findings confirm the beneficial cardiologic effects of beta-adrenergic blockade in congestive heart failure and demonstrate that metoprolol is also useful for reversing the metabolic damage caused by exaggerated plasma norepinephrine levels.

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Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia.

Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = -0.52, P less than 0.01).

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Daily magnesium supplements improve glucose handling in elderly subjects.

We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations (2.18 +/- 0.04 vs 1.86 +/- 0.03 mmol/L, P less than 0.01) in twelve aged (77.8 +/- 2.1 y) vs 25 young (36.1 +/- 0.4 y), nonobese subjects. Subsequently, aged subjects were enrolled in a double-blind, randomized, crossover study in which placebo (for 4 wk) and chronic magnesium administration (CMA) (4.5 g/d for 4 wk) were provided. At the end of each treatment period an intravenous glucose tolerance test (0.33 g/kg body wt) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed. CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action. Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action. In aged patients, correction of a low erythrocyte magnesium concentration may allow an improvement of glucose handling.

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Chronic magnesium administration enhances oxidative glucose metabolism in thiazide treated hypertensive patients.

In newly-diagnosed untreated (n = 24) and thiazide treated (n = 18) hypertensive patients erythrocyte ion content and plasma ion and metabolite levels were determined. Thiazide treated patients had lower arterial blood pressure, plasma ion levels, erythrocyte magnesium and potassium content but higher fasting plasma insulin (66 +/- 7 v 87 +/- 8 pmol/L P < .02), triglycerides (1.88 +/- 0.24 v 2.34 +/- 0.44 mmol/L P < .05), free fatty acids (0.68 +/- 0.11 v 0.81 +/- 0.18 mmol/L P < .05). Subsequently, in a double-blind fashion and in random order thiazide diuretic treated patients were assigned to two groups: the first (n = 9) taking magnesium (15.8 mmol/day) and the other (n = 9) a placebo. Each treatment period lasted 8 weeks. At the end of each treatment period, each patient underwent blood sampling for determination of erythrocyte ion content and plasma ion and metabolite levels and was submitted to an euglycemic hyperinsulinemic (1 mU/kg/min for 120 min) glucose clamp. In this latter test D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation respectively. Chronic magnesium administration (CMA) raised fasting plasma (0.79 +/- 0.03 v 0.83 +/- 0.02 mmol/L, P < .05) and erythrocyte (1.98 +/- 0.08 v 2.35 +/- 0.03 mmol/L, P < .01) magnesium content. Along with insulin infusion, CMA improved glucose uptake, glucose metabolic clearance rate, and oxidative glucose metabolism. In the multiple linear regression analysis of the pooled basal data (n = 42), erythrocyte magnesium content displayed an independent correlation with basal plasma insulin levels (t = -2.08, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Impaired glucose metabolism and reduced insulin clearance in elderly hypertensives.

Diabetes mellitus and essential hypertension are characterized by a continuous rise of prevalence with aging and this association may not be casual. Thirty nonobese nondiabetic elderly patients with primary hypertension and 28 healthy normotensives matched for age, sex, and body weight were evaluated for insulin secretion (oral glucose tolerance test, day-long glycemic and insulinemic profiles), action (euglycemic moderately hyperinsulinemic glucose clamp associated with 3H-3-glucose dilution technique), and clearance (120 min insulin/glucose infusion at two prefixed doses). Compared with normotensives, hypertensive elderly patients were characterized by the following: 1) plasma insulin and C-peptide were similar in basal conditions but significantly enhanced in response to both oral glucose and a mixed meal; 2) insulin-stimulated glucose uptake was significantly impaired with a similar rate of hepatic glucose production; 3) exogenous insulin metabolic clearance rate was significantly lower at both insulin infusion rates. The multiple alterations of insulin secretion, action and metabolism found in nonobese nondiabetic elderly hypertensives seem to support a role for this hormone in the regulation of arterial blood pressure.

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Progressive impairment of left ventricular diastolic filling with advancing age: a Doppler echocardiographic study.

OBJECTIVE: To identify the sequence and significance of left ventricular filling abnormalities associated with progressive aging in humans. DESIGN: Cross-sectional study comparing three age groups. SETTING: Department of Geriatrics at University of Naples. PARTICIPANTS: Seventy-five healthy subjects in three age groups: 25 subjects from 25 to 45 years (Group I), 25 subjects from 46 to 65 years (Group II), and 25 subjects from 66 to 85 years (Group III). INTERVENTION: None. MAIN OUTCOME MEASURES: All underwent pulsed-doppler echocardiography under color guide to measure the following parameters: peak velocity flow for early (E wave) and late (A wave) mitral flow; A/E wave ratio; deceleration time of mitral flow (MDt); isovolumic relaxation time (IRT); ratio of velocity time integrals of the A wave to the velocity time integrals of the entire mitral spectrum (VTIA/VTIM). RESULTS: Peak velocity of the E wave was slightly lower in Group II and III compared to Group I; in contrast, peak velocity of the A wave was greater (P less than 0.005) in aged individuals. Also A/E wave ratio, MDt, and IRT were significantly greater with advancing age (P less than 0.01; P less than 0.05 and P less than 0.001, respectively). Finally, VTIA/VTIM tended to be greater in the oldest group, but not significantly so. CONCLUSIONS: Left ventricular relaxation is progressively impaired in late middle age and old age, presumably an early marker of cardiac aging. Increased left atrial pressure is compromised only in the oldest group, presumably representing a compensation for impaired left ventricular relaxation.

Adult↗

Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin-dependent diabetics.

In healthy subjects (n = 10) and non-insulin-dependent (type II) diabetics (n = 10) matched for age [43.1 +/- 2.2 vs. 41 +/- 4.4 yr, P = not significant (NS)], body mass index (25.1 +/- 1.1 vs. 26 +/- 0.8 kg/m2, P = NS), gender ratio [5 males (M)/5 females (F) vs. 5M/5F], and mean arterial blood pressure (105 +/- 7 vs. 106 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after glutathione infusion (15 mg/min) and the relative increase in the plasma reduced (GSH)/oxidized (GSSG) glutathione ratio. The rise in the plasma GSH/GSSG ratio significantly improved total body glucose disposal in healthy subjects and in diabetic patients. In this latter group, GSH infusion potentiated the beta-cell response to glucose slightly. In controls and diabetics, insulin infusion with a simultaneous increase in the plasma GSH/GSSG ratio significantly enhanced nonoxidative glucose disposal without affecting oxidative glucose metabolism. After glutathione infusion, all metabolic and hormonal changes correlated with a significant decline in plasma membrane microviscosity. In conclusion, the plasma GSH/GSSG ratio seems to play a major role in the modulation of glucose homeostasis mainly in diabetics.

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