PubMed Health⌕ Search

Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 145 records · Page 8Linked to original sources
PubMed1993

Insulin sensitivity in familial hypercholesterolemia.

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of acute hypercarnitinemia during increased fatty substrate oxidation in man.

To test whether carnitine availability is rate-limiting for fat oxidation under conditions of augmented oxidative use of fatty substrates, two series of studies were performed. In study no. 1, L-carnitine (1 g + 0.5 g/h intravenously [i.v.]) or saline was given to eight volunteers during a 4-hour infusion of a 10% triglyceride emulsion, thereby increasing plasma free-carnitine levels from 38 +/- 4 to 415 +/- 55 mumol/L. Fat infusion increased plasma triglyceride levels (80%) and lipid oxidation (30%), and decreased (28%) carbohydrate oxidation (as measured by indirect calorimetry); hypercarnitinemia had no influence on these responses. In study no. 2 in 12 healthy subjects a bolus of L-carnitine (3 g) or saline was administered 40 minutes before aerobic exercise (bicycling for 40 minutes at 60 W), followed by 2 minutes of anaerobic exercise (250 W) and 50 minutes of recovery. Oxygen consumption (VO2), increased to 18.3 +/- 0.7 mL.min-1 x kg-1 during aerobic exercise, reached a maximum of 46.0 +/- 0.8 mL.min-1 x kg-1 during the anaerobic bout, and returned to baseline within a few minutes, with no difference between control and carnitine. At virtually identical mean energy expenditure rates (196 +/- 7 v 197 +/- 7 J.min-1 x kg-1, saline v carnitine), after carnitine administration the entire exercise protocol was sustained by a lower mean carbohydrate oxidation rate (42.1 +/- 3.6 v 36.5 +/- 2.3 mumol.min-1 x kg-1, P < .03) and a higher mean lipid oxidation rate (6.7 +/- 1.0 v 8.3 +/- 0.7 mumol.min-1 x kg-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Insulin action and substrate competition.

An increased supply of FFAs for oxidation leads to a reduced rate of glucose oxidation and interferes with the inhibitory action of insulin on hepatic glucose production. Available evidence indicates that in humans skeletal muscle is a site for such substrate competition, which involves both pyruvate oxidation and glycogen synthesis. The insulin resistance of obesity is thought to be mostly of metabolic origin, and fully reversible. A reduction in FFA supply by weight reduction can, however, reverse this defect. The insulin resistance associated with NIDDM is thought to be primary, with a strong genetic basis, and partially irreversible. Patients with NIDDM are unable to increase their glucose oxidation normally in response to insulin to meet the energy demands of the body. Increased oxidation of lipids represents a compensatory phenomenon to meet these demands. Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has yielded conflicting results. Studies are in progress to develop agents that inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid derivatives seem to enhance glycogen synthesis acutely by activating glycogen synthetase. Whether these or similar agents can be used to restore impaired glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be answered until the effect has been proven in chronic studies. The existence of substrate competition between amino acids and glucose, and an intrinsic hypoaminoacidaemic property of amino acids, makes it possible to expand the Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of substrate disposition at the whole body level.

Animals↗
PubMed1993

Relationship between insulin release, antinatriuresis and hypokalaemia after glucose ingestion in normal and hypertensive man.

1. Insulin simultaneously causes hypokalaemia and antinatriuresis, and it has been suggested that the two effects are tightly coupled. Whether these actions are preserved in patients with essential hypertension is not known. 2. Eight hypertensive patients and eight normotensive control subjects were studied before and after the ingestion of 75 g of glucose. Despite similar glycaemic profiles, the patients showed a hyperinsulinaemic response incremental area 49 +/- 8 versus 27 +/- 6 nmol l-1 3 h, P < 0.04) but a blunted hypokalaemic response (-7 +/- 1 versus -16 +/- 1%, P < 0.001). Both absolute and fractional urinary excretion of sodium and potassium were significantly decreased during glucose-induced hyperinsulinaemia in hypertensive patients as well as in normotensive subjects (P < 0.05 for all changes). 3. To test whether hypokalaemia is required for insulin-induced antinatriuresis, each hypertensive patient received another oral glucose load during which enough potassium chloride was given to clamp the plasma potassium concentration at baseline. Under these conditions, significant insulin-induced antinatriuresis still occurred. In addition, whereas the glycaemic profile was superimposable, the response of the plasma insulin concentration was significantly greater with than without maintenance of the plasma potassium concentration (total area 79 +/- 14 versus 63 +/- 8 nmol l-1 3 h, P < 0.04). 4. We conclude that (a) insulin causes antinatriuresis, antikaliuresis and hypokalaemia under physiological conditions; (b) in hyperinsulinaemic (insulin-resistant) patients with essential hypertension, the antinatriuretic action of insulin is quantitatively preserved; and (c) clamping plasma potassium levels prevents insulin-induced antikaliuresis but not antinatriuresis, and potentiates the insulin secretory response to glucose.

Adult↗
PubMed1993

Insulin resistance of stress: sites and mechanisms.

1. Stress is associated with a severe, yet reversible, form of insulin resistance. The aim of this study was to quantify the kinetics of insulin action (sensitivity and responsiveness) on intermediary metabolism during post-surgical stress. 2. We studied nine patients 6-8 h after major uncomplicated surgery, and eight healthy subjects matched for age, weight, glucose tolerance and duration of fast. A three-step isoglycaemic insulin clamp was combined with indirect calorimetry, [6-3H]glucose infusion and the forearm technique. 3. The following significant (P < 0.05 or less) abnormalities were found in the patients. Hepatic glucose production was higher at baseline, and less suppressed by insulin. Whole-body glucose disposal was impaired at all insulin doses (by 33-60%). Glucose oxidation was depressed throughout the dose range but its increments in response to insulin were normal. In contrast, non-oxidative glucose disposal was essentially unresponsive. At all insulin levels, forearm glucose extraction was markedly depressed and forearm lactate release was in excess of concurrent glucose uptake, suggesting ongoing glycogenolysis despite insulin. Total lipolysis (plasma free fatty acid and glycerol levels) promptly responded to insulin but remained higher than in the control subjects throughout. In the forearm, even the highest insulin dose could not suppress net free fatty acid and glycerol release. Total lipid oxidation was increased throughout the insulin range, and calculated direct free fatty acid (as opposed to plasma free fatty acid) oxidation was virtually unaffected by insulin. Protein oxidation was slightly (35%) increased, but was suppressed normally in response to insulin. Energy expenditure was 20% higher at baseline, and failed to rise with insulin. Arterial blood pH values were consistently (if slightly) lower, and net forearm proton release was higher, both at baseline and during insulin infusion. 4. Post-surgical insulin resistance is characterized by normal sensitivity but decreased responsiveness of glucose oxidation, lipolysis and plasma free fatty acid oxidation, whereas glycogen synthesis and direct free fatty acid oxidation are virtually unresponsive. For both glucose and lipid metabolism, the insulin resistance is particularly severe in forearm tissues, in which mild metabolic acidosis may play an additional role.

Blood Glucose↗
PubMed1993

Metabolic and hemodynamic effects of insulin on human hearts.

Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta-hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1993

Metabolic and thermogenic effects of lactate infusion in humans.

Lactate has been suggested to interfere with intermediary metabolism by restricting both lipolysis and glucose utilization. To test this hypothesis, in paired studies in healthy volunteers, sodium lactate (25 mumol.min-1 x kg-1) or saline was infused for 1 h in the fasting state and during 2 h of euglycemic (4.75 mM) hyperinsulinemia (approximately 400 pmol/l). Hyperlactatemia (approximately 2 mM) had no inhibitory effect on fasting free fatty acid or glycerol levels nor did it alter the suppressive action of insulin on these substrates. Likewise, sodium lactate infusion did not influence hepatic glucose production ([3-3H]glucose technique) or its suppression by insulin. During the clamp, hyperlactatemia was associated with a small increase in whole body glucose disposal (34.9 +/- 4.1 vs. 30.3 +/- 3.7 mumol.min-1 x kg-1, P < 0.05) with no major change in the pattern of substrate (carbohydrate vs. lipid) oxidation. By simultaneously measuring arteriovenous gradients across the deep tissues of the forearm (forearm technique), it was found that hyperlactatemia did not impede insulin-mediated glucose uptake; furthermore, it could be estimated that muscle tissues were responsible for the disposal of roughly one-fifth of the lactate load. Whole body energy expenditure was stimulated above the level achieved with hyperinsulinemia when lactate was also infused. Thus, under the present experimental conditions, physiological hyperlactatemia did not interfere with lipolysis, hepatic glucose production, or whole body or forearm muscle glucose utilization, or with insulin action on these processes, and was accompanied by a strong thermogenic effect.

Adult↗
PubMed1993

Syndrome X.

Using cross-sectional and longitudinal analysis of data from the San Antonio Heart Study, syndrome X (primary insulin resistance syndrome) has been redefined in terms of hyperinsulinaemia combined with changes in glucose tolerance, lipid pattern, blood pressure and body fat distribution. Syndrome X is itself an atherogenic cardiovascular risk factor, which interacts with environmental and genetic factors to lead to the eventual development of the endpoint of cardiovascular disease.

Adipose Tissue↗
PubMed1993

Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.

Adult↗
PubMed1993

Glucose transport in human skeletal muscle. The in vivo response to insulin.

Transmembrane glucose transport plays a key role in determining insulin sensitivity. We have measured in vivo WBGU, FGU, and K(in) and K(out) of 3-O-methyl-D-glucose in forearm skeletal muscle by combining the euglycemic clamp technique, the forearm-balance technique, and a novel dual-tracer (1-[3H]-L-glucose and 3-O-[14C]-methyl-D-glucose) technique for measuring in vivo transmembrane transport. Twenty-seven healthy, lean subjects were studied. During saline infusion, insulin concentration, FGU (n = 6), K(in), and K(out) (n = 4) were similar to baseline. During SRIF-induced hypoinsulinemia (insulin < 15 pM, n = 4) WBGU was close to 0, and FGU, K(in), and K(out) were unchanged from basal (insulin = 48 pM) values. During insulin clamps at plasma insulin levels of approximately 180 (n = 4), approximately 420 (n = 5), approximately 3000 (n = 4), and approximately 9500 pM (n = 4), WBGU was 14.2 +/- 1.3, 34.2 +/- 4.1 (P < 0.05 vs. previous step), 55.8 +/- 1.8 (P < 0.05 vs. previous step), and 56.1 +/- 6.3 mumol.min-1.kg-1 of body weight (NS vs. previous step), respectively. Graded hyperinsulinemia concomitantly increased FGU from a basal value of 4.7 +/- 0.5 mumol.min-1.kg-1 up to 10.9 +/- 2.3 (P < 0.05 vs. basal value), 26.6 +/- 4.5 (P < 0.05 vs. previous step), 54.8 +/- 4.3 (P < 0.05 vs. previous step), and 61.1 +/- 10.8 mumol.min-1.kg-1 of forearm tissues (NS vs. previous step), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Energy expenditure and gas exchange measurements in postoperative patients: thermodilution versus indirect calorimetry.

OBJECTIVE: To compare a method of measuring energy expenditure and gas exchange using the Fick principle with the standard indirect calorimetry technique. DESIGN: Prospective study of a consecutive sample of postoperative patients. Oxygen consumption (VO2), CO2 production (VCO2), respiratory quotient, and energy expenditure were derived from measurements of variables, including oxygen content and cardiac output. Energy expenditure and gas exchange were measured simultaneously by continuous indirect calorimetry over a 60-min period. SETTING: Surgical ICU in a university hospital. PATIENTS: Twenty-six consecutive patients (45 to 80 yrs) who underwent sustained surgical trauma. Excluded from the study entry were patients with time-related fluctuations of hemodynamic variables, poor cooperation, patients who required supplemental oxygen, or mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While the measurements of VO2 and VCO2 by calorimetry and thermodilution were significantly correlated with one another (for VO2, r2 = .93, p less than .001; for VCO2, r2 = .26, p less than .01), VO2 and VCO2 values by indirect calorimetry were consistently greater than VO2 and VCO2 values by the Fick method (p less than .01). The respiratory quotient calorimetric measurements ranged between 0.69 and 0.99, whereas the corresponding thermodilution measurements spread to impossible values, from 0.24 to 1.30 (0.821 +/- 0.07 vs. 0.740 +/- 0.24, p less than .05). There was an insignificant relationship (r2 = .06, p = .21) between the values of respiratory quotient by the two methods. A strong, positive correlation between energy expenditure measured by indirect calorimetry and energy expenditure measured by the Fick method was observed (r2 = .92, p less than .001). The limit of agreement between the two methods was -0.24 +/- 73 kcal/day/m2 (-1.00 +/- 305 kJ/day/m2). CONCLUSIONS: In postoperative patients, while VO2 and energy expenditure measurements by thermodilution are easy to perform and accurate for clinical purposes, VCO2, and respiratory quotient measurements are too imprecise and inaccurate to serve any useful function. Therefore, in those clinical situations in which an evaluation of respiratory quotient and substrate utilization may be useful for purposes of metabolic care of the surgical patient, precise measurements of gas exchange with indirect calorimetry are mandatory.

Calorimetry, Indirect↗
PubMed1992

Potassium as a link between insulin and the renin-angiotensin-aldosterone system.

PURPOSE: To focus on the interactions between insulin secretion, glucose tolerance and insulin sensitivity on the one hand and the renin-angiotensin-aldosterone system on the other. EFFECTS ON INSULIN: Insulin is a potent stimulus for hypokalaemia, sparing body potassium from urinary excretion by transporting it into cells. Potassium also appears to play a key role in the antinatriuretic effect of insulin. Insulin-induced hypokalaemia increases plasma renin and angiotensin II levels while decreasing the serum aldosterone concentration. In turn, the renin-angiotensin-aldosterone system affects glucose tolerance by modulating plasma potassium levels, which act as a stimulus for glucose-induced insulin release. EFFECTS OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITION: Interference with the renin-angiotensin-aldosterone system by ACE inhibition blunts the hypokalaemic response to insulin, thereby improving glucose-induced insulin release and oral glucose tolerance. ACE inhibition, however, does not cause major changes in insulin sensitivity. POTASSIUM AND BLOOD PRESSURE: Plasma potassium levels are inversely related to blood pressure, both in population surveys and in intervention studies. In addition, in patients with essential hypertension, the level of plasma potassium appears to predict the blood pressure response to ACE inhibition. SUMMARY: Potassium metabolism is an important link between carbohydrate metabolism and the renin-angiotensin-aldosterone system by way of a double-feedback mechanism. Through the potential effects on blood pressure control, plasma levels of potassium represent a link between insulin and blood pressure in humans.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

The haemodynamics of obesity: a theoretical analysis.

BACKGROUND: Obesity and hypertension are frequently associated with one another, and changes in body weight are usually accompanied by consensual changes in blood pressure. OBJECTIVE: To examine formally the haemodynamic conditions required for a weight gain to cause a rise in blood pressure in the resting state. METHODS: The relevant equations were developed, and then used in a simulation to predict blood pressure and peripheral vascular resistance in response to changes in body weight. The model was tested on data taken from published reports. Furthermore, the impact of the composition of the excess weight, i.e. fat versus muscle tissue, on the haemodynamics of obesity was incorporated into the simulation by using a range of tissue-specific blood flow rates taken from published reports. RESULTS: The key determinant of weight-induced increases in blood pressure is a disproportional increase in cardiac output, which is not fully accounted for by the haemodynamic contribution of new tissues. An increase in muscle tissue relative to fat in newly gained weight is a further factor in the blood pressure increase arising from any given level of excess weight. CONCLUSIONS: The disproportional increase in cardiac output in obesity is best attributed to stimulation of cardiac dynamics by the adrenergic nervous system. The low resistance of adipose tissue relative to muscle may be the physiologic basis for the dominance of fat-free mass in multiple regression analyses of blood pressure determinants in the population; it further suggests that in the obese hypertensive, fat tissue may provide protection against cardiovascular disease by limiting increases in total peripheral resistance.

Blood Pressure↗
PubMed1992

The insulin resistance syndrome.

Insulin resistance is a frequently occurring abnormality. Although there can be insensitivity to any of insulin's actions, insulin resistance par excellence is a decreased insulin-mediated whole-body glucose disposal rate. A distinction is made between primary and secondary insulin resistance. Primary insulin resistance is of unknown origin, is only partially experimentally reproducible, and is essentially irreversible (spontaneously or by treatment). In addition, it is both pathway-specific (ie, glucose storage) and organ-specific (mostly skeletal muscle), and is compatible with a postreceptor defect in insulin action. Primary insulin resistance is found in a proportion (approximately 25%) of otherwise healthy people, in non-insulin-dependent diabetes mellitus, essential hypertension, and some forms of dyslipidemia. The idea of an insulin resistance syndrome derives from the striking pattern of overlap among these clinical conditions. Their tendency to cluster in the same individuals is evident from both cross-sectional and longitudinal observations. It is proposed that the insulin resistance syndrome is a large constellation of interrelated changes in metabolic, anthropometric, and hemodynamic variables centered around insulin resistance or hyperinsulinemia. There is a significant genetic component, a predisposing influence for non-insulin-dependent diabetes mellitus, hypertension, dyslipidemia, and possibly, a distinct atherogenic potential.

Diabetes Mellitus, Type 2↗
PubMed1992

Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in hypertensive type 2 diabetic patients.

The question, of whether long-term treatment of essential hypertension with angiotensin-converting enzyme (ACE) inhibitors is capable of modifying glucose tolerance or insulin sensitivity in Type 2 (non-insulin dependent) diabetes, is still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period and again after 3 months of antihypertensive treatment with the ACE inhibitor, captopril. Glucose tolerance was tested with a 75-g oral glucose load and insulin sensitivity was measured by the insulin suppression test, while dietary and drug treatment of the diabetes remained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 +/- 3 mmHg to a final value of 115 +/- 2 mmHg (p < 0.005); in six patients, the change in MBP was < 5 mmHg (non-responders), thus giving a clinical response rate of approximately 60%. After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycated haemoglobin concentrations were unchanged from baseline. During the oral glucose tolerance test, the incremental glucose area-under-curve was 0.75 +/- 0.05 mol 120 min l-1 before and 0.76 +/- 0.06 mol 120 min l-1 after treatment (p = ns). Endogenous insulin response and suppression of plasma FFA levels were superimposable on the two occasions. During the insulin suppression test, steady-state plasma glucose levels were 14.4 +/- 1.3 vs 14.2 +/- 1.1 mmol l-1 before and after chronic ACE inhibition, respectively, at comparable hyperinsulinaemic plateaux (291 +/- 21 vs 287 +/- 14 pmol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle.

The effects of daily chronic treatment for 6 months with pravastatin was evaluated on the performance of the skeletal muscle system of different rat groups. At all doses (0.1 mg/kg-20 mg/kg) the righting reflex and the electromyographic signals observed in vivo did not show any abnormality. At the end of the treatment the Extensor digitorum longus muscles were dissected from treated and control rats and their passive and active electrical parameters were analyzed in vitro by standard microelectrodes technique. Pravastatin did not modify the chloride conductance nor the excitability characteristics of the fibers. Chronic treatment with pravastatin does not produce any alteration of skeletal muscle function.

Animals↗
PubMed1992

Clustering of cardiovascular risk factors in confirmed prehypertensive individuals.

Numerous studies have indicated that hypertensive subjects have an atherogenic lipoprotein pattern, hyperinsulinemia, and impaired glucose tolerance relative to normotensive individuals. These abnormalities could be due to adverse effects of certain antihypertensive agents, to pathophysiological concomitants of the hypertensive state itself, or to both. In this report, we describe the cardiovascular risk factor profile of 1,440 subjects who were normotensive and were not taking any antihypertensive medications when first examined and who subsequently participated in the 8-year follow-up of the San Antonio Heart Study. Hypertension developed in 130 subjects during the follow-up period. At baseline these prehypertensive individuals had significantly higher levels of blood pressure, fasting total and low density lipoprotein cholesterol, triglyceride, glucose, and insulin, and 2-hour glucose than those who remained free of hypertension. In addition, they had higher body mass indexes, a less favorable body fat distribution, and lower levels of high density lipoprotein cholesterol. In multiple linear regression analyses, baseline levels of triglyceride and blood pressure remained significantly higher and high density lipoprotein cholesterol remained significantly lower in the subjects who later converted to hypertension than in those who remained normotensive. Although baseline insulin levels were also higher in the prehypertensive subjects, this difference was not statistically significant. In nonobese subjects, however, those with high baseline insulin concentrations had an increased incidence of hypertension compared with those with low insulin concentrations. The present results suggest that the cluster of atherogenic changes associated with hypertension actually precede the development of the hypertensive state.

Adult↗